Association between brain and upper cervical spinal cord atrophy assessed by MRI and disease aggressiveness in amyotrophic lateral sclerosis.
To study the relative contributions of brain and upper cervical spinal cord compartmental atrophy to disease aggressiveness in amyotrophic lateral sclerosis (ALS). Twenty-nine ALS patients and 24 age- and gender-matched healthy controls (HC) were recruited. Disease duration and the Revised-ALS Functional Rating Scale (ALSFRS-R) at baseline, 3- and 6-months follow-up were assessed. Patients were clinically differentiated into fast (n=13) and slow (n=16) progressors according to their ALSFRS-R progression rate. Brain grey (GM) and white matter, brainstem sub-structures volumes and spinal cord cross-sectional area (SC-CSA) at C1-C2 vertebral levels were measured from a 3D-T1-weighted MRI. Fast progressors showed significant GM, medulla oblongata and SC atrophy compared to HC (p<0.001, p=0.013 and p=0.008) and significant GM atrophy compared to slow progressors (p=0.008). GM volume correlated with the ALSFRS-R progression rate (Rho/p=-0.487/0.007), the ALSFRS-R at 3-months (Rho/p=0.622/0.002), and ALSFRS-R at 6-months (Rho/p=0.407/0.039). Medulla oblongata volume and SC-CSA correlated with the ALSFRS-R at 3-months (Rho/p=0.510/0.015 and Rho/p=0.479/0.024). MRI measures showed high performance to discriminate between fast and slow progressors. Our study suggests an association between compartmental atrophy and disease aggressiveness. This result is consistent with the combination of upper and lower motor neuron degeneration as the main driver of disease worsening and severity in ALS. Our study highlights the potential of brain and spinal cord atrophy measured by MRI as biomarker of disease aggressiveness signature.


[Prevention and treatment of cardiovascular complications of oral therapy].
Acute cardiovascular event is common acute complication in oral therapy. This article describes how to assess risk of cardiovascular complications before oral treatment, and elabrates the prevention and treatment of angina, acute myocardial infarction, arrhythmia, cardiac arrest, cardiopulmonary resuscitation and other cardiovascular complications. Detailed assessment and comprehensive management of patients are important guarantee for safe oral treatment.


Nanocapsules of unprecedented internal volume seamed by calcium ions.
The inception of an unprecedented class of voluminous Platonic solids displaying hierarchical geometry based on pyrogallol[4]arene moieties seamed by divalent calcium ion is described. Single-crystal X-ray structural determination has established the highly conserved geometry of two original Ca2+-seamed nanocapsules to be essentially cubic in shape with C-ethylpyrogallol[4]arene units located along the twelve edges of the cube which are then bridged by metallic polyatomic cations ([Ca4Cl]7+ or [Ca(HCO2)Na4]5+) at the six cube faces. The accessible volume of the nanocapsules is ca. 3500 Å3 and 2500 Å3 and is completely isolated from the exterior of the capsules. These remarkable nanocapsule discoveries cast a spotlight on a marginalized area of synthetic materials chemistry and encourage future exploration of diversiform supramolecular assemblies, networks, and capsules built on calcium, with clear benefits deriving from the intrinsic biocompatibility of calcium. Finally, a proof-of-concept is demonstrated for fluorescent reporter encapsulation and sustained release from the calcium-seamed nanocapsules, suggesting their potential as delivery vehicles for drugs, nutrients, preservatives, or antioxidants.


Negative inotropic effect of the combination of theophylline and ouabain in rabbit right ventricle: relation to elevated baseline tension.
The effects of the combined administration of theophylline and ouabain were examined in isolated right ventricular strips from the rabbit heart. Separately, each drug produced positive inotropism. If ouabain was added 10 minutes after theophylline, a decrease in dF/dt was observed. The presence of theophylline augmented the increase in baseline tension induced by ouabain, although theophylline, by itself, did not augment baseline tension at the concentrations tested. There was a significant correlation between the decrease in dF/dt and the rise in baseline tension. Theophylline did not enhance the ability of ouabain to induce arrhythmia. The actions of caffeine, theobromine and digoxin were also examined and gave similar results.


Female preferences for male golden snub-nosed monkeys vary with male age and social context.
Age is a key factor affecting sexual selection, as many physical and social traits are age-related. Although studies of primate mate choice often consider particular age-related traits, few consider the collective effects of male age. We tested the hypothesis that female golden snub-nosed monkeys Rhinopithecus roxellana prefer prime aged males (10-15 years) over younger and older males. We examined a habituated, provisioned troop during a 3-year study in the Qinling Mountains, China. Prime age males were more likely to be resident males of 1-male units (OMUs) than males of other ages. Since females are free to transfer between OMUs, the number of females per OMU can be indicative of female preferences. We examined the number of females per OMU, and found that it increased with resident male age up to 7-8 years, and declined after 12 years, such that prime age resident males had more females than other resident males. Females also initiated extra-unit copulations with high-ranking prime age males at significantly higher rates than with other males. Nevertheless, females tended to transfer from OMUs with high-ranking, older resident males to those with low-ranking, younger resident males. Thus, females appear to use different strategies when choosing social mates and extra-unit mates (i.e., different social contexts). We speculate that females may perceive early signs of aging in males and trade off the benefits and costs of high rank versus male senescence. This study lays the groundwork for future studies that examine possible direct and indirect benefits of such strategies.


Lifewide Learning for Early Reading Development.
The authors examine the relationships between children's reading abilities and the enabling environment for learning in the context of Save the Children's Literacy Boost program. They conceptualize the enabling environment at a micro level, with two components: the home literacy environment, represented by reading materials/habits at home, and the community learning environment (community reading activities). Using longitudinal reading scores of 6,874 students in 424 schools in 12 sites across Africa and Asia, there was 1) a modest but consistent relationship between students' home literacy environments and reading scores, and 2) a strong relationship between reading gains and participation in community reading activities, suggesting that interventions should consider both home and community learning environments and their differential influences on interventions across different low-resource settings.


Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium.
The hallmark of the menstrual cycle is extensive steroid-dependent tissue turnover. Estrogen mediates endometrial cell growth and structural remodeling, whereas progesterone suppresses estrogen-dependent proliferation and promotes cellular differentiation. In nonfertile cycles, tissue degradation and menstruation occur as a consequence of steroidal deprivation as the ovarian corpus luteum fails. Stromal-epithelial interactions are recognized as a necessary component in mediating steroid-induced endometrial turnover. Specific mRNAs for metalloproteinases of the stromelysin family are expressed during endometrial growth and menstrual breakdown but are absent in the progestin-dominated secretory phase. This expression pattern suggests involvement of stromelysins in remodeling the extracellular matrix of the endometrium during tissue growth and breakdown and implicates progesterone in the suppression of these enzymes. We examined the regulation of endometrial stromelysins in explant cultures and found no acute effect of estradiol on their expression, whereas progesterone was a potent inhibitor of stromelysin expression. Progesterone also suppressed stromelysin expression in cultures of isolated stromal cells, but epithelial cells were progesterone insensitive. Coculture of recombined stromal and epithelial cells restored steroidal suppression of the epithelial-specific metalloproteinase. Our data confirm that progesterone inhibits endometrial stromelysins and further demonstrate the necessity for a stromal-derived factor(s) as a mediator of steroid suppression of an epithelial metalloproteinase.


Is pulmonary artery catheterization necessary for the diagnosis of pulmonary edema?
The ability to differentiate cardiac from permeability edema on the basis of clinical and radiographic criteria was studied in 70 ICU patients in whom subsequent pulmonary artery catheterization (PAC) was performed. Our study demonstrated that the clinical assessment of permeability pulmonary edema was correct in 17 of 20 patients (85%). In contrast, of the 50 patients initially suspected of having cardiac edema, only 31 (62%) were predicted correctly (p less than 0.05). Complications relating to catheterization occurred in 25% of patients, with 3 deaths. We conclude that the diagnosis of cardiogenic pulmonary edema, based on clinical criteria alone, is often inaccurate in the intensive care setting. The failure of patients to respond to initial therapy should mandate pulmonary artery catheterization, despite the attendant risks. Furthermore, even though the clinical diagnosis is correct in 85% of patients with permeability pulmonary edema, PAC data may be necessary for optimal management.


Views and Decisions of Physicians in Encountering Neonates with Poor Prognosis.
With the development of neonatal intensive care units (NICUs), new issues have emerged for physicians working in this area, including the ethical aspects of providing invasive and advanced care to neonates with extremely poor prognosis. This research was undertaken with the aim of investing the factors affecting physicians' practice in management of newborns in such complicated circumstances. A cross-sectional study was carried out over a period of 5 months (Jan 2012 to Jun 2012) in 9 different tertiary levels and academic NICUs affiliated to Tehran University of Medical Sciences in Tehran, Iran. Checklists related to management of 3 hypothetical cases with very poor prognosis and factors affecting pertinent decisions were administered to 88 neonatologists and pediatricians. Totally, 81.4% of participants approved the use of advanced invasive methods of treatment in the premature neonate. Concerning the neonate with genetic malformations, 51.3% recommended advanced methods. In severe asphyxia, 42.1% disagreed with use of advanced invasive procedures. Overall, 34.2% of the target physicians approved the use of aggressive procedures in all 3 cases. Age, gender, marital status, parental status, and work experience were identified as influencing factors. With the prediction of acceptable levels of survivability in very premature infants, physicians are more inclined to treat this group. However, they do not favor aggressive measures in infants with severe asphyxia and advanced anomalies.


From soma to psyche: the crucial connection. Part 2. 'Cross-cultural medicine' decoded: learning about 'us' in the act of learning about 'them'.
The scorpion's bite--a culturally inept response to a medical emergency. Margaret Clark's criteria--keys to cultural barriers in medical care. Clifford Geertz's injunction: to view the culturally "different" as mirrors of the unacknowledged self. The case of José--scandal of his "compartmentalized" treatment. How much context may a physician be willing to absorb? Shawcross's The Quality of Mercy: western medical teams in Cambodian refugee camps--their good intentions versus their ethnocentric gaffes. The elderly as avatars of a "culture within a culture." Their beliefs, fears, dreams, and intimations--a "terra incognita" for service providers. Sardonic recoil against them (as in Shem's novel House of God) by residents--a professionally sanctioned response, deflecting what might otherwise be unendurable demands on their varied quotas of pity. Sisela Bok's moral claims: (1) for the integrity of decision making among the sick; (2) for the autonomy of the "dying response" among the aged. Steinberg's The Ethnic Myth: indictment of those using cultural difference to "explain" (or rationalize) health--and other--deficits rooted in historic, social, or economic inequity.


An investigation of the tylosis with oesophageal cancer (TOC) locus in Iranian patients with oesophageal squamous cell carcinoma.
Oesophageal cancer is one of the ten leading causes of cancer mortality worldwide. Earlier loss of heterozygosity (or allelic imbalance) studies have implicated regions on chromosomes 3p, 5q, 9p, 13q, 17p, 17q, and 18q in the development of sporadic oesophageal cancer and recent data have linked the familial tylosis with oesophageal cancer (TOC) gene-containing region on chromosome 17q25 with this cancer. We have studied allelic imbalance (AI) at microsatellite markers both closely linked to and distant from the TOC gene locus in 60 sporadic squamous cell oesophageal cancers from Iran and have investigated the most likely candidate gene by mutation analysis in these tumours. Forty-four out of these 60 samples (73%) show allelic imbalance at one or more loci within or adjacent to the TOC minimal region, while the highest incidence of AI was observed at the D17S2244 and D17S2246 loci (almost 70% AI in informative cases), correlating with the TOC minimal region. Analysis of the coding regions of a candidate gene in these tumours failed to show an equivalently high incidence of mutation, although two mutations and one polymorphism were observed. These data support and extend previous observations that the TOC region of chromosome 17q25 may be involved in the aetiology of the sporadic form of oesophageal cancer from a number of different geographical populations and suggest that the causative gene may be epigenetically silenced rather than mutated.


Apobec1 complementation factor (A1CF) and RBM47 interact in tissue-specific regulation of C to U RNA editing in mouse intestine and liver.
Mammalian C to U RNA is mediated by APOBEC1, the catalytic deaminase, together with RNA binding cofactors (including A1CF and RBM47) whose relative physiological requirements are unresolved. Although A1CF complements APOBEC1 for in vitro RNA editing, A1cf-/- mice exhibited no change in apolipoproteinB (apoB) RNA editing, while Rbm47 mutant mice exhibited impaired intestinal RNA editing of apoB as well as other targets. Here we examined the role of A1CF and RBM47 in adult mouse liver and intestine, following deletion of either one or both gene products and also following forced (liver or intestinal) transgenic A1CF expression. There were minimal changes in hepatic and intestinal apoB RNA editing in A1cf-/- mice and no changes in either liver- or intestine-specific A1CF transgenic mice. Rbm47 liver-specific knockout (Rbm47LKO ) mice demonstrated reduced editing in a subset (11 of 20) of RNA targets, including apoB. By contrast, apoB RNA editing was virtually eliminated (<6% activity) in intestine-specific (Rbm47IKO ) mice with only five of 53 targets exhibiting C-to-U RNA editing. Double knockout of A1cf and Rbm47 in liver (ARLKO ) eliminated apoB RNA editing and reduced editing in the majority of other targets, with no changes following adenoviral APOBEC1 administration. Intestinal double knockout mice (ARIKO ) demonstrated further reduced editing (<10% activity) in four of five of the residual APOBEC1 targets identified in ARIKO mice. These data suggest that A1CF and RBM47 each function independently, yet interact in a tissue-specific manner, to regulate the activity and site selection of APOBEC1 dependent C-to-U RNA editing.


Rose bengal in poly(2-hydroxyethyl methacrylate) thin films: self-quenching by photoactive energy traps.
The effect of dye concentration on the fluorescence,ΦF, and singlet molecular oxygen,ΦΔ, quantum yields of rose bengal loaded poly(2-hydroxyethyl methacrylate) thin films (∼200 nm thick) was investigated, with the aim of understanding the effect of molecular interactions on the photophysical properties of dyes in crowded constrained environments. Films were characterized by absorption and fluorescence spectroscopy, singlet molecular oxygen (1O2) production was quantified using a chemical monitor, and the triplet decay was determined by laser flash-photolysis. For the monomeric dilute dye, ΦF = 0.05 ± 0.01 and ΦΔ = 0.76 ± 0.14. The effect of humidity and the photostability of the dye were also investigated. Spectral changes in absorption and fluorescence in excess of 0.05 M and concentration self-quenching after 0.01 M are interpreted in the context of a quenching radius model. Calculations of energy migration and trapping rates were performed assuming random distribution of the dye. Best fits of fluorescence quantum yields with concentration are obtained in the whole concentration range with a quenching radius r Q = 1.5 nm, in the order of molecular dimensions. Agreement is obtained only if dimeric traps are considered photoactive, with an observed fluorescence quantum yield ratio ΦF,trap/ΦF,monomer ≈ 0.35. Fluorescent traps are capable of yielding triplet states and 1O2. Results show that the excited state generation efficiency, calculated as the product between the absorption factor and the fluorescence quantum yield, is maximized at around 0.15 M, a very high concentration for random dye distributions. Relevant information for the design of photoactive dyed coatings is provided.


Can perfusion MRI predict response to preoperative treatment in rectal cancer?
Dynamic contrast-enhanced MRI (DCE-MRI) provides information on perfusion and could identify good prognostic tumors. Aim of this study was to evaluate whether DCE-MRI using a novel blood pool contrast-agent can accurately predict the response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Thirty patients underwent DCE-MRI before and 7-10weeks after chemoradiotherapy. Regions of interest were drawn on DCE-MRI with T2W-images as reference. DCE-MRI-based kinetic parameters (initial slope, initial peak, late slope, and AUC at 60, 90, and 120s) determined pre- and post-CRT and their Δ were compared between good (TRG1-2) and poor (TRG3-5) responders. Optimal thresholds were determined and sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were calculated. Pre-therapy, the late slope was able to discriminate between good and poor responders (-0.05×10(-3) vs. 0.62×10(-3), p<0.001) with an AUC of 0.90, sensitivity 92%, specificity 82%, PPV 80%, and NPV 93%. Other pre-CRT parameters showed no significant differences, nor any post-CRT parameters or their Δ. The kinetic parameter 'late slope' derived from DCE-MRI could potentially be helpful to predict before the onset of neoadjuvant chemoradiotherapy which tumors are likely going to respond. This could allow for personalized treatment-options in rectal cancer patients.


Interferon-induced changes in the monocyte membrane: inhibition by retinol and retinoic acid.
The effects of human interferon-beta on human peripheral blood monocyte function were examined in vitro. Interferon-beta was shown to increase substantially the expression of both Fc gamma receptors and HLA-DR antigens defined by monoclonal antibody. Retinol and retinoic acid were found to be antagonistic to these effects of interferon and physiological concentrations were sufficient to inhibit changes in the monocyte membrane induced by relatively high concentrations of interferon.


Combining entacapone with levodopa/DDCI improves clinical status and quality of life in Parkinson's Disease (PD) patients experiencing wearing-off, regardless of the dosing frequency: results of a large multicentre open-label study.
The efficacy of entacapone and its impact on patient quality of life (QOL) was investigated in an open-label study of 899 patients with idiopathic Parkinson's Disease (PD) experiencing wearing-off fluctuations. Patients were divided into 3 groups (3, 4 or 5 doses daily) based on their current levodopa dosage frequency. Patients received 200 mg entacapone with each levodopa/dopa-decarboxylase inhibitor (DDCI) dose, while continuing their same levodopa/DDCI dosage regimen for 4 weeks. Primary efficacy measure was the Investigators' Clinical Global Impression of Change (CGIC). Patient QoL was assessed using the validated 8-item Parkinson's Disease Questionnaire (PDQ-8). Investigators' CGIC revealed that 76.5% of entacapone treated patients experienced an improvement in global status after 4 weeks. Treatment with entacapone was also associated with improvement in patient QoL, with a mean reduction (improvement) in PDQ-8 score of 1.8 from baseline. This study confirms and extends the results of earlier studies demonstrating that, independent of dosing frequency, completing levodopa/DDCI therapy with entacapone provides clinically relevant improvements in global status and QoL in PD patients experiencing wearing-off on their current levodopa dosing frequency.


VALIDA: A Validation Therapy-Training Program for Staff of a Residential Care Facility.
Behavioral and psychological symptoms of dementia are a major reason for institutionalization, and high demanding for staff in Residential Care Facilities. This article reports the design, implementation, and evaluation of a Validation Therapy pilot-training program (VALIDA) for staff members of a residential care facility in Aveiro, Portugal. This pilot study involved 22 members of the staff, including qualified professionals and nonqualified direct care workers, who were involved in the design. The pilot-training program comprises two components: training sessions in group and individual monitoring between those sessions. The evaluation indicates that the structure of the pilot-program was well accepted, and participants reported positive impacts in professional (better skilled to deal with residents with dementia) and personal (better trained to deal with elderly relatives) lives. This pilot-training program shows potential to be used in residential care facilities and needs to be replicated.


New oleanene and fernane-type triterpenes from the stem bark of Betula pendula roth.
A new oleanene-type triterpene, named betuloleanolic acid acetate and fernane-type triterpenes, namely betufernanediol A and betufernanediol B (isomers) have been isolated from the stem bark of Betula pendula. Their structures have been established as olean-12-en-3beta-ylacetate-29-oic acid, fern-22(29)-en-3beta,12beta-diol and fem-22(29)-en-3alpha,12beta-diol, respectively, on the basis of spectral data analysis and chemical reactions.


Overweight trends among Polish schoolchildren before and after the transition from communism to capitalism.
This study aims to reveal the secular trends in body mass index (BMI) and the prevalence of overweight and obesity among Polish schoolchildren between the years 1966-2012, during which intense socio-political changes took place. Four surveys were conducted in several districts of Poland looking at 69,746 schoolchildren aged 7-18. Significant increase in mean BMI as well as in the prevalence of overweight and obesity was observed. During this time the highest increase in both mean BMI and excess weight was observed between 1988 and 2012, i.e. after the political transformation, resulting in the improvement of living conditions. However, with respect to girls in late adolescence, between these years, the mean BMI as well as the prevalence of overweight were leveling off, while the percentage of boys with excess body fat in the same developmental category significantly increased in 2012. In the years 1966-1978 and 1978-1988 the pattern of changes in the prevalence of overweight and obesity reflected the social and economic circumstances, i.e. temporary economic improvements, or deepening political crises and food shortage. In conclusion, the weight status of schoolchildren strongly reflects socio-political changes that took place in Poland, as well as in most of the Central European countries in the last half century.


Development of a peer support intervention to improve the experience and outcomes of discharge from inpatient mental health care: the role of experiential knowledge in a coproduced approach.
Peer support is rapidly being introduced into mental health services internationally, yet peer support interventions are often poorly described, limiting the usefulness of research in informing policy and practice. This paper reports the development of a peer support intervention that aims to improve outcomes of discharge from inpatient to community mental health care. People with experiential knowledge of using mental health services-peer workers and service user researchers-were involved in all stages of developing the intervention: generating intervention components; producing the intervention handbook; piloting the intervention. Systematic review and expert panels, including our Lived Experience Advisory Panel, identified 66 candidate intervention components in five domains: Recruitment and Role Description of Peer Workers; Training for Peer Workers; Delivery of Peer Support; Supervision and Support for Peer Workers; Organisation and Team. A series of Local Advisory Groups were used to prioritise components and explore implementation issues using consensus methods, refining an intervention blueprint. A peer support handbook and peer worker training programme were produced by the study team and piloted in two study sites. Feedback workshops were held with peer workers and their supervisors to produce a final handbook and training programme. The ENRICH trial is registered with the ISRCTN clinical trial register, number ISRCTN 10043328, and was overseen by an independent steering committee and a data monitoring committee.


Mechanisms of central conduction time prolongation in brain-stem auditory evoked potentials.
The wave I-wave V delay in the auditory brain-stem response is commonly used as a diagnostic tool in otoneurology. Normative values have been established for different populations and different types of stimuli. This I-V delay has been known for some time as "central conduction time" or "central transmission time." This implies that the measure reflects in normal and in pathologic cases delays due to nerve conduction, synaptic transmission, and neural integration and is not caused by cochlear processes. By virtue of the traveling wave delay in the cochlea, amounting to some 4 ms from the base to the "500-Hz place," it is conceivable that this delay contributes to the I-V delay. From a series of 69 pontine angle tumors in which the auditory brain-stem response was recorded, we selected cases with an apparent peripheral origin of a prolonged I-V delay by comparing the whole-click response to responses derived from high-pass noise masking. It seems that cases with an increased I-V delay in the whole-click response but (almost) normal I-V delays in the narrow-band response are indicative of small intracanalicular acoustic neuroma.


Artificial neural network modeling for drug dialyzability prediction.
The purpose of this study was to develop an artificial neural network (ANN) model to predict drug removal during dialysis based on drug properties and dialysis conditions. Nine antihypertensive drugs were chosen as model for this study. Drugs were dissolved in a physiologic buffer and dialysed in vitro in different dialysis conditions (UFRmin/UFRmax, with/without BSA). Samples were taken at regular intervals and frozen at -20ºC until analysis. Extraction methods were developed for drugs that were dialysed with BSA in the buffer. Drug concentrations were quantified by high performance liquid chromatography (HPLC) or mass spectrometry (LC/MS/MS). Dialysis clearances (CLDs) were calculated using the obtained drug concentrations. An ANOVA with Scheffe's pairwise adjustments was performed on the collected data in order to investigate the impact of drug plasma protein binding and ultrafiltration rate (UFR) on CLD. The software Neurosolutions was used to build ANNs that would be able to predict drug CLD (output). The inputs consisted of dialysis UFR and the herein drug properties: molecular weight (MW), logD and plasma protein binding. Observed CLDs were very high for the majority of the drugs studied. The addition of BSA in the physiologic buffer statistically significantly decreased CLD for carvedilol (p= 0.002) and labetalol (p<0.001), but made no significant difference for atenolol (p= 0.100). In contrast, varying UFR does not significantly affect CLD (p>0.025). Multiple ANNs were built and compared, the best model was a Jordan and Elman network which showed learning stability and good predictive results (MSEtesting = 129). In this study, we have developed an ANN-model which is able to predict drug removal during dialysis. Since experimental determination of all existing drug CLDs is not realistic, ANNs represent a promising tool for the prediction of drug CLD using drug properties and dialysis conditions.


Fibroblast Growth Factor-2 (FGF-2) Expression in Pterygia Using Cell Spot Arrays.
Fibroblast growth factor (FGF) is a main regulator of cell differentiation, cell migration and angiogenesis in normal and abnormal conjunctiva epithelia, but specific mechanisms of its aberrant expression are yet to be investigated. In the present study, we investigated FGF-2 protein expression within several pterygia. Using a liquid-based cytology assay, we obtained cell specimens from pterygia and healthy tissues directly from patients. A combination of immunocytochemistry followed by digital image analysis showed significant overexpression of FGF-2 in all the examined pterygia. In 30/60 (50%) cases there were high levels of staining intensity, whereas in the remaining 30/60 (50%) cases there were moderate levels of expression. FGF-2 levels of the control group were significantly lower in comparison with the pterygia group. There was no significant correlation between FGF-2 levels and either sex or location of the pterygium. FGF-2 levels had a significant correlation with morphological characteristics of the pterygia. More specifically, FGF-2 levels were significantly higher in the pterygia with a fleshy morphology. Interestingly, recurrent lesions demonstrated high expression levels. An overexpression of FGF-2 has been observed frequently in pterygia, where it may play a crucial role in determining the lesion's progression. FGF-2 upregulation correlates with the morphology of pterygia and its tendency to recur. Cell spot analysis based on liquid-based cytology is a simple, yet effective, method for detecting a broad spectrum of protein markers and could be useful in analyzing potential pterygia patient samples.


The GPCR adaptor protein norbin suppresses the neutrophil-mediated immunity of mice to pneumococcal infection.
Streptococcal pneumonia is a worldwide health problem that kills ∼2 million people each year, particularly young children, the elderly, and immunosuppressed individuals. Alveolar macrophages and neutrophils provide the early innate immune response to clear pneumococcus from infected lungs. However, the level of neutrophil involvement is context dependent, both in humans and in mouse models of the disease, influenced by factors such as bacterial load, age, and coinfections. Here, we show that the G protein-coupled receptor (GPCR) adaptor protein norbin (neurochondrin, NCDN), which was hitherto known as a regulator of neuronal function, is a suppressor of neutrophil-mediated innate immunity. Myeloid norbin deficiency improved the immunity of mice to pneumococcal infection by increasing the involvement of neutrophils in clearing the bacteria, without affecting neutrophil recruitment or causing autoinflammation. It also improved immunity during Escherichia coli-induced septic peritonitis. It increased the responsiveness of neutrophils to a range of stimuli, promoting their ability to kill bacteria in a reactive oxygen species-dependent manner, enhancing degranulation, phagocytosis, and the production of reactive oxygen species and neutrophil extracellular traps, raising the cell surface levels of selected GPCRs, and increasing GPCR-dependent Rac and Erk signaling. The Rac guanine-nucleotide exchange factor Prex1, a known effector of norbin, was dispensable for most of these effects, which suggested that norbin controls additional downstream targets. We identified the Rac guanine-nucleotide exchange factor Vav as one of these effectors. In summary, our study presents the GPCR adaptor protein norbin as an immune suppressor that limits the ability of neutrophils to clear bacterial infections.


Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll-like receptor 2 cascade and inflammasomes.
Toll-like receptor 2 (TLR2) and nucleotide-binding and oligomerization domain-like receptors with a pyrin domain 3 (NLRP3) inflammasomes have been presumed to participate in the pathogenesis of aseptic implant loosening. The aim of this study is to analyze the cellular localization of TLR2 and NLRP3 inflammasomes in the periprosthetic tissue from aseptically loose hip implants as well as the expression of these molecules in macrophages stimulated in vitro with titanium particles (Ti) coated with lipoteichoic acid (LTA). Using immunohistochemistry, immunoreactivity of TLR2 and NLRP3 inflammasomes was found in macrophages within the foreign body granulomatosis. Using RAW264.7 cells, stimulation with Ti increased the messenger RNA (mRNA) levels of TLR2 and TNF-α. Stimulation with LTA-coated Ti enhanced mRNA levels of NLRP3 and IL-1β, whereas reinforced secretion of IL-1β was not detected in spite of marked release of TNF-α. Finally, the same cells with silenced Irak2, an adaptor protein in the TLR2 cascade, suppressed this NLRP3 upregulation. This study suggests that TLR2 and NLRP3 inflammasomes are factors involved in cross-talk mediating the foreign body type response to wear particles. In addition, discrepant behavior in the release between TNF-α and IL-1β release may explain the variable pathomechanisms of aseptic implant loosening without acute inflammatory reactions.


CHSE-214: A model for studying extracellular dsRNA sensing in vitro.
Double-stranded RNA (dsRNA) is produced by almost all viruses during their replicative cycle and is a potent inducer of the innate antiviral immune response including inducing expression of type I interferons (IFNs) and interferon-stimulated genes (ISGs). During lytic virus infections intracellular dsRNA can escape into the extracellular space, where surface pattern recognition receptors, such as class A scavenger receptors (SR-As) facilitate its binding and entry into neighbouring cells. Studying extracellular dsRNA entry is difficult due to the ubiquitous expression profile and compensatory dsRNA binding characteristics of SR-As; a SR-A deficient cell line has yet to be identified. The present study suggests the Chinook salmon embryonic cell line, CHSE-214, as a model for studying extracellular dsRNA sensing in vitro. CHSE-214 is unable to bind and respond to extracellular dsRNA, can only respond to dsRNA when it is transfected into the cells, and is able to bind dsRNA when overexpressing human SR-AI. The applications for this model could include elucidating: dsRNA binding and entry mechanisms, including sequence and length effects, as well as SR-A and other putative surface dsRNA receptor ligand binding studies.


C@PA: Computer-Aided Pattern Analysis to Predict Multitarget ABC Transporter Inhibitors.
Based on literature reports of the last two decades, a computer-aided pattern analysis (C@PA) was implemented for the discovery of novel multitarget ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP) inhibitors. C@PA included basic scaffold identification, substructure search and statistical distribution, as well as novel scaffold extraction to screen a large virtual compound library. Over 45,000 putative and novel broad-spectrum ABC transporter inhibitors were identified, from which 23 were purchased for biological evaluation. Our investigations revealed five novel lead molecules as triple ABCB1, ABCC1, and ABCG2 inhibitors. C@PA is the very first successful computational approach for the discovery of promiscuous ABC transporter inhibitors.


The influence of obesity and body mass index on the outcome of laparoscopic colorectal surgery: a systematic literature review.
The relationship between obesity, body mass index (BMI) and laparoscopic colorectal resection is unclear. Our object was to assess systematically the available evidence to establish the influence of obesity and BMI on the outcome of laparoscopic colorectal resection. A search of PubMed/Medline databases was performed in May 2015 to identify all studies investigating the impact of BMI and obesity on elective laparoscopic colorectal resection performed for benign or malignant bowel disease. Clinical end-points examined included operation time, conversion rate to open surgery, postoperative complications including anastomotic leakage, length of hospital stay, readmission rate, reoperation rate and mortality. For patients who underwent an operation for cancer, the harvested number of lymph nodes and long-term oncological data were also examined. Forty-five studies were analysed, the majority of which were level IV with only four level III (Oxford Centre for Evidence-based Medicine 2011) case-controlled studies. Thirty comparative studies containing 23 649 patients including 17 895 non-obese and 5754 obese showed no significant differences between the two groups with respect to intra-operative blood loss, overall postoperative morbidity, anastomotic leakage, reoperation rate, mortality and the number of retrieved lymph nodes in patients operated on for malignancy. Most studies, including 15 non-comparative studies, reported a longer operation time in patients who underwent a laparoscopic procedure with the BMI being an independent predictor in multivariate analyses for the operation time. Laparoscopic colorectal resection is safe and technically and oncologically feasible in obese patients. These results, however, may vary outside of high volume centres of expertise.


The development of differential mnemonic effects of false denials and forced confabulations.
The current experiment was designed to assess the mnemonic consequences of false denials and forced confabulations. Children (aged 6-8 and 10-12 years) and adults viewed a video and then their memory and belief about the event were tested. Participants were then divided into three groups. In the "cued recall" condition, participants were asked to answer true- and false-event questions, but could choose not to respond if they did not know the answer. In the "forced confabulation" group, participants received the same set of questions, but were forced to answer all of them. In the "false denial" group, participants were instructed to falsely deny in response to each question. One week later, participants received a source memory test, and they had to provide memory and belief ratings once more. Forced confabulations resulted in false memories in the youngest group. Moreover, our analyses showed that repeated false denials led children and adults to be highly inclined to falsely deny that they had talked to the experimenter about certain presented details, when in fact they had done so. Furthermore, false denial and non-believed memory rates were more pronounced in younger than in older children and adults. Our results imply that denying experienced events is not a good strategy in an interviewing setting, as it adversely affects memory statements about the interview.


Improved nonparaxial accelerating beams due to additional off-axis spiral phases.
An accelerating beam with a Gaussian transverse profile can preserve its shape while propagating along a quarter of a circle. When an off-axis spiral phase is imposed, however, the beam will have an additional acceleration perpendicular to the circle. A two-dimensional accelerating beam is constructed and is found to accelerate along both the x and the y directions, but its transverse intensity profile cannot be maintained well due to the interaction of accelerations along different directions. The intensity profile can be improved by imposing two off-axis spiral phases onto the input beam.


[Why ovarian cancer cells escape from immune surveillance?]
Ovarian cancer is a malignancy of high mortality rates. In respect of the number of deaths caused by cancers it occupies the fourth place among women in Poland. Recent studies are focusing on the role of immune system in ovarian cancer pathogenesis. It has been reported that immune response against ovarian cancer cells may be inhibited by a number of immunosuppressive mechanisms active in cancer microenvironment. It causes difficulties in recognizing and destroying cancer cells by immune system which leads to the development of immune tolerance and is associated with a low efficacy of standard therapeutic strategies. In the presented paper we have described selected, new immunosuppressive mechanisms in ovarian cancer patients. They may be a novel, additional and relevant criterion that should be considered whilst developing new therapeutic strategies. Possibly, modulation of immunosuppressive mechanisms could contribute to modifying standard therapies and in consequence improve treatment outcome in ovarian cancer patients.


The epidemiology of acute urinary retention in benign prostatic hyperplasia.
One of the most important events in the natural history of BPH is acute urinary retention (AUR). Better estimates of AUR incidence are now available from both population-based studies and placebo control groups (patients diagnosed with BPH). Several strong risk factors for AUR have been identified by analytical epidemiology, the most important being serum PSA levels. When counseling patients with BPH who are considering watchful waiting, clinicians should also take into account prostate volume, maximum flow rate, and symptom severity.


[Acute hemorrhagic necrotizing pancreatitis. Analysis of 58 patients].
The authors stress the therapeutic importance of peritoneal lavage for eliminating toxic substances from the abdominal cavity. In cases of a stenosing papilla or an impacted gallstone, endoscopic papillotomy and stone extraction are recommended. The indication for surgical interventions, like nekrosectomy or segmental resection of the pancreas, are discussed in detail. In case of diffuse recurrent peritonitis the technique of the "open abdomen" should be taken into consideration. The results of 44 resections and 14 necrosectomies are represented. The overall mortality rate comes up to 35 or 40% respectively.


In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease.
Protease inhibitors are another class of compounds for treatment of human immunodeficiency virus (HIV)-caused disease. The emergence of resistance to the current anti-HIV drugs makes the determination of potential resistance to protease inhibitors imperative. Here we describe the isolation of an HIV type 1 (HIV-1) resistant to an HIV-protease inhibitor. Serial passage of HIV-1 (strain RF) in the presence of the inhibitor, [2-pyridylacetylisoleucylphenylalanyl-psi (CHOH)]2 (P9941), failed to yield a stock of virus with a resistance phenotype. However, variants of the virus with 6- to 8-fold reduced sensitivity to P9941 were selected by using a combination of plaque assay and endpoint titration. Genetic analysis and computer modeling of the variant proteases revealed a single change in the codon for amino acid 82 (Val-->Ala), which resulted in a protease with lower affinity and reduced sensitivity to this inhibitor and certain, but not all, related inhibitors.


Relaxation Dynamics of the Triazene Compound Berenil in DNA-Minor-Groove Confinement after Photoexcitation.
The effects of biomolecular embedding on the photoinduced relaxation process of the DNA-minor-groove binder berenil, diminazene aceturate, are studied with quantum mechanics/molecular mechanics, QM/MM, calculations that employ the algebraic diagrammatic construction through second-order, ADC(2), for the quantum mechanical part and an atomistic polarizable embedding for the classical part. The lowest singlet excitation to the S1 state is a bright transition with a ππ* character and a perichromatic red shift, due to the interactions with the solvent and DNA. The excited-state relaxation pathway is a two-step mechanism, an N═N azo-bond stretch followed by a volume-conserving bicycle-pedal twist. The DNA confinement and the coupling to solvent molecules via hydrogen bonds lead, for the excited-state relaxation process, only to small deviations from the ideal bicycle-pedal relaxation. Because of its volume-conserving character, the S1 excited-state relaxation proceeds almost unhindered, even in a fully rigid minor-groove confinement. With a fully frozen DNA minor groove and solvent, the energy gap for deexcitation from S1 to the ground state increased to 2.0 eV compared to 0.16 eV in aqueous solution. When the relaxation of the first solvation shell is included, the relaxation process on the S1 potential energy surface proceeds to a region on the potential energy surface, where only a small gap to the ground-state potential energy surface remains, 0.43 eV. These results show that the solvent relaxation has a significant effect in controlling the energy gap between the ground and S1 electronically excited states, which explains the experimental observations of the fluorescence characteristics of berenil in DNA confinement.


Clinical predictors for the manifestation of late gadolinium enhancement after acute myocardial infarction.
Despite prompt revascularization, some patients with acute myocardial infarction (AMI) develop myocardial scars, which can be visualized by late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR). Our goal was to identify angiographic findings that were predictive for scar development in patients after reperfused AMI.We examined 136 patients after first ST-elevated myocardial infarction by CMR after a median of 4 days (range: 2-7). Patients with manifestation of LGE were matched to patients without LGE by means of age and gender. Clinical follow-up with a combined primary endpoint including myocardial reinfarction, congestive heart failure, stroke, death and development of left ventricular thrombus was reported after 24 months.Patients with manifestation of LGE had a significant longer time of symptom-to-intervention, a higher prevalence of anterior AMI, and more proximal culprit lesions. Furthermore, left ventricular ejection fraction was significantly decreased, and peak values of infarct markers were significantly higher in these patients. Preinterventional thrombolysis in myocardial infarction-0-flow was significantly more frequent in patients with LGE manifestation. The presence of 3-vessel disease (odds ratio 53.99, 95% confidence interval 8.22-354.63, P <.001), a proximal culprit lesion, and high creatine kinase myocardial band (CK-MB) values were identified as independent predictors of LGE. Follow-up demonstrated a higher incidence of clinical events in the group with LGE, with the most common cause of heart failure (38.2% vs 7.4%, P <.001).The extent of angiographic findings in AMI plays a major role in the manifestation of LGE. The presence of a multivessel disease, a proximal culprit lesion, and high values of CK-MB are strong independent predictors for LGE manifestation.


Comparative analysis of avian hearts provides little evidence for variation among species with acquired endothermy.
Mammals and birds acquired high performance hearts and endothermy during their independent evolution from amniotes with many sauropsid features. A literature review shows that the variation in atrial morphology is greater in mammals than in ectothermic sauropsids. We therefore hypothesized that the transition from ectothermy to endothermy was associated with greater variation in cardiac structure. We tested the hypothesis in 14 orders of birds by assessing the variation in 15 cardiac structures by macroscopic inspection and histology, with an emphasis on the atria as they have multiple features that lend themselves to quantification. We found bird hearts to have multiple features in common with ectothermic sauropsids (synapomorphies), such as the presence of three sinus horns. Convergent features were shared with crocodylians and mammals, such as the cranial offset of the left atrioventricular junction. Other convergent features, like the compact organization of the atrial walls, were shared with mammals only. Pacemaker myocardium, identified by Isl1 expression, was anatomically node-like (Mallard), thickened (Chicken), or indistinct (Lesser redpoll, Jackdaw). Some features were distinctly avian, (autapomorphies) including the presence of a left atrial antechamber and the ventral merger of the left and right atrial auricles, which was found in some species of parrots and passerines. Most features, however, exhibited little variation. For instance, there were always three systemic veins and two pulmonary veins, whereas among mammals there are 2-3 and 1-7, respectively. Our findings suggest that the transition to high cardiac performance does not necessarily lead to a greater variation in cardiac structure.


Stress-dependent opposing roles for mitophagy in aging of the ascomycete Podospora anserina.
Mitochondrial dysfunction is causatively linked to organismal aging and the development of degenerative diseases. Here we describe stress-dependent opposing roles of mitophagy, the selective autophagic degradation of mitochondria, in aging and life-span control. We report that the ablation of the mitochondrial superoxide dismutase which is involved in reactive oxygen species (ROS) balancing, does not affect life span of the fungal aging model Podospora anserina, although superoxide levels are strongly increased and complex I-dependent respiration is impaired. This unexpected phenotype depends on functional autophagy, particularly mitophagy, which is upregulated during aging of this mutant. It identifies mitophagy as a prosurvival response involved in the control of mitohormesis, the well-known beneficial effect of mild mitochondrial oxidative stress. In contrast, excessive superoxide stress turns mitophagy to a prodeath pathway and leads to accelerated aging. Overall our data uncover mitophagy as a dynamic pathway that specifically responds to different levels of mitochondrial oxidative stress and thereby affects organismal aging.


Reduced pancreatic volume and beta-cell area in patients with chronic pancreatitis.
Chronic pancreatitis (CP) often leads to the development of diabetes. To understand better this pathogenic mechanism, we investigated whether islet cell area and pancreatic volume are reduced in CP patients, islet cell turnover increases in CP patients, and islet cells are less vulnerable to apoptosis than acinar cells. Pancreatic tissues from 43 patients with CP and 27 controls were examined by immunohistochemistry and quantitative morphometry. Pancreas volume was determined using abdominal computed tomography data. The pancreatic volumes were 64.9 +/- 4.3 cm(3) in CP patients and 82.3 +/- 6.7 cm(3) in controls (P = .035). beta-cell areas were 0.69% +/- 0.08% in CP patients and 0.97% +/- 0.08% in controls (P = .017), whereas alpha-cell areas did not differ between the groups (P = .47). There were no differences in the frequencies of replication among groups of alpha-cells, beta-cells, duct cells, or acinar cells nor were there differences in numbers of apoptotic alpha-cells or beta-cells between CP patients and controls. However, CP patients had an approximately 10-fold increase in numbers of apoptotic acinar cells compared with controls (P < .0001). Pancreatic volume was reduced by 21%, and the area comprising beta-cells was reduced by 29% in patients with CP. The lack of increased beta-cells turnover in CP patients, despite an approximately 10-fold increase in the number of apoptotic acinar cells, suggests that the damage to the pancreas is highly specific for the exocrine compartment and affects the endocrine islets to a lesser extent.


Characterization of a resistance-nodulation-cell division transporter system associated with the syr-syp genomic island of Pseudomonas syringae pv. syringae.
A tripartite resistance-nodulation-cell division (RND) transporter system, called the PseABC efflux system, was identified at the left border of the syr-syp genomic island of Pseudomonas syringae pv. syringae strain B301D. The PseABC efflux system was located within a 5.7-kb operon that encodes an outer membrane protein (PseA), a periplasmic membrane fusion protein (PseB), and an RND-type cytoplasmic membrane protein (PseC). The PseABC efflux system exhibited amino acid homology to a putative RND efflux system of Ralstonia solanacearum, with identities of 48% for PseA, 51% for PseB, and 61% for PseC. A nonpolar mutation within the pseC gene was generated by nptII insertional mutagenesis. The resultant mutant strain showed a larger reduction in syringopeptin secretion (67%) than in syringomycin secretion (41%) compared to parental strain B301D (P < 0.05). A beta-glucuronidase assay with a pseA::uidA reporter construct indicated that the GacS/GacA two-component system controls expression of the pseA gene. Quantitative real-time reverse transcription-PCR was used to determine transcript levels of the syringomycin (syrB1) and syringopeptin (sypA) synthetase genes in strain B301D-HK4 (a pseC mutant). The expression of the sypA gene by mutant strain B301D-HK4 corresponded to approximately 13% of that by parental strain B301D, whereas the syrB1 gene expression by mutant strain B301D-HK4 was nearly 61% (P < 0.05). In addition, the virulence of mutant strain B301D-HK4 for immature cherry fruits was reduced by about 58% compared to parental strain B301D (P < 0.05). Although the resistance of mutant strain B301D-HK4 to any antibiotic used in this study was not reduced compared to parental strain B301D, a drug-supersensitive acrB mutant of Escherichia coli showed two- to fourfold-increased resistance to acriflavine, erythromycin, and tetracycline upon heterologous expression of the pseA, pseB, and pseC genes (pseABC efflux genes). The PseABC efflux system is the first RND transporter system described for P. syringae, and it has an important role in secretion of syringomycin and syringopeptin.


Thermally Induced Tensile Strain of Epitaxial Ge Layers Grown by a Two-Step e-Beam Evaporation Process on Si Substrates.
We have investigated the thermally induced tensile strain in Ge-on-Si for use in optical sources of interconnection systems. Epitaxial Ge layers were grown using a two-step hetero-epitaxy at low and high temperatures. The as-grown Ge-on-Si was then annealed for direct bandgap conversion. A tensile strain of 0.06% in the as-grown Ge increased to 0.31% after annealing at 850 degrees C. As the thermal budget of this post-growth anneal was increased, the tensile strain of relaxed Ge-on-Si also increases and a Si-Ge alloy forms. Physical characterization indicates a tunable tensile stain in Ge-on-Si can be realized using post-growth annealing, which will allow for a wide range of frequencies in optical interconnections.


Mathematical evaluation of two parameter flow cytometric histograms.
A general procedure was developed to evaluate two-parameter flow cytometric data. These data usually show overlapping distributions representing different subpopulations. To calculate the fractions of cells in the various subpopulations, the maximum likelihood method is used, assuming an unknown number of Gaussian distributions with constant coefficient of variation in the histogram. A test on simulated data shows that Gaussians can be separated clearly by the procedure if the distance between their mean values is larger than twice the maximum standard deviation. The analysis of different measurements of double-stained (DNA/protein) cultured cells out of the same pool yield the same fractions in the phases of the cell cycle with acceptable error rates. To simulate samples with different fractions in the phases of the cell cycle, defined mixtures of proliferating and resting cells of the same type were prepared and measured for DNA and cell size. The calculated fractions are consistent with the expected variation of G1, S and G2 + M fractions depending on the mixture ratio.


Association of Rigid-Compulsive Behavior with Functional Constipation in Autism Spectrum Disorder.
Based upon checklist data from the Autism Speaks Autism Treatment Network, we hypothesized that functional constipation (FC) would be associated with rigid-compulsive behavior in children with autism spectrum disorder (ASD). We used the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III to assess FC symptoms in 108 children with ASD. As hypothesized, FC was associated with parent ratings on the Repetitive Behavior Scales-Revised (RBS-R) Compulsive, Ritualistic, and Sameness subscales in the overall population. Of note, FC was less common in children who were not taking medications that target behavior or treat FC. In the medication-free children, rigid-compulsive behavior was not significantly associated with FC. More research is needed to understand the mechanisms underlying these associations.


Effect of montelukast on exhaled NO in asthmatic children exposed to relevant allergens.
The level of exhaled nitric oxide (FENO) is increased in house dust mite (HDM)-sensitized asthmatic children after exposure to HDM antigen, and inhaled steroids can prevent this increase. The aim of this study was to evaluate whether montelukast could prevent an increase in FENO levels in allergic asthmatic children after a brief period of exposure to relevant allergens. Sixteen children were evaluated at the residential house 'Istituto Pio XII' (Misurina, Bellunio, Italy) in the Italian Alps, a dust mite-free environment. FENO levels were evaluated before (t0) and immediately after (t1) the children were exposed to HDM allergens for 2 weeks in their homes at sea level. No significant difference in FENO was observed in the fluticasone-treated group of children after 2 weeks at sea level. In the group treated with montelukast, an increase in FENO was observed between t0 and t1, which failed to reach statistical significance. These preliminary data suggest that oral montelukast could be effective in preventing the relapse in airway inflammation in allergic asthmatic children who are occasionally exposed to relevant allergens for a short period of time.


Reconstruction of lower third of face with three simultaneous free flaps.
A case of massive osteoradionecrosis is presented that required angle-to-angle resection of the mandible and replacement of skin of the chin and neck as well as the entire floor of the mouth. In this heavily irradiated patient, three microvascular free flaps were transferred in one operation. A large radial forearm flap was used to reconstruct the floor of the mouth. A second large radial forearm flap was used to reconstruct the chin and neck defects and a fibular osseous flap was used to reconstruct the mandible. All wounds healed primarily. For extremely complicated and large defects, the transfer of multiple free flaps may provide the best reconstruction.


The anaplastic transformation of differentiated thyroid carcinoma. An ultrastructural study.
The authors studied 60 thyroid carcinomas (29 folliculo-papillary carcinomas, 20 follicular carcinomas and 11 undifferentiated carcinomas), using ultrastructural, morphometrical and immunohistochemical methods. The anaplastic transformation correlates with the following aspects: decrease of intercellular junctions and of microvilli together with alteration of cell organelles. Immunohistochemically, thyroglobulin is present in various amounts in differentiated carcinoma, but it is absent in undifferentiated tumors. A good correlation is found between the pattern of thyroglobulin and the ultrastructural aspects of neoplastic cells. The authors consider that anaplastic tumors originate from differentiated carcinomas. The decrease of junctions, the modifications in the number and shape of microvilli, the alterations of cell organelles and the changes of thyroglobulin pattern are the principal parameters involved in the anaplastic transformation. These criteria can be also used in order to ascertain an early diagnosis in the thyroid carcinoma evolving anaplastic changes.


Infection of porcine colon explants with "Brachyspira hampsonii" leads to increased epithelial necrosis and catarrhal exudate.
Mucohemorrhagic diarrhea in pigs caused by Brachyspira spp. has a global distribution, and an economic impact on affected farms due to poor performance of animals. Demonstrations that "Brachyspira hampsonii" is pathogenic have been achieved using in vivo animal models, but a critical knowledge gap exists regarding the pathogenic mechanisms employed by Brachyspira. Here, we used in vitro organ culture of porcine colon to investigate interactions between "B. hampsonii" and explants during the first 12 h of contact. Explants were either inoculated with "B. hampsonii" or sterile culture broth. Responses to infection were evaluated by optical microscopy and quantitative PCR. Significantly greater numbers of necrotic crypt cells and thicker catarrhal exudate were observed on infected explants compared to controls. Spirochaetes were observed in the mucus layer, in contact with necrotic exfoliated cells, in crypts and the lamina propria. Statistical differences were observed in mRNA levels between inoculated and control explants for IL-1α, TNF-α and ZO-1 using a Bayesian analysis, but not observed using the ΔΔCq method. These results provide a demonstration of a porcine colon explant model for investigating interactions of Brachyspira with its host and show that initial effects on the host are observed within the first 12 h of contact.


Urinary tract obstruction and renal failure due to uterine prolapse.
Three women are described in whom obstructive uropathy was found secondary to uterine prolapse. Two of these patients had severe renal failure. It is important to exclude this condition in any woman presenting with renal functional impairment. Potentially damaging urinary tract obstruction should be considered in every patient with a uterine prolapse.


What's the fuss about? Parent presentations of fussy eating to a parenting support helpline.
To characterise parent presentations of fussy eating and mealtime interactions at a point of crisis, through analyses of real-time recordings of calls to a parenting helpline. Qualitative analysis included an inductive thematic approach to examine clinical parent presentations of fussy eating and derive underlying themes relating to mealtime interactions. Calls made to the Child Health Line regarding feeding concerns were recorded and transcribed verbatim. From a corpus of 723 calls made during a 4-week period in 2009, twelve were from parents of children aged 6-48 months. Parents of infants (≤12 months, n 6) presented feeding concerns as learning challenges in the process of transitioning from a milk-based to a solid-based diet, while parents of toddlers (13-48 months, n 6) presented emotional accounts of feeding as an intractable problem. Parents presented their child's eating behaviour as a battle (conflict), in which their children's agency over limited intake and variety of foods (child control) was constructed as 'bad' or 'wrong'. Escalating parent anxiety (parent concern) had evoked parent non-responsive feeding practices or provision of foods the child preferred. Real-time descriptions of young children's fussy eating at a time of crisis that initiated parents' call for help have captured the highly charged emotional underpinnings of mealtime interactions associated with fussy eating. Importantly, they show the child's emerging assertion of food autonomy can escalate parents' emotional distress that, in the short term, initiates non-responsive feeding practices. The current study identifies the importance of educational and emotional support for parents across the period of introducing solids.


Neuronal degeneration and glial cell-responses following trimethyltin intoxication in the rat.
Trimethyltin (TMT) preferentially induces neuronal changes in the hippocampus and pyriform cortex. In the present study we investigated the time course of microglial and astroglial responses associated with neurodegeneration after the administration of TMT (i.p. 9 mg/kg or 12 mg/kg body weight) in the rat. At a dosage of 9 mg/kg TMT, neurodegeneration was clearly demonstrated in the CA1 and CA3 regions of the hippocampus as argyrophilic (dark) neurons by day 4 using the Gallyas-Braak (G-B) impregnation method that has been shown to be sensitive and specific for neurodegeneration. Early microglial response was immunohistochemically shown with anti-microglial response factor-1 (MRF-1) antibody in the CA3 by day 1, preceding neurodegeneration morphologically detected by the G-B method. Activation of astrocytes was revealed by immunohistochemical staining for glial fibrillary acidic protein (GFAP) by day 2. In parallel with the maximal neurodegeneration, large numbers of hypertrophied microglia and astrocytes were observed in the CA1 and CA3 by day 7. Numbers of degenerative neurons appeared to be closely associated with adjacent microglia by the double staining of G-B impregnation and MRF-1 immunohistochemistry. The number of reactive microglia considerably decreased to the resting state by day 14, while hypertrophied astrocytes were still prominent in the CA3 up to day 21. With the high dose of TMT, granule cells in the dentate gyrus and CA1 and CA3 pyramidal cells were significantly impregnated. After TMT treatment, accompaning neurodegeneration we observed early response of microglia and prolonged activation of astrocytes, suggesting an individual role of glial cells in maintenance and repair of damaged neurons following brain injury.


Duration of anti-tuberculous therapy in children with persistent tuberculomas.
The usual treatment duration of tuberculomas recommended is 1 year. While anti-tuberculous therapy is of absolute necessity for the treatment of central nervous system tuberculosis, no clear guidelines exist regarding the duration of therapy in case of persistent tuberculomas. We present a series of six cases of children with central nervous system tuberculosis who received anti-tuberculous therapy for a period varying between 23 and 32 months depending on the resolution of lesion seen in neuroradiological scans of the patients. Decrease in number and size of granuloma were noted in all patients while one patient showed complete resolution. After stopping anti-tuberculous therapy, the size of the granuloma remained the same, while in one patient an increase was noted. Thus, the duration of anti-tuberculous therapy in patients with tuberculoma may vary and may be required for longer time based on treatment response.


SepPCNET: Deeping Learning on a 3D Surface Electrostatic Potential Point Cloud for Enhanced Toxicity Classification and Its Application to Suspected Environmental Estrogens.
Deep learning (DL) offers an unprecedented opportunity to revolutionize the landscape of toxicity prediction based on quantitative structure-activity relationship (QSAR) studies in the big data era. However, the structural description in the reported DL-QSAR models is still restricted to the two-dimensional level. Inspired by point clouds, a type of geometric data structure, a novel three-dimensional (3D) molecular surface point cloud with electrostatic potential (SepPC) was proposed to describe chemical structures. Each surface point of a chemical is assigned its 3D coordinate and molecular electrostatic potential. A novel DL architecture SepPCNET was then introduced to directly consume unordered SepPC data for toxicity classification. The SepPCNET model was trained on 1317 chemicals tested in a battery of 18 estrogen receptor-related assays of the ToxCast program. The obtained model recognized the active and inactive chemicals at accuracies of 82.8 and 88.9%, respectively, with a total accuracy of 88.3% on the internal test set and 92.5% on the external test set, which outperformed other up-to-date machine learning models and succeeded in recognizing the difference in the activity of isomers. Additional insights into the toxicity mechanism were also gained by visualizing critical points and extracting data-driven point features of active chemicals.


Human Adipose-Derived Stem Cells Delay Retinal Degeneration in Royal College of Surgeons Rats Through Anti-Apoptotic and VEGF-Mediated Neuroprotective Effects.
Stem cell therapy is a promising therapeutic approach for retinal degeneration (RD). Our study investigated the effects of human adipose derived stem cell (hADSCs) on Royal College of Surgeons (RCS) rats. Green fluorescent protein (GFP)-labeled hADSCs were transplanted subretinally into RCS rats at postnatal (PN) 21 days to explore potential therapeutic effects, while adeno-associated viral vector (AAV2)-vascular endothelial growth factor (VEGF) and siVEGF-hADSCs were used to aid the mechanistic dissections. Visual function was evaluated by Electroretinogram (ERG) recording. Potential transdifferentiations were examined by Immunofluorescence (IF) and gene expressions were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Apoptotic retinal cells were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay and the cytokines secreted by hADSCs were measured by Enzyme-linked Immunosorbent Assay (ELISA). The visual function of RCS rats began to decrease one week after their eyes opened at PN week 3 and almost lost in PN 5 weeks, accompanied by the loss of retinal outer nuclear layer (ONL). Subretinal transplantation of hADSCs significantly improved the visual function 2 weeks after the transplantation and such therapeutic effect persisted up to 8 weeks after the treatment (PN 11 weeks), with 3-4 rows of photoreceptors remained in the ONL and reduced apoptosis. Consistent with these phenotypic changes, the gene expression of rod photoreceptor markers Rhodopsin (Rho), Crx and Opsin (Opn1) in RCS rats showed obvious decreasing trends over time after PN 3 weeks, but were elevated with hADSC treatment. hADSC transplantation also repressed the expressions of Bax, Bak and Caspase 3, but not the expression of anti-apoptotic genes, including Bcl-2 and Bcl-XL. Finally, substantial VEGF, hepatocyte growth factor (HGF) and pigment epithelium-derived factor (PEDF) secretions from hADSCs were detected, while endogenous Vegf expression level decreased over time in RCS rats. The treatment of AAV2-VEGF showed comparable therapeutic effects as hADSCs but siRNA knockdown of VEGF in hADSCs essentially abolished the therapeutic effects. Subretinal transplantation of hADSCs in RCS rats effectively delayed the retinal degeneration, enhanced the retinal cell survival and improved the visual function. Mechanistically this was mainly due to hADSC dependent anti-apoptotic and neuroprotective effects through its secretion of growth and neurotrophic factors including VEGF. Clinical application of hADSCs merits further investigation.


Redox-neutral α-allylation of amines by combining palladium catalysis and visible-light photoredox catalysis.
An unprecedented α-allylation of amines was achieved by combining palladium catalysis and visible-light photoredox catalysis. In this dual catalysis process, the catalytic generation of allyl radical from the corresponding π-allylpalladium intermediate was achieved without additional metal reducing reagents (redox-neutral). Various allylation products of amines were obtained in high yields through radical cross-coupling under mild reaction conditions. Moreover, the transformation was applied to the formal synthesis of 8-oxoprotoberberine derivatives which show potential anticancer properties.


Efficacy and safety of biologics in the treatment of moderate to severe psoriasis: a comprehensive meta-analysis of randomized controlled trials.
We conducted a systematic review and metaanalysis of randomized placebo-controlled trials in moderate-to-severe psoriasis treated with biological agents, with a follow-up of 10-14 weeks. Overall, 41 studies, with mean Jadad score of 4.4, and 15,586 patients were included. For the efficacy outcomes PASI 50, 75 and 90 our findings are not conclusive to point what biological agent has the greatest response in short term follow-up. There were no statistical differences between placebo and biologics for the occurrence of infections and serious adverse events. Ustekinumab 45 mg showed lower withdrawal due to adverse events compared with the placebo. Based on data available up to now, it is not possible to determine which biological agent is the best for PASI 50, 75 or 90 after 10-14 weeks of treatment. At the same follow-up, overall safety seems to be the same for all biological agents and Ustekinumab 45 mg the most well tolerated drug. To better understand efficacy and safety, indirect meta-analysis comparing drug-to-drug is required since randomized placebo-controlled trials may not be feasible.


Fetal Doppler echocardiography in pulmonary atresia.
The prenatal diagnosis of pulmonary atresia is of particular importance because the affected neonate may be dependent on ductal blood flow to the lung, requiring urgent administration of prostaglandins. We review eight cases studied by ultrasonography in utero. Severe tricuspid regurgitation was present in six fetuses. Right ventricular size varied among cases. Right atrial enlargement was present in seven, usually with tricuspid regurgitation. Failure to identify the main pulmonary artery or valve on a single examination was not specific. Doppler flow studies were most reliable for the diagnosis by establishing the existence of retrograde flow in the ductus arteriosus from the aorta.


Monoclonal Antibody Therapies for Hematological Malignancies: Not Just Lineage-Specific Targets.
Today, monoclonal antibodies (mAbs) are a widespread and necessary tool for biomedical science. In the hematological cancer field, since rituximab became the first mAb approved by the Food and Drug Administration for the treatment of B-cell malignancies, a number of effective mAbs targeting lineage-specific antigens (LSAs) have been successfully developed. Non-LSAs (NLSAs) are molecules that are not restricted to specific leukocyte subsets or tissues but play relevant pathogenic roles in blood cancers including the development, proliferation, survival, and refractoriness to therapy of tumor cells. In consequence, efforts to target NLSAs have resulted in a plethora of mAbs-marketed or in development-to achieve different goals like neutralizing oncogenic pathways, blocking tumor-related chemotactic pathways, mobilizing malignant cells from tumor microenvironment to peripheral blood, modulating immune-checkpoints, or delivering cytotoxic drugs into tumor cells. Here, we extensively review several novel mAbs directed against NLSAs undergoing clinical evaluation for treating hematological malignancies. The review focuses on the structure of these antibodies, proposed mechanisms of action, efficacy and safety profile in clinical studies, and their potential applications in the treatment of hematological malignancies.


Risk of cardiovascular disease in inflammatory bowel disease.
Cardiovascular disease (CVD) can arise because of chronic inflammation and inflammatory bowel disease (IBD) is one such disease where the risk for CVD and eventual heart failure is increased considerably. The incidence of IBD, which refers to both ulcerative colitis and Crohn's disease, has been on the increase in several countries and is a potential risk factor for CVD. Although IBD can potentially cause venous thromboembolism, its significance in arterial stiffening, atherosclerosis, ischemic heart disease and myocardial infarction is only being realized now and it is currently under debate. However, several studies with large groups of patients have demonstrated the association of IBD with heart disease. It has been suggested that systemic inflammation as observed in IBD patients leads to oxidative stress and elevated levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), which lead to phenotypic changes in smooth muscle cells and sets into motion a series of events that culminate in atherosclerosis and CVD. Besides the endogenous factors and cytokines, it has been suggested that due to the compromised intestinal mucosal barrier, endotoxins and bacterial lipopolysaccharides produced by intestinal microflora can enter into circulation and activate inflammatory responses that lead to atherosclerosis. Therapeutic management of IBD-associated heart diseases cannot be achieved with simple anti-inflammatory drugs such as corticosteroids and anti-TNF-α antibodies. Treatment with existing medications for CVDs, aspirin, platelet aggregation inhibitors and statins is found to be acceptable and safe. Nevertheless, further research is needed to assess their efficacy in IBD patients suffering from heart disease.


Penetration of Filled and Unfilled Resin Sealants on Different Enamel Substrates.
To evaluate the penetration ratio of filled and unfilled resin-based sealants on different enamel substrates and pit and fissure morphologies. Forty-eight occlusal enamel blocks obtained from impacted human third molars were randomly divided (n equals eight) according to enamel substrates (sound; caries-like lesion; caries-like lesion plus topical fluoride application) and sealant material (FluroShield; Helioseal Clear Chroma). Sealants were applied on the enamel surface. The specimens were stored in 100 percent humidity for 24 hours at 37 degrees Celsius, sectioned in a buccal-lingual direction (at approximately 50 μm), and examined to determine the sealant penetration ratio (b x 100/a; a equals total fissure length and b equals sealant penetration length) and pit and fissure morphology (V-, U-, or Y-shaped). Statistical analysis was performed using Friedman and Kruskal-Wallis tests (P<0.05). Enamel substrate and sealant material did not affect the sealant penetration ratio, with no interactions between these factors. Moreover, the morphology significantly affected the sealant penetration, with the "Y"-shaped fissures presenting the lowest sealant penetration ratio compared to "U-"shaped (P=0.0001) and "V-" shaped fissures (P=0.0018). Pit and fissure morphology was a critical factor on sealant's penetration capacity; however, enamel substrate and sealant type did not affect sealant's penetration ratio.


Factor analysis of the hospital anxiety and depression scale among a Huntington's disease population.
Depression and anxiety are common in Huntington's disease, a genetic neurodegenerative disorder. There is a need for measurement tools of mood to be validated within a Huntington's disease population. The current study aimed to analyze the factor structure of the Hospital Anxiety and Depression Scale in Huntington's disease. Data from the European Huntington's Disease Network study REGISTRY 3 were used to undertake a factor analysis of the scale among a sample of 492 Huntington's disease mutation carriers. The sample was randomly divided into two equal subsamples and an exploratory factor analysis conducted on the first subsample suggested a two-factor interpretation, using eight of the items. A confirmatory factor analysis was then performed to test six possible models for goodness of fit. A bifactor model, with all items loading onto a general distress factor, with two group factors, comprising four depression and four anxiety items, provided the best fit of the data. The salience of loadings on the bifactor model suggested that loadings were high on the general factor (accounting for 64% of the variance) and low on the group factors (21% for anxiety and 15% for depression). The findings suggest that eight items from the scale perform well among the sample. Consistent with recent developments in modeling the Hospital Anxiety and Depression Scale, a bifactor interpretation for an eight-item version outperformed other extant models. Our findings provide support for an eight-item version of the scale to be used as a measure of general distress within Huntington's disease populations.


Honey prevents hepatic damage induced by obstruction of the common bile duct.
To examine the possible effects of honey supplementation on hepatic damage due to obstruction of the common bile duct in an experimental rat model. The study was performed with 30 male rats divided into three groups: a sham group, an obstructive jaundice group, and an obstructive jaundice plus honey group. At the end of the study period, the animals were sacrificed, and levels of nitric oxide (NO), and NO synthase (NOS) activities were measured in liver tissues, and levels of adenosine deaminase (ADA) and alanine transaminase (ALT) activities were measured in serum. Blood ALT and ADA activities were significantly elevated in the jaundice group as compared to those of the sham group. In the obstructive jaundice plus honey group, blood ALT and ADA activities were significantly decreased as compared to those of the jaundice group. In erythrocytes and liver tissues, NO levels were found to be significantly higher in the obstructive jaundice plus honey group compared to those of the sham group. Additionally, NO levels were found to be significantly higher in liver tissues from the animals in the obstructive jaundice plus honey group than those of the jaundice group. Honey was found to be beneficial in the prevention of hepatic damage due to obstruction of the common bile duct.


Effects of labetalol on cocaine pharmacokinetics in neonatal piglets.
Developmental exposure to cocaine can produce adverse neurobehavioral and cardiovascular effects. Few animal models of human neonatal exposure have been established. A pharmacokinetic study was therefore conducted to characterize the disposition of cocaine and a major metabolite benzoylecgonine (BE) using piglets as an animal model. Eight piglets (postnatal days 8-9) were instrumented with a jugular cannula for drug administration and blood sampling. One group of subjects (controls) received 6.0 mg/kg of cocaine-HCl (i.v.) and blood samples were drawn over 0-24 h. In another group (labetalol), 0.25 mg/kg labetalol-HCl was coadministered 15 min following cocaine dosing. Plasma levels of cocaine and BE were determined using GC-MS methods. Pharmacokinetics were evaluated by using a model-independent approach and compartmental modeling. For controls model-independent results were as follows: AUC = 148.9 +/- 9.0 mg/l x min, systemic clearance = 0.041 +/- 0.003 liters/min/kg, volume of distribution = 1.543 +/- 0.470 liters/kg, and t1/2 beta = 29.4 +/- 6.8 min. Cocaine followed two-compartment model kinetics with distribution and elimination half-lives of 0.3 +/- 0.1 and 58.0 +/- 18.0 min, respectively. Labetalol significantly decreased systemic clearance to 0.029 +/- 0.004 liters/min/kg. BE kinetics revealed a elimination half-life of 230.0 +/- 83.2 min. The results demonstrate a rapid distribution and metabolism of cocaine to BE followed by a prolonged elimination phase which is extended by labetalol treatment.


Primary hyperparathyroidism during pregnancy.
To provide an up-to-date review of primary hyperparathyroidism (HPT) as a complication of pregnancy. We discuss the initial manifestations of primary HPT in pregnant patients, the diagnosis, the differential diagnosis of hypercalcemia, and the recommended treatment strategies. In the nonpregnant state, 50 to 80% of patients with primary HPT are asymptomatic. In contrast, pregnant patients with primary HPT have a wide variety of symptoms and findings: gastrointestinal symptoms (nausea, vomiting, and anorexia), weakness and fatigue, headaches and confusion, nephrolithiasis, bone disease, pancreatitis, urinary tract infection, and hypertension. Occasionally, neonatal hypocalcemia is the initial manifestation of maternal HPT. Diagnosis of primary HPT during pregnancy is dependent on the clinical history and laboratory findings. In general, management of maternal primary HPT during pregnancy should be individualized and based on the patient's symptoms, general medical condition, severity of disease, and gestational stage at the time of diagnosis. If HPT is diagnosed during the first two trimesters, surgical intervention is the treatment of choice. Although uncommon, HPT during pregnancy may be associated with maternal and perinatal complications. Therefore, clinicians should be aware of the usual characteristics of this disorder and the preferred management options.


Adolescent partner-type experience: psychosocial and behavioral differences.
Adolescents behave differently with main and casual sexual partners. These differences in behavior may be due to how adolescents perceive main and casual partners, but may also be informed by which types of partners adolescents have had experience with. Data were collected in interviews with 276 sexually experienced STD clinic attendees in 1996-1998. Chi square tests and one-way analyses of variance were conducted to compare risk and protective variables among groups with different types of partner experience (main only, casual only, main and casual). Post hoc analyses determined differences between pairs of groups. Adolescents with different partner-type experiences evidenced different risk and protective factors. For example, adolescents who had had only main partners perceived a greater risk of contracting STDs from both main and casual partners than those who had had both partner types. Women in the casual-only group were the least likely to have been pregnant. Adolescents who had had main and casual partners intended a significantly shorter delay in initiating sex with a new main partner than did those in the main-only group; they also more strongly intended to have a side partner than did those who had had only main partners. The design of risk reduction and prevention interventions for at-risk sexually experienced adolescents ought to consider adolescents' sexual partner-type experiences and tailor messages to capitalize on associated protective factors and address or minimize associated risk factors.


Catalytic Asymmetric Synthesis of Cyclohexanes by Hydrogen Borrowing Annulations.
Hydrogen borrowing catalysis serves as a powerful alternative to enolate alkylation, enabling the direct coupling of ketones with unactivated alcohols. However, to date, methods that enable control over the absolute stereochemical outcome of such a process have remained elusive. Here we report a catalytic asymmetric method for the synthesis of enantioenriched cyclohexanes from 1,5-diols via hydrogen borrowing catalysis. This reaction is mediated by the addition of a chiral iridium(I) complex, which is able to impart high levels of enantioselectivity upon the process. A series of enantioenriched cyclohexanes have been prepared and the mode of enantioinduction has been probed by a combination of experimental and DFT studies.


Sucralose Promotes Colitis-Associated Colorectal Cancer Risk in a Murine Model Along With Changes in Microbiota.
Sucralose is a calorie-free high-intensity artificial sweetener that is widely used in thousands of foods and beverages all over the world. Although it was initially regarded as a safe, inert food additive, its adverse effect on gut microbiota and health has drawn more and more attention as evidence accumulates. Studies by us and others revealed that sucralose exacerbated gut damage and inflammation in animal models for inflammatory bowel disease (IBD), including those for both ulcerative colitis, and Crohn's disease. Our study demonstrated that sucralose greatly aggravated dextran sulfate sodium (DSS)-induced colitis along with causing changes in gut microbiota, the gut barrier and impaired inactivation of digestive proteases mediated by deconjugated bilirubin. It is well-documented that IBD greatly increases the risk of colorectal cancer (CRC), the globally third-most-common cancer, which, like IBD, has a high rate in the developed countries. Azoxymethane (AOM)/DSS has been the most commonly used animal model for CRC. In this study, we further explored the effect of sucralose on tumorigenesis and the possible mechanism involved using the AOM/DSS mouse model. First, 1.5 mg/ml sucralose was included in the drinking water for 6 weeks to reach a relatively stable phase of impact on gut microbiota. Then, 10 mg/kg AOM was administered through intraperitoneal injection. Seven days later, 2.5% DSS was put in the drinking water for 5 days, followed by 2 weeks without DSS. The 5 days of DSS was then repeated, and the mice were sacrificed 6 weeks after AOM injection. The results showed that sucralose caused significant increases in the number and size of AOM/DSS-induced colorectal tumors along with changes in other parameters such as body and spleen weight, pathological scores, mortality, fecal β-glucuronidase and digestive proteases, gut barrier molecules, gut microbiota, inflammatory cytokines and pathways (TNFα, IL-1β, IL-6, IL-10, and TLR4/Myd88/NF-κB signaling), and STAT3/VEGF tumor-associated signaling pathway molecules. These results suggest that sucralose may increase tumorigenesis along with dysbiosis of gut microbiota, impaired inactivation of digestive protease, damage to the gut barrier, and exacerbated inflammation.


[Assessment of fracture risk using quantitative ultrasound (QUS) ].
Previous studies have demonstrated close associations between QUS parameters and osteoporotic status. However, due to the ambiguities in assessing accuracy of QUS and the moderate correlation of DXA and QUS results, currently there is no agreement on how results of QUS devices should be interpreted in order to diagnose osteoporosis. However, I could recommend for clinical application that QUS should be used as the predictor of the risk of osteoporotic fractures. Good portability and low cost of QUS technique might make QUS an attractive technology for assessing risk of fractures in large populations.


Interaction of the anionic surfactant SDS with a cellulose thin film and the role of electrolyte and poyelectrolyte. 2 Hydrophilic cellulose.
The interaction of the anionic surfactant, sodium dodecylsulfate (SDS), with the hydrophilic surface of a thin cellulose film and the role of electrolyte (0.1 M NaCl) and the polyelectrolyte, poly(dimethyldiallyl ammonium chloride) [polydmdaac], have been studied by neutron reflectivity (NR). The thin cellulose films were prepared by Langmuir-Blodgett (LB) deposition of trimethylsilyl-cellulose (TMSC) on silicon, and the hydrophilic surface was produced by the cleaving of the terminal methyl groups of the TMSC by HCl vapor. Despite both the surfactant and cellulose surfaces being nominally anionic, SDS adsorption and swelling of the cellulose film occurred during adsorption. The results show that the nature of the adsorption and the extent of the penetration into the cellulose film can be controlled by the addition of electrolyte, NaCl, and cationic polyelectrolyte, polydmdaac.


Bovine immature oocytes acquire developmental competence during meiotic arrest in vitro.
To test the hypothesis that oocytes require time to acquire developmental competence during meiotic arrest, we investigated the effects of butyrolactone I (BL I), a potent and specific inhibitor of cyclin-dependent kinase, on the developmental competence of bovine oocytes after in vitro fertilization (IVF) following release from meiotic arrest. In the present study, 4 culture conditions were used: addition of BSA or fetal bovine serum (FBS) under 2 oxygen tensions (5% vs. 20%) during meiotic arrest with 100-microM BL I. The developmental competence to the blastocyst stage was higher (P < 0.01) in oocytes that were arrested in FBS-supplemented medium under 5% O2 (37%) than in oocytes that were arrested under other conditions (5%-24%) or that matured directly following follicle aspiration (23%). The time course of nuclear maturation of BL I-treated oocytes was also examined. The results demonstrated that oocytes treated with BL I start germinal vesicle (GV) breakdown and reach the metaphase II stage 5.5-6.0 h earlier than nonarrested oocytes. The developmental rates to the blastocyst stage of BL I-treated oocytes matured for 15.5 and 21 h were higher (P < 0.05) than those of nontreated oocytes matured for 21 and 26.5 h, respectively. These results demonstrate that bovine immature oocytes, which were arrested at the GV stage with BL I in FBS-supplemented medium under low oxygen tension, acquire higher developmental competence during meiotic arrest.


[Cause of Bell's palsy: herpes simplex virus].
At present Bell's palsy (BP) is still defined as idiopathic unilateral facial paralysis of sudden onset. More than 20 years ago an aetiological link between herpes simplex virus (HSV) and BP was proposed. Numerous experiments in animals and in humans have been performed to test this hypothesis. However, the human facial nerve tissue itself was investigated in only a few of these studies. Two research lines were followed: (a) search for presence of latent HSV in the facial nerve of asymptomatic individuals (as shown earlier in the trigeminal nerve); (b) find 'active' HSV in tissues from BP patients with recent onset of disease. The application of new molecular biological techniques, notably polymerase chain reaction (PCR), to facial nerve tissues has provided ample evidence for a causal relationship between BP and HSV. Therefore it might now be the time to change the name 'Bell's palsy' into 'herpetic facial paralysis'.


A DFT study of hydrogen and methane activation by B(C6F5)3/P(t-Bu)3 and Al(C6F5)3/P(t-Bu)3 frustrated Lewis pairs.
This contribution presents a computational study aimed at understanding factors affecting barriers associated with the activation of the H-H bond in molecular hydrogen and the H-CH3 bond in methane mediated by intermolecular Frustrated Lewis Pairs (FLPs). The classical phosphine P(t-Bu)3 Lewis base in conjunction with two Lewis acids, B(C6F5)3 and Al(C6F5)3, were used as representative models of intermolecular FLPs. DFT calculations were performed using the dispersion corrected ωB97x-D functional, including toluene as a solvent through the PCM-SMD implicit solvent scheme. The results show that, in all cases, the activation barrier is larger for methane than for hydrogen. We conclude that the observed increase in the barrier for methane activation is due primarily to a larger distortion in methane compared to hydrogen to reach the transition state. Second, a large distortion of the Lewis acid to attain a better interaction with the σ-bond in methane was observed. Finally, we found that, for both hydrogen and methane activation, a considerable reduction in the free energy activation barrier is observed when the Lewis acid Al(C6F5)3 is used. From the results extracted in this study, we propose the use of alanes acids as good candidates for methane activation.


Effects of Low Glycemic Index Diets on Gestational Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Clinical Trials.
Studies of the effects of low glycemic index (LGI) diets on gestational diabetes mellitus (GDM) have reported conflicting findings.The aim of the study was to evaluate the results of randomized controlled trials (RCTs) that investigated the effects of LGI diets with and without added dietary fiber (DF) on maternal and neonatal outcomes in GDM patients.We searched the MEDLINE, EMBASE, EBSCO, Springer, Ovid, and Cochrane Library databases for studies of the effects of LGI diets in GDM patients. We performed a meta-analysis of the effects of the LGI diets with and without added dietary fiber (DF) on GDM outcomes. Risk ratios (RR) and 95% confidence intervals (CIs) were calculated using random- and fixed-effects models.Five RCTs involving 302 participants were included in our meta-analysis. No statistically significant differences in the risks of cesarean section delivery, large for gestational age, and small for gestational age were observed. The risk of macrosomia in the LGI groups was significantly lower (RR = 0.27; 95% CI: 0.10-0.71; P = 0.008) than that in the control groups. Our subgroup analysis of the effects of DF showed that LGI diets with an increased level of DF, relative to the control diet, reduced the risk of macrosomia beyond that of the LGI diets alone (RR: 0.17 vs 0.47, respectively). The subgroup analysis also showed that LGI diets in which the level of DF was approximately equivalent to that in the control diets significantly reduced the risk of insulin usage (RR = 0.69; 95% CI: 0.52-0.92; P = 0.01).The LGI diets reduced the risk of macrosomia in GDM patients, and LGI diets with added DF reduced the risk of macrosomia further. The LGI diets with levels of DF approximately equivalent to that in the control diets reduced the risk of insulin usage in GDM patients.


Nursing care of the pregnant woman with diabetes mellitus.
The woman with diabetes who becomes pregnant faces increased risk of morbidity, urinary tract infections, vaginitis, difficult delivery, hemorrhage, cesarean section, preeclampsia, and hydramnios. Chronic disease alone produces emotional tension. Added to this she has increased general life stresses such as added financial responsibility, increases time commitments, and changes in lifestyle demands. The infant of the diabetic is often large for dates, faces respiratory distress syndrome with early delivery, may experience hypoglycemia, and may have fetal anomalies. Clinical specialists of nursing, consulting and working together, can develop a plan of nursing care for the pregnant woman with diabetes. Because the pregnant diabetic woman faces the usual adjustments to pregnancy plus problems dealing with a chronic condition of diabetes, nursing care should combine consideration of the physical, emotional and educational needs. In view of the many health team members providing care to the pregnant diabetic, one central figure with continued interaction can decrease fragmentation and provide continuity of care.