Inhibition of mouse skin tumor promotion and of promoter-stimulated epidermal polyamine biosynthesis by alpha-difluoromethylornithine.
Application of the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin leads to a manifold induction of ornithine decarboxylase (ODC) activity within 5 hr and an increased accumulation of putrescine. The relevance of these TPA-induced changes to the mechanism of tumor promotion was investigated using alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. DFMO applied to mouse skin (0.3 mg in 0.2 ml of solvent) or administered in the drinking water (1%) in conjunction with skin tumor promotion by TPA inhibited the formation of mouse skin papillomas by 50 and 90%, respectively. TPA-induced ODC activity and the accumulation of putrescine were almost completely inhibited. DFMO given in the drinking water decreased spermidine levels, but DFMO treatment by any route did not alter the spermine levels of mouse epidermis. DFMO decreased TPA-induced hyperplasia by 25 to 40%, and the TPA-caused increases in DNA synthesis and mitotic index were inhibited by 60 and 50%, respectively. Therefore, in mouse epidermis, enhanced cell proliferation can be dissociated from ODC induction and the accumulation of putrescine. At the tested dose levels and routes of administration, DFMO did not inhibit the inflammatory response to TPA in several tissues. These results provide evidence for an essential role of ODC induction and the accumulation of putrescine in tumor promotion by TPA and add strength to the proposal that DFMO may be a promising drug for the prevention and treatment of cancer in human beings.


Use of titanium mesh for reconstruction of large anterior cranial base defects.
The authors evaluated the role of titanium mesh used in combination with vascularized pericranium to provide rigid support during reconstruction of anterior skull base defects. Thirteen patients with large anterior skull base defects caused by tumor invasion or traumatic injury involving the cribriform plate, orbital roof, and planum sphenoidale were included in the study. The reconstruction technique involved placement of titanium mesh between two layers of continuous vascularized pericranium. Surgical glue and routine lumbar cerebrospinal fluid (CSF) drainage were not used in any patient. At a mean postoperative follow-up time of 22 months (range 8-39 months), none of the patients had developed infection or meningocele. Postoperative CSF rhinorrhea occurred in two patients with extensive dural defects, which resolved with temporary lumbar drainage. Use of titanium mesh and a two-layer vascularized pericranial graft is a safe, reproducible, and feasible method for reconstructing the anterior skull base. Patients with large dural defects may need temporary CSF diversion to avoid postoperative fistula formation.


Experiential and hormonal correlates of maternal behavior in teen and adult mothers.
This study explores the role of cortisol and early life experiences in the regulation of maternal behavior and mood in teen and adult mothers. Primiparous mothers (n=119) (teen mothers < 19 years, n=42), young mothers (19-25 years, n= 4), and mature mothers, (>25 years, n=43) were assessed for their maternal behavior, mood, and hormonal profile at approximately 6 weeks postpartum. Outcome measures were analyzed as a function of age and early life experience. Results showed an interaction between age and type of maternal behavior, where teen mothers engaged in more instrumental (e.g. changing diapers, adjusting clothes) less affectionate (e.g., stroking, kissing, patting) behavior, and mature mothers engaged in more affectionate and less instrumental behavior. When groups were reassessed based on early life experience (consistency of care during the first 12 years of life: consistent care; having at least one consistent caregiver, inconsistent care; having multiple and changing caregivers), an interaction was also found between consistency of care and type of behavior shown, where mothers who received inconsistent care engaged in more instrumental and less affectionate behavior. Compared to mature mothers, teen mothers who were breast feeding also had higher salivary cortisol levels, and high cortisol in teen mothers related to decreased fatigue and increased energy. These results suggest that early life experiences are linked to mothering behavior and are consistent with the emerging human and animal literature on intergenerational effects of mothering style.


Comparing segmented ASL perfusion of vascular territories using manual versus semiautomated techniques in children with sickle cell anemia.
Elevated cerebral blood flow (CBF) in sickle cell anemia (SCA) is an adaptive pathophysiologic response associated with decreased vascular reserve and increased risk for ischemia. We compared manual (M) and semiautomated (SA) vascular territory delineation to facilitate standardized evaluation of CBF in children with SCA. ASL perfusion values from 21 children were compared for gray matter and white matter (WM) in vascular territories defined by M and SA delineation. SA delineated CBF was compared with clinical and hematologic variables acquired within 4 weeks of the MRI. CBF measurements from M (MCA 82 left, 79 right) and SA (MCA 81 left, 81 right) delineated territories were highly correlated (R = 0.99, P < 0.0001). Bland-Altman plots had close-fitting limits of agreement of -1.8 to -3.5 lower limit and 0 to 1.8 upper limit. SA vascular territory delineation was comparable to the expert delineation with a kappa index of 0.62-0.85 and was considerably faster. Median territorial CBF values did not differ by gender or age. WM perfusion in the posterior cerebral artery territories was positively correlated with degree of hemolysis (R = 0.58, P = 0.01 left, 0.73, P < 0.001 right) and negatively correlated with hemoglobin (R = -0.48; P = 0.03 left; -0.47; P = 0.04 right) and hemoglobin F (R = -0.42; P = .09 left; -0.47; P = 0.049 right). We established the validity of the SA method, which in our experience was much faster than the M method for delineation of vascular territories. Associations between CBF and hematologic variables may demonstrate pathophysiologic changes that contribute to clinical variation in CBF.


The challenges of implementing and evaluating a pilot music and movement intervention for people with dementia: Innovative practice.
This paper reports on the challenges associated with implementing and evaluating an innovative pilot music and movement project. The evaluation documents that participants enjoyed the sessions and that they created the opportunity for social engagement although there is little to suggest this is unique to this particular type of intervention. Difficulties included matching the programme to the needs of participants, communicating effectively, and over burdensome paperwork. The paper also comments on the challenges associated with last minute, limited funding opportunities for both the organisation commissioning a project and the team evaluating it. In this case, the evaluation team found that many of the more difficult issues associated with the pilot could have been resolved with more time for planning and preparation.


An image-based modeling framework for predicting spatiotemporal brain cancer biology within individual patients.
Imaging is central to the clinical surveillance of brain tumors yet it provides limited insight into a tumor's underlying biology. Machine learning and other mathematical modeling approaches can leverage paired magnetic resonance images and image-localized tissue samples to predict almost any characteristic of a tumor. Image-based modeling takes advantage of the spatial resolution of routine clinical scans and can be applied to measure biological differences within a tumor, changes over time, as well as the variance between patients. This approach is non-invasive and circumvents the intrinsic challenges of inter- and intratumoral heterogeneity that have historically hindered the complete assessment of tumor biology and treatment responsiveness. It can also reveal tumor characteristics that may guide both surgical and medical decision-making in real-time. Here we describe a general framework for the acquisition of image-localized biopsies and the construction of spatiotemporal radiomics models, as well as case examples of how this approach may be used to address clinically relevant questions.


Novel hyaluronic acid (HA) coated drug carriers (HCDCs) for human breast cancer treatment.
Hyaluronic acid (HA) coated drug carriers (HCDCs) were successfully synthesized by chemical conjugation method for targeted delivery of doxorubicin (DOX) as a prototype anticancer drug to CD44 expressed human breast cancer cell. From XPS analysis, the HCDCs by conjugation methods demonstrated the superior HA fixation amount and colloidal stability compared with the nanoparticles by nanoprecipitation. The cytotoxicity of the HCDCs formulation accessed by the MTT assay against the higher CD44 expressed cell line (MDA-MB-231) and lower CD44 expressed cell line (ZR-75-1) human breast cancer cell lines demonstrated that the HCDCs formulation exhibited excellent tumoricidal effect and their affinity to cancer cells was predominant. The in vitro drug release profile of the HCDCs showed sustained release behavior and after 14 days, 80% of the encapsulated DOX was released due to a high release rate of DOX from HCDCs. We synthesized that HCDCs have therapeutic potentials of cancer as a target specific fashion by increasing the tumoricidal efficacy of targeted cancer cells while reducing their cytotoxicity of non-targeted cells to minimize the side effect.


An immediate access dialysis graft designed to prevent needle-related complications: Results from the initial pre-clinical studies.
No technology has been specifically developed with the intent to reduce needle-related vascular access injuries; a significant source of complications and abandonment. We present the initial pre-clinical study results of a novel, self-sealing, immediate cannulation dialysis graft that aims to prevent needle-related complications; to promote safe, reliable needle access; to reduce catheter use; and could facilitate home hemodialyisis. The innovative graft design consists of two cannulation chambers with self-sealing properties and materials that prevent side and back wall needle puncture. Study and control grafts (expanded polytetrafluoroethylene) were implanted in one pig and 10 sheep in two studies over the course of 1 year. First cannulation occurred immediately post implant for all study grafts. Post-cannulation time to hemostasis, hematoma and seroma formation, infection, and patency were recorded. The two studies account for nearly 60 weeks (average 6.4 weeks/graft) of study graft follow-up. In the ovine study, average study graft time to hemostasis was 27.3 s (standard deviation = 26.3, range = 0-120), and the control averaged 177.2 s (standard deviation = 113.4, range = 60-600), p < 0.0001. Secondary patency was 75% and 67% for the study and control grafts, respectively. Neither study nor control groups experienced seroma, graft infections, or deaths. All novel grafts in the studies were implanted successfully and functioned as intended. There were no complications related to tunneling of the study graft and the chamber prevented back/side wall needle injury. This novel technology may help to mitigate these needle-related complications, while allowing for early/immediate cannulation which could also reduce catheter contact time.


"When the Fun Stops, Stop": An analysis of the provenance, framing and evidence of a 'responsible gambling' campaign.
When the Fun Stops, Stop, is a prominent 'responsible gambling' campaign in the UK, originally funded and delivered by the industry-initiated and funded Senet Group. Since the Senet Group's dissolution in 2020, the campaign has been overseen by the Betting and Gambling Council (BGC), the main gambling industry trade body. There has been no prior analysis of the activities, ideas and framing adopted by the Senet Group, who claimed to be acting as an industry 'watchdog' and oversaw what they characterised as a major public education campaign. We collated written and image-based material related to the Senet Group and its When the Fun Stops, Stop campaign from multiple sources. Guided by Entman's four functions of framing, we analysed the Senet Group's framing of the issues it sought to address, particularly harmful gambling, as well as its causes, and the solutions, focusing on the group's main activity: the delivery of the When the Fun Stops, Stop campaign. We also critically appraised an evaluation of the campaign funded by the Senet Group, using the findings to interrogate the stated claims about the campaign's effectiveness. The analysis showed that the Senet Group's framing of the problem, its causes, and proposed responses resemble those adopted by other industries and industry-funded groups. This involves portraying any harms caused by their products as limited to an atypical minority, rejecting upstream determinants of harm, and promoting individually-targeted voluntary measures, all contrary to the evidence of what works in health promotion, and what would characterise a public health approach. Neither the existing evidence base nor the evidence presented by the Senet Group support their claims about the campaign's effectiveness. These findings add to concerns about industry-funded campaigns in other areas. To minimise conflicts of interest, interventions intended to address gambling-related harms, such as public education campaigns, should be evidence-based and developed, implemented and evaluated completely independent of the industry and industry-funded organisations.


Medical management of chronic orchialgia.
Chronic idiopathic orchialgia is a urologic disease process that is as frustrating as it is common. While no consensus exists on management for otherwise-unexplained testicular pain, most providers would agree that once other treatable organic causes are ruled out, initial management should be symptom focused, and should be medical rather than surgical. This chapter presents a review of the evidence available for a variety of pharmacotherapies commonly employed in the treatment of idiopathic chronic orchialgia.


Outcomes After Arthroscopic Hip Labral Reconstruction: A Systematic Review and Meta-analysis.
The acetabular labrum is critical to maintenance of hip stability and has been found to play a key role in preservation of the hip fluid seal. For irreparable labral damage, arthroscopic labral reconstruction is an evolving technique that has been shown to decrease hip pain and restore function. To provide a comprehensive review of current literature for arthroscopic hip labral reconstruction, with a focus on determining if outcomes differ between autograft or allograft tissue. Systematic review and meta-analysis. PubMed and Scopus online databases were searched with the key terms "hip,""labrum,""reconstruction," and "graft" in varying combinations. Procedures performed, complications, failures, and functional outcome measures were included in this analysis. The inverse variance method was used to calculate pooled estimates and 95% CIs. Eight studies with 537 hips were included. Mean age was 37.4 years (95% CI, 34.5-40.4 years), and mean follow-up time was 29 months (95% CI, 26-33 months). Survivorship after autograft reconstruction ranged from 75.7% to 100%, as compared with 86.3% to 90.0% in the allograft cohort. In the autograft cohort, failures included 0% to 13.2% conversion to total hip arthroplasty and 0% to 11.0% revision hip arthroscopy. Failures in the allograft cohort included 0% to 12.9% total hip arthroplasty conversion, 0% to 10.0% revision arthroscopy, and 0% to 0.8% open revision surgery. Based on 6 studies, the modified Harris Hip Score improved by a mean 29.0 points after labral reconstruction (P < .0001). Arthroscopic hip labral reconstruction results in clinically significant improvements in patient-reported outcomes. Our analysis indicates that there are no significant differences in outcomes based on graft type alone. A number of factors may determine graft choice, including patient preference, surgeon experience, operative time, morbidity, and cost. Proper patient selection based on age and severity of degenerative joint disease will also optimize outcomes after labral reconstruction.


Tianeptine Abuse Leading to an Episode of Psychosis: A Case Report and Literature Review.
Tianeptine is an atypical mu-opioid receptor agonist. It is available as an antidepressant outside the United States, but it is also classified as a controlled substance in many other countries. It is not approved by the United States Food and Drug Administration for the treatment of depression but it can be obtained online without a prescription. The case described in this article involved a patient who developed symptoms of psychosis on supratherapeutic doses of tianeptine, highlighting the importance of inquiring into all supplements taken by patients when conducting an initial psychiatric evaluation.


Cytoplasmic localization of endothelial constitutive nitric oxide synthase in endometrial carcinomas.
Production of nitric oxide by nitric oxide synthase (NOS) has been implicated in numerous physiologic and pathophysiologic processes including mutagenesis. This study was designed to examine the expression of the endothelial constitutive isoform of NOS (ecNOS) in endometrial carcinomas. Fifty endometrial carcinomas (42 endometrioid, 4 serous papillary, 2 clear cell, and 2 adenosquamous carcinomas) and 21 normal endometrial gland tissue specimens (5 cases of proliferative, 5 early secretory, 5 mid-secretory, and 5 late secretory and 1 menstrual phase endometrium), previously formalin fixed and paraffin embedded, were immunostained using a commercially available anti-ecNOS monoclonal antibody. Localization of ecNOS staining to the plasma membrane, cytoplasm and nuclei was graded with respect to overall staining intensity (0-3+ scale) and frequency (percentage of immunoreactive cells). Relatively little staining for ecNOS was localized to the plasma membrane in either normal or neoplastic tissues. Normal and hyperplastic endometrial glands demonstrated moderate cytoplasmic and weak nuclear staining in a small percentage of cells. While ecNOS expression was most prominent in epithelial cells, weak expression was also rarely noted in endometrial stroma, blood vessel walls, and endothelium. We found a broad range of ecNOS expression in endometrial carcinomas, predominantly localized to the cytoplasm and nuclei. No statistically significant difference in ecNOS staining frequency or intensity was found between different histologic subtypes of endometrial carcinomas. No apparent correlation was found between ecNOS expression and tumor stage, grade, extension to the lower uterine segment or cervix, nodal or distant metastases, recurrence, or final patient status among patients with endometrioid adenocarcinomas. Endometrioid tumors invading more than 1/2 of myometrial thickness (n = 18) had significantly higher cytoplasmic staining intensity than those tumors limited to the inner 1/2 of myometrium (n = 27; 2.0 vs. 1.3, p < 0.04). Furthermore, a trend toward shorter disease-free survival was noted with increased staining intensity and decreased staining frequency. Cytoplasmic and nuclear expression of ecNOS, which is primarily limited to the glandular elements of normal endometrium, is also found to be expressed in endometrial carcinoma. Increased ecNOS staining intensity and decreased frequency tends to correlate with decreased disease-free survival. Lastly, increased cytoplasmic ecNOS staining intensity correlates with increased myometrial invasion.


E-beam irradiation-induced synthesis of hydroxyethyl cellulose/(Cu2O-rGO)/BiVO4-based nanocomposite for photocatalytic remediation of wastewater under visible light.
Using E-beam irradiation as an eco-friendly technique for initiation and crosslinking, a series of Hydroxyethyl Cellulose-poly vinyl alcohol copolymer hydrogels were synthesized as templates for cuprous oxide (Cu2O), reduced graphene oxide (rGO) and bismuth vanadate (BiVO4) nanoparticles to be used as nanocomposites photocatalysts for methylene blue (MB) dye decolorization using visible light. Preparation conditions were optimized to ensure the construction of a good network architecture and therefore the highest gelation degree. For the preparation of (Cu2O@rGO)/BiVO4 nanocomposites, a series of rGO was decorated by Cu2O using the precipitation method, followed by mixing with BiVO4 which was synthesized hydrothermally. (EDX), (XRD), (TEM), and (SEM) were used for nanoparticle characterization. The thermal characteristics of the fabricated nanocomposites were evaluated using thermal gravimetric analysis. The presence of rGO enhanced the decolorization efficiency of MB about 20 % higher than that of (HEC-PVA/Cu2O) which achieves only (59 %) decolorization efficiency. After the addition of BiVO4 NPs, the decolorization efficiency increased to reach 90 % after 150 min at pH 11 using a 10 ppm MB solution. The developed (HEC-PVA)/(Cu2O@rGO)/BiVO4 photocatalyst exhibits efficient reusability for 5 cycles. Treated dyed water shows a germination index (GI) of 82 % suggesting its suitability for irrigation of playgrounds and gardens.


Face value: amygdala response reflects the validity of first impressions.
The human amygdala responds to first impressions of people as judged from their faces, such as normative judgments about the trustworthiness of strangers. It is unknown, however, whether amygdala responses to first impressions can be validated by objective criteria. Here, we examined amygdala responses to faces of Chief Executive Officers (CEOs) where real-world outcomes could be measured objectively by the amounts of profits made by each CEO's company. During fMRI scanning, participants made incidental judgments about the symmetry of each CEO's face. After scanning, participants rated each CEO's face on leadership ability. Parametric analyses showed that greater left amygdala response to the CEOs' faces was associated with higher post-scan ratings of the CEOs' leadership ability. In addition, greater left amygdala response was also associated with greater profits made by the CEOs' companies and this relationship was statistically mediated by external raters' perceptions of arousal. Thus, amygdala response reflected both subjective judgments and objective measures of leadership ability based on first impressions.


[Expression of Bcl-2 and Bax protein in endometriosis].
To study the pathophysiological effect of the expression of the apoptosis-regulating protein Bcl-2 and Bax in endometrosis. Samples were obtained from 16 patients with adenomyosis, 12 ovarian endometriosis, and 17 normal endometrum. Bcl-2 and Bax expression were examined by immunohistochemical ABC staining with specific monoclonal antibodies. 1. The expression of Bcl-2 or Bax in the eutopic endometrium was the same as the normal endometrium and their immunoreactivity was found predominately in the glandular epithelial cells, showing obvious cyclic changes. 2. The Bcl-2 and Bax expression in adenomyosis was not the cyclic change in ectopic glandular cells. 3. Less expression of Bcl-2 and Bax was found in the ovarian endometriosis. 1. The Bcl-2 and Bax cyclic change may play an important role in the proliferation and physiologic death of normal and eutopic endometrial glandular epithelial cells. 2. Bcl-2 may play an important role in forming adenomyosis. 3. Bcl-2 may be the cause of forming chocolate cyst by prompting apoptosis.


A new species of the genus Aulacorthum (Hemiptera: Aphididae) from the Korean Peninsula and its discrimination from a closely-related species using morphological and molecular characters.
Aulacorthum sp. collected on Artemisia princeps and Artemisia stolonifera (Asteraceae) in the Korean Peninsula was compared with the eight Aulacorthum species using molecular and morphological characters. In the sequence analysis, the genetic divergences of two mitochondrial genes, COI and CytB, between Aulacorthum sp. and the congeneric species were higher than those among the congeneric species. In the morphometric analysis, principal components analysis using 13 morphological characters reveals that Aulacorthum sp. is distinguished from the congeneric species, especially Aulacorthum albimagnoliae, which is morphologically most similar to Aulacorthum sp.. Based on these results, we propose a new species, Aulacorthum (Aulacorthum) artemisiphaga Lee, Havelka, and Lee sp. nov., with a description of apterous and alate viviparous females and an identification key to species in the genus Aulacorthum in the Korean Peninsula based on apterous viviparous females.


Remediation of bentazone contaminated water by Trametes versicolor: Characterization, identification of transformation products, and implementation in a trickle-bed reactor under non-sterile conditions.
Bentazone, an herbicide widely applied in rice and cereal crops, is widespread in the aquatic environment. This study evaluated the capacity of Trametes versicolor to remove bentazone from water. The fungus was able to completely remove bentazone after three days at Erlenmeyer-scale incubation. Both laccase and cytochrome P450 enzymatic systems were involved in bentazone degradation. A total of 19 transformation products (TPs) were identified to be formed during the process. The reactions involved in their formation included hydroxylations, oxidations, methylations, N-nitrosation, and dimerization. A laccase mediated radical mechanism was proposed for TP formation. In light of the results obtained at the Erlenmeyer scale, a trickle-bed reactor with T. versicolor immobilized on pine wood chips was set up to evaluate its stability during bentazone removal under non-sterile conditions. After 30 days of sequencing batch operation, an average bentazone removal of 48% was obtained, with a considerable contribution of adsorption onto the lignocellulosic support material. Bacterial contamination, which is the bottleneck in the implementation of fungal bioreactors, was successfully addressed by this particular system according to its maintained performance. This research is a pioneering step forward to the implementation of fungal bioremediation on a real scale.


Molecular cloning and characterization of three beta-defensins from canine testes.
Mammalian beta-defensins are small cationic peptides possessing broad antimicrobial and physiological activities. Because dogs are particularly resilient to sexually transmitted diseases, it has been proposed that their antimicrobial peptide repertoire might provide insight into novel antimicrobial therapeutics and treatment regimens. To investigate this proposal, we cloned the full-length cDNA of three canine beta-defensin isoforms (cBD-1, -2, and -3) from canine testicular tissues. Their predicted peptides share identical N-terminal 65-amino-acid residues, including the beta-defensin consensus six-cysteine motif. The two longer isoforms, cBD-2 and -3, possess 4 and 34 additional amino acids, respectively, at the C terminus. To evaluate the antimicrobial activity of cBD, a 34-amino-acid peptide derived from the shared mature peptide region was synthesized. Canine beta-defensin displayed broad antimicrobial activity against gram-positive bacteria (Listeria monocytogenes and Staphylococcus aureus; MICs of 6 and 100 mug/ml, respectively), gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, and Neisseria gonorrhoeae; MICs of 20 to 50, 20, and 50 mug/ml, respectively), and yeast (Candida albicans; MIC of 5 to 50 mug/ml) and lower activity against Ureaplasma urealyticum and U. canigenitalium (MIC of 200 mug/ml). Antimicrobial potency was significantly reduced at salt concentrations higher than 140 mM. All three canine beta-defensins were highly expressed in testis. In situ hybridization indicated that cBD-1 was expressed primarily in Sertoli cells within the seminiferous tubules. In contrast, cBD-2 was located primarily within Leydig cells. The longest isoform, cBD-3, was detected in Sertoli cells and to a lesser extent in the interstitium. The tissue-specific expression and broad antimicrobial activity suggest that canine beta-defensins play an important role in host defense and other physiological functions of the male reproductive system.


Antioxidant activity of Ziziphora tenuoir methanolic extracts and comparison of the essential oil in two stages of growth.
Flavonoids, anthocyanins, antioxidant capability, total phenolic, ascorbic acid contents, and essential oils compounds of Ziziphora tenuoir (Lamiaceae) for polar and non-polar subfraction in different stages of growth (pre-flowering and flowering) were evaluated in this work. Antioxidant activities of the samples were determined by three testing systems namely DPPH, β-carotene/linoleic acid, and reducing power assay. In the DPPH system, the highest radical scavenging activity was seen by the nonpolar subfraction of the methanol extract in the flowering stage (IC50 43.17 ± 3.68 μg·mL(-1)). Large differences in the amount of phenolic compounds, antioxidant activity, anthocyanins, and flavonoids of Z. tenuoir in two stages of growth were detected. The chemical composition of the hydrodistilled essential oil of the aerial parts of Z. tenuoir was analyzed by GC/MS and compared in the two stages of growth. The main constituents of the 28 identified compounds in the oil were found to be pulegone (67.34% vs 59.61%), β-humulene (3.24% vs 3.25%), and limonene (5.06% vs 2.57%) at the flowering and pre-flowering stages, respectively.


Effects of an S6 strain of Mycoplasma gallisepticum inoculation before beginning of lay on the leukocytic characteristics of commercial layers.
A clinical study was conducted on commercial layers housed in biological isolation units, within which exogenous stress factors potentially affecting bird performance were minimized. This set-up was devised in order to assess how a pre-lay inoculation of S6 strain Mycoplasma gallisepticum affects the leukocytic properties of laying chickens. Previous studies have demonstrated relative decreases in lymphocyte and relative increases in heterophil percentages in birds infected with other strains of Mycoplasma gallisepticum. However, current results showed that the differential percentages of lymphocytes were decreased, whereas those of heterophils were increased, in both sham-inoculated control birds and birds inoculated with S6 Mycoplasma gallisepticum between 19 and 26 wk of age. This study clearly shows that a pre-lay inoculation of S6 Mycoplasma gallisepticum alone had no apparent effect on the leukocyte profile of commercial layers housed in biological isolation units.


[Kama, a new virus (Flaviviridae, Flavivirus, Tiulenii antigenic group), isolated from Ixodes lividus ticks].
Three identical strains of a new virus Kama (Flaviviridae, Flavivirus, Tyuleny antigenic group) were isolated from Ixodes lividus Roch, obligate parasites of Riparia riparia L. The ticks were collected in June, 1990 in Tatarstan on the islands in the basin of the Kama river. The strains were examined under electron microscope and by serological tests (neutralization, complement fixation, hemagglutination inhibition, and indirect immunofluorescence). The virus is antigenically related but not identical to Tyuleny virus. Hence, the Tyuleny antigenic group at present includes viruses Tyuleny, Meaban, Gadgest Gally, Saumares Reef, and Kama. All these viruses are associated with an ecosystem including ixodide ticks, obligate parasites of colonial birds.


Monoclonal antibodies that detect differentiation surface antigens on human myelomonocytic cells.
We describe here the production and characterization of several new monoclonal antibodies that recognize differentiation antigens present on human cells of the myelomonocytic lineage. The lineage and the stage specificities of our reagents (myeloid-, monocytic-, and myelomonocytic-specific) were determined on the basis of their reactivity with human cell lines and with human peripheral blood and bone marrow cells. Cross-competition experiments demonstrated that some of the antibodies react with the same or closely associated antigenic determinants. Five antigens have been identified in this way: one present on myeloid, one on monocytic, and three on both myeloid and monocytic cells. The possible relationship of our antibodies with other established monoclonal antibodies is discussed, in addition to their use in the in vitro study of the differentiation pathways of human hemopoietic cells and in the characterization of leukemias.


Carnitine and fat oxidation.
Fat and carbohydrate are the primary fuel sources for mitochondrial ATP production in human skeletal muscle during endurance exercise. However, fat exhibits a relatively low maximal rate of oxidation in vivo, which begins to decline at around 65% of maximal oxygen consumption (VO₂max) when muscle glycogen becomes the major fuel. It is thought that if the rate of fat oxidation during endurance exercise could be augmented, then muscle glycogen depletion could be delayed and endurance improved. The purpose of the present review is to outline the role of carnitine in skeletal muscle fat oxidation and how this is influenced by the role of carnitine in muscle carbohydrate oxidation. Specifically, it will propose a novel hypothesis outlining how muscle free carnitine availability is limiting to the rate of fat oxidation. The review will also highlight recent research demonstrating that increasing the muscle carnitine pool in humans can have a significant impact upon both fat and carbohydrate metabolism during endurance exercise which is dependent upon the intensity of exercise performed.


Early HIV-1 infection is associated with reduced frequencies of cervical Th17 cells.
The hallmark of HIV infection is progressive but variable rates of systemic and mucosal CD4 depletion, leading to immunodeficiency. The impact of early HIV infection on cervical CD4 T-cell populations in humans remains poorly described. We analyzed cytobrush-derived immune cells by flow cytometry and cytokines in cervicovaginal lavage from participants in early HIV (<6 months postinfection), chronic HIV, and HIV-uninfected controls. CD4:CD8 ratios declined rapidly in both the cervix and the blood following HIV infection. In contrast, absolute cervical CD4 T-cell counts in early HIV were comparable to HIV-uninfected participants, declining only in chronic infection. Early HIV infection was associated with increases in RANTES and MIP3a in cervicovaginal fluids. Concurrently, slight increases in activated cells (CD38HLA-DR) and higher levels of CTLA4 expression on Tregs in the cervix were observed. Although study groups did not differ with respect to levels of CCR5, integrin B7, or CD69, the frequencies of Th17 cells (defined as CCR6CCR10) was reduced by >10-fold in early HIV infection and Th1 cells (defined as CCR6CXCR3) were reduced by >2-fold. Although CCR6CCR10 cells did not differ in HIV receptor expression, these cells produced higher levels of interferon gamma and interleukin 17. These data support the model of initial CD4 T-cell depletion followed by overall T-cell influx in response to infection and concomitant increases in immune activation, inflammation, and regulatory markers. These data are among the earliest characterization of the cellular milieu in the female genital tract following male-to-female HIV transmission.


The influence of the severity of community-acquired pneumonia on the usefulness of blood cultures.
The value of blood cultures in community-acquired pneumonia (CAP) has been questioned. At issue is the potential for blood cultures to change management. We prospectively studied the yield and impact of blood cultures in patients admitted with CAP. Two hundred and nine subjects had at least two blood cultures prior to receiving antibiotics. The severity of CAP was graded using the Pneumonia Severity Index (PSI). Twenty-nine patients (13.9%) had a pathogen identified by blood culture. The yield of blood cultures increased with PSI grade (I--5.3%, II--10.2%, III--10.3%, IV--16.1%, V--26.7%), as did the likelihood of blood cultures changing antibiotic therapy (I to III--0%, IV--9.7%, V--20.0%). One hundred and seventy-nine (85.6%) patients received a quinolone, limiting the impact of pathogens resistant to beta-lactams. Four of 16 patients (25.0%) with a culture (blood or sputum)-guided change in antibiotic therapy died, compared to five of 31 patients (16.1%) who had an empiric change. Blood cultures are of minimal value in mild to moderate CAP, and should be limited to patients with PSI grade IV or V CAP unless a specific risk factor for pathogens resistant to the empiric therapy is present.


Astrocyte-targeted IL-10 production decreases proliferation and induces a downregulation of activated microglia/macrophages after PPT.
When central nervous system (CNS) homeostasis is altered, microglial cells become rapidly activated, proliferate and release a broad range of molecules. Among the plethora of molecules involved in the regulation of microglial activation, cytokines are considered crucial. Although production of interleukin-10 (IL-10) has been demonstrated after different types of CNS injuries and associated with protective functions, the specific role played by IL-10 modulating microglial cells remains unclear. Hence, the objective of this study was to evaluate the effects of transgenic astrocyte IL-10 production on microglial activation associated with axonal anterograde degeneration. To address it, the hippocampal area subjected to perforant pathway transection (PPT) was analyzed by immunohistochemistry (IHC), flow cytometry and protein microarray in transgenic (GFAP-IL10Tg) mice and their corresponding wild types (WT) littermates. Our results demonstrated increased microglial/macrophages density in nonlesioned and PPT-lesioned GFAP-IL10Tg animals when compared with nonlesioned and lesioned WT, respectively. This increase was not due to proliferation, as GFAP-IL10Tg mice showed a reduced proliferation of microglial cells, but was related to an increased population of CD11b+/CD45high monocyte/macrophages. Despite this higher number, the microglia/macrophage population in transgenic animals displayed a downregulated phenotype characterized by lower MHCII, ICOSL, and CD11c. Moreover, a sustained T-cell infiltration was found in transgenic animals. We strongly suggest these modifications must be associated with indirect effects derived from the influence of IL-10 on astrocytes and/or neurons, which express IL-10R. We finally suggested that TGF-β produced by astrocytes, along with IL-2 and CXCL10 might be crucial molecules mediating the effects of transgenic IL-10.


Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes.
Although ibrutinib is highly effective in patients with relapsed/refractory mantle cell lymphoma (MCL), a substantial proportion of patients have resistant disease. The subsequent outcomes of such patients are unknown. We carried out a retrospective review of all patients with MCL treated with ibrutinib at MD Anderson Cancer Center between January 2011 and January 2014 using pharmacy and clinical databases. Patients who had discontinued ibrutinib for any reason were included in the study. We identified 42 patients with MCL who discontinued therapy due to disease progression on treatment (n = 28), toxicity (n = 6), elective stem-cell transplant in remission (n = 4) or withdrawn consent (n = 4). The median age was 69 years, 35 (83%) were male; the median number of prior treatments was 2 (range 1-8) and the median time from initial diagnosis of MCL to commencing ibrutinib was 3.0 (range 0.5-15.5) years. Patients had received a median of 6.5 (range 1-43) cycles of ibrutinib. Among 31 patients who experienced disease progression following ibrutinib and underwent salvage therapy, the overall and complete response rates were 32% and 19%, respectively. After a median follow-up of 10.7 (range 2.4-38.9) months from discontinuation of ibrutinib, the median overall survival (OS) among patients with disease progression was 8.4 months. By univariate analysis, elevated serum lactate dehydrogenase at progression was associated with inferior OS. The outcome of patients with MCL who experience disease progression following ibrutinib therapy is poor, with both low response rates to salvage therapy and short duration of responses. Further studies to better understand and overcome ibrutinib resistance are urgently needed.


Fatty acid substituted polyvinyl alcohol as a supporting material for microsphere preparation.
Polyvinyl alcohol, substituted with lauric, myristic, palmitic, and stearic acids at different substitution degrees was employed for the preparation of biodegradable microspheres containing progesterone or indomethacin. A solvent extraction/method was followed, starting from an oil-in-water dispersion containing the polymer and drug in the inner phase. Microspheres were obtained with high loading efficiency, whose release properties were dependent on the nature of the acyl substituent and the substitution degree. Kinetics approaching zero-order were obtained for the most hydrophile microspheres such as those based on the least substituted polymers and lowest molecular weight substituents. The hydrophilicity of these systems hindered protein absorption on their surface, suggesting their suitability for parenteral use.


Fine Motor Function Skills in Patients with Parkinson Disease with and without Mild Cognitive Impairment.
The objective of this study was to investigate the relation between impaired fine motor skills in Parkinson disease (PD) patients and their cognitive status, and to determine whether fine motor skills are more impaired in PD patients with mild cognitive impairment (MCI) than in non-MCI patients. Twenty PD MCI and 31 PD non-MCI patients (mean age 66.7 years, range 50-84, 36 males/15 females), all right-handed, took part in a motor performance test battery. Steadiness, precision, dexterity, velocity of arm-hand movements, and velocity of wrist-finger movements were measured and compared across groups and analyzed for confounders (age, sex, education, severity of motor symptoms, and disease duration). Statistical analysis included t tests corrected for multiple testing, and a linear regression with stepwise elimination procedure was used to select significant predictors for fine motor function. PD MCI patients performed significantly worse in precision (p < 0.05), dexterity (p < 0.05), and velocity (arm-hand movements; p < 0.05) compared to PD non-MCI patients. The fine motor function skills were confounded by age. Fine motor skills in PD MCI patients are impaired compared to PD non-MCI patients. Investigating the relation between the fine motor performance and MCI in PD might be a relevant subject for future research.


Addressing the contradictions: health promotion and community health action in the United Kingdom.
Within mainstream health education/promotion in the United Kingdom, the last few years have witnessed an upsurge of interest in community development, sometimes coupled with an undermining of the fundamental principles of this approach. This article addresses some of the contradictions and dilemmas that this development has presented for the community health movement. Current trends in health promotion policy and practice are examined in relation to broader health and welfare policy of the 1980s, the history of community development in health, and the background to the World Health Organization's "Health for All by the Year 2000" and health promotion initiatives. The possibilities and limitations of utilizing the rhetoric, to support community health action, are explored with reference to recent attempts by the community health movement to "reclaim" Health for All.


Successful engraftment of cryopreserved autologous bone marrow in patients with malignant lymphoma.
In an effort to evaluate the possible utility of cryopreserved autologous bone marrow infusions in man, 22 patients with malignant lymphoma resistant to conventional chemotherapy were treated with high-dose chemotherapy. This was followed in 12 patients by an infusion of their cryopreserved autologous bone marrow; 10 patients received chemotherapy alone and serve as controls. Following chemotherapy, severe leukopenia (less than 100 leukocytes/mm3) lasted 6-10 (median 8) days in patients receiving cryopreserved marrow, compared to 10-29 (median 16) days in controls (p less than 0.001). Recovery to 1000 leukocytes/mm3 occurred 10-18 (median 13) days after chemotherapy in autograft recipients but was delayed until 12-38 (median 23) days after chemotherapy in controls (p less than 0.001). Autografted patients also recovered granulocyte and platelet function significantly faster and had significantly fewer febrile days after chemotherapy than did controls. Cryopreserved autologous bone marrow infusions can hasten hemopoietic recovery in man after high-dose chemotherapy; this earlier reconstitution may be of clinical benefit to the patient.


Hormonal influence on the release of endothelial nitric oxide: gender-related dimorphic sensitivity of rat aorta for noradrenaline.
Male gender shows a higher incidence of vascular disorders and this phenomenon could be explained by sexual dimorphic behaviour of vessels. Both gonadal hormones and endothelial nitric oxide (NO) are involved in the regulation of the vascular reactivity. This study aimed to evaluate a possible sexual dimorphic sensitivity of rat aorta for the catecholamine noradrenaline. To understand the role played by physiological concentrations of sex hormones, the experimental procedures were performed on isolated preparations from intact (sham-operated) and gonadectomized rats of both sexes. In parallel sets of experiments, the biosynthesis of NO was inhibited by N'-nitro-L-arginine methyl ester (L-NAME) to reveal any potential involvement of the endothelial modulator and its possible link with the endocrinous factor. In aortae from intact male and female rats, noradrenaline induced contractile effects with different potencies (mean+s.d. EC50 values 12.15 +/- 5.25 nM and 84.10 +/- 18.68 nM, respectively). Gonadectomy resulted in an increased sensitivity for noradrenaline in female vessels and a decreased sensitivity for the agonist in male vessels (EC50 values 25.64 +/- 5.04 nM and 21.70 +/ 1 1.13 nM, respectively). In aortae from intact male rats, the inhibition of NO biosynthesis resulted in a weak increase in sensitivity for noradrenaline (EC50 value 6.08 +/- 4.53 nM), whereas the increase was higher in vessels from intact female rats (EC50 value 10.38 +/- 8.40 nM). After treatment with L-NAME, aortae from gonadectomized male and female rats presented almost equivalent increases in sensitivity for the adrenergic agonist (EC50 values 6.02 +/- 3.63 nM and 9.10+/- 9.63 nM,respectively),and no significant difference in sensitivity could be recorded between intact and orchidectomized male rats, or between intact and ovariectomized female rats. It was concluded that rat aorta showed a sexual dimorphic sensitivity for noradrenaline and the female sex was more protected against the adrenergic contractile stimulus because of a higher release of endothelial NO. The gender-related difference in NO release was influenced by gonadal hormones, with the female hormones inducing an increase and the male hormones causing a reduction.


The inhibitory effect of melatonin on osteoclastogenesis of RAW 264.7 cells in low concentrations of RANKL and MCSF.
RAW 264.7 cells are one of the most recommended cell lines for investigating the activity and differentiation of osteoclasts. These cells differentiate into osteoclasts in the presence of two critical components: receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony stimulating factor (MCSF). Melatonin (MEL) hormone has recently become one of the small molecules used in the field of bone regeneration and bone disease treatment, as it has the ability to inhibit the differentiation of osteoclasts directly by suppression of the NF-κB signaling pathway. The main aim of the current study is to determine sufficient RANKL/MCSF concentrations for differentiation of the cells to osteoclasts and to describe the repressive effect of MEL on the osteoclastogenesis of these cells. In this regard, it was found that 10 ng/mL of RANKL- and MCSF-containing medium is suitable for inducing osteoclastogenesis of the cells. In addition, melatonin at doses in the range of 100-1000 µM does not have a cytotoxic effect. Subsequently, results of tartrate resistant acid phosphatase (TRAP) activity, TRAP staining, and relative expressions of cathepsin K, nuclear factor of activated T cells one (NFATC1), and TRAP genes showed a suppressive effect of MEL -especially 800 µM- on RANKL-induced osteoclastogenesis of these cells.


Acute Adverse Events and Postoperative Complications in a Randomized Trial of Preoperative Short-course Radiotherapy Versus Long-course Chemoradiotherapy for T3 Adenocarcinoma of the Rectum: Trans-Tasman Radiation Oncology Group Trial (TROG 01.04).
To compare acute adverse events (AE) and postoperative complication rates in a randomized trial of short-course (SC) versus long-course (LC) preoperative radiotherapy. Evidence demonstrates that adding neoadjuvant radiotherapy to surgery offers better local control in the management of rectal cancer. With both SC and LC therapy there is a potential for acute treatment-related toxicity and increased patient morbidity. Eligible patients had clinical-stage T3 rectal adenocarcinoma within 12 cm of the anal verge with no evidence of metastasis. SC consisted of pelvic radiotherapy 5 × 5 Gy in 1 week, early surgery and 6 courses of adjuvant chemotherapy. LC was 50.4 Gy administered in 28 fractions during 5.5 weeks, with infusion 5-fluorouracil, surgery in 4 to 6 weeks, and 4 courses of chemotherapy. All SC patients and 93% of LC patients received preoperative planned radiotherapy. There was no 30-day operative mortality. A statistically significant higher percentage of at least 1 AE occurred in the LC group (SC, 72.3%; LC, 99.4%; P < 0.001). There were significant differences in favor of SC for grade 3 AE: radiation dermatitis (0% vs 5.6%, P = 0.003), proctitis (0% vs 3.7% P = 0.016), nausea (0% vs 3.1%, P = 0.029), fatigue (0% vs 3.7%, P = 0.016) and grade 3/4 diarrhea rates (1.3% vs 14.2% P < 0.001). No statistically significant differences in surgical complication rates were seen (SC 53.2 vs 50.4% LC, p = 0.68), although permanent stoma (38.0% vs 29.8%, P = 0.13) and anastomotic breakdown (7.1% vs 3.5%, P = 0.26) rates favored LC with perineal wound complications (38.3% vs 50.0%, P = 0.26) in favor of SC. LC had significantly higher AEs compared with SC with no statistically significant differences in postoperative complications. There were clinical trends in permanent stoma rates and anastomotic leaks in favor of LC but with an increased perineal wound breakdown rate.


Performance of Plasma Biomarkers and Diagnostic Panels for Nonalcoholic Steatohepatitis and Advanced Fibrosis in Patients With Type 2 Diabetes.
The 2019 Standards of Medical Care in Diabetes suggested that patients with nonalcoholic fatty liver disease (NAFLD) should be evaluated for liver fibrosis. However, the performance of noninvasive clinical models/scores and plasma biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and advanced fibrosis has not been carefully assessed in patients with type 2 diabetes mellitus (T2DM). In this cross-sectional study, patients (n = 213) had a liver MRS, and those with a diagnosis of NAFLD underwent a percutaneous liver biopsy. Several noninvasive clinical models/scores and plasma biomarkers were measured to identify NASH and advanced fibrosis (NASH: ALT, cytokeratin-18, NashTest 2, HAIR, BARD, and OWLiver; advanced fibrosis: AST, fragments of propeptide of type III procollagen [PRO-C3], FIB-4, APRI, NAFLD fibrosis score, and FibroTest). None of the noninvasive tools assessed for the diagnosis of NASH in patients with T2DM had an optimum performance (all areas under the curve [AUCs] <0.80). Of note, none of the panels or biomarkers was able to outperform plasma ALT (AUC 0.78 [95% CI 0.71-0.84]). Performance was better to diagnose advanced fibrosis, in which plasma PRO-C3, AST, and APRI showed better results than the other approaches (AUC 0.90 [0.85-0.95], 0.85 [0.80-0.91], and 0.86 [0.80-0.91], respectively). Again, none of the approaches did significantly better than plasma AST. Sequential use of plasma AST and other noninvasive tests may help in limiting the number of liver biopsies required to identify patients with advanced fibrosis. Performance of noninvasive clinical models/scores and plasma biomarkers for the diagnosis of NASH or advanced fibrosis was suboptimal in patients with T2DM. Combination of multiple tests may provide an alternative to minimize the need for liver biopsies to detect fibrosis in these patients.


Relaxation therapy as an adjunct treatment for essential hypertension.
Essential hypertension is one of the leading problems seen by a family physician, and it is not easily treated. In some instances, a behavioral therapy may serve as a useful adjunct to the pharmacological treatment of this disease. Evidence indicates that relaxation therapy in combination with medical treatment results in significantly greater reductions in systolic and diastolic blood pressure than the use of medical treatment alone. Progressive muscle relaxation, Benson's "relaxation response," hypnosis, and blood pressure biofeedback are the four most common behavioral treatments for essential hypertension. The first two of these are both effective and well suited to use in a family practice.


Comparative susceptibility of European corn borer, southwestern corn borer, and sugarcane borer (Lepidoptera: Crambidae) to Cry1Ab protein in a commercial Bacillus thuringiensis corn hybrid.
One field strain each of the European corn borer, Ostrinia nubilalis (Hübner); southwestern corn borer, Diatraea grandiosella Dyar; and sugarcane borer, Diatraea saccharalis (F.); were collected from cornfields in northeastern Louisiana. Susceptibilities of the field strain and a corresponding laboratory strain of the three borer species to Cry1Ab protein in DK69-70 Bacillus thuringiensis (Bt) corn hybrid were determined by exposing neonates to intact leaf tissues from whorl stage plants or by feeding neonates or third instars on a meridic diet treated with different concentrations of Cry1lAb protein extracted from Bt corn leaves. Mortality and growth of larvae were evaluated after 2 and 4 d posttreatment in the bioassays by using intact leaf tissues or after 7 d in the bioassays by using diet incorporating Cry1Ab protein. D. saccharalis was the least susceptible species to Cry1Ab protein among the three species, followed by D. grandiosella, whereas O. nubilalis was most susceptible. The 2-d mortality of D. saccharalis neonates on intact Bt leaf tissues was lower than that of O. nubilalis and D. grandiosella. All neonates of O. nubilalis were killed on the diet treated with Cry1Ab protein at 0.5 and 1 mg/kg. The mortality of D. grandiosella was > 75% at 1 mg/kg, but it was < 6% for D. saccharalis at 1 mg/kg. The LC50 values of D. saccharalis were 3- and 11-fold higher than those of D. grandiosella and O. nubilalis, respectively. The LC90 values of D. saccharalis were 8- and 32-fold higher than those of D. grandiosella and O. nubilalis, respectively. Larval growth of the three species on Cry1Ab-treated diet was inhibited, but the inhibition was greater for O. nubilalis and D. grandiosella than for D. saccharalis. The lower susceptibility of D. saccharalis to Cry1Ab protein suggests that it is necessary to verify if a high-dose Bt corn for O. nubilalis and D. grandiosella is also a high dose for D. saccharalis.


Loss of connexin40 is associated with decreased endothelium-dependent relaxations and eNOS levels in the mouse aorta.
Upon agonist stimulation, endothelial cells trigger smooth muscle relaxation through the release of relaxing factors such as nitric oxide (NO). Endothelial cells of mouse aorta are interconnected by gap junctions made of connexin40 (Cx40) and connexin37 (Cx37), allowing the exchange of signaling molecules to coordinate their activity. Wild-type (Cx40(+/+)) and hypertensive Cx40-deficient mice (Cx40(-/-)), which also exhibit a marked decrease of Cx37 in the endothelium, were used to investigate the link between the expression of endothelial connexins (Cx40 and Cx37) and endothelial nitric oxide synthase (eNOS) expression and function in the mouse aorta. With the use of isometric tension measurements in aortic rings precontracted with U-46619, a stable thromboxane A(2) mimetic, we first demonstrate that ACh- and ATP-induced endothelium-dependent relaxations solely depend on NO release in both Cx40(+/+) and Cx40(-/-) mice, but are markedly weaker in Cx40(-/-) mice. Consistently, both basal and ACh- or ATP-induced NO production were decreased in the aorta of Cx40(-/-) mice. Altered relaxations and NO release from aorta of Cx40(-/-) mice were associated with lower expression levels of eNOS in the aortic endothelium of Cx40(-/-) mice. Using immunoprecipitation and in situ ligation assay, we further demonstrate that eNOS, Cx40, and Cx37 tightly interact with each other at intercellular junctions in the aortic endothelium of Cx40(+/+) mice, suggesting that the absence of Cx40 in association with altered Cx37 levels in endothelial cells from Cx40(-/-) mice participate to the decreased levels of eNOS. Altogether, our data suggest that the endothelial connexins may participate in the control of eNOS expression levels and function.


Spatiotemporal video segmentation based on graphical models.
This paper proposes a probabilistic framework for spatiotemporal segmentation of video sequences. Motion information, boundary information from intensity segmentation, and spatial connectivity of segmentation are unified in the video segmentation process by means of graphical models. A Bayesian network is presented to model interactions among the motion vector field, the intensity segmentation field, and the video segmentation field. The notion of the Markov random field is used to encourage the formation of continuous regions. Given consecutive frames, the conditional joint probability density of the three fields is maximized in an iterative way. To effectively utilize boundary information from the intensity segmentation, distance transformation is employed in local objective functions. Experimental results show that the method is robust and generates spatiotemporally coherent segmentation results. Moreover, the proposed video segmentation approach can be viewed as the compromise of previous motion based approaches and region merging approaches.


Neutrophil to lymphocyte ratio as an indicative of diabetic control level in type 2 diabetes mellitus.
Type 2 diabetes mellitus is associated with chronic low grade inflammation. One of the novel inflammatory markers is hemogram derived neutrophil to lymphocyte ratio (NLR). We aimed to compare NLR levels of diabetic subjects and healthy controls and to observe possible correlation between NLR and HbA1c. Medical data of type 2 diabetic subjects admitted to out-patient clinics of our institution between April to July in 2017 were obtained from database and retrospectively analyzed. Control group was chosen from healthy subjects who visited our institution for a routine check-up. Anthropometric measures, laboratory data, including, HbA1c, NLR were recorded. Median NLR of the type 2 DM group 2.44 (1.9) was significantly elevated when compared to healthy controls (1.5 (0.9), (p<0.001). In addition, a Pearson's correlation test revealed that NLR was strongly correlated with age (r=0.26, p=0.008), fasting plasma glucose (r=0.38, p<0.001), and HbA1c (r=0.49, p<0.001). Elevated NLR in otherwise healthy subjects may be indicative of underlying impaired glucose metabolism and moreover, NLR should be used as a marker of diabetic control level in addition to HbA1c in type 2 diabetic subjects.


Efferents and centrifugal afferents of the main and accessory olfactory bulbs in the snake Thamnophis sirtalis.
This study reinvestigates the efferent projections of the main and accessory olfactory bulbs and describes for the first time the centrifugal projections to the main and accessory olfactory bulbs in the snake Thamnophis sirtalis, using the intraaxonal transport of the anterograde and retrograde tracer biotinylated dextran amine and the retrograde tracer horseradish peroxidase. The olfactory projection consists of three tracts: the lateral olfactory tract, which projects bilaterally to the lateral cortex and the rostral amygdala, crossing the midline through the stria medullaris-habenular commissure system; the intermediate olfactory tract, which projects ipsilaterally to the olfactory tubercle and contributes to the contralateral projection; and the medial olfactory tract, which projects ipsilaterally to the dorsomedial retrobulbar formation. The vomeronasal projection is formed by a single tract, the accessory olfactory tract, that projects ipsilaterally to the nucleus of the accessory olfactory tract, the medial amygdala and the nucleus sphericus. The centrifugal projections to the main and accessory olfactory bulb are composed of two components: one that arises in areas that receive the olfactory or vomeronasal input (neurons in the olfactory tubercle, retrobulbar formation and lateral cortex project to the main olfactory bulb; and neurons in the nucleus of the accessory olfactory tract, the medial amygdala and the nucleus sphericus project to the accessory olfactory bulb), and another that arises in areas not directly implicated in processing the chemosensory information (the nucleus of the diagonal band of Broca and the dorsal cortex). These data allow the recognition of the general pattern of organization of the reptilian olfactory and vomeronasal systems.


Sequential inhibition of polyamine synthesis. A phase I trial of DFMO (alpha-difluoromethylornithine) and methyl-GAG [methylglyoxal-bis(guanylhydrazone)].
Both DFMO and methyl-GAG inhibit sequential enzymatic reactions in the pathway of polyamine biosynthesis. Since polyamines may be important factors in proliferation of cancer cells, we initiated a phase-I study of these agents in patients with advanced cancer. DFMO was given by mouth at a constant daily dose of 4 g/m2 starting on day 1 of the treatment protocol. The dose of methyl-GAG ranged from 200 to 700 mg/m2 administered IV every 2 weeks beginning on day 4. Twenty-two patients were entered into the protocol. Toxic reactions to this therapy were dose-related and included nausea, fatigue, diarrhea, and myelosuppression. One patient with colon cancer experienced a greater than 50% decrease in measurable disease but developed severe myelotoxicity. While DFMO was well tolerated, the combination of drugs appeared to cause substantially more hematologic and gastrointestinal toxicity than encountered during our recent experience with methyl-GAG used alone. We suggest that future studies of this drug combination carefully evaluate levels of polyamines and inhibition of enzymatic activity to minimize toxicity.


Transplantation with allogenic bone marrow from a donor with systemic lupus erythematosus (SLE): successful outcome in the recipient and induction of an SLE flare in the donor.
To investigate the transfer of autoimmunity by allogenic bone marrow transplantation. Bone marrow transplantation was performed in a 43 years old man with acute myeloid leukaemia (AML) in remission. The donor was his HLA identical brother who had a mild systemic lupus erythematosus (SLE). Autoantibodies, including antinuclear, anti-C1q, and anticardiolipin antibodies, were measured before and after transplantation. Transient mild graft versus host disease (GvHD) developed in the recipient in the weeks following transplantation. The donor had persistently high concentrations of anti-C1q antibodies to the collagenous region of the complement component C1q. Three months after transplantation the recipient developed antiC1q antibodies that persisted for two months. No other autoantibodies and no SLE-like manifestations appeared. Chronic GVHD started five months posttransplant and responded to intensified immunosuppressive treatment. Three years post-transplant the patient was in unmaintained remission. Within a few weeks after bone marrow donation the donor's disease was exacerbated with development of severe pulmonary alveolitis which required treatment with cyclophosphamide. When bone marrow transplantation was performed in a patient with AML with bone marrow from an HLA identical brother who had SLE, no evidence of transfer of disease was obtained. However, the recipient temporarily produced anti-C1q antibodies which was a characteristic feature of the donor's SLE and was probably produced by the transplant. The flare of the donor's SLE might be related to the bone marrow tap.


DNA "fingerprints" and segregation analysis of multiple markers in human pedigrees.
Tandem-repetitive DNA hybridization probes based on a putative human recombination signal detect multiple polymorphic minisatellite fragments in human DNA. The genetic complexity of the resulting individual-specific DNA "fingerprints" was investigated by studying a large sibship affected by neurofibromatosis and a more extensive pedigree segregating for two different hemoglobinopathies. The segregation of up to 41 different heterozygous DNA fragments from each parent could be analyzed in a single sibship, using two different repeat probes. Most of these variable DNA fragments could not be paired as alleles, to an extent which suggests that the DNA fingerprints are together derived from approximately 60 heterozygous loci (approximately 120 variable fragments), only a proportion of which can be scored in a given individual. Two or three of the DNA fragments detected by one probe showed tight linkage and may be derived from long minisatellite(s) that are cleaved to produce more than one polymorphic DNA fragment. Excluding allelic and linked DNA fragments, almost all remaining scorable fragments segregated independently, allowing up to 34 unlinked loci to be examined simultaneously. These loci are scattered over most or all of the human autosomes. Minisatellite probes are therefore suitable for rapid marker generation and can be applied to linkage analysis in human pedigrees.


Cortical decoding of individual finger and wrist kinematics for an upper-limb neuroprosthesis.
Previous research has shown that neuronal activity can be used to continuously decode the kinematics of gross movements involving arm and hand trajectory. However, decoding the kinematics of fine motor movements, such as the manipulation of individual fingers, has not been demonstrated. In this study, single unit activities were recorded from task-related neurons in M1 of two trained rhesus monkey as they performed individuated movements of the fingers and wrist. The primates' hand was placed in a manipulandum, and strain gauges at the tips of each finger were used to track the digit's position. Both linear and non-linear filters were designed to simultaneously predict kinematics of each digit and the wrist, and their performance compared using mean squared error and correlation coefficients. All models had high decoding accuracy, but the feedforward ANN (R = 0.76-0.86, MSE = 0.04-0.05) and Kalman filter (R = 0.68-0.86, MSE = 0.04-0.07) performed better than a simple linear regression filter (0.58-0.81, 0.05-0.07). These results suggest that individual finger and wrist kinematics can be decoded with high accuracy, and be used to control a multi-fingered prosthetic hand in real-time.


Specific Dietary Components and Gut Microbiota Composition are Associated with Obesity in Children and Adolescents with Prader-Willi Syndrome.
Prader-Willi syndrome is a rare genetic disorder associated with impaired body composition, hyperphagia, and excessive weight gain. Strict dietary restrictions from an early age is crucial to prevent or delay the early onset of obesity, which is the main driver of comorbidities in these patients. The aim of this study was to identify dietary and gut microbiota components closely linked to weight status of these patients. We studied a cohort of children and adolescents with genetic diagnosis of Prader-Willi syndrome (N = 31), in which we determined adiposity by Dual-energy X-ray absorptiometry (DXA) and dietary composition with 4-day food records. Furthermore, we obtained fecal samples to assess microbiota composition by 16S sequencing. Multivariate regression models showed that body mass index standard deviation score (BMI-SDS) and body fat mass were directly associated with saturated fat intake and meat consumption, and inversely associated with fruit consumption. Furthermore, the gut microbiome from normal weight patients was characterized by higher phylogenetic diversity compared to those overweight or obese, with differential abundance of several genera, including Alistipes, Klebsiella, and Murimonas. Notably, Alistipes abundance was inversely correlated to adiposity, lipid and glucose homeostasis parameters, and meat intake. Our results suggest that limiting meat and increasing fruit intake might be beneficial for body weight management in children and adolescents with Prader-Willi syndrome.


Catalase: kinetics of photooxidation.
The kinetics of photooxidation of catalase is a four-step consecutive reaction, if each of the four porphyrin moieties acts independently. The rate of enzyme inactivation is a first-order reaction resulting from destruction of a single porphyrin. The kinetics of absorbancy is more complex, depending upon the absorption probabilities of each of the microspecies. With equal probabilities. the log of the sum of the normalized absorptivities is a linear function of time.


A comparative evaluation of single-balloon enteroscopy and spiral enteroscopy for patients with mid-gut disorders.
Single-balloon enteroscopy (SBE) and spiral enteroscopy (SE) are recently described device-assisted techniques in endoluminal evaluation of the small bowel. No studies comparing SBE and SE in patients with suspected small-bowel disorders have previously been reported. The aims of this study were to compare SBE and SE in terms of diagnostic yield, procedure time, depth of maximal insertion, and complications. Retrospective cohort study. Tertiary-care referral center. A retrospective analysis was performed on all patients at our institution undergoing anterograde SBE or SE between 2007 and 2009. Patients with altered anatomy or prior small-bowel surgery were excluded. Deep enteroscopy. Diagnostic yield. During the study period, 92 patients underwent 105 procedures (52 SBE, 53 SE). The most common indication for small-bowel endoscopy was obscure GI bleeding (n = 42). The diagnostic yield was not statistically different between SBE and SE (59.6% and 43.4%, respectively, P = .12). The overall diagnostic yield in patients with obscure GI bleeding was 67%. There was no significant difference between mean SBE and SE procedure times (53 minutes [range 15-99 minutes] vs 47 minutes [range 20-125 minutes], respectively; P = .2). The mean depth of maximal insertion beyond the ligament of Treitz for SE was significantly higher than that for SBE (301 cm [range 175-400 cm] vs 222 cm [range 110-400 cm], respectively; P < .001). Perforation occurred in one SBE procedure. Retrospective design and nonstandardized gas insufflation. This is the first report comparing SE and SBE. Although SE yielded greater depth of maximal insertion than SBE, both techniques had similar diagnostic yields and procedure times. In addition, both techniques were safe and were particularly useful in patients with obscure GI bleeding.


Rare Earth Ion-Doped Upconversion Nanocrystals: Synthesis and Surface Modification.
The unique luminescent properties exhibited by rare earth ion-doped upconversion nanocrystals (UCNPs), such as long lifetime, narrow emission line, high color purity, and high resistance to photobleaching, have made them widely used in many areas, including but not limited to high-resolution displays, new-generation information technology, optical communication, bioimaging, and therapy. However, the inherent upconversion luminescent properties of UCNPs are influenced by various parameters, including the size, shape, crystal structure, and chemical composition of the UCNPs, and even the chosen synthesis process and the surfactant molecules used. This review will provide a complete summary on the synthesis methods and the surface modification strategies of UCNPs reported so far. Firstly, we summarize the synthesis methodologies developed in the past decades, such as thermal decomposition, thermal coprecipitation, hydro/solvothermal, sol-gel, combustion, and microwave synthesis. In the second part, five main streams of surface modification strategies for converting hydrophobic UCNPs into hydrophilic ones are elaborated. Finally, we consider the likely directions of the future development and challenges of the synthesis and surface modification, such as the large-scale production and actual applications, stability, and so on, of the UCNPs.


Effects of the need fulfillment given by opposite-sex friends on breakup considerations: A moderated mediation model.
The purpose of this study was to investigate the impact of need fulfillment given by opposite-sex friends (NFOF) on breakup considerations, the mediating role of love commitment in this relationship, and the moderating role of need fulfillment given by romantic partners (NFRP). A total of 334 unmarried individuals in romantic relationships from Northwest China were invited to participate in the study. The findings revealed the following: (1) NFOF significantly and positively predicted breakup considerations. (2) This relationship is mediated by love commitment (3) The association between NFOF and breakup considerations was moderated by NFRP (in terms of the first mediation path). Specifically, those who hold higher levels of NFRP are appreciably buffered against the negative impact of NFOF on love commitment. These findings emphasize the crucial role of NFOF and NFRP in shaping love commitment and breakup considerations. Moreover, our research has important realistic implications: NFOF, as a trigger, has a negative effects the quality of romantic relationships and leads to breakup considerations. And, the key to maintaining a romantic relationship is to focus on their partners' need fulfillment as much as possible and increasing the level of their love commitment.


A bridging water anchors the tethered 5-(3-aminopropyl)-2'-deoxyuridine amine in the DNA major groove proximate to the N+2 C.G base pair: implications for formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards.
Site-specific insertion of 5-(3-aminopropyl)-2'-deoxyuridine (Z3dU) and 7-deaza-dG into the Dickerson-Drew dodecamers 5'-d(C (1)G (2)C (3)G (4)A (5)A (6)T (7)T (8)C (9) Z (10)C (11)G (12))-3'.5'-d(C (13)G (14)C (15)G (16)A (17)A (18)T (19)T (20)C (21) Z (22)C (23)G (24))-3' (named DDD (Z10)) and 5'-d(C (1)G (2)C (3)G (4)A (5)A (6)T (7) X (8)C (9) Z (10)C (11)G (12))-3'.5'-d(C (13)G (14)C (15)G (16)A (17)A (18)T (19) X (20)C (21) Z (22)C (23)G (24))-3' (named DDD (2+Z10)) (X = Z3dU; Z = 7-deaza-dG) suggests a mechanism underlying the formation of interstrand N+2 DNA cross-links by nitrogen mustards, e.g., melphalan and mechlorethamine. Analysis of the DDD (2+Z10) duplex reveals that the tethered cations at base pairs A (5).X (20) and X (8).A (17) extend within the major groove in the 3'-direction, toward conserved Mg (2+) binding sites located adjacent to N+2 base pairs C (3).Z (22) and Z (10).C (15). Bridging waters located between the tethered amines and either Z (10) or Z (22) O (6) stabilize the tethered cations and allow interactions with the N + 2 base pairs without DNA bending. Incorporation of 7-deaza-dG into the DDD (2+Z10) duplex weakens but does not eliminate electrostatic interactions between tethered amines and Z (10) O (6) and Z (22) O (6). The results suggest a mechanism by which tethered N7-dG aziridinium ions, the active species involved in formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards, modify the electrostatics of the major groove and position the aziridinium ions proximate to the major groove edge of the N+2 C.G base pair, facilitating interstrand cross-linking.


A comparative study of GNN and MLP based machine learning for the diagnosis of Alzheimer's Disease involving data synthesis.
Alzheimer's Disease (AD) is a neurodegenerative disease that commonly occurs in older people. It is characterized by both cognitive and functional impairment. However, as AD has an unclear pathological cause, it can be hard to diagnose with confidence. This is even more so in the early stage of Mild Cognitive Impairment (MCI). This paper proposes a U-Net based Generative Adversarial Network (GAN) to synthesize fluorodeoxyglucose - positron emission tomography (FDG-PET) from magnetic resonance imaging - T1 weighted imaging (MRI-T1WI) for further usage in AD diagnosis including its early-stage MCI. The experiments have displayed promising results with Structural Similarity Index Measure (SSIM) reaching 0.9714. Furthermore, three types of classifiers are developed, i.e., one Multi-Layer Perceptron (MLP) based classifier, two Graph Neural Network (GNN) based classifiers where one is for graph classification and the other is for node classification. 10-fold cross-validation has been conducted on all trials of experiments for classifier comparison. The performance of these three types of classifiers has been compared with the different input modalities setting and data fusion strategies. The results have shown that GNN based node classifier surpasses the other two types of classifiers, and has achieved the state-of-the-art (SOTA) performance with the best accuracy at 90.18% for 3-class classification, namely AD, MCI and normal control (NC) with the synthesized fluorodeoxyglucose - positron emission tomography (FDG-PET) features fused at the input level. Moreover, involving synthesized FDG-PET as part of the input with proper data fusion strategies has also proved to enhance all three types of classifiers' performance. This work provides support for the notion that machine learning-derived image analysis may be a useful approach to improving the diagnosis of AD.


Polyvinyl alcohol sponge for embolotherapy: particle size and morphology.
The size and morphology of particulate polyvinyl alcohol (PVA) sponge prepared by a blender technique for embolotherapy were analyzed by light and scanning electron microscopy. Techniques for preparation and sizing of PVA sponge particles are described. Two types of particulate material, differing in both size and morphology, were found. Large particles (greater than 50 micron) had irregular shapes and sharp, jagged edges. Smaller particles (2-50 micron) were more numerous. Attempts to characterize the smaller particles were unsuccessful. Preparation of PVA sponge particles using the blender technique is a viable choice in external carotid neuroembolization procedures. However, the potential effects of small particles possibly causing cranial nerve palsies does need consideration.


ESERINE AND AMPHETAMINE: INTERACTIVE EFFECTS ON SLEEPING TIME IN MICE.
The sleeping time of mice given pentobarbital was found to be significantly shortened by the injection of eserine or amphetamine. When both eserine and amphetamine were given with pentobarbital the sleeping time, though much shortened, was significantly longer than with the addition of amphetamine alone. Though possessing an analeptic effect of its own, eserine appears to antagonize the analeptic effect of amphetamine.


Translational Aspects of the Human Respiratory Virome.
Despite the dominant role of community-acquired respiratory viruses as etiological agents of disease, there has been little focus to date on the translation of rapidly developing diagnostic modalities, such as next-generation sequencing techniques in the examination of lower respiratory tract samples. When applied, these techniques should inform strategies to both understand the nexus between health and disease states of the respiratory virome, and drive a paradigm shift in how the practicing pulmonologist views the conceptual framework of respiratory infections. The lower respiratory tract was once thought to be a sanctuary site from microbiological colonization owing to the efficacy of upper airway-protective mechanisms and the host mucosal barrier function of the lower airways, combined with both innate and adaptive immune responses. As a small number of recent studies confirm, this is a naive vision of the lung, the viral component of which parallels recent revelations from respiratory microbiome studies. Hence, it is now timely to revise our thinking regarding the constituents, diversity, and changing nature of the respiratory virome in health and disease. One area worthy of focus is the interface between community-acquired respiratory viruses and the respiratory virome to better understand the dynamics in acute infection, as well as the factors that may lead to viral persistence and chronic disease. Given recent advances in metagenomics, the tools are now at hand to accomplish these goals.


Importance of nucleotide sequence and chemical modifications of antisense oligonucleotides.
The antisense approach is conceptually simple and elegant; to design an inhibitor of a specific mRNA, one needs only to know the sequence of the targeted mRNA and an appropriately modified complementary oligonucleotide. Of the many analogs of oligodeoxynucleotides explored as antisense agents, phosphorothioate analogs have been studied the most extensively. The use of phosphorothioate oligodeoxynucleotides as antisense agents in various studies have shown promising results. However, they have also indicated that quite often, biological effects observed could be solely or partly non-specific in nature. It is becoming clear that not all phosphorothioate oligodeoxynucleotides of varying length and base composition are the same, and important consideration should be given to maintain antisense mechanisms while identifying effective antisense oligonucleotides. In this review, I have summarized the progress made in my laboratory in understanding the specificity and mechanism of actions of phosphorothioate oligonucleotides and the rationale for designing second-generation mixed-backbone oligonucleotides.


Gold-Etched Silver Nanowire Endoscopy: Toward a Widely Accessible Platform for Surface-Enhanced Raman Scattering-Based Analysis in Living Cells.
Recently, our group introduced the use of silver nanowires (AgNWs) as novel non-invasive endoscopic probes for detecting intracellular Raman signals. This method, although innovative and promising, relies exclusively on the plasmonic waveguiding effect for signal enhancement. It, therefore, requires sophisticated operational tools and protocols, drastically limiting its applicability. Herein, an advanced strategy is offered to significantly enhance the performance of these endoscopic probes, making this approach widely accessible and versatile for cellular studies. By uniformly forming gold structures on the smooth AgNW surface via a galvanic replacement reaction, the density of the light coupling points along the whole probe surface is drastically increased, enabling high surface-enhanced Raman scattering (SERS) efficiency upon solely focusing the excitation light on the gold-etched AgNW. The applicability of these gold-etched AgNW probes for molecular sensing in cells is demonstrated by detecting site-specific and high-resolved SERS spectra of cell compartment-labeling dyes, namely, 4',6-diamidino-2-phenylindole in the nucleus and 3,3'-dioctadecyloxacarbocyanine on the membrane. The remarkable spectral sensitivity achieved provides essential structural information of the analytes, indicating the overall potential of the proposed approach for cellular studies of drug interactions with biomolecular items.


Clickers in the large classroom: current research and best-practice tips.
Audience response systems (ARS) or clickers, as they are commonly called, offer a management tool for engaging students in the large classroom. Basic elements of the technology are discussed. These systems have been used in a variety of fields and at all levels of education. Typical goals of ARS questions are discussed, as well as methods of compensating for the reduction in lecture time that typically results from their use. Examples of ARS use occur throughout the literature and often detail positive attitudes from both students and instructors, although exceptions do exist. When used in classes, ARS clickers typically have either a benign or positive effect on student performance on exams, depending on the method and extent of their use, and create a more positive and active atmosphere in the large classroom. These systems are especially valuable as a means of introducing and monitoring peer learning methods in the large lecture classroom. So that the reader may use clickers effectively in his or her own classroom, a set of guidelines for writing good questions and a list of best-practice tips have been culled from the literature and experienced users.


Neural organization and evolution of thermal regulation in mammals.
This article proposes a modification of the currently accepted view of the central neural integration of body temperature. In place of a single integrator with multiple inputs and outputs, the new model includes as many integrators as there are thermoregulatory responses. Futhermore, these integrators are postulated to be represented at many levels of the nervous system, with each level facilitated or inhibited by levels above and below. The purpose of such a complicated arrangement is to achieve finer and finer control over body temperature. A consideration of how endothermy might have evolved, with originally nonthermally related responses gradually coming under thermal control, makes such a brain organization highly reasonable.


Characterization of endogenous fluorescence in nonsmall lung cancerous cells: A comparison with nonmalignant lung normal cells.
Monitoring fluorescence properties of endogenous fluorophores such as nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) in normal and cancerous cells provide substantial information noninvasively on biochemical and biophysical aspects of metabolic dysfunction of cancerous cells. Time-resolved spectral profiles and fluorescence lifetime images of NADH and FAD were obtained in human lung nonsmall carcinomas (H661 and A549) and normal lung cells (MRC-5). Both fluorophores show the fast and slowly decaying emission components upon pulsed excitation, and fluorescence spectra of NADH and FAD show blue- and red-shifts, respectively, during their decay. All identified lifetime components of NADH and FAD were found to be shorter in cancerous cells than in normal cells, no matter how they were measured under different extra-cellular conditions (cells suspended in cuvette and cells attached on glass substrate), indicating that the changes in metabolism likely altered the subcellular milieu and potentially also affected the interaction of NADH and FAD with enzymes to which these cofactors were bound. The intensity ratio of NADH and FAD of cancerous cells was also shown to be larger than that of normal cells.


Effect of temperature and cardiopulmonary bypass on the pharmacokinetics of remifentanil.
Sixteen patients undergoing coronary revascularization requiring cardiopulmonary bypass received remifentanil 2 micrograms kg-1 or 5 micrograms kg-1 by infusion over 1 min after sternotomy but before commencing cardiopulmonary bypass, during hypothermic cardiopulmonary bypass and during cardiopulmonary bypass after rewarming. Hypothermic cardiopulmonary bypass reduced the clearance of remifentanil by an average of 20%, and this was attributed to the effect of temperature on blood and tissue esterase activity. Reductions in arterial pressure occurred with administration of both doses during normothermia only.


Parathyroid Carcinoma: Diagnosis and Clinical Implications.
Parathyroid carcinoma is a rare type of endocrine cancer, with significant morbidity and mortality associated with parathyroid hormone (PTH)-mediated hypercalcemia. Concerning clinical features for parathyroid cancer include severe hypercalcemia (albumin-corrected calcium > 3 mmol/L), a palpable neck mass ( > 3 cm), 3rd/2nd generation PTH assay ratio ( > 1), and intraoperative suspicion of local invasion or regional metastasis. A definite diagnosis of malignancy is rendered when a parathyroid tumor presents one of the following clinicopathological features: (1) vascular invasion, (2) perineural invasion, (3) gross invasion into adjacent anatomical structures, and/or (4) metastasis. In difficult cases, the use of ancillary biomarkers is critical to establish an accurate diagnosis. Recent advances in molecular pathology have uncovered the important role of CDC73/HRPT2, a tumor suppressor gene deregulated in parathyroid carcinomas. Loss of nuclear and/or nucleolar expression of parafibromin (the gene product of CDC73/HRPT2) is now regarded as a diagnostic, prognostic and predictive biomarker for parathyroid carcinoma. Furthermore, over 15-20% of seemingly sporadic parathyroid carcinomas have underlying germline CDC73/HRPT2 mutations. As a result, many centers have integrated the use of ancillary biomarkers, notably parafibromin staining, in their routine practise. Radical surgery with en bloc resection has emerged as a primary treatment modality in parathyroid cancer, achieving cure in some patients. However, in those with inoperable disease, there remains a dire need for new therapies, as current treatments are largely ineffective. This review provides an update on the current knowledge of parathyroid carcinoma and highlights its exciting changes in endocrine practice.


Modulation of Moloney leukemia virus long terminal repeat transcriptional activity by the murine CD4 silencer in retroviral vectors.
We investigated whether CD4 gene regulatory sequences might be useful for developing transcriptionally targeted Moloney murine leukemia virus (Mo-MLV)-based retroviral vectors for gene expression specifically in CD4(+) cells. We could modulate Mo-MLV long terminal repeat (LTR) activity by inserting a 438-bp-long fragment containing the murine CD4 silencer in the LTR of the vector; both beta-galactosidase and green fluorescent protein reporter gene activities were strongly down-regulated in both murine and human CD8(+) cells, but not in CD4(+) lymphoid cell lines and freshly isolated lymphocytes transduced with this vector, compared with the findings using a control vector carrying wild-type LTRs. Titration experiments on NIH-3T3 cells revealed that inclusion of the CD4 silencer in the LTRs did not reduce the titer of the vectors. These findings indicate that a cellular silencer can be successfully included in retroviral vectors, where it maintains its transcription-regulatory function, thus suggesting a novel approach to transcriptional targeting.


Effects of acetylsalicylic acid on the ductus arteriosus and circulation in fetal lambs in utero.
Intra-arterial and intravenous catheters were inserted in six fetal lambs at 125-130 days of gestation. On the following day, fetal arterial pressures and blood gases were monitored and fetal cardiac output and its distribution were measured by injection of radionuclide-labeled microspheres 15 mum in diameter. Acetylsalicylic acid, 55-90 mg/kg of estimated fetal weight, then was administered into the fetal stomach. Fetal pulmonary arterial pressure rose significantly after an average of 58 minutes, increasing the pressure difference between the pulmonary artery and the aorta from 2 +/- 0.3 (SEM) mm Hg during control to 11.2 +/- 1.6 mm Hg. Resistance across the ductus arteriosus rose from 4.2 +/- 0.5 (SEM) to 27.4 +/- 4.01 units, and flow fell from 495 +/- 44 (SEM) to 409 +/- 20 ml/minute. The proportion of combined ventricular output distributed to the placenta, adrenals, heart, and lungs increased, whereas the proportion of combined ventricular output distributed to the brain, liver, intestine, kidneys, and upper and lower body fell. In two fetuses infusion of prostaglandin E1 reversed the pulmonary hypertension. Inhibition of prostaglandin synthesis in fetal lambs produced constriction of the ductus arteriosus and redistribution of cardiac output. It is probable that prostaglandins, particularly E1, are involved in regulation of blood flow through the ductus arteriosus and various vascular beds in the normal resting fetus.


SUMO and Transcriptional Regulation: The Lessons of Large-Scale Proteomic, Modifomic and Genomic Studies.
One major role of the eukaryotic peptidic post-translational modifier SUMO in the cell is transcriptional control. This occurs via modification of virtually all classes of transcriptional actors, which include transcription factors, transcriptional coregulators, diverse chromatin components, as well as Pol I-, Pol II- and Pol III transcriptional machineries and their regulators. For many years, the role of SUMOylation has essentially been studied on individual proteins, or small groups of proteins, principally dealing with Pol II-mediated transcription. This provided only a fragmentary view of how SUMOylation controls transcription. The recent advent of large-scale proteomic, modifomic and genomic studies has however considerably refined our perception of the part played by SUMO in gene expression control. We review here these developments and the new concepts they are at the origin of, together with the limitations of our knowledge. How they illuminate the SUMO-dependent transcriptional mechanisms that have been characterized thus far and how they impact our view of SUMO-dependent chromatin organization are also considered.


A Puccinia striiformis f. sp. tritici secreted protein activates plant immunity at the cell surface.
Pathogens secrete effector proteins to suppress host immunity, mediate nutrient uptake and subsequently enable parasitism. However, on non-adapted hosts, effectors can be detected as non-self by host immune receptors and activate non-host immunity. Nevertheless, the molecular mechanisms of effector triggered non-host resistance remain unknown. Here, we report that a small cysteine-rich protein PstSCR1 from the wheat rust pathogen Puccinia striiformis f. sp. tritici (Pst) activates immunity in the non-host solanaceous model plant Nicotiana benthamiana. PstSCR1 homologs were found to be conserved in Pst, and in its closest relatives, Puccinia graminis f. sp. tritici and Puccinia triticina. When PstSCR1 was expressed in N. benthamiana with its signal peptide, it provoked the plant immune system, whereas no stimulation was observed when it was expressed without its signal peptide. PstSCR1 expression in N. benthamiana significantly reduced infection capacity of the oomycete pathogens. Moreover, apoplast-targeted PstSCR1 triggered plant cell death in a dose dependent manner. However, in Brassinosteroid insensitive 1-Associated Kinase 1 (SERK3/BAK1) silenced N. benthamiana, cell death was remarkably decreased. Finally, purified PstSCR1 protein activated defence related gene expression in N. benthamiana. Our results show that a Pst-secreted protein, PstSCR1 can activate surface mediated immunity in non-adapted hosts and contribute to non-host resistance.


Application and optimisation of air-steam cooking on selected vegetables: impact on physical and antioxidant properties.
Several studies investigated the impact of different cooking techniques on the quality of vegetables. However, the use of the combined air-steam cooking is still scarcely debated, despite the advantages informally referred by professional catering workers. In this study, its optimisation was studied on Brussels sprouts and pumpkin cubes to obtain the best physical (texture, colour) and antioxidant (FRAP, total phenols) response, in comparison to a conventional steaming treatment. Increasing the strength of the air-steam treatment, Brussels sprouts resulted to be softer, less green (higher a* value), richer in phenols and exhibited lower FRAP values than the steamed ones. The air-steamed pumpkin cubes exhibited an equivalent softening degree to that of steamed ones and, under the strongest cooking conditions, a higher antioxidant quality and a yellow darkening (lower b* value). Varying the cooking time and/or temperature, a linear change of force/compression hardness and a* (negative a*: greenness) for Brussels sprouts, b* (yellowness) and total phenol content for pumpkin cubes was observed. A predictive model for these variables was obtained by response surface methodology. The best process conditions to achieve the optimal desirability were also identified. The application of air-steam cooking under suitable time/temperature conditions could be proposed as an alternative method to a traditional steam cooking on Brussels sprouts and pumpkin cubes, being able to preserve or improve their quality. The best air-steam cooking conditions were 25 min at 90 °C for Brussels sprouts and 10 min at 110 °C for pumpkin. © 2017 Society of Chemical Industry.


Structural descriptions and inexact matching.
In this paper we formally define the structural description of an object and the concepts of exact and inexact matching of two structural descriptions. We discuss the problems associated with a brute-force backtracking tree search for inexact matching and develop several different algorithms to make the tree search more efficient. We develop the formula for the expected number of nodes in the tree for backtracking alone and with a forward checking algorithm. Finally, we present experimental results showing that forward checking is the most efficient of the algorithms tested.