Trans-ethnical shift of the risk genotype in the CETP I405V with longevity: a Chinese case-control study and meta-analysis.
The I405V polymorphism of the cholesteryl ester transfer protein gene (CETP) has been suggested to be a protective factor conferring longevity in Ashkenazi Jews, although findings in other races are not supportive. This paper describes a case-control study and a meta-analysis conducted to derive a more precise estimation of the association between CETP 405V and longevity. We enrolled 1,021 ethnic Han Chinese participants (506 in the longevity group and 515 controls), then performed a meta-analysis that integrated the current study and previously published ones. Pooled odds ratios (OR) were calculated for allele contrasts, dominant and recessive inheritance models to assess the association between CETP 405V and longevity according to the ethnic stratification. Our case-control data indicated that CETP 405V is a longevity risk allele in all genetic models (P additive =0.008; P dominant =0.008, OR(dominant)=0.673; P recessive =0.017, OR(recessive)=0.654) after adjustment for the apolipoprotein E (APOE) ε4 allele, body mass index and high-density lipoprotein cholesterol. A synergy was detected between 405V and APOE ε4 (P=0.001, OR=0.530). Eight studies were eligible for meta-analysis, which confirmed 405V is the risky allele against longevity in all genetic models: allele contrasts (OR=0.81, 95%CI=0.74-0.88), dominant model (OR=0.72, 95%CI=0.64-0.82) and recessive model (OR=0.80, 95%CI=0.67-0.96). After ethnic stratification, 405V remained a risk allele in East Asians but no significant association was found in Europeans or white Americans. Our case-control study suggests CETP 405V as a risk allele against longevity in Chinese. The meta-analysis suggests the involvement of CETP 405V is protective in Ashkenazi Jews but is a risk allele against longevity in the East Asian (Chinese) population.


Different binding properties of muscarinic M2-receptor subtypes for agonists and antagonists in porcine gastric smooth muscle and mucosa.
The hypothesis that muscarinic receptors on smooth muscle differ from those in epithelial glands was tested by comparing the properties of muscarinic binding sites in porcine fundic smooth muscle with those in mucosal membranes. The binding of agonists and of antagonists was assessed by displacement of [3H]N-methylscopolamine. Pirenzepine (M1-antagonist) labeled low-affinity binding sites in smooth muscle (KD = 229 nM) and in mucosa (KD = 124 nM) consistent with the presence of M2 sites. Carbachol interacted with a high-affinity (KD = 164 nM) and a low-affinity (KD = 18.2 microM) state of binding sites in smooth muscle. Guanyl 5'-yl-imidodiphosphate converted all sites to the low-affinity state. N-ethylmaleimide pretreatment increased the affinity of carbachol and the proportion of high-affinity sites. In clear contrast, only low-affinity sites of carbachol were detectable in mucosa (KD = 17 microM) that were not modulated by N-ethylmaleimide or guanyl 5'-yl-imidodiphosphate. The cardioselective antagonist AF-DX 116 displayed low affinity to mucosal binding sites (KD = 3.4 microM), whereas its affinity to smooth muscle was 503 nM. The antagonist hexahydro-sila-difenidol had a very high affinity (KD = 2.9 nM) to mucosal receptors, whereas its affinity to smooth muscle sites was 88 nM. These data show that muscarinic M2 binding sites in mucosa and smooth muscle can be distinguished by both agonist and antagonist binding experiments, and suggest the existence of different subtypes of M2-binding sites in these tissues.


Liquid-crystalline Metallomacrocycles Composed of Bis(hydroxypyridono)toluene Ligand and Cu2+ Ions.
A series of π-extended chelating scaffolds incorporating two hydroxypyridone moieties were synthesized. X-ray crystallographic analysis revealed that a bis(hydroxypyridono)toluene ligand possessed a unique π-extended structure and exhibited efficient phase segregation from the aliphatic chains attached at the heterocyclic nitrogen. The bis-bidentate ligand formed a metal-coordination-induced macrocycle with Cu2+ ions. During the complexation, a spectral change in the visible region was induced. Furthermore, the successful development of a liquid crystal of the metallomacrocycle with appropriate side chains was achieved. Examples of liquid-crystalline macrocycles formed via metal-mediated self-assembly are still rare. Among them, the macrocycle described in this paper showed an obvious hexagonal columnar phase reflecting the three-fold symmetric planar structure of the mesogenic metal complex.


Transfer characteristics of an ink-jet writer for cardiovascular studies.
The transfer characteristic of a 16 channel ink-jet writer used in a cardiovascular laboratory is described. The test method for measuring linearity, gain and phase response is described and results given. The transfer function was calculated from the normalized experimental results and allows prediction of the behaviour of the writer for different input signals. It is shown that the ink-jet galvanometers are linear for signal input amplitudes between 0 and 2.5 V, and have a flat frequency response between DC and 640 Hz (+/- 1%).


Genital warts: current and future management options.
Genital warts are a cosmetic nuisance. They are caused by low-risk human papillomavirus types, have no oncogenic potential and are not linked to cervical cancer. However, they often cause significant psychological morbidity. Treatments are aimed at eradicating the unsightly lesions and stimulating the immune system to generate clearance and prevent recurrence. Commonly used physical treatment methods include cryotherapy, trichloroacetic acid, laser, and electrocautery. However, many patients respond extremely well to home therapies with either podophyllotoxin or imiquimod. Patients prefer the comfort and dignity of home treatment, and this should be the first-line of treatment for the majority of patients. A routine screen for sexually transmitted infections is appropriate in most cases. Detailed explanation and reassurance are of paramount importance in reducing the psychological distress associated with this unpleasant genital condition.


Unusual histological lesions in the eye of a leprosy patient.
A pathological study of an eye from a leprosy patient is reported. In addition to the granulomatous lesions in the anterior aspect of the eye, microgranulomas are demonstrated in the retina of this patient, a very uncommon finding in leprosy.


Movies of dopamine transporter occupancy with ultra-high resolution focusing pinhole SPECT.
A pivotal question in neuropharmacology is how the function of neurotransmitter systems relates to psychiatric diseases. In experimental neuropharmacology, we have dreamt about a looking glass that would allow us to see neurotransmitter systems in action, and about animals that would faithfully serve us as models for human psychiatric disease. Analysis of animal models has been limited by the availability of methods to study in vivo neurotransmitter dynamics. Now, a single photon emission computed tomography system called U-SPECT can localize dopamine transporters in sub-compartments of the mouse brain during a range of points in time. Applied to the midbrain dopamine system of different models of disease, this will aid the understanding of dynamic processes of this neurotransmitter that underlie brain functions and human brain pathology.


Morphological studies on the mantle of the fresh-water mussel Amblema (Unionidae): scanning electron microscopy.
The scanning electron microscope has been used to describe the surface morphology of the mantle in mantle-shell preparations from the fresh-water mussel Amblema. In some regions (adductor muscle insertions), the mantle is firmly attached to the shell. In other areas (along the main course of the mantle), transient adhesions between the outer mantle epithelial cells and the nacre appear to temporally further compartmentalize the extrapallial fluid possibly as a prerequisite for the initial crystallization phenomenon. At the mantle edge, as well as at the isthmus, the periostracum was seen to extrude from the periostracal groove. At the siphonal edge, peculiar finger-like processes were identified; these may represent primitive photoreceptors. The epithelial cells of the outer mantle epithelium are all microvillated whereas those of the inner mantle epithelium are both microvillated and ciliated. Specific differences in surface morphology are described for various regions of the outer mantle epithelium. These may be related to precise regionalized functional differences of this tissue. Several functions of the mantle, in addition to shell formation, and based on its various morphologies, are also discussed.


Significance of MRI-confirmed atrophy of the cranial spinal cord in Friedreich's ataxia.
The severity of Friedreich's ataxia was graded in ten patients by clinical examination and in five by use of posturography. These data were compared with neuroradiology findings. CT-confirmed infratentorial atrophy occured only in advanced cases of Friedreich's ataxia; the correlation with the clinical score was poor. On mid-sagittal MRI planes the diameters of fourth ventricle, brain stem at the level of the inferior olive and spinal cord at the levels of the foramen magnum and C3 were measured. Patients with Friedreich's ataxia had significant MRI-confirmed atrophy of the cranial spinal cord as compared with a normal, age-matched control group. This was also observed in patients with Friedreich's ataxia in the early stages. A reliable correlation between atrophy of the cranial spinal cord and the clinical score, however, could again not be found. MRI exploration of the cranial spinal cord may be recommended as an additional diagnostic marker in Friedreich's ataxia.


The Cost of Implementing New Strategies (COINS): A Method for Mapping Implementation Resources Using the Stages of Implementation Completion.
Illustrate the value of a strategy used for measuring the costs and resources used in the implementation process over and above the costs of the intervention itself in the context of a two-arm randomized controlled trial. Counties in California and Ohio (sites) were invited to implement Multidimensional Treatment Foster Care (MTFC), an alternative to congregate care for youth. Participating sites (n=53) were randomized to one of two implementation = sites share information and move through the implementation process as a cohort facilitated by an MTFC purveyor or (2) Individual Implementation (IND: "as usual") where sites work individually with the MTFC purveyor. The implementations were monitored using the Stages of Implementation Completion (SIC) measure of a number of observable activities, developed as part of the trial to segment the implementation process into 8 stages of implementation. Resource data gathered from the implementation purveyors and site participants were used to map costs onto each of the 8 stages to generate total cost measures stratified by type of resource and stage of implementation for each of the study arms. The SIC provided a feasible costing template to map costs onto observable activities and to enable the examination of important differences in implementation strategies for an evidence-based practice. The average total implementation cost prior to program start-up of CDT was $133,106; IND cost $118,699. While CDT cost more in a number of stages, it resulted in fewer county staff hours being used and shorter mean times to implementation than IND. In cases where rapidity of implementation of reducing staff time required for implementation is valued, then CDT would be the preferable implementation approach. The SIC is a useful tool for determining implementation resources needed for new evidence-based practice programs for youth and particularly for comparing different implementation strategies that might be tried in pilot programs.


GCW-UNet segmentation of cardiac magnetic resonance images for evaluation of left atrial enlargement.
Left atrial enlargement (LAE) is an anatomical variation of the left atrium and the result of the long-term increase of left atrial pressure. Most of the increase in stress or volume is due to potential cardiovascular disease. Studies have shown that LAE can independently predict the development of clinically significant cardiovascular disease and heart failure. If the left atrial volume is accurately measured, it will be an essential indicator of human health and an essential means for doctors to find patients' potential diseases. We can analyze the dynamic changes in the left atrial structure and analyze left atrial dilation. However, manual segmentation was inefficient and error-prone before the 3D reconstruction of the left atrium. In order to solve this problem, a convolution neural network (CNN) method based on cardiac magnetic resonance image (MRI) is proposed to automatically segment the left atrial region. In this paper, we have proposed and developed a novel U-Net with Gaussian blur and channel weight neural network (GCW-UNet) to automatically segment the left atrial region in the MRI of a patient with LAE. After Gaussian blur, different resolutions of the MRI are obtained. High-resolution MRI clearly shows the detailed features of the left atrium, while low-resolution MRI clearly shows the overall outline of the left atrium, which can solve the problem of more minor MRI features. Adaptive channel weights can enhance the atrial segmentation capability of the network. Compared with the state-of-the-art left atrial segmentation methods, our CNN-based technique results in the segmentation of the left atrium being closer to the manual segmentation by an experienced radiologist. On the test datasets, the mean Dice similarity coefficient reaches 93.57%. Firstly, MRI has a small number of imaging artifacts, which results in low segmentation accuracy. Our method successfully solves the problem. Secondly, due to the high similarity between the background (the area outside the left atrium) and the foreground (the left atrium) in MRI, traditional neural networks misclassify the background as the foreground. Our GCW-Unit can address the imbalanced number of pixels between the foreground and background. Finally, after segmenting the left atrium in the MRI by GCW-Unit, we reconstructed the left atrium to model a three-dimensional heart of a patient suffering from LAE. Based on the different time frames of one heartbeat, we could present the dynamics of the left atrial structure during a cardiac cycle. This can better assist in the evaluation of LAE in heart patients.


Implementing an energetic life cycle analysis to prove the benefits of lignocellulosic feedstocks with protein separation for the chemical industry from the existing bioethanol industry.
The biofuel ethanol is currently being produced in large quantities from corn in the US and from wheat in the EU and further capacity expansion is expected. Relying on the so-called 1st generation technology, only the starch contained in the edible portion of the crops (ears/grains) is subjected to fermentation. Following life cycle calculations reveals minute levels of fossil fuel replacement placing doubt on its renewability and an imbalance on the domestic animal feed markets are immerging due to the by-product distiller grains. Additional utilization of the lignocellulosic and protein components of the by-product through new developments has the potential to alleviate both setbacks. A cradle-to-factory gate analysis was performed on a variety of bioethanol production layouts incorporating the newest technological developments to determine the maximum fossil fuel reduction potential. Expanding to include lignocellulose pretreatment for ethanol production with protein separation for amine-based chemical production can increase the fossil fuel mitigation potential by seven- to ninefold for US-corn and five- to eightfold for EU-wheat bioethanol facilities.


High-throughput detection of drugs binding to proteins using desorption electrospray ionization mass spectrometry.
In this paper, we present a strategy for screening drugs that bind to proteins by combining centrifugal filtration with desorption electrospray ionization mass spectrometry (DESI-MS). Membrane filtration was used to remove any unbound drugs. Then, drug-protein complexes deposited on the DESI substrate were dissociated during the DESI-MS analytical process, and the liberated drugs were measured. To validate the methodology, the screening of a series of drugs against two types of proteins was performed. Three DNA topoisomerase I (Topo I) inhibitors (camptothecin (CPT), hydroxycamptothecin (OHCPT) and 7-ethyl-10-hydroxycamptothecin (SN-38)) were screened against Topo I and the DNA-Topo I complex using DESI-MS. The results indicated that none of the inhibitors bound to Topo I, because the inhibitors had binding affinities only to the DNA-Topo I complex. Among the three drugs that bound to the DNA-Topo I complex, SN-38 had the strongest relative binding affinity, and CPT had the weakest relative binding affinity. The impact of the DESI spray solvent composition on the analysis of drug-protein complex binding was evaluated. Seven alkaloid drugs were also screened against Topo I using DESI-MS. Berberine and palmatine had good binding affinities. A screening of 21 types of drugs was carried out to determine whether the drugs bound to human serum albumin (HSA). The DESI-MS screening process could be achieved within 1.75min. The study provides a method to qualitatively detect compounds that bind to proteins, showing great potential in drug design and screening.


[Staphylococcal toxic shock syndrome at a chronic hemodialysis].
Staphylococcal toxic shock syndrome is an acute and systemic infectious syndrome associated with the super-antigenic activity of staphylococcal toxins. It is a pathology that is rather rare but remains burdened with a considerable mortality despite the therapeutic management. The gateway is usually cutaneous with secondary bacteremic spread could be subject to preventive measures. We report the case of a rapidly fatal staphylococcal toxic shock, developed in a chronic hemodialysis whose entry from the arteriovenous fistula was suspected.


Allergic diseases do not impair the cognitive development of children but do damage the mental health of their caregivers.
This study aimed to investigate whether children with atopic diseases exhibited different neurodevelopment function from healthy controls and whether their caregivers had differential parental stress. In total, we recruited 109 patients with atopic diseases (mean age 6.8 years, 54.1% male) and 82 healthy children (mean age 6.3 years, 54.9% male). Based on the children's age, they underwent developmental, cognitive evaluations and attention deficit/hyperactivity disorder (ADHD) symptoms. The parenting stress of children's caregivers was evaluated using the Chinese Health Questionnaire (CHQ-12) and Family APGAR. Of the children with atopic diseases, 87.2%, 74.3%, 29.4%, and 8.3% of them had allergic rhinitis, asthma, atopic dermatitis, and urticaria, respectively. None of these conditions were associated with children's cognitive profiles or ADHD symptoms. However, the caregivers of patients who had asthma suffered from higher CHQ-12 scores than those of patients without asthma. Furthermore, the number of atopic diseases had a dose-response effect on caregivers' CHQ-12 scores. In conclusion, allergic diseases did not impair the cognitive development of children. However, caregivers of patients with asthma or multiple atopic diseases may suffer a greater mental health burden with regard to caring for their children. Such caregivers may require support to effectively fulfill their parenting roles.


Knowledge, attitudes, and practices of young adults regarding the impact of electronic cigarette use on oral health.
The popularity and prevalence of electronic cigarette (EC) usage has continued to surge to 35 million worldwide, with one-half of users younger than 34 years. Despite emerging research suggesting deleterious oral health effects, the perceptions of EC users concerning oral health effects remain unknown. The purpose of this study was to explore knowledge, attitudes, and practices of young adults regarding the impact of EC use on oral health. A cross-sectional survey used a validated tool to investigate vaping and oral health knowledge, attitudes, and practices among a convenience sample of EC users (N = 220). Outcomes were analyzed using descriptive and inferential statistics. People 18 through 24 years (N =168) indicated a lack of knowledge (mean [standard deviation {SD}], 2.9 [1.7]) and familiarity with oral health effects of vaping (mean [SD], 2.7 [1.7]). Participants expressed willingness to discuss oral health effects of vaping with dental care professionals (n = 111 [66%]), and most (n = 109 [65%]) would potentially reduce (30%) or quit (24%) if they believed it was harmful to their oral health. Participants 18 through 24 years were more likely to agree they would quit (n = 54 [68%]) than those 25 through 34 years (n = 36 [42%]; χ2 = 11.03; P = .004; φ = 0.26). Those who visit their dental care professional every 6 months (n = 82 [57%]) agreed they would quit vaping versus those who do not (n = 26 [37%]; χ2 = 9.84; P = .007; φ, 0.22). Respondents reported low knowledge regarding the implications of vaping on oral health but expressed a willingness to discuss vaping with their dental care professionals. Most EC users are willing to accept guidance from dental care professionals regarding quitting use.


QSPR models for predicting generator-column-derived octanol/water and octanol/air partition coefficients of polychlorinated biphenyls.
Octanol/water (K(OW)) and octanol/air (K(OA)) partition coefficients are two important physicochemical properties of organic substances. In current practice, K(OW) and K(OA) values of some polychlorinated biphenyls (PCBs) are measured using generator column method. Quantitative structure-property relationship (QSPR) models can serve as a valuable alternative method of replacing or reducing experimental steps in the determination of K(OW) and K(OA). In this paper, two different methods, i.e., multiple linear regression based on dragon descriptors and hologram quantitative structure-activity relationship, were used to predict generator-column-derived log K(OW) and log K(OA) values of PCBs. The predictive ability of the developed models was validated using a test set, and the performances of all generated models were compared with those of three previously reported models. All results indicated that the proposed models were robust and satisfactory and can thus be used as alternative models for the rapid assessment of the K(OW) and K(OA) of PCBs.


Central implants of diluted estradiol: independent effects on ingestive and reproductive behaviors of ovariectomized rats.
The present experiment was undertaken to evaluate the hypothesis that the effects of estrogens on feeding and sexual behaviors are organized separately within the brain. Thirty-three ovariectomized rats were implanted with bilateral guide cannulae aimed at either the paraventricular nucleus (PVN), medial preoptic area (MPOA), or posterior hypothalamus (PH). Subjects that received PVN implants were stimulated with either undiluted estradiol, a 3:1, or 10:1 mixture of cholesterol and estradiol. Animals in the other groups were treated with undiluted estradiol. All females were stimulated unilaterally with cholesterol and estradiol, yielding a total of 66 stimulation sites. Histological analysis revealed that, compared to cholesterol implants, undiluted estradiol in the PVN reduced food intake and body weight. More importantly, diluted estradiol implants in the PVN significantly lowered food intake and body weight. In contrast, undiluted estradiol in the MPOA, PH, or ventromedial hypothalamus (VMH) had no significant effects on feeding or body weight. Analyses of variance revealed significant main effects of implant location on female sexual behavior. Newman-Keuls tests indicated that diluted estradiol implants in the PVN produced lordosis quotients and quality scores that were significantly lower than those obtained with VMH implants. The possibility that the behavioral changes observed were due to peripheral rather than central effects of the hormone was evaluated by comparing the results of implants that produced vaginal cell cornification to those that did not. There were no significant differences between these groups on any of the other dependent variables, indicating that peripheral estradiol sufficient to induce vaginal cell cornification was neither necessary nor sufficient to account for the behavioral changes.(ABSTRACT TRUNCATED AT 250 WORDS)


[HPV vaccination: not only female adolescents and not only prophylactic. Review and position paper of the Italian HPV Study Group (IHSG)].
HPV vaccination has been introduced in clinical practice in recent years and represents the most effective strategy of primary prevention of cervical carcinoma and of female genital preneoplastic conditions. One of the major issues of the subject is represented by vaccination coverage of the target population. Since its introduction, HPV vaccine efficacy has been progressively demonstrated also towards extragenital HPV-correlated conditions and in males too. Moreover, even subjects of older age groups or subjects who already had HPV infections have been demonstrated to received benefits from vaccination, due to improvements of their immunological response. Recently, vaccine efficacy has also been investigated in terms of adjuvant administration after treatments of preneoplastic or benign conditions of the female lower genital tract caused by HPVs; preliminary results indicate an interesting and promising field of application. On this basis, in this article an analysis of the state of the art has been performed, with specific regard to the Italian scenario and with the focus of future perspectives of implementation of the HPV vaccination policy. From the available evidences, the Italian HPV Study Group recommends the extension of systematic HPV vaccination to males too, to adult subjects and also after conservative treatment of genital HPV correlated conditions.


Opisthorchis viverrini-like liver fluke in birds from Vietnam: morphological variability and rDNA/mtDNA sequence confirmation.
Flukes were found in the bile ducts of domestic ducks (Anas platyrhynchos), necropsied in the Binh Dinh province of Central Vietnam. Following staining, morphological characteristics of the bird flukes were compatible with Opisthorchis viverrini, although some characteristics differed from those described in specimens collected from mammal hosts. Computation of the phylogenetic trees on the partial sequences of the second internal ribosomal spacer (ITS2) of the ribosomal DNA and cytochrome c oxidase subunit I (COI) markers of the mitochondrial DNA showed close similarity of the 'bird' Opisthorchis sp. with O. viverrini. We speculate that these bird flukes are O. viverrini that show intraspecies morphological and molecular variability compared to isolates from mammals. This demonstrates the complex epidemiological situation of opisthorchiasis in Vietnam and urges investigations on the potential of birds as a reservoir host of this zoonotic fluke.


The association of bound aldehyde content with bioprosthetic tissue calcification.
The rapid progression of mineralization seen in glutaraldehyde-treated valves has prompted a wide variety of secondary treatments aimed at mitigating dystrophic calcification. We tested the hypothesis that aldehyde residuals bound to bioprosthetic tissue is a significant promoter of calcification. We developed a novel assay to measure residual aldehyde functional groups and assessed aldehyde content in three different groups: glutaraldehyde-fixed tissue (Glut-only), Edwards ThermaFix™ treated tissue and Edwards RESILIA™ tissue. The amount of tissue calcification in these same groups was assessed in vivo using a well-established rabbit model, in which tissue samples were implanted intramuscularly for 60 days. The aldehyde content of the Glut-only, ThermaFix™ treated and RESILIA™ tissues were 225.7 ± 31.5, 101.9 ± 79.7 and 32.5 ± 48.4 nmol/g, respectively. The differences among all three groups were highly significant (p < 0.001, Student's unpaired t test). The median (interquartile range) calcium content of the Glut-only, ThermaFix™ treated and RESILIA™ tissues were 227.4 (221.8-243.6), 101.0 (23.05-169.6), and 10.1 (0.28-51.7) μg/mg. The differences among all three groups were highly significant (p < 0.001, Mann-Whitney U test). The results indicated that our novel assay was able to reliably measure aldehyde content in bovine pericardial tissue. Furthermore, there appeared to be a close association between aldehyde content and tissue calcium content. The processing of bioprosthetic valves to reduce their aldehyde content may offer a significant advantage in terms of reducing the potential for long-term calcification in human implants.


The role of whole-body FDG-PET in preoperative assessment of tumor staging in oral cancers.
The aim of this study is to clarify the clinical utility of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) in determining the TNM classification in patients with oral cancer. Twenty-five consecutive patients (14 male and 11 female; age range, 40 yr to 86 yr) with oral cancer were included in this study. The diagnostic accuracy for detecting cervical lymph nodes was investigated by comparing the results of CT and/or MRI and physical findings. For the semi-quantitative analysis, the tumor standardized uptake value (SUV) and tumor to background SUV ratio (T/B ratio) were assessed in primary tumors and cervical lymph nodes. All primary lesions were visualized on FDG-PET images. Even though artifacts from dental materials near the lesion hampered the delineation of primary tumors on CT/MRI, the extent of primary tumors was accurately assessed by FDG-PET. The SUV and T/B ratio in the primary tumor classified in higher T grade (T3 and T4) was significantly higher than that in lower T grade (T1 and T2) (mean +/- SD of SUV; 8.32 +/- 2.99 vs. 5.15 +/- 3.77, p < 0.01, mean +/- SD of T/B ratio; 6.96 +/- 3.23 vs. 3.61 +/- 2.76, p < 0.01). The SUV and T/B ratio of metastatic lymph nodes were also significantly higher than those of normal lymph nodes (mean +/- SD of SUV; 3.39 +/- 1.69 vs. 1.55 +/- 0.57, p < 0.001, mean +/- SD of T/B ratio; 2.46 +/- 1.08 vs. 1.03 +/- 0.22, p < 0.001). Among these three methods, FDG-PET in conjunction with CT/MRI showed the highest accuracy of 92%, but there were no significant differences in diagnostic accuracy among the three methods. For the semi-quantitative analysis, a threshold SUV of 2.0 provided 100% sensitivity, 82% specificity, and 88% accuracy. Furthermore, a threshold T/B ratio of 1.5 provided 100% sensitivity, 100% specificity, and 100% accuracy. Regarding the detection of distant metastasis, there was one positive result in FDG-PET showing distant pulmonary metastasis. Whole-body FDG-PET is an effective and convenient diagnostic tool for the evaluation of tumor staging in patients with oral cancer. Tumor staging by whole-body FDG-PET may, in fact, supplement the conventional staging by means of CT/MRI and physical findings.


Urotensin I- and CRF-like peptides in Catostomus commersoni brain and pituitary--HPLC and RIA characterization.
Two distinct neuronal systems, containing urotensin I-like immunoreactivity (UI-LI) and CRF-LI respectively, have previously been demonstrated immunocytochemically in the brain and pituitary of the teleost Catostomus commersoni. In the present studies, we used HPLC followed by UI- and CRF-RIA to further characterize these UI- and CRF-LI substances. HPLC of Catostomus brain extracts (including extracts modified by dilute H2O2 oxidation or dilute acid cleavage) suggests that the major form of brain UI-LI is very likely identical to the previously characterized urophysial UI; the small amount of pituitary UI-LI is not yet fully characterized. The behavior of brain CRF-LI on reversed phase (RP) extraction suggests that it may exist largely in precursor form. Pituitary CRF-LI, however, behaved as expected for a peptide on RP extraction, and eluted from HPLC as essentially a single (though somewhat broad) peak. The HPLC behavior of pituitary CRF-LI, and its crossreactivity with various CRF antisera, suggest that it represents authentic fish CRF, apparently similar to (but not identical with) human/rat CRF.


The characteristics of a variant strain of Brucella melitensis Rev 1.
Circumstantial evidence is presented for the occurrence of a variant of a vaccine strain of B. melitensis Rev 1, designated "FSA" (foreign South African). FSA resembles Rev 1 in its reactions to penicillin and streptomycin but reacts closer to a field strain of B. melitensis as regards dye (thionine and basic fuchsin) sensitivity and colony size. Although colonies of Rev 1 were consistently smaller than other B. melitensis strains, their size was 0,75 mm as opposed to the 1-2 mm reported in the literature, while B. melitensis 16M colonies were 1,25-1,5 mm as opposed to the 3-4 mm previously reported. Rev 1 was found to be urease positive, unless a test of low sensitivity was applied.


Individual and combined effects of herbicide prometryn and nitrate enrichment at environmentally relevant concentrations on photosynthesis, oxidative stress, and endosymbiont community diversity of coral Acropora hyacinthus.
Nitrogen pollution and pesticides such as photosystem II (PSII) inhibitor herbicides have several detrimental impacts on coral reefs, including breakdown of the symbiosis between host corals and photosynthetic symbionts. Although nitrogen and PSII herbicide pollution separately cause coral bleaching, the combined effects of these stressors at environmentally relevant concentrations on corals have not been assessed. Here, we report the combined effects of nitrate enrichment and PSII herbicide (prometryn) exposure on photosynthesis, oxidative status and endosymbiont community diversity of the reef-building coral Acropora hyacinthus. Coral fragments were exposed in a mesocosm system to nitrate enrichment (9 μmol/L) and two prometryn concentrations (1 and 5 μg/L). The results showed that sustained prometryn exposure in combination with nitrate enrichment stress had significant detrimental impacts on photosynthetic apparatus [the maximum quantum efficiency of photosystem II (Fv/Fm), nonphotochemical quenching (NPQ) and oxidative status in the short term. Nevertheless, the adaptive mechanism of corals allowed the normal physiological state to be recovered following 1 μg/L prometryn and 9 μmol/L nitrate enrichment individual exposure. Moreover, exposure for 9 days was insufficient to trigger a shift in Symbiodiniaceae community. Most importantly, the negative impact of exposure to the combined environmental concentrations of 1 μg/L prometryn and 9 μmol/L nitrate enrichment was found to be significantly greater on the Fv/Fm, quantum yield of non-regulated energy dissipation [Y(NO)], NPQ, and oxidative status of corals compared to the impact of individual stressors. Our results show that interactions between prometryn stress and nitrate enrichment have a synergistic impact on the photosynthetic and oxidative stress responses of corals. This study provides valuable insights into combined effects of nitrate enrichment and PSII herbicides pollution for coral's physiology. Environmental concentrations of PSII herbicides may be more harmful to photosystems and antioxidant systems of corals under nitrate enrichment stress. Thus, future research and management of seawater quality stressors should consider combined impacts on corals rather than just the impacts of individual stressors alone.


Decreased intestinal nutrient response in diet-induced obese rats: role of gut peptides and nutrient receptors.
Diet-induced obesity (DIO) is an excellent model for examining human obesity comprising both genotypic and environmental (diet) factors. Decreased responsiveness to peripheral satiety signaling may be responsible for the hyperphagia in this model. In this study, we investigated responses to nutrient-induced satiation in outbred DIO and DIO-resistant (DR) rats fed a high-energy/high-fat (HE/HF) diet as well as intestinal satiety peptide content, intestinal nutrient-responsive receptor abundance and vagal anorectic receptor expression. Outbred DIO and DR rats fed a HE/HF diet were tested for short-term feeding responses following nutrient (glucose and intralipid (IL)) gastric loads. Gene and protein expressions of intestinal satiety peptides and fatty acid-responsive receptors were examined from isolated proximal intestinal epithelial cells and cholecystokinin-1 receptor (CCK-1R) and leptin receptor (LepR) mRNA from the nodose ganglia of DIO and DR animals. DIO rats were less responsive to IL- (P<0.05) but not glucose-induced suppression of food intake compared with DR rats. DIO rats exhibited decreased CCK, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1; P<0.05 for each) protein expression compared with DR rats. Also, DIO rats expressed more G-protein-coupled receptor 40 (GPR40; P<0.0001), GPR41 (P<0.001) and GPR120 (P<0.01) relative to DR rats. Finally, there were no differences in mRNA expression for CCK-1R and LepR in the nodose ganglia of DIO and DR rats. Development of DIO may be partly due to decreased fat-induced satiation through low levels of endogenous satiety peptides, and changes in intestinal nutrient receptors.


A Bayesian Analysis to Determine the Prevalence of Barth Syndrome in the Pediatric Population.
To determine the prevalence of Barth syndrome in the pediatric population. Data were collected from the Barth Syndrome Foundation Registry and relevant literature. With the advent of genetic testing and whole-exome sequencing, a multipronged Bayesian analysis was used to estimate the prevalence of Barth syndrome based on published data on the incidence and prevalence of cardiomyopathy and neutropenia, and the respective subpopulations of patients with Barth syndrome indicated in these publications. Based on 7 published studies of cardiomyopathy and 2 published studies of neutropenia, the estimated prevalence of Barth syndrome is approximately 1 case per million male population. This contrasts with 99 cases in the Barth Syndrome Foundation Registry, 58 of which indicate a US location, and only 230-250 cases known worldwide. It appears that Barth syndrome is greatly underdiagnosed. There is a need for better education and awareness of this rare disease to move toward early diagnosis and treatment.


Effects of bacterial inoculation and calcium source on microbial-induced carbonate precipitation for lead remediation.
Heavy metal contamination has caused serious threats to surrounding fragile environments and human health. While the novel microbial-induced carbonate precipitation (MICP) technology in the recent years has been proven effective in improving material mechanical and durability properties, the mechanisms remedying heavy metal contamination still remain unclear. In this study, the potential of applying the MICP technology to the lead remediation under the effects of urease activity and calcium source was explored. The values of OD600 corresponding to the ureolytic bacterial activity, electrical conductivity (EC), urease activity (UA) and pH were applied to monitor the degree of urea hydrolysis. Further, the carbonate precipitations that possess different speciations and cannot be distinguished through test tube experiments were reproduced using the Visual MINTEQ software package towards verifying the validity of the proposed simulations, and revealing the mechanisms affecting the lead remediation efficiency. The findings summarised in this work give deep insights into lead-contaminated site remediation engineering.


Advances in the treatment of varicose veins: ambulatory phlebectomy, foam sclerotherapy, endovascular laser, and radiofrequency closure.
Several recent advances in the treatment of varicose veins have improved the safety, efficacy, comfort, efficiency, and long-term success of therapy. The advances of ambulatory phlebectomy, foam sclerotherapy, endovascular laser, and radiofrequency ablation with closure have made a significant positive impact on patient satisfaction. Duration of treatment and recovery is shorter, discomfort is minimized, and results are generally excellent. Studies assessing long-term outcomes are ongoing, and treatment modalities are continuing to evolve.


Depletion of highly abundant proteins in blood plasma by ammonium sulfate precipitation for 2D-PAGE analysis.
Ammonium sulfate precipitation (ASP) was explored as a method for depleting some highly abundant proteins from blood plasma, in order to reduce the dynamic range of protein concentration and to improve the detection of low abundance proteins by 2D-PAGE. 40% ammonium sulfate saturation was chosen since it allowed depleting 39% albumin and 82% α-1-antitrypsin. ASP-depletion showed high reproducibility in 2D-PAGE analysis (4.2% variation in relative abundance of albumin), similar to that offered by commercial affinity-depletion columns. Besides, it allowed detecting 59 spots per gel, very close to the number of spots detected in immuno-affinity-depleted plasma. Thus, ASP at 40% saturation is a reliable depletion method that may help in proteomic analysis of blood plasma. Finally, ASP-depletion seems to be complementary to hydrophobic interaction chromatography (HIC)-depletion, and therefore an ASP-step followed by a HIC-step could probably deplete the most highly abundant plasma proteins, thus improving the detection of low abundance proteins by 2D-PAGE.


Manganese potentiation of autologous anti-Meth A tumor vaccines. A developmental study.
This study was set up to develop methods for increasing the potency of vaccines against pre-existing transplanted subcutaneous Meth A tumors in Balb/c mice. The vaccines were prepared from particles and surface membrane ghosts from Meth A cells, a transplantable lymphosarcoma originally induced in a Balb/c mouse with methylcholanthrene. It was not possible to increase vaccine potency by conventional methods, but a major increase was achieved by adding manganese and phosphate. Vaccines prepared with these substances stimulated significant numbers of mice to completely reject target tumors transplanted 3 days before immunization. Possible mechanisms for this manganese effect on vaccine potency are discussed in this paper.


Bisatellited microchromosomes and multiple congenital malformations.
The significance of small additional metacentric chromosomes is still unclear. A patient is reported with multiple congenital malformations involving craniofacial structures, the cardiovascular system and gastrointestinal tract, in whom an extra small bisatellited chromosome was detected. The maternal karyotype revealed a marker number 9 chromosome. These cases present a true diagnostic dilemma in genetic counseling, since chromosomal instability may occur in the presence of parental minor structural chromosomal changes.


Risk Factors for Portal Vein System Thrombosis After Laparoscopic Splenectomy in Cirrhotic Patients with Hypersplenism.
Portal vein system thrombosis (PVST) is a frequent and potentially life-threatening complication after laparoscopic splenectomy (LS) in cirrhotic patients with hypersplenism. The mechanisms and risk factors of PVST are poorly understood. This study investigated risk factors for PVST following LS in cirrhotic patients with hypersplenism. A total of 56 consecutive cirrhotic patients with hypersplenism who underwent successful LS between 2013 and 2014 were included in this retrospective study. Based on the absence or presence of postoperative PVST on postoperative day (POD) 7, the patients were divided into non-PVST and PVST groups. Demographic and preoperative factors were analyzed. PVST increased in size in 24 (42.9%) of 56 patients after LS on POD 7. Logistic multivariate regression showed that a portal vein diameter >13 mm (relative risk 35.796, 95% confidence interval 4.534-282.614, and P = .001) and age >50 years (relative risk 20.127, 95% confidence interval 3.598-112.578, and P = .001) were significant independent risk factors for PVST. The incidence of PVST after LS in the portal vein diameter >13 mm group was significantly higher than that in the portal vein diameter ≤13 mm group (P = .001). Similarly, the incidence of PVST after LS in the age >50 years group was significantly higher than that in the age ≤50 years group (P = .001). A portal vein diameter >13 mm and age >50 years are independent risk factors for PVST after LS in cirrhotic patients with hypersplenism due to portal hypertension.


Ultrasonographic prediction of birth weight in diabetic pregnancies.
To compare diabetic and nondiabetic pregnant women near term regarding the accuracy of predicted birth weight by the gestation-adjusted projection method using ultrasonographic measurements. Patients with singleton pregnancies who had diabetes and who underwent sonograms between 34.0 weeks and 36.9 weeks formed the study group. The control group was comprised of nondiabetic women who had sonograms in the same gestational age range. The absolute birth weight errors and absolute percent errors in the study group and the controls were compared with t tests. A total of 133 diabetic women and 1690 controls were included in the study. The mean (+/- standard deviation) absolute error of the predicted birth weight was 265 +/- 210 g in the diabetic women and 261 +/- 204 g in the control group (P =.87). The mean (+/- standard deviation) absolute percent error was 7.4% +/- 6.3% for diabetic women compared with 8.3% +/- 6.6% for the controls (P =.14). Prediction of birth weight using the gestation-adjusted projection method is as accurate in diabetic women as in controls.


Chimerism studies with quantitative real-time PCR in stem cell recipients with acute myeloid leukemia.
Chimerism is well-established for surveillance of acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (HSCT), but interpretation of the results and techniques is not standardized. We correlated chimerism in 75 AML patients (38 male, 37 female) who underwent myeloablative (n = 36)/reduced (n = 39) allo-HSCT with the risk of relapse and survival. Chimerism was evaluated by quantitative real-time polymerase chain reaction for donor/recipient specific polymorphisms/Y-specific sequences. After HSCT, 40 patients (53%) achieved stable complete donor chimerism (≥ 99.0% of donor alleles), while 35 (47%) failed to achieve stable donor chimerism. Thirty-one patients (41%) showed decreasing donor alleles after having first achieved complete donor chimerism. To investigate the kinetics of mixed chimerism, patients were separated whether they showed subsequent increasing or decreasing donor alleles. Subsequent decrease of donor alleles was associated with relapses in 17 of 18 cases (94%), while no patient with subsequent increasing donor alleles relapsed (p < 0.001). Patients with mixed chimerism and increasing donor alleles had better 2-year disease-free survival (85%) than those with decreasing donor alleles (0%; p < 0.001). The kinetics of mixed chimerism as assessed by quantitative real-time polymerase chain reaction is an important prognostic predictor in the post-transplantation period of AML patients.


Biosystematics and distribution of simuliid vectors of human onchocerciasis in South America.
A brief review is given of the taxonomic status, biology and medical importance, and distribution of the vectors of human onchocerciasis in Latin America. Key reference works are cited and distribution maps of each vector species in relation to the known onchocerciasis foci are given.


Single-cell quantification of ribosome occupancy in early mouse development.
Translation regulation is critical for early mammalian embryonic development1. However, previous studies had been restricted to bulk measurements2, precluding precise determination of translation regulation including allele-specific analyses. Here, to address this challenge, we developed a novel microfluidic isotachophoresis (ITP) approach, named RIBOsome profiling via ITP (Ribo-ITP), and characterized translation in single oocytes and embryos during early mouse development. We identified differential translation efficiency as a key mechanism regulating genes involved in centrosome organization and N6-methyladenosine modification of RNAs. Our high-coverage measurements enabled, to our knowledge, the first analysis of allele-specific ribosome engagement in early development. These led to the discovery of stage-specific differential engagement of zygotic RNAs with ribosomes and reduced translation efficiency of transcripts exhibiting allele-biased expression. By integrating our measurements with proteomics data, we discovered that ribosome occupancy in germinal vesicle-stage oocytes is the predominant determinant of protein abundance in the zygote. The Ribo-ITP approach will enable numerous applications by providing high-coverage and high-resolution ribosome occupancy measurements from ultra-low input samples including single cells.


Intracellular singlet oxygen generation by phagocytosing neutrophils in response to particles coated with a chemical trap.
To determine if singlet oxygen (O2(1 delta g)) is produced by neutrophils (PMNs) during the process of phagocytosis, glass beads were coated with a specific chemical trap for O2(1 delta g), 9,10-diphenylanthracene (DPA). Singlet oxygen, but not other reactive oxygen species, reacts rapidly with DPA at a rate of kr = 1.3 x 10(6) M-1 s-1 to form a stable product, DPA-endoperoxide (Corey, E. J., and Taylor, W. C. (1964) J. Am. Chem. Soc. 86, 3881-3882; Wasserman, H. H., Scheffer, J. R., and Cooper, J. L. (1972) J. Am. Chem. Soc. 94, 4991-4996; Turro, N. J., Chow, M.-F., and Rigaudy, J. (1981) J. Am. Chem. Soc. 103, 7218-7224). The production of DPA-endoperoxide was determined by ultraviolet spectroscopy as a decrease in DPA absorbance at 355 nm. The absorbance of DPA was normalized to the absorbance of perylene, which was included in the coating on the beads as a nonreactive, internal standard. In the present study, DPA- and perylene-coated beads were initially allowed to adhere to fibronectin-coated coverslips. PMNs were then added to the bead-coated coverslips and allowed to adhere and phagocytose the beads for 1 h at 37 degrees C. In some experiments, 4B-phorbol-12-myristate-13-acetate (PMA) (1 ng/2.5 x 10(7) cells/ml), a known activator of the PMN NADPH-oxidase, was added as a co-stimulant. The amount of O2(1 delta g) produced by phagocytically stimulated PMNs was calculated to be 11.3 +/- 4.9 nmol of O2(1 delta g)/1.25 x 10(6) cells. Low dose PMA co-stimulation increased the production of O2(1 delta g) to 14.1 +/- 4.1 nmol/1.25 x 10(6) cells. Averaged together these amounts represent approximately 19 +/- 5.0% of the total oxygen consumed by PMNs in response to DPA- and perylene-coated beads. The specificity of the DPA reaction with O2(1 delta g) was confirmed by warming to 120 degrees C, which releases O2(1 delta g) from the DPA-endoperoxide, regenerating the parent DPA compound (Wasserman et al., 1972; Turro et al., 1981) and the absorbance at 355 nm. In addition, beta-carotene, an avid quencher of O2(1 delta g), was included in the coating of some bead preparations; assays in which these beads were used showed no change in the absorbance at 355 nm. Singlet oxygen production by myeloperoxidase was also measured using the coated bead assay and the results suggest that this is a major pathway by which singlet oxygen is generated in phagocytically stimulated PMNs.(ABSTRACT TRUNCATED AT 400 WORDS)


Aluminum(III) facilitates the oxidation of NADH by the superoxide anion.
Al(III) augments the oxidation of reduced nicotinamide adenine dinucleotide (NADH) by enzymatic or photochemical sources of O2-. Superoxide dismutase, but not catalase, inhibited this action of Al(III). It thus appears that Al(III) forms a complex with O2-, which is a stronger oxidant than is O2- itself and which may contribute to the adverse biological effects of Al(III).


Outcome of patients with differentiated thyroid cancer treated with empirical radioiodine therapy on the basis of Thyroglobulin Elevation Negative Iodine Scintigraphy (TENIS) syndrome without structural disease: a retrospective cohort study.
For differentiated thyroid cancer (DTC) patients with thyroglobulin (Tg) elevation and negative iodine scintigraphy (commonly termed "TENIS" syndrome) after thyroidectomy, radioactive iodine (RAI) therapy, and thyroid-stimulating hormone (TSH) suppression therapy, empirical RAI therapy may be considered. However, the outcome data of TENIS syndrome without structural disease after empirical RAI therapy have not shown clear evidence of improvement in survival. We assessed the efficacy of such empirical RAI therapy in TENIS syndrome without structural disease and evaluated the progression-free survival (PFS). A total of 80 papillary thyroid cancer (PTC) patients with TENIS syndrome without structural disease were included in this retrospective study. 52 patients were treated with empirical RAI therapy while another 28 patients were untreated. The progression-free survival (PFS) of both groups was defined as the main outcome. The secondary outcome was the comparison of serum Tg levels 12 months after being diagnosed as TENIS syndrome. The PFS of the empirical RAI therapy group was better than the untreated group (p < 0.001). Moreover, there was significant difference in Tg normalization between patients treated with empirical therapy and without treatment (p = 0.001). Empirical RAI therapy (p = 0.001) predicts better PFS. Male gender (p = 0.041) and empirical RAI therapy (p = 0.002) predict better remission in serum Tg level. Patients with TENIS syndrome without structural disease can benefit from empirical RAI therapy in both PFS and Tg normalization.


Aminophosphate precursors for the synthesis of near-unity emitting InP quantum dots and their application in liver cancer diagnosis.
InP quantum dots (QDs) are a promising and environment-friendly alternative to Cd-based QDs for in vitro diagnostics and bioimaging applications. However, their poor fluorescence and stability severely limit their biological applications. Herein, we synthesize bright (∼100%) and stable InP-based core/shell QDs by using cost-effective and low-toxic phosphorus source, and then aqueous InP QDs are prepared with quantum yield over 80% by shell engineering. The immunoassay of alpha-fetoprotein can be detected in the widest analytical range of 1-1000 ng ml-1 and the limit of detection of 0.58 ng ml-1 by using those InP QDs-based fluorescent probes, making it the best-performing heavy metal-free detection reported so far, comparable to state-of-the-art Cd-QDs-based probes. Furthermore, the high-quality aqueous InP QDs exhibit excellent performance in specific labeling of liver cancer cells and in vivo tumor-targeted imaging of live mice. Overall, the present work demonstrates the great potential of novel high-quality Cd-free InP QDs in cancer diagnosis and image-guided surgery.


Peripheral Innervation in the Regulation of Glucose Homeostasis.
Precise regulation of circulating glucose is crucial for human health and ensures a sufficient supply to the brain, which relies almost exclusively on glucose for metabolic energy. Glucose homeostasis is coordinated by hormone-secreting endocrine cells in the pancreas, as well as glucose utilization and production in peripheral metabolic tissues including the liver, muscle, and adipose tissue. Glucose-regulatory tissues receive dense innervation from sympathetic, parasympathetic, and sensory fibers. In this review, we summarize the functions of peripheral nerves in glucose regulation and metabolism. Dynamic changes in peripheral innervation have also been observed in animal models of obesity and diabetes. Together, these studies highlight the importance of peripheral nerves as a new therapeutic target for metabolic disorders.


Flow directionality of pristine meandering rivers is embedded in the skewing of high-amplitude bends and neck cutoffs.
Information concerning the dynamics of river meandering is embedded in their planforms. Here, we focus on how bend skewing varies with increasing sinuosity, and how flow direction is embedded in bend skewing. It has often been thought that upstream-skewed bends are dominant within a sufficiently long reach. These bends may allow a reasonable inference as to the direction of flow. Here we consider this issue using 20 reaches of freely meandering alluvial rivers that are in remote locations, generally far from human influence. We find that low-amplitude bends tend to be downstream-, rather than upstream-skewed. Bends with sinuosity greater than 2.6, however, are predominantly upstream-skewed. Of particular interest are the neck cutoffs, all chosen to be relatively recent according to their position related to the main channel: 84% of these are upstream-skewed. Neck cutoffs, which have likely evolved directly from bends of the highest sinuosity, represent the planform feature most likely to have flow direction embedded in them. The field data suggest that meander bends without external forcing such as engineering works tend to evolve from downstream-skewed low-sinuosity bends to upstream-skewed high-sinuosity bends before cutoff. This process can be reproduced, to some extent, using models coupling sedimentary dynamics with flow dynamics.


Heritable induced resistance in Arabidopsis thaliana: Tips and tools to improve effect size and reproducibility.
Over a decade ago, three independent studies reported that pathogen- and herbivore-exposed Arabidopsis thaliana produces primed progeny with increased resistance. Since then, heritable induced resistance (h-IR) has been reported across numerous plant-biotic interactions, revealing a regulatory function of DNA (de)methylation dynamics. However, the identity of the epi-alleles controlling h-IR and the mechanisms by which they prime defense genes remain unknown, while the evolutionary significance of the response requires confirmation. Progress has been hampered by the relatively high variability, low effect size, and sometimes poor reproducibility of h-IR, as is exemplified by a recent study that failed to reproduce h-IR in A. thaliana by Pseudomonas syringae pv. tomato (Pst). This study aimed to improve h-IR effect size and reproducibility in the A. thaliana-Pst interaction. We show that recurrent Pst inoculations of seedlings result in stronger h-IR than repeated inoculations of older plants and that disease-related growth repression in the parents is a reliable marker for h-IR effect size in F1 progeny. Furthermore, RT-qPCR-based expression profiling of genes controlling DNA methylation maintenance revealed that the elicitation of strong h-IR upon seedling inoculations is marked by reduced expression of the chromatin remodeler DECREASE IN DNA METHYLATION 1 (DDM1) gene, which is maintained in the apical meristem and transmitted to F1 progeny. Two additional genes, MET1 and CHROMOMETHYLASE3 (CMT3), displayed similar transcriptional repression in progeny from seedling-inoculated plants. Thus, reduced expression of DDM1, MET1, and CMT3 can serve as a marker of robust h-IR in F1 progeny. Our report offers valuable information and markers to improve the effect size and reproducibility of h-IR in the A. thaliana-Pst model interaction.


Surgical management of secondary hyperparathyroidism: how to effectively reduce recurrence at the time of primary surgery.
Successful parathyroidectomy (PTX) often results in a dramatic drop in the parathyroid hormone (PTH) levels, relieves the patient from clinical symptoms, and reduces mortality. Although PTX is generally a successful treatment for progressive secondary hyperparathyroidism (SHPT) patients subjected to surgery, a significant proportion develops recurrent SHPT following PTX. SHPT requiring PTX occurs more commonly in progressive chronic kidney disease and in long-term lithium therapy. Operative approaches include subtotal PTX, total PTX with or without autotransplantation, and possible thymectomy. Each approach has its proponents, advantages, and disadvantages. Although PTX offers the highest percentage cure for SHPT, compared to all other medical and surgical treatment, recurrent hyperparathyroidism can be observed in some patients dependent on follow-up time. A literature review and analysis of recent data regarding how to reduce recurrence of SHPT at the time of primary surgery was performed. The current literature and our own experience in the field have confirmed that pre-operative imaging, thymectomy, stereo magnifier, and surgical procedure may effectively reduce recurrence of SHPT at the time of primary surgery.


Stent-assisted balloon-induced intimal disruption and relamination in aortic dissection repair: the STABILISE concept.
The study objective was to describe the Stent-Assisted Balloon-Induced Intimal Disruption and Relamination in Aortic Dissection Repair technique for aortic dissection repair using proximal descending aortic endografting with distal aortic relamination through bare-metal stent and balloon-induced intimal disruption with immediate intimal reapposition. Between April 2007 and September 2011, 11 selected patients (10 male; median age, 50 years) underwent proximal descending aortic endografting plus stent-assisted balloon-induced intimal disruption of the thoracoabdominal aorta to treat complicated aortic dissection (7 type A, 4 acute type B). Patients with type A dissection underwent open surgical intervention plus adjunctive retrograde endovascular repair. Serial computed tomography angiography was used to assess aortic remodeling. There were no intraprocedural complications. Thirty-day incidence of death, stroke, and paralysis/visceral ischemia was 9% (n = 1), 0%, and 0%, respectively. Median follow-up was 18 months (range, 4-54 months). Two patients (18%) required secondary endovascular reintervention. No late adverse events or aortic-related deaths occurred. Complete false lumen obliteration occurred in 90% (n = 10) of patients, with stable maximal diameters in the thoracic (P = .6) and abdominal aortas (celiac trunk: P = .34; renal; P = .6; infrarenal: P = .7) at latest follow-up. The Stent-Assisted Balloon-Induced Intimal Disruption and Relamination in Aortic Dissection Repair approach is a feasible endovascular technique that shows promise to achieve complete repair of the dissected aorta by inducing complete false lumen obliteration. The restoration of uniluminal flow in the thoracoabdominal aorta has the potential to improve long-term outcomes. Prospective, multicenter investigations are required to implement this strategy more broadly.


Cardiovascular and metabolic risk factors: how can we improve outcomes in the high-risk patient?
Risk assessment algorithms, such as that used in the third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program (NCEP) for treating low-density lipoprotein cholesterol, can be used to classify patients' risk for cardiovascular and metabolic problems and to determine the appropriate level of therapeutic intervention. Patients at highest risk should receive the most intensive therapy. The presence of the metabolic syndrome, a clustering of atherogenic risk factors including dyslipidemia, elevated blood pressure, elevated blood glucose, and other problems, confers additional risk for diabetes mellitus and atherosclerotic cardiovascular disease at every level of risk. Pharmacotherapy with lipid-lowering, antiplatelet, antihypertensive, or insulin-sensitizing agents to modify specific risk factors is indicated in patients at higher risk, but lifestyle change (e.g., smoking cessation, weight reduction, increased physical activity, and "heart-healthy" dietary modifications) and blood pressure control can be used across all categories of risk.


Myocardial mechanics explains the time course of benefit for septal ethanol ablation for hypertrophic cardiomyopathy.
We hypothesized that the time course of left ventricular (LV) outflow tract gradient reduction during septal ethanol ablation for patients with symptomatic hypertrophic obstructive cardiomyopathy is related to changes in myocardial mechanics. A total of 21 patients with hypertrophic obstructive cardiomyopathy undergoing septal ethanol ablation were analyzed. LV outflow tract gradient decreased with septal balloon occlusion, further decreased postethanol injection, and partially rebounded at discharge (5-6 days postprocedure). During balloon occlusion longitudinal and circumferential strain significantly decreased in all analyzed segments, significantly improved with alcohol injection only at sites distant to infarction, and normalized at all segments except infarcted ones at discharge. LV twist significantly improved with ethanol injection and remained high at discharge. Myocardial mechanics suggest that the decrease in LV outflow tract gradient during septal ethanol ablation coincides with global LV dysfunction despite only local ischemia during septal balloon occlusion. Global dysfunction is transient and the gradient rebounds when dysfunction is limited to the basal septum.


Imaging in forensic radiology: an illustrated guide for postmortem computed tomography technique and protocols.
Forensic radiology is a new subspecialty that has arisen worldwide in the field of forensic medicine. Postmortem computed tomography (PMCT) and, to a lesser extent, PMCT angiography (PMCTA), are established imaging methods that have replaced dated conventional X-ray images in morgues. However, these methods have not been standardized for postmortem imaging. Therefore, this article outlines the main approach for a recommended standard protocol for postmortem cross-sectional imaging that focuses on unenhanced PMCT and PMCTA. This review should facilitate the implementation of a high-quality protocol that enables standardized reporting in morgues, associated hospitals or private practices that perform forensic scans to provide the same quality that clinical scans provide in court.


Covid-19 and the impact on the physical activity level of elderly people: A systematic review.
Social isolation and lifestyle changes provoked by the COVID-19 pandemic have negatively affected the level of physical activity of the elderly people. To evaluate the available evidence related to the level of physical activity (PA) of elderly people during the COVID-19 pandemic. This is a systematic review, registered on PROSPERO (CRD42021241116), which included cross-sectional and cohort studies. Embase, Pubmed, Cochrane, Web of Science and Scopus databases were used to search for the studies. Finally, the New Castle-Ottawa Quality Assessment scale was used to measure the quality of the studies. 25 studies were found, being 14 cross-sectional and 11 cohort studies. The studies showed that the elderly population was highly affected in relation to the level of physical activity and lifestyle during restrictions, quarantine and lockdowns caused by the COVID-19. There was a significant reduction in physical activity levels, leading to declines in physical fitness and increased sedentary lifestyle, factors directly related to the increase in frailty in this population. The level of physical activity in the elderly population decreased during the quarantine period of COVID-19 worldwide. Strategies to maintain physical condition must be encouraged with physical exercises that meets the needs of the elderly in the current pandemic scenario, in order to maintain and improve the health of this population.


Mechanism of biosynthesis of trimethylamine oxide from choline in the teleost tilapia, Oreochromis niloticus, under freshwater conditions.
The mechanism of biosynthesis of trimethylamine oxide (TMAO) from dietary precursors in the teleost tilapia (Oreochromis niloticus) was investigated. Diets supplemented with quaternary ammonium choline, glycine betaine, carnitine or phosphatidylcholine were administered and significant increases in TMAO levels in the muscle were only observed with choline. [Methyl-14C] and [1,2-14C] cholines were given through dietary and intraperitoneal injection routes, but 14C-TMAO was detected only in fish with dietary administration of [methyl-14C] choline. Dietary treatment with [15N] choline resulted in the formation of [15N] TMAO in the muscle. The incorporation of radioactivity into TMAO was also observed both following dietary administration and intraperitoneal injection of [14C] trimethylamine (TMA). When choline was introduced into the isolated intestine, marked increases in TMA levels occurred. These increases were significantly suppressed in the presence of penicillin. [14C]-TMA derived from [methyl-14C] choline was detected in the cavity of the isolated intestine. The introduction of [15N] choline into the intestinal cavity resulted in the formation of [15N] TMA. TMA mono-oxygenase activities were detected in the liver and kidney. We conclude that tilapia possess the ability to produce TMAO from choline, which is related to intestinal microorganisms and tissue mono-oxygenase under freshwater conditions.


Probing the potential metal binding site in Escherichia coli 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (phenylalanine-sensitive).
The active site residues of the proposed metal binding site of DAH 7-P synthase (phe) were probed by site-directed mutagenesis of C61 to glycine and serine, H64 to glycine, and with the double mutant C61H/H64C. While C61S and C61H/ H64C were inactive, both C61G and H64G were active. All mutants, regardless of enzymatic activity, bound one equivalent of Fe2+ per monomeric unit. Even though C61 and H64 were shown not to be metal ligands for the DAH 7-P synthase (phe), they may provide some of the backbone interactions/secondary structural elements necessary to properly form the metal binding pocket.


"Aberrant sialylation plays a significant role in oral squamous cell carcinoma progression".
Aberrant glycosylation, mainly sialylation and fucosylation, is recently considered as a major hallmark of cancer. Aberrant sialylation has long been associated with various neoplastic diseases. However, role of aberrant sialylation in oral cancer is still in its infancy. The present study aimed to examine mRNA expressions of α-2, 3, α-2, 6 sialyltransferase (ST) families and sialidase in 160 human oral cancer tissues. mRNA expression of ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL6, ST6GAL1, and neuraminidase 3 (NEU3) was analyzed by RT-qPCR in 80 paired malignant and adjacent normal tissues from oral cancer patients. The results indicated significant (P ≤ .05) down-regulation of various STs (ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL6, and ST6GAL1) and sialidases (NEU3) in malignant tissues as compared to adjacent normal tissues. Higher mRNA levels of ST3GAL2 and ST3GAL3 were significantly associated with advanced stage of the disease, lymph node involvement, and perineural invasion, which denote their role in progression and metastasis of oral cancer. Present study also revealed altered sialylation patterns according to anatomical site of the disease and tobacco habit. The study demonstrated significant role of elevated mRNA levels of ST3GAL2 and ST3GAL3 in disease progression and metastasis of oral carcinoma.


Anoxygenic phototrophy across the phylogenetic spectrum: current understanding and future perspectives
The phylogenetic heterogeneity of anoxygenic phototrophic bacteria has been revealed by 16S rRNA sequence analysis, the results of which have led to extensive taxonomic rearrangements within previously defined taxa of phototrophs and stimulated interest in this group of organisms. Anoxygenic photosynthetic bacteria can be found within 4 of the 12 phylogenetic lineages, and in some cases are highly related to non-photosynthetic members of these groups. The largest number of phototrophs are found in the class Proteobacteria. Comparative phylogenetic analysis using 23S rDNA sequences generally supports the topology obtained from 16S rDNA sequences. The photosynthetic reaction centers are conserved in all photosynthetic bacteria, and are of two types. One is shared by the Proteobacteria and Chloroflexus aurantiacus and is similar to Photosystem II of cyanobacteria, while heliobacteria and Chlorobium and relatives possess a reaction center similar to the cyanobacterial Photosystem I. These similarities are supported by sequence analysis of core reaction center peptides, but contradict phylogenies reconstructed from rRNA sequence analysis. Genome analysis by means of physical mapping has been performed for only three species of anoxygenic phototrophs. Some conservation of operon structure and gene sequence has been found within the Proteobacteria, but does not extend to other phototrophs.


Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase.
Cyclooxygenase (COX-1 and COX-2)- and 5-lipoxygenase (5-LOX)-catalyzed biosynthesis of eicosanoids play important roles in inflammation and chronic diseases. The vitamin E family has four tocopherols and tocotrienols. We have shown that the metabolites of δ-tocopherol (δT) and δ-tocotrienol (δTE), i.e., δT-13'-carboxychromanol (COOH) and δTE-13'-COOH, respectively, inhibit COX-1/-2 and 5-LOX activity, but the nature of how they inhibit 5-LOX is not clear. Further, the impact of tocopherols and tocotrienols on COX-1/-2 or 5-LOX activity has not been fully delineated. In this study, we found that tocopherols and tocotrienols inhibited human recombinant COX-1 with IC50s of 1-12 µM, and suppressed COX-1-mediated formation of thromboxane in collagen-stimulated rat's platelets with IC50s of 8-50 µM. None of the vitamin E forms directly inhibited COX-2 activity. 13'-COOHs inhibited COX-1 and COX-2 enzyme activity with IC50s of 3-4 and 4-10 µM, respectively, blocked thromboxane formation in collagen- and ionophore-stimulated rats' platelets with IC50s of 1.5-2.5 µM, and also inhibited COX-2-mediated prostaglandins in stimulated cells. Using enzyme kinetics, we observed that δT-13'-COOH, δTE-13'-COOH and δTE competitively inhibited 5-LOX activity with Ki of 1.6, 0.8 and 2.2 µM, respectively. These compounds decreased leukotriene B4 from stimulated neutrophil-like cells without affecting translocation of 5-LOX from cytosol to the nucleus. Our study reveals inhibitory effects of vitamin E forms and 13'-COOHs on COX-1 activity and thromboxane formation in platelets, and elucidates mechanisms underlying their inhibition of 5-LOX. These observations are useful for understanding the role of these compounds in disease prevention and therapy.


Efficacy of programmes based on Conductive Education for young children with cerebral palsy.
Conductive Education (CE)-based programmes have been introduced to Australia over the past 10 years. The aim of this project was to compare these programmes with traditional neurodevelopmental programmes of rehabilitation for young children (12 to 36 months, mean age 22 months 3 weeks) with cerebral palsy. Thirty-four children were matched by age, motor impairment, and cognitive ability and randomly allocated to CE-based or equivalent-intensity control programmes. Those unwilling to be randomized (32) were still studied but their outcomes were treated separately. Our results indicate that children involved in CE-based programmes made similar progress to those involved in traditional programmes. Statistically significant changes were spread among the four groups of subjects. The findings also endorsed the measures used and the expected maturational effect was detected. Although there were major difficulties in conducting this randomized trial, it was achieved by gathering parental and professional support, and adequate funding.


Low thoracic muscle radiation attenuation is associated with postoperative pneumonia following partial hepatectomy for colorectal metastasis.
Low skeletal muscle radiation attenuation (SM-RA) is indicative of myosteatosis and diminished muscle function. It is predictive of poor outcome following oncological surgery in several cancer types. Postoperative pneumonia is a known risk factor for increased postoperative mortality. We hypothesized that low SM-RA of the respiratory muscles at the 4th thoracic-vertebra (T4) is associated with postoperative pneumonia following liver surgery. Postoperative pneumonia was identified using prospective infection control data. Computed tomography body composition analysis was performed at the L3-and T4 level to determine SM-RA. Body composition variables were corrected for confounders and related to postoperative pneumonia and admission time by multivariable logistic regression. Body composition analysis of 180 patients was performed. Twenty-one patients developed postoperative pneumonia (11.6%). Multivariable analysis showed that low T4 SM-RA as well as low L3 SM-RA were significantly associated with postoperative pneumonia (OR 3.65, 95% CI 1.41-9.49, p < 0.01) and (OR 3.22, 95% CI 1.20-8.61, p = 0.02, respectively). Low SM-RA at either the L3-or T4-level is associated with a higher risk of postoperative pneumonia following CLRM resection.


Proactive Versus Reactive Control Strategies Differentially Mediate Alcohol Drinking in Wistar and P rats.
Problematic alcohol consumption is associated with deficits in decision-making, and alterations in prefrontal cortex neural activity likely contributes. We hypothesized that differences in cognitive control would be evident between male Wistar rats and a model for genetic risk for alcohol use disorder (alcohol-preferring P rats). Cognitive control can be split into proactive and reactive components. Proactive control maintains goal-directed behavior independent of a stimulus whereas reactive control elicits goal-directed behavior at the time of a stimulus. We hypothesized that Wistars would show proactive control over alcohol-seeking whereas P rats would show reactive control over alcohol-seeking. Neural ensembles were recorded from prefrontal cortex during an alcohol seeking task that utilized two session types. On congruent sessions the CS+ was on the same side as alcohol access. Incongruent sessions presented alcohol opposite the CS+. Wistars, but not P rats, exhibited an increase in incorrect approaches during incongruent sessions, suggesting that Wistars utilized the previously learned task-rule. This motivated the hypothesis that ensemble activity reflecting proactive control would be observable in Wistars but not P rats. While P rats showed differences in neural activity at times relevant for alcohol delivery, Wistars showed differences prior to approaching the sipper. These results support our hypothesis that Wistars are more likely to engage proactive cognitive-control strategies whereas P rats are more likely to engage reactive cognitive control strategies. Although P rats were bred to prefer alcohol, differences in cognitive control may reflect a sequela of behaviors that mirror those in humans at risk for an AUD.


Normal values for ventricular size as determined by real time sonographic techniques.
Seventy-three real time sonographic scans were performed through the anterior fontanelle of 67 infants between 28 and 48 weeks post-conception who had no evidence of intracranial disease. Several anatomical measurements were plotted against independent variables such as post-conception age, weight and head circumference at the time of the examination. All of the measurements increased as age, weight and head circumference increased. Ratios formed by dividing transventricular diameters by transcalvarial diameters at the two levels in the coronal plane and by dividing occipital mantle thickness by frontal mantle thickness in the parasagittal planes remained stable as all of the independent variables increased. In 88% of cases the occipital mantle could not be measured since the occipital horns of the lateral ventricles could not be identified. Since dilation of the ventricular system starts in the occipital horns of the lateral ventricles, non-visualization of this area is an important negative finding.


Coil embolization with open frozen hybrid graft for complex left subclavian artery/proximal descending aortic aneurysm in a young patient.
An LSCA aneurysm is a rare disease. When and how to operate are debated. While open surgery was initially considered the sole option, emerging endovascular techniques have been described. The present report describes a novel hybrid technique to treat an LSCA aneurysm combined to a proximal descending aneurysm in a young 25-year-old patient.


Allergens in corticosteroid vehicles.
Whereas allergy to vehicle ingredients (ie, excipients and preservatives) in topical steroid vehicles is well recognized, there are no data regarding which vehicle ingredients are in common use or on which vehicles and active molecules are associated with which ingredients. To produce descriptive data on the use of allergenic vehicle ingredients in prescription topical corticosteroids. The package insert for every steroid in widespread use in the United States was obtained from the manufacturer and used to generate an ingredient list for the product. There are seven vehicle ingredients that are commonly used in topical corticosteroid vehicles that are well-known allergens: propylene glycol, sorbitan sesquioleate, formaldehyde-releasing preservatives, parabens, methylchloroisothiazolinone/methylisothiazolinone, lanolin, and fragrance. Of 166 topical corticosteroids, 128 (including all creams) had at least one of these vehicle ingredients. More generic products were free of allergens than were branded products. Solutions and ointments were the least allergenic vehicles. The most commonly present potential allergens were propylene glycol and sorbitan sesquioleate. Most prescription topical corticosteroids have the potential to cause allergic contact dermatitis owing to vehicle ingredients. Dermatologists should be aware of this possibility and should consider prescribing agents that do not contain potentially allergenic vehicle ingredients.


Assessment of trace metal contamination of wetland sediments from eastern and western coastal region of India dominated with mangrove forest.
Ecosystem and biodiversity of India's coastal areas dominated with mangrove forest have been threatened by growing anthropogenic activities. The present work aims to investigate the contamination of wetland sediments with trace elements and assess the sediment quality at different sampling locations in eastern and western costal region dominated with mangrove forest. The longitudinal profile of trace elements in sediments from different sampling locations analyzed by employing Energy Dispersive X-ray Fluorescence (EDXRF) spectrometer shows variations in distribution of elements like Al, Si, K, Ca, V, Cr, Mn, Fe, Ni, Cu, Zn and Pb. The enrichment factor (EF) and Geo-accumulation index (Igeo) values suggested depletion of clay minerals and enrichment of heavy metals like Cr, Cu Fe and Mn. Depending on the variations in Igeo values, the elements are put into Igeo Class 0 to 3 levels of contamination. Contamination factor (Cf) and pollution load index (PLI) suggested deterioration of sediments analyzed in the present study. Assessment of ecological risk potential of elements suggests that few elements (Cr and Cu) are moderately contaminated and may cause environmental stress on the exposed flora and fauna.


Percutaneous transluminal coronary angioplasty in a child with Kawasaki disease.
A successful attempt at percutaneous transluminanl coronary angioplasty (PTCA) to relieve stenosis of the mid-portion of the left anterior descending artery was achieved in a 6-year 9-month old boy who had multiple coronary aneurysms and stenosis due to Kawasaki disease. Despite the progression of coronary stenosis he had been well except for the perfusion defect of the anterior wall of myocardium on 99mTc-MIBI SPECT with dipyridamole infusion until PTCA was carried out after 4-year 4-months of the onset of illness. The area of stenosis was 70% before PTCA and 20% after PTCA. No restenosis at the site of PTCA was observed on follow-up angiography at 26 months after PTCA. This successful attempt may indicate that this procedure should be considered early in subclinical stenosis to prevent ischemic cardiac damage.


CD9 regulates keratinocyte differentiation and motility by recruiting E-cadherin to the plasma membrane and activating the PI3K/Akt pathway.
During keratinocyte stratification and wound healing, keratinocytes undergo a switch between differentiation and motility. However, limited knowledge exists on the mechanisms of the switch. We have previously demonstrated that the expression of CD9 was changed in different wound stages and involved in the regulation of keratinocyte migration. In this study, we showed that CD9 expression was increased in both human and mouse keratinocytes undergoing differentiation. CD9 overexpression in keratinocytes stimulated terminal differentiation and reduced cell motility. CD9 silencing inhibited calcium-induced keratinocyte differentiation and increased cell motility. Furthermore, CD9 overexpression recruited E-cadherin to the plasma membrane and subsequently activated PI3K/Akt signaling, while CD9 knockdown inhibited the recruitment of E-cadherin to the plasma membrane and PI3K/Akt activation. Importantly, silencing E-cadherin expression or inhibiting PI3K/Akt signaling reversed CD9 overexpression-induced differentiation and -reduced motility. These results demonstrate that CD9 acts as an important node that regulates keratinocyte differentiation and motility. The recruitment of E-cadherin to the plasma membrane and activation of the PI3K/Akt signaling pathway mediated by CD9 play an important role in these processes.


Nanotechnological interventions of the microbiome as a next-generation antimicrobial therapy.
The rise of antimicrobial resistance (AMR) impacts public health due to the diminished potency of existing antibiotics. The microbiome plays an important role in the host's immune system activity and shows the history of exposure to antimicrobials and its manipulation in combating antimicrobial resistance. Advancements in gene technologies, DNA sequencing, and computational biology have emerged as powerful platforms to better understand the relationship between animals and microorganisms (MOs). The past few years have witnessed an increase in the use of nanotechnology, both in industry and in academia, as tools to tackle antimicrobial resistance. New strategies of microbiome manipulation have been developed, such as the use of prebiotics, probiotics, peptides, antibodies, an appropriate diet, phage therapy, and the use of various nanotechnological techniques. Owing to the research outcomes, targeted delivery of antimicrobials with some modifications with nanoparticles can lead to the destruction of resistant microbial cells. In addition, nanoparticles have been studied for their potential antimicrobial effects both in vitro and in vivo. In this review, we highlight key opportunistic areas for applying nanotechnologies with the aim of manipulating the microbiome for the treatment of antimicrobial resistance. Besides providing a detailed review on various nanomaterials, technologies, opportunities, technical needs, and potential approaches for the manipulation of the microbiome to address these challenges, we discuss future challenges and our perspective.


Binding characteristics of a monoclonal beta-endorphin antibody recognizing the N-terminus of opioid peptides.
The present paper describes the isolation and characterization of a clone of hybrid myelomas (3-E7) secreting a mouse monoclonal antibody to beta-endorphin. An examination of its specificity against a series of human beta-lipotropin fragments and other opioid peptides revealed that the N-terminus portion of beta-endorphin is the determinant. Complete or almost complete cross-reactivity was obtained to methionine- and leucine-enkephalin, beta-lipotropin 60-65, and BAM 22; partial cross-reactivity was seen to dynorphin1-13 and alpha-neo-endorphin, whereas beta-lipotropin, alpha-N-acetyl-beta-endorphin, Des-Tyr1-beta-endorphin, in addition to a series of synthetic enkephalin derivatives, completely lacked cross-reactivity. The use of the monoclonal antibody in radioimmunoassay (RIA) for beta-endorphin resulted in a lower sensitivity related to respective polyclonal antibodies. An increase of 100% in tracer binding could, however, be obtained by use of beta-endorphin iodinated with its N-terminal tyrosine protected by coupling to an antibody. A solid-phase RIA was developed involving the internally 3H-labeled monoclonal antibody, which resulted in a 10-fold increase in sensitivity as compared with the homogenous RIA. These data indicate that for the binding to this antibody a tyrosine residue in position 61 is essential, and it thus recognizes a site that is of functional significance for many naturally occurring opioid peptides.


Phenotypic plasticity of circadian entrainment under a range of light conditions.
The response to a zeitgeber, particularly the light/dark cycle, may vary phenotypically. Phenotypic plasticity can be defined as the ability of one genome to express different phenotypes in response to environmental variation. In this opinion paper, we present some evidence that one of the most prominent effects of the introduction of electric light to the everyday life of humans is a significant increase in phenotypic plasticity and differences in interindividual phases of entrainment. We propose that the healthy limits of phenotypic plasticity have been surpassed in contemporary society.


Quantification of IgG and IgG4 antibodies to bee venom phospholipase A2 by competitive inhibition in ELISA.
Phospholipase A2 (PLA) is the major antigen of bee venom. Individuals often stung by bees, such as bee keepers, show a restricted immune response mainly of anti-PLA IgG4 antibodies. In contrast, patients allergic to bee venom produce high levels of PLA-specific IgE. This isotype restriction, the clinical relevance and the well defined structure of the PLA antigen, provide a useful model for the study of the principles regulating isotype expression in the human antibody response. A fundamental requirement for such studies is the availability of quantitative and sensitive assays to measure PLA-specific antibodies. Here we describe an ELISA method for direct isotype-specific quantification of anti-PLA IgG and IgG4 antibodies. Serum containing anti-PLA IgG antibodies was added at a predetermined dilution to PLA coated microtiter plates. Then mouse monoclonal antibodies to human IgG or IgG4 and different concentrations of purified human IgG and IgG4, respectively, were added simultaneously. The concentration of anti-PLA IgG and IgG4 antibodies in the serum was calculated from the resulting inhibition curve. Additionally, an analytical method to compare unknown antibody samples with a standard in ELISA - avoiding problems of different affinities - is described. Using the technique described here, isotype-specific quantification of anti-PLA antibodies can be performed at a sensitivity of approximately 70 pg/ml with a reproducibility range of 10-15%.


Gestational and congenital syphilis.
The frequency of congenital syphilis continues to increase throughout the United States during the 1980s. Untreated maternal infection can lead to stillbirth, premature labor, congenital infection, and neonatal death. Preventive measures, based on control of early syphilis in women, prenatal care, improved diagnosis and diligent followup, can help to decrease the incidence of congenital syphilis. The clinical presentation and recommended regimens for therapy of the gravida with syphilis and neonates with suspected congenital syphilis are reviewed.


[A retrospective study on the incidence of chronic renal failure in the Department of Internal Medicine and Nephrology at University Hospital of Antananarivo (the capital city of Madagascar)].
Chronic renal failure is a global public health problem. In developed countries, this disease occurs mainly in the elderly, but in Africa it rather affects active young subjects. This disease need for expensive treatments in a low income country, because of its costs. Our aim is to describe the epidemiology of new cases of chronic renal failure in Madagascar. This is a retrospective, descriptive study of 239 patients with chronic renal failure over a 3 year period, starting from 1 January 2007 to 31 December 2009, in the Department of Internal Medicine and Nephrology at University Hospital of Antananarivo. The incidence was 8.51% among patients hospitalized in the Department. The average age of patients was 45.4 years with extremes of 16 and 82 years and a sex ratio 1,46. The main antecedent was arterial hypertension (59.8%). Chronic renal failure was terminal in 75.31% of the cases (n=180). The causes of chronic renal failure were dominated by chronic glomerulonephritis (40.1%), nephroangiosclerosis (35.5%). Hemodialysis was performed in 3 patients (1.26%), no patient was scheduled for a renal transplantation. Mortality rate in the Department was 28.87%. Chronic renal failure is a debilitating disease with a dreadful prognosis which affects young patients in Madagascar. Its treatment remains inaccessible to the majority of patients. The focus must be mainly on prevention, especially on early effective management of infections, arterial hypertension and diabetes to reduce its negative impacts on the community and public health. The project on renal transplantation: living donor, effective and less expensive treatment compared to hemodialysis could also be a good solution for these Malagasy young subjects.


Prediction models in the design of neural network based ECG classifiers: a neural network and genetic programming approach.
Classification of the electrocardiogram using Neural Networks has become a widely used method in recent years. The efficiency of these classifiers depends upon a number of factors including network training. Unfortunately, there is a shortage of evidence available to enable specific design choices to be made and as a consequence, many designs are made on the basis of trial and error. In this study we develop prediction models to indicate the point at which training should stop for Neural Network based Electrocardiogram classifiers in order to ensure maximum generalisation. Two prediction models have been presented; one based on Neural Networks and the other on Genetic Programming. The inputs to the models were 5 variable training parameters and the output indicated the point at which training should stop. Training and testing of the models was based on the results from 44 previously developed bi-group Neural Network classifiers, discriminating between Anterior Myocardial Infarction and normal patients. Our results show that both approaches provide close fits to the training data; p = 0.627 and p = 0.304 for the Neural Network and Genetic Programming methods respectively. For unseen data, the Neural Network exhibited no significant differences between actual and predicted outputs (p = 0.306) while the Genetic Programming method showed a marginally significant difference (p = 0.047). The approaches provide reverse engineering solutions to the development of Neural Network based Electrocardiogram classifiers. That is given the network design and architecture, an indication can be given as to when training should stop to obtain maximum network generalisation.


Laparoscopic renal surgery in the octogenarian.
To describe our experience with laparoscopic renal surgery (LRS) in the octogenarian. Octogenarians are generally suboptimal surgical candidates but the recent upsurge of minimally invasive options for the management of kidney lesions, such as laparoscopic excision, cryoablation and radiofrequency ablation (RFA), have changed that perception. In all, 26 patients aged >or=80 years underwent LRS at Brown University and the University of Wisconsin between 2000 and 2006. Demographic information, anatomical location, tumour stage, comorbidities, type of laparoscopic approach, management and outcomes were assessed. Complications during and after LRS, hospital stay, analgesia requirements and return to normal activity were analysed. The mean age of the patients was 81 years. The procedures performed included hand-assisted laparoscopic partial nephrectomy (three patients), hand-assisted laparoscopic radical nephrectomy (10), hand-assisted laparoscopic nephroureterectomy (four), laparoscopic-assisted cryoablation (seven), laparoscopic RFA (one), and laparoscopic unroofing of a renal cyst (one). The mean (range) follow-up was 40 (8-84) months. The mean American Society of Anesthesiologists score was 2.5. The average hospital stay was 5.6 days and the mean time to normal activity after discharge was 19 days. There were two major and five minor complications. Nineteen of 22 patients evaluable had no evidence of disease at the last follow-up. The three deceased patients died of unrelated causes. LRS in the octogenarian is safe to perform in patients with multiple comorbidities. The major and minor complication rates were 7% and 19%, respectively. Recent trends show that ablative procedures are being performed more commonly than surgical excision in this age group.


Radioimmunofixation of human ferritin following serum isoelectric focusing.
Radioimmunofixation of human ferritin following isoelectric focusing of serum was developed to study the microheterogeneity of this protein in native serum without previous purification or concentration. This method requires only 2-10 microliter of serum and can be used with levels of ferritin as low as 10 micrograms/l. In this way, the extensive microheterogeneity of this protein was revealed, since in some cases it produced as many as 35 bands with isoelectric points in a pH range of 4.95-5.9. Very different isoelectric focusing patterns (spectrotypes) of ferritin were observed during the investigation of pathological sera. The high sensitivity of this technique makes it useful for the investigation of serum ferritin in diseases involving modifications of the metabolism of this protein.