A Comparative Theoretical and Computational Study on Robust Counterpart Optimization: II. Probabilistic Guarantees on Constraint Satisfaction.
Probabilistic guarantees on constraint satisfaction for robust counterpart optimization are studied in this paper. The robust counterpart optimization formulations studied are derived from box, ellipsoidal, polyhedral, "interval+ellipsoidal" and "interval+polyhedral" uncertainty sets (Li, Z., Ding, R., and Floudas, C.A., A Comparative Theoretical and Computational Study on Robust Counterpart Optimization: I. Robust Linear and Robust Mixed Integer Linear Optimization, Ind. Eng. Chem. Res, 2011, 50, 10567). For those robust counterpart optimization formulations, their corresponding probability bounds on constraint satisfaction are derived for different types of uncertainty characteristic (i.e., bounded or unbounded uncertainty, with or without detailed probability distribution information). The findings of this work extend the results in the literature and provide greater flexibility for robust optimization practitioners in choosing tighter probability bounds so as to find less conservative robust solutions. Extensive numerical studies are performed to compare the tightness of the different probability bounds and the conservatism of different robust counterpart optimization formulations. Guiding rules for the selection of robust counterpart optimization models and for the determination of the size of the uncertainty set are discussed. Applications in production planning and process scheduling problems are presented.


Ziconotide.
Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topics addressed in this issue are ziconotide, a novel approach to pain management that is derived from a snail toxin, its uses and possible side effects.


Zinc Cations Uniquely Stabilize Cell Membrane for Cell Cryopreservation.
We report, for the first time, merely using a small amount of (0.039% w/w) Zn(II) instead of very high concentration (25%-50% w/w) of conventional cryoprotective agents (CPAs), i.e., glycerol, during the cryopreservation of red blood cells (RBCs) can lead to a comparable post-thaw recovery rate of ∼95% while avoiding the tedious gradient washout process for the removal of CPA afterward. The result is remarkable, since Zn(II) does not have the ice-controlling ability reported to be critical for CPA. It benefits from its moderate interaction with lipid molecules, facilitating the formation of small and dynamic lipid clusters. Consequently, the membrane fluidity is maintained, and the cells are resilient to osmotic and mechanical stresses during cryopreservation. This study first reports the ion-specific effect on stabilizing the cell membrane; meanwhile, reversibly tuning the structure of biological samples against injuries during the cooling and rewarming provides a new strategy for cryopreservation.


Waist-to-height ratio and cardiovascular risk factors among Chinese adults in Beijing.
To examine whether waist-to-height ratio (WHtR) performed better than, body mass index (BMI) or waist circumference (WC) in relation to hypertension, diabetes, and dyslipidemia among Chinese adults in Beijing. A total of 5720 adults (2371 men and 3349 nonpregnant women) aged 18 to 79 years were selected from the general population in a cross-sectional study. Data from a standardized questionnaire, physical examination, and blood sample were obtained. The area under curve (AUC) values for WHtR (0.661-0.773) were significantly higher than those for BMI for all outcomes in both sexes, except that WHtR and BMI had similar AUCs for dyslipidemia in men. The AUCs for WHtR were significantly higher than those for WC with respect to hypertension in both sexes, and to diabetes in women. AUCs for the relationships between anthropometric indices and the three outcomes were larger in women than in men, and tended to decrease with age. Optimal cutoffs for WHtR were 0.51-0.53 and 0.48-0.50 in men and women, respectively. With regard to the current Chinese criteria for BMI (≥ 24 kg/m(2)), WC (≥ 90 cm for men, and ≥ 85 cm for women), and the recommended cutoff of WHtR (≥ 0.5), WHtR yielded the greatest odds ratio for hypertension and diabetes in both sexes, and dyslipidemia in women. BMI had the highest odds ratio for dyslipidemia in men. The odds ratios of anthropometric indices for hypertension and diabetes, but not for dyslipidemia, were higher in women than in men. The association between anthropometric indices and the three outcomes decreased with age. WHtR performed better than BMI and WC for the association with hypertension and diabetes. More studies should be conducted to explore the age differences in the relationships between obesity indices and cardiovascular risk factors.


Ezetimibe for lowering blood cholesterol.
Ezetimibe is the first drug in a new class called cholesterol absorption inhibitors. There is no evidence that ezetimibe will reduce rates of death or hospitalization. When it is taken alone or when it is added to existing statin therapy, ezetimibe can reduce serum cholesterol in patients who have an increased risk of future coronary artery disease. The safety and tolerability of ezetimibe alone or combined with a statin has not been established in trials beyond 12 weeks.


Wound Myiasis Caused by Sarcophaga (Liopygia) Argyrostoma (Robineau-Desvoidy) (Diptera: Sarcophagidae): Additional Evidences of the Morphological Identification Dilemma and Molecular Investigation.
In Mediterranean countries, Sarcophaga (Liopygia) crassipalpis, Sarcophaga (L.) argyrostoma, and Sarcophaga (L.) cultellata share the same ecological niche and can be responsible of myiasis. In this study, the main morphological characters of a larva found in a hospitalized woman were described and illustrated by light and SEM microscopy and the features discussed. Then, a fragment within the mitochondrial encoded cytochrome c oxidase subunit I (coxI) gene of ~735 bp was amplified and sequenced. The molecular investigation was necessary to confirm the species Sarcophaga (Liopygia) argyrostoma (99% of identity). Our findings showed that morphological descriptions of larvae of three Mediterranean species of Liopygia available in several papers might not be clear enough to allow for comparison and correct identification. Until results of reliable comparative studies of larvae of all three species will be available, the use of molecular tools is crucial, to avoid misleading or incomplete identification, and in particular when a myiasis becomes a legal issue.


The impact of the teachers' non-verbal communication on success in teaching.
Non-verbal communication skills, also called sign language or silent language, include all behaviors performed in the presence of others or perceived either consciously or unconsciously. The main aim of this review article was to determine the effect of the teachers' non-verbal communication on success in teaching using the findings of the studies conducted on the relationship between quality of teaching and the teachers' use of non-verbal communication and also its impact on success in teaching. Considering the research method, i.e. a review article, we searched for all articles in this field using key words such as success in teaching, verbal communication and non-verbal communication. In this study, we did not encode the articles. The results of this revealed that there was a strong relationship among the quality, amount and the method of using non-verbal communication by teachers while teaching. Based on the findings of the studies reviewed, it was found that the more the teachers used verbal and non-verbal communication, the more efficacious their education and the students' academic progress were. Under non-verbal communication, some other patterns were used. For example, emotive, team work, supportive, imaginative, purposive, and balanced communication using speech, body, and pictures all have been effective in students' learning and academic success. The teachers' attention to the students' non-verbal reactions and arranging the syllabus considering the students' mood and readiness have been emphasized in the studies reviewed. It was concluded that if this skill is practiced by teachers, it will have a positive and profound effect on the students' mood. Non-verbal communication is highly reliable in the communication process, so if the recipient of a message is between two contradictory verbal and nonverbal messages, logic dictates that we push him toward the non-verbal message and ask him to pay more attention to non-verbal than verbal messages because non-verbal cues frequently reveal the intention of the sender of the information and reflect his/her emotional reactions. Based on the obtained results of this study, it is recommended that attention to non-verbal communication skills can make a positive change in the future of a student's life. It seems necessary for the teachers to practice and learn effective communication skills, especially for those who always interact with a large group of students. One of the factors contributing to the success or failure of students is the quality of the relationship and how the teacher builds this relationship with students. Especially, it is more effective for students who are more responsive to human relations and communication skills. Finally, it is recommended that the teachers should improve their communication skills to have better communication with their audience. The authorities are recommended to help improve the teachers' level of communication skills through holding training courses.


Cost-of-illness study for axillary hyperhidrosis in Japan.
The prevalence of primary axillary hyperhidrosis in Japan is 5.75% (males, 6.60%; females, 4.72%) in the population aged 5-64 years. No study on comprehensively evaluated direct medical costs, hygiene product costs, and productivity loss in axillary hyperhidrosis patients has been published in Japan. The aim of this study was to estimate the cost of illness for axillary hyperhidrosis in Japan by conducting a nationwide insurance claims database analysis and a cross-sectional Web-based survey. Among patients diagnosed with primary axillary hyperhidrosis at least once between November 2012 and October 2019, health insurance receipt data of 1447 patients were analyzed. A cross-sectional Web-based survey was conducted on 321 patients aged 16-59 years with axillary hyperhidrosis to calculate hygiene product costs and productivity loss using a Work Productivity and Activity Impairment questionnaire. Furthermore, nationwide estimation was performed for the hygiene product costs and productivity loss based on the number of patients estimated from the prevalence. The annual direct medical costs per axillary hyperhidrosis patient were ¥91 491 in 2016, ¥93 155 in 2017, and ¥75 036 in 2018. In all of these years, botulinum toxin type A injection accounted for approximately 90% of the total costs. The annual total cost of hygiene products per axillary hyperhidrosis patient was ¥9325. The overall work impairment (%) of working patients with axillary hyperhidrosis was 30.52%, and its monthly productivity loss was ¥120 593/patient. The activity impairment (%) of full-time housewives with axillary hyperhidrosis was 49.05% and its monthly productivity loss was ¥176 368/patient. The annual hygiene product cost based on the nationwide estimation was ¥24.5 billion and the monthly productivity loss was ¥312 billion. The significant cost associated with axillary hyperhidrosis was clarified. If out-of-pocket expenses for treatments not covered by health insurance are included in the estimation, the cost will further increase.


Feasibility, and validity aspects of Entrustable Professional Activity (EPA)-based assessment in general practice training.
Entrustable Professional Activities (EPAs) are developed to support the practical application of competency frameworks in postgraduate medical education (PGME) programmes. EPAs are used for the assessment of the trainees' competence development, which takes place by means of an entrustment decision, aiming to stimulate learning and independent practice in trainees. In this pilot study, we explore the feasibility and validity of EPA-based assessment in a General Practice (GP) training programme. We used questionnaires to evaluate trainers' and trainees' experiences with the use of six EPAs for trainee learning, assessment and independent practice at the Out-of-Hours GP Center. Data were analysed quantitatively and qualitatively. Additionally, we examined the inter-item correlation between scores on EPA-based assessment and competency-based assessment using Spearman's Rho. EPA-based assessment provided opportunities for giving concrete feedback and substantiating competency-based assessment. No consistent correlation between EPA-based assessment and competency-based assessment could be detected. Only later in the course of the training programme a correlation was found between the EPA scores and the degree of independence of trainees. Results of this pilot study confirm the theories behind EPAs, as well as earlier research on EPAs in the workplace regarding trainee learning, assessment and independent practice. An important limitation of this study was the COVID-19 pandemic, as it influenced the results through reduced inclusion and follow-up, and through the impact on the workplace and trainee learning possibilities. Further research is needed to determine how EPAs support independent practice of trainees, as well as the assessment of trainee competency development.


Internal carotid artery flow arrest/reversal cerebral protection techniques.
We report on the progress of an ongoing prospective non-randomized trial evaluating carotid artery stenting (CAS) with adjuvant cerebral protection in patients who are considered high risk for surgery. The 62 patients (34M/28F) in this study underwent CAS with interruption or reversal of flow in the internal carotid artery to protect the brain from embolization of particulate debris that may otherwise egress to the brain resulting in a stroke. Twenty-seven patients (44%) had restenotic lesions after remote carotid endarterectomy and 11 (18%) had previous radical neck surgery with external beam radiation therapy for cancer. The average length of hospital stay was 1.3 +/- 0.7 days. There were no strokes or transient ischemic attacks during the procedure or follow-up. Intolerance to ICA flow arrest or reversal was noted in five patients, but the procedures were completed in stages without sequella. No significant change in NIH scale was reported based on independent neurology evaluation when baseline average scores (0.72 +/- 1.1) were compared to follow-up at 30 days (0.50 +/- .05) P > 0.05. The positive outcome in this small study suggests that CAS may be a safe alternative to CEA in high-risk patients.


Anticoagulant efficacy of solid oral formulations containing a new heparin derivative.
The need for an efficacious and safe oral anticoagulant that does not require monitoring has been largely unmet. Many efforts have centered on preparing orally available heparin to improve patient compliance. In this study, novel orally active heparin derivatives (LHD), i.e. low molecular weight heparin (LMWH) conjugated with deoxycholic acid (DOCA), were evaluated in vitro and in vivo for their enhancement effect of oral heparin absorption. After oral administration of 10 mg/kg of water-soluble LHD, Ws-LHD1.5 showed optimum oral efficacy and its bioavailability was about 24% in rats. The oral absorption of LHD1.5 was also enhanced by several solubilizers, among which Poloxamer 407 provided the best results. When 5 mg/kg of LHD1.5 with Poloxamer 407 was orally administered to monkeys, the maximum anti-FXa activity in plasma was 0.26 +/- 0.04 IU/mL and its bioavailability was 17.4%. In a rat thrombosis model, 5 mg/kg of orally administered LHD1.5 formulated with Poloxamer reduced thrombus formation by 63.9 +/- 16.6%, which was higher than the efficacy of clinically used enoxaparin (49.4 +/- 17.8% at 100 IU/kg, sc). Considering the oral absorption efficacy and therapeutic effect, the conjugation ratio was optimized as about 1.5 molecules of DOCA per mole of heparin. Therefore, LHD1.5 with Poloxamer 407 can be further formulated as a solid oral anticoagulant drug.


Acquired factor VIII inhibitor associated with chronic interferon-alpha therapy in a patient with haemophilia A.
Both the development of factor VIII inhibitors and infection by hepatitis C virus are serious complications of haemophilia A. We describe the first reported case of the subsequent development of a factor VIII inhibitor in a patient with haemophilia A after treatment with interferon-alpha for chronic active hepatitis C.


The long-wavelength chlorophyll states of plant LHCI at room temperature: a comparison with PSI-LHCI.
The red antenna states of the external antenna complexes of higher plant photosystem I, known as LHCI, have been analyzed by measurement of their preequilibrium fluorescence upon direct excitation at 280 K. In addition to the previously detected F735 state, a hitherto undetected low-energy state with emission maximum around 713 nm was observed. The 280 K bandwidths (FWHM) are 55 nm for the F735 state and approximately 27 nm for the F713-nm state, much greater than for non-red-shifted antenna chlorophylls. The origin absorption band for the F735-nm state was directly detected by determination of its excitation (action) spectrum and lies at 709-710 nm. The absorption spectrum for F735, calculated using the Stepanov expression, closely overlaps the excitation spectrum, indicating that the very large Stokes shift (25 nm) is due to vibrational relaxation within the excited-state manifold and solvent effects can be excluded. Fluorescence anisotropy measurements, with direct excitation of F735, indicate that the transition dipoles of the two red states are parallel. Similar experiments performed in the long-wavelength absorbing tail of PSI-LHCI indicate the presence of emission state(s) that are red-shifted with respect to F735 of isolated LHCI. It is suggested that these are brought about by interactions between the complexes in PSI-LHCI, which occur in some yet undefined way, and which are broken upon solubilization of the component parts.


Developmental differences in praxis in learning-disabled and normal children and adults.
Gestures made on tasks in response to verbal command or to imitation and on tasks involving axial and distal movements were compared for groups of learning-disabled and normal children and adults. The 15 learning-disabled children and 15 adults scored lower than the 15 normal children and 15 adults on all tasks. All groups scored higher on imitation than on verbal command and scored similarly on the axial and distal tasks. The findings from this study suggest that it would be worthwhile to test the hypothesis that dyspraxic behaviors may persist into adulthood.


Age differences in the neural representation of working memory revealed by multi-voxel pattern analysis.
Working memory function declines across the lifespan. Computational models of aging attribute such memory impairments to reduced distinctiveness between neural representations of different mental states in old age, a phenomenon termed dedifferentiation. These models predict that neural distinctiveness should be reduced uniformly across experimental conditions in older adults. In contrast, the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH) model predicts that the distinctiveness of neural representations should be increased in older adults (relative to young adults) at low levels of task demand but reduced at high levels of demand. The present study used multi-voxel pattern analysis to measure the effects of age and task demands on the distinctiveness of the neural representations of verbal and visuospatial working memory. Neural distinctiveness was estimated separately for memory encoding, maintenance, and retrieval, and for low, medium, and high memory loads. Results from sensory cortex during encoding and retrieval were consistent with the dedifferentiation hypothesis: distinctiveness of visual cortical representations during these phases was uniformly reduced in older adults, irrespective of memory load. However, maintenance-related responses in prefrontal and parietal regions yielded a strikingly different pattern of results. At low loads, older adults showed higher distinctiveness than younger adults; at high loads, this pattern reversed, such that distinctiveness was higher in young adults. This interaction between age group and memory load is at odds with the dedifferentiation hypothesis but consistent with CRUNCH. In sum, our results provide partial support for both dedifferentiation- and compensation-based models; we argue that comprehensive theories of cognitive aging must incorporate aspects of both models to fully explain complex patterns of age-related neuro-cognitive change.


MAS C-Terminal Tail Interacting Proteins Identified by Mass Spectrometry- Based Proteomic Approach.
Propagation of signals from G protein-coupled receptors (GPCRs) in cells is primarily mediated by protein-protein interactions. MAS is a GPCR that was initially discovered as an oncogene and is now known to play an important role in cardiovascular physiology. Current literature suggests that MAS interacts with common heterotrimeric G-proteins, but MAS interaction with proteins which might mediate G protein-independent or atypical signaling is unknown. In this study we hypothesized that MAS C-terminal tail (Ct) is a major determinant of receptor-scaffold protein interactions mediating MAS signaling. Mass-spectrometry based proteomic analysis was used to comprehensively identify the proteins that interact with MAS Ct comprising the PDZ-binding motif (PDZ-BM). We identified both PDZ and non-PDZ proteins from human embryonic kidney cell line, mouse atrial cardiomyocyte cell line and human heart tissue to interact specifically with MAS Ct. For the first time our study provides a panel of PDZ and other proteins that potentially interact with MAS with high significance. A 'cardiac-specific finger print' of MAS interacting PDZ proteins was identified which includes DLG1, MAGI1 and SNTA. Cell based experiments with wild-type and mutant MAS lacking the PDZ-BM validated MAS interaction with PDZ proteins DLG1 and TJP2. Bioinformatics analysis suggested well-known multi-protein scaffold complexes involved in nitric oxide signaling (NOS), cell-cell signaling of neuromuscular junctions, synapses and epithelial cells. Majority of these protein hits were predicted to be part of disease categories comprising cancers and malignant tumors. We propose a 'MAS-signalosome' model to stimulate further research in understanding the molecular mechanism of MAS function. Identifying hierarchy of interactions of 'signalosome' components with MAS will be a necessary step in future to fully understand the physiological and pathological functions of this enigmatic receptor.


Long-chain base kinase Lcb4 Is anchored to the membrane through its palmitoylation by Akr1.
Sphingoid long-chain base kinase Lcb4 catalyzes the production of the bioactive lipid molecules the long-chain base 1-phosphates. Although Lcb4 has no apparent transmembrane-spanning domain, it is tightly associated with the membrane. Here, we demonstrate that Lcb4 is modified by palmitoylation. This modification was greatly reduced in mutants for AKR1, which was recently identified as encoding a protein acyltransferase. In vitro experiments revealed that Akr1 indeed acts as a protein acyltransferase for Lcb4. Studies using site-directed mutagenesis indicated that Cys-43 and Cys-46 are palmitoylated. The loss of palmitoylation on Lcb4 caused several effects, including mislocalization of the protein to the cytosol, reduced phosphorylation, and loss of downregulation during the stationary phase. Although Akr2 is highly homologous to Akr1, the deletion of AKR2 did not result in any remarkable phenotypes. However, overproduction of Akr2 resulted in reduced amounts of Lcb4. We demonstrated that Akr2 is an unstable protein and is degraded in the vacuole. Akr2 exhibits high affinity for Lcb4, and in Akr2-overproducing cells this interaction caused unusual delivery of Lcb4 to the vacuole and degradation.


[Recurrent spontaneous regression of aleukemic leukemia cutis in a girl with acute monocytic leukemia].
Aleukemic leukemia cutis is a rare form of leukemia manifestation, defined as a skin infiltration of leukemic cells with no evidence of leukemia in the bone marrow. A 4-month-old girl was referred to our hospital because of exanthema that appeared and regressed repeatedly. Histological examination revealed partial infiltration of histiocytic cells in the skin lesion. However, the diagnosis could not be made at that time. At 9 and at 13 months old, appearances of exanthema similar to the previous time were combined with systemic fever, abnormal coagulation tests, and the marked increases of atypical lymphocytes in peripheral blood: however, these symptoms resolved spontaneously. At 14 months old, deterioration of the exanthema and an increase in the peripheral leukocyte counts were observed. Bone marrow aspiration revealed the predominance of monocytic blasts (76.4%), and the patient was diagnosed as having acute monocytic leukemia (M5b) with leukemia cutis. Complete remission was obtained with standard chemotherapy. Six months after the therapy was completed, an extramedullary relapse occurred in the inguinal lymph nodes, which was successfully treated with allogeneic bone marrow transplantation from an HLA-matched unrelated donor, and the patient has been free of disease for two years after the transplantation.


[The state and perspective in bone regeneration].
Treatments for locomotive organs, such as bone and joint, have been investigated and preceded in recent decades. Especially, in orthopaedic field, therapeutic alternatives for total joint arthroplasty for osteoarthritis and spinal fusion have remarkably advanced. However, bone regeneration required in massive bone defect or broad spinal fusion have been treated with bone graft mainly using auto grafted bone here in Japan. These methods have several issues such as limited bone regeneration or pain in harvest sites. We would like to describe perspectives and biology in bone regeneration focusing on bone morphogenetic protein (BMP).


Carcinoma of the uterine cervix. High-resolution turbo spin-echo MR imaging with contrast-enhanced dynamic scanning and T2-weighting.
To compare high-resolution contrast-enhanced (Gd-DTPA) dynamic MR imaging with T2-weighted turbo spin-echo (TSE) imaging in the evaluation of uterine cervical carcinoma. Thirty-two patients with cervical carcinoma underwent MR imaging on a 1.5 T superconductive unit to have the extension of the disease assessed before treatment. A phased-array coil was used in all patients. In 25 patients, surgical confirmation of the diagnosis was obtained after imaging. Radiation therapy was selected for the remaining 7 patients with advanced carcinoma. Qualitative and quantitative image analyses were also performed. The cervical carcinomas showed maximum contrast in the cervical stroma and myometrium in the early dynamic phase. The tumor/cervical-stroma contrast in the early dynamic phase obtained with the T1-weighted TSE technique (contrast-to-noise ratio 22.6) was significantly higher than that obtained in T2-weighted TSE imaging (contrast-to-noise ratio 4.3). In the evaluation of parametrial invasion, the accuracy of T2-weighted imaging was 71.8% and contrast-enhanced dynamic imaging 81.2%. High-resolution contrast-enhanced (Gd-DTPA) dynamic MR imaging in cervical cancer offers improved tumor/cervical-stroma contrast and provides useful information on parametrial invasion.


Meanings of the phenomenon of fatigue as narrated by 4 patients with cancer in palliative care.
The disabling experience of fatigue suffered in connection with incurable cancer is an area within nursing that has generated only limited research interest. The need for a change in focus is presented in the literature: from treating the symptom itself to facilitating living with the fatigue caused by a life-threatening disease. This implies that helping to alleviate fatigue must start from the patients' own understanding and interpretation of this experience. Our study attempts to achieve this understanding through illuminating the meanings of fatigue as experienced by 4 patients with cancer in palliative care. The research interviews were analyzed using a phenomenological-hermeneutic approach inspired by the philosophy of Ricoeur. Our findings indicate a world in which one meaning of fatigue connected with incurable cancer is a lived bodily experience of approaching death. Comprehending fatigue in this way allows us to understand the paradoxes we found in the text, such as struggling in vain against fatigue, and hoping to overcome fatigue but expecting failure. The paradoxes represent a struggle between body and mind, between bodily experiences and intellectual understanding, and have important implications for how we communicate with patients about fatigue.


Phosphinidene-Bridged MoMn Derivatives of the Thiophosphinidene Complex [Mo2Cp2(μ-κ2:κ1,η6-SPMes*)(CO)2] (Mes* = 2,4,6-C6H2tBu3).
The title complex (1) reacted with [Mn2(CO)10] under visible-UV irradiation (toluene solution and quartz glassware) to give a mixture of the phosphinidene complex [MnMoCp(μ-κ1:κ1,η6-PMes*)(CO)4], the cluster [Mn2Mo2Cp2(μ-κ1:κ1,η6-PMes*)(μ3-S)(CO)8], and the thiophosphinidene complex [MnMoCp(μ-κ2:κ1,η4-SPMes*)(CO)5], in yields of ca. 60, 20, and 10% respectively (Mes* = 2,4,6-C6H2tBu3). The major product follows from formal replacement of the SMoCp(CO)2 fragment in 1 with a Mn(CO)4 fragment, and displayed multiple bonding to phosphorus (Mn-P = 2.1414(8) Å); the tetranuclear cluster results from formal insertion of a Mn2(CO)6 fragment in 1, with cleavage of P-S and P-Mo bonds, to render a μ3-S bridged Mn2Mo core bearing an exocyclic phosphinidene ligand involved in multiple bonding to one of the Mn atoms (Mn-P = 2.140(2) Å); the thiophosphinidene complex (Mn-P = 2.294(1) Å) formally results from addition of sulfur and carbon monoxide to the major MnMo product, a transformation which actually could be performed stepwise, via the MnMo thiophosphinidene complex [MnMoCp(μ-κ2:κ1,η6-SPMes*)(CO)4]. When the photolysis of 1 and [Mn2(CO)10] was performed in tetrahydrofuran solution and using conventional glassware, then the V-shaped cluster [Mn2MoCp{μ-κ1:κ1:κ1,η5-P(C6H3tBu3)}(CO)8] was obtained selectively (Mo-Mn = 3.2910(5) Å, Mn-Mn = 2.9223(5) Å), which unexpectedly displays a cyclohexadienylidene-phosphinidene ligand resulting from H atom abstraction at the aryl ring of the precursor. Density functional theory calculations on the complexes [LnM(μ-κ1:κ1,η6-PMes*)MoCp] (MLn = MoCp(CO)2, Mn(CO)4, Co(CO)3) revealed that the degree of delocalization of the metal-phosphorus π-bonding interaction over the Mo-P-M chain is significantly conditioned by the heterometal fragment MLn, it being increased in the order Mn ≤ Mo < Co.


Early development of eye and retina in lanternfish larvae.
The morphological characteristics of the eyes and the retinae of lanternfish larvae of Lampanyctus crocodilus, Benthosema glaciale, and Myctophum punctatum were analyzed in pre-flexion, flexion, and post-flexion stages. Pre-flexion larvae of L. crocodilus, the species with the shallowest depth distribution, had spherical eyes located antero-laterally on a strongly laterally-compressed head, suggesting a forward binocular visual field. B. glaciale and M. punctatum larvae live deeper in the water column and had eyes elongated in the dorsal-ventral plane. The eyes of B. glaciale were prominent, projecting slightly outward from a laterally-compressed head, suggesting a strongly laterally-directed visual field. M. punctaum had stalked elongated eyes projecting from a dorso-ventrally flattened head. The eyes can be freely rotated allowing lateral, anterior and dorsally-directed vision. A prominent choroidal gland was situated beneath the ventral portion of the eye in M. punctatum and B. glaciale, while a smaller gland was present in the dorsal and ventral portions of the eye of L. crocodilus. In pre-flexion stage larvae, the retina of all three species was differentiated with numerous rod photoreceptors in the peripheral retinal areas and fewer cone photoreceptors mainly distributed in the central retina. This distribution suggests concomitant enhancement of scotopic sensitivity in the vertical visual plane and improved photopic acuity in the lateral and forward visual directions. The concurrent development of cones and rods, as observed in the pre-flexion stage of myctophid larvae, is consistent with meeting the special demands of visual planktivory in sub-surface waters. During larval development a gradual increase of ROS length was also accompanied by a progressive loss of cones that were almost totally absent in post-flexion larvae. This can be interpreted as an adaptive response to an impending deep mesopelagic adult life.


A novel approach for quantitative determination of cellulose content in tobacco via 2D HSQC NMR spectroscopy.
Cellulose is an important component of tobacco (Nicotiana tabacum L.) cell walls, which can be precursors for many harmful compounds in smoke. Traditional cellulose content analysis methods involve sequential extraction and separation steps, which are time-consuming and environmentally unfriendly. In this study, a novel method was first introduced to analyze cellulose content in tobacco via two-dimensional heteronuclear single quantum coherence (2D HSQC) NMR spectroscopy. The method was based on derivatization approach to allow the dissolution of insoluble polysaccharide fractions of tobacco cell walls in DMSO‑d6/pyridine-d5 (4:1 v/v) for NMR analysis. The NMR results suggested that besides the main NMR signals of cellulose, partial signals of hemicellulose including mannopyranose, arabinofuranose, and galactopyranose units could also be identified. In addition, the utilization of relaxation reagents has proved to be an effective way to improve the sensitivity of 2D NMR spectroscopy, which was beneficial for quantification of biological samples with limited quantities. To overcome the limitations of quantification using 2D NMR, the calibration curve of cellulose with 1,3,5-trimethoxybenzene as internal reference was constructed and thus the accurate measurement of cellulose in tobacco was achieved. Compared with the chemical method, the interesting method was simple, reliable, and environmentally friendly, which provided a new insight for quantitative determination and structure analysis of plant macromolecules in complex samples.


[Use of Nobuto's method for controlling the immune titer of poultry against Newcastle disease].
The use of Nobuto 's method for blood sampling with birds and mammals, using filter paper, suggests various advantages in the practice of serologic investigations. Studies were carried out to determine the immune titer of birds against Newcastle disease. Parallel blood samples were taken routinely and after the method of Nobuto with filter paper. Serologic examination was performed through the hemagglutination-inhibition test, beta procedure, with 10 HAU /0.5 cm3. As many as five parallel experiments with blood samples from birds were conducted within the period of from the 15th to the 40th day following vaccination. The results of HI-tests on filter paper, variants a and b, proved mathematically reliable, coinciding with the HI results with the samples studied with sera (P = 0.05). Further studies of blood samples from birds after the HI, beta micromethod, are currently carried out.


Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis.
Accelerated arteriosclerosis has emerged as a major life-threatening complication in long-term survivors of heart transplantation. It has been proposed that accelerated arteriosclerosis is an immune-mediated complication of rejection. We observed a striking endothelialitis in the coronary arteries of two explanted hearts obtained from patients with severe transplant-related accelerated arteriosclerosis. This finding prompted us to review the pathologic changes in the coronary arteries of 23 autopsied patients who had received heart transplants. The infiltrate in these vessels was characterized using immunohistochemical stains for lymphocytes (CD45), macrophages (MAC-387), T lymphocytes (CD45RO), B lymphocytes (L-26), and smooth muscle cells (actin). In addition, a full panel of monoclonal antibodies was used on the fresh-frozen tissue available from one of the two explanted hearts. Ten of the eleven recipients with accelerated arteriosclerosis had a moderate to marked lymphocytic endothelialitis compared to 3 of 14 without transplant-related arteriosclerosis (P less than 0.005). Immunohistochemical staining of the paraffin-embedded material demonstrated that most of the lymphocytes in the subendothelial space of these vessels were T lymphocytes and that this infiltrate was associated with an accumulation of macrophages and a proliferation of smooth muscle cells in the intima. In the explanted heart from which fresh-frozen tissue was available for more detailed cell typing, the T cells marked predominantly as cytotoxic T lymphocytes (CD8+, CD2+). These results suggest that accelerated arteriosclerosis may be mediated, in part, by a cytotoxic T-lymphocyte-directed endothelialitis.


Therapeutic Activity of Green Tea Epigallocatechin-3-Gallate on Metabolic Diseases and Non-Alcoholic Fatty Liver Diseases: The Current Updates.
Green tea polyphenols have numerous functions including antioxidation and modulation of various cellular proteins and are thus beneficial against metabolic diseases including obesity, type 2 diabetes, cardiovascular and non-alcoholic fatty liver diseases, and their comorbidities. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea and is attributed to antioxidant and free radical scavenging activities, and the likelihood of targeting multiple metabolic pathways. It has been shown to exhibit anti-obesity, anti-inflammatory, anti-diabetic, anti-arteriosclerotic, and weight-reducing effects in humans. Worldwide, the incidences of metabolic diseases have been escalating across all age groups in modern society. Therefore, EGCG is being increasingly investigated to address the problems. This review presents the current updates on the effects of EGCG on metabolic diseases, and highlights evidence related to its safety. Collectively, this review brings more evidence for therapeutic application and further studies on EGCG and its derivatives to alleviate metabolic diseases and non-alcoholic fatty liver diseases.


Enhanced Adsorption of a Protein-Nanocarrier Complex onto Cell Membranes through a High Freeze Concentration by a Polyampholyte Cryoprotectant.
The transportation of biomolecules into cells is of great importance in tissue engineering and as stimulation for antitumor immune cells. Previous freezing strategies at ultracold temperatures (-80 °C) used for intracellular transportation exhibit certain limitations such as extended time requirements and harsh delivery system conditions. Thus, the need remains to develop simplified methods for safe nanomaterial delivery. Here, we demonstrated a unique strategy based on the ice-crystallization-induced freeze concentration for protein intracellular delivery in combination with a polyampholyte cryoprotectant. We found that upon sustained lowering of the temperature from -6 to -20 °C over a short duration, the adsorption of proteins onto the peripheral cell membrane was markedly increased through the facile ice-crystallization-induced freeze concentration. Furthermore, we proposed a freeze concentration factor (α) that depends on the freezing-point depression and is estimated from an analysis of the fraction of frozen water. Notably, the α values of the polyampholyte cryoprotectant were 8-fold higher than those of the currently used cryoprotectant dimethyl sulfoxide (DMSO) at particular temperatures of interest. Our results illustrate that the presence of a polyampholyte cryoprotectant significantly enhanced the adsorption of the protein/nanocarrier complex onto membranes compared to that obtained with DMSO because of the high freeze concentration. The present study demonstrated the direct relationship between freezing and the penetration of proteins across the periphery of the cell membrane by means of increased concentration during freezing. These results may be useful in providing a guideline for the intracellular delivery of biomacromolecules using ice-crystallization-induced continuous freezing combined with polyampholyte cryoprotectants.


Combination of preoperative tumour markers and lymphovascular invasion with TNM staging as a cost and labour efficient subtyping of colorectal cancer.
Tumour-Node-Metastasis (TNM) staging of colorectal cancer (CRC) needs further classification for better treatment because of disease heterogeneity. Although molecular classifications which are expensive and laborious are under study, cost and labour efficient subtyping is desirable. We assessed the combinations of preoperative tumour marker (TM) elevation and tumour lymphovascular invasion (LVI) as a solution. We used the pooled data of 7151 colon cancer (CC) patients and 4620 rectal cancer (RC) patients who received curative surgery between 2004 and 2008 in Japan. The best-matched subtyping for predicting relapse-free survival (RFS) was statistically selected using the c-index and Akaike's information criterion. This subtyping (TM-LVI), which consisted of three categories by TM elevation status and severity of LVI status, was an independent prognostic factor for RFS of CC (stage IIa, IIIb, and IIIc) and RC (stage I, IIa, IIb, IIIa, and IIIb) and also for disease specific survival of CC (stage IIa, IIb, IIIb, and IIIc) and RC (all stage except for IIc). Although TM-LVI classified CRC patients into low and high recurrence risk groups, the application of adjuvant therapy was not accordance with the TM-LVI status. TM-LVI may be a cost and labour efficient subtyping of colorectal cancer for better treatment strategy.


Text Messaging as an Adjunct to CBT in Low-Income Populations: A Usability and Feasibility Pilot Study.
This article outlines the development and usability-feasibility testing of an automated text-messaging adjunct to cognitive- behavioral therapy (CBT) for depression in a public sector clinic serving low-income patients. The text-messaging adjunct is aimed at increasing homework adherence, improving self-awareness, and helping track patient progress. Daily text messages were sent to patients, inquiring about their mood. Additional daily messages corresponded to themes of a manualized group CBT intervention. These included (1) thought tracking (both positive and negative), (2) tracking of pleasant activities, (3) tracking of positive and negative contacts, and (4) tracking of physical well-being. We tested the adjunct in 2 CBT groups (1 English & 1 Spanish) consisting of 12 patients total during and after treatment. Participants responded at a rate of 65% to text messages, and they reported overall positive experiences. We propose that text messaging has the potential to improve mental health care broadly, and among low-income populations specifically, with cost-effective means.


Metal-organic framework derived magnetic nanoporous carbon: novel adsorbent for magnetic solid-phase extraction.
The fabrication of a magnetic nanoporous carbon (MNPC) via one-step direct carbonization of Co-based metal-organic framework has been achieved without using any additional carbon precursors. The morphology, structure, and magnetic behavior of the as-prepared Co-MNPC were characterized by using the techniques of scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, Raman spectroscopy, N2 adsorption, and vibrating sample magnetometer. The Co-MNPC has a high specific surface area, large pore volume, and super paramagnetism. Its performance was evaluated by the magnetic solid-phase extraction of some neonicotinoid insecticides from water and fatmelon samples followed by high-performance liquid chromatographic analysis. The effects of the main experimental parameters that could affect the extraction efficiencies were investigated. The results demonstrated that the Co-MNPC had an excellent adsorption capability for the compounds.


The minimal genome paradox.
The concept of a 'minimal genome' has appeared as an attempt to answer the question what the minimum number of genes or minimum amount of DNA to support life is. Since bacteria are cells bearing the smallest genomes, it has been generally accepted that the minimal genome must belong to a bacterial species. Currently the most popular chromosome in studies on a minimal genome belongs to Mycoplasma genitalium, a parasite bacterium whose total genetic material is as small as approximately 580 kb. However, the problem is how we define life, and thus also a minimal genome. M. genitalium is a parasite and requires substances provided by its host. Therefore, if a genome of a parasite can be considered as a minimal genome, why not to consider genomes of bacteriophages? Going further, bacterial plasmids could be considered as minimal genomes. The smallest known DNA region playing the function of the origin of replication, which is sufficient for plasmid survival in natural habitats, is as short as 32 base pairs. However, such a small DNA molecule could not form a circular form and be replicated by cellular enzymes. These facts may lead to an ostensibly paradoxical conclusion that the size of a minimal genome is restricted by the physical size of a DNA molecule able to replicate rather, than by the amount of genetic information.


Children's understanding of their emotionally disturbed peers: a replication.
Despite increasing recognition of the early importance of peer relations, virtually no systematic information exists on the way in which normal children view their emotionally disturbed peers. This paper reports a replication of recent findings on children's use of the concept of emotional disturbance. Ss were 40 fourth and sixth graders. Five vignettes that described one normal and four emotionally disturbed boys were read to individual Ss; who were interviewed about their understanding of the central figures (CFs). Interviews were coded to a 5-point scale of degree of perceived emotional disturbance. Earlier findings were replicated to a remarkable degree. Ss differentiated among the CFs in a manner congruent with clinician judges' ratings. Grade differences indicate the differential attention to and valuing of specific behaviors, rather than global differences in perception of emotional disturbance.


[Influence of nutritional status on the effectiveness of a dietary supplement of live lactobacillus to prevent and cure diarrhoea in children].
The influence of undernutrition on the effectiveness of a dietary supplement of live lactobacillus regarding prevention and treatment of infantile diarrhoea was studied on 200 children 6 to 24m old. Children, undernourished (D) or controls (C), received for 90 days, in a blind experiment, a fermented milk providing L. Acidofilus y L. Casei (10(7)-10(8)/ml) (LB) or an equivalent amount of fluid milk (L). diarrhoea episodes were recorded and classified according duration: 1-4, 5-14 days, and protracted diarrhea (DP) those lasting beyond 14 days. Study requirements were fulfilled by 119 children: D-L: n=25; D-LB: n=32; C-L: n=27 y C-LB: n=35. Preventive aspects were evaluated through number of episodes and through their lasting the therapeutic ones. Episodes recorded were 134: 29 in D-L; 48 in D-LB; 37 in C-L and 20 in C-LB. In the D-LB group over 90% episodes were very short (1-4 days), percentage far higher to that observed in D-L and similar to C-LB. There were 12 episodes of DP, 9 D and 3 in C, all in the L groups. In conclusion, although the fermented milk prevent half episode in the controls but not in the undernourished, it was able to shorter episodes duration and prevent protracted diarrhoea irrespectively of nutritional status. Therefore, undernutrition impaired the ability of the lactobacillus supplement to prevent children diarrhoea, which implicates immune system, but not curative effects which are the result of local actions.


The validity of broadly defined hysteria and DSM-III conversion disorder: outcome, family history, and mortality.
Patients who fail to meet criteria for Briquet's syndrome (or somatization disorder) despite a chart diagnosis of hysteria have been shown previously to resemble patients with primary depression in terms of familial psychopathology. The same patients are shown here to have excess mortality which also resembles that seen in patients with primary depression. The isolation of patients meeting DSM-III criteria for conversion disorder yielded very similar results. Outcome and mortality data clearly separated conversion disorder from Briquet's syndrome patients; family history data suggested substantial diagnostic heterogeneity. Until the validity of this diagnosis is established, the label "conversion disorder" is recommended as a descriptive alternative to the label "undiagnosed."


Host-parasite interaction and microbiome response: effects of fungal infections on the bacterial community of the Alpine lichen Solorina crocea.
The lichen symbiosis allows a self-sustained life under harsh environmental conditions, yet symbiotic integrity can be affected by fungal parasites. Nothing is known about the impact of these biologically diverse and often specific infections on the recently detected bacterial community in lichens. To address this question, we studied the arctic-alpine 'chocolate chip lichen' Solorina crocea, which is frequently infected by Rhagadostoma lichenicola. We sampled healthy and infected lichens at two different sites in the Eastern Alps. High abundances of Acidobacteria, Planctomycetes, and Proteobacteria were identified analyzing 16S rRNA gene regions obtained by barcoded pyrosequencing. At the phylum and genus level, no significant alterations were present among infected and healthy individuals. Yet, evidence for a differentiation of communities emerged, when data were analyzed at the strain level by detrended correspondence analysis. Further, a profile clustering network revealed strain-specific abundance shifts among Acidobacteria and other bacteria. Study of stability and change in host-associated bacterial communities requires a fine-grained analysis at strain level. No correlation with the infection was found by analysis of nifH genes responsible for nitrogen fixation.


Recurrent sebaceous gland carcinoma of eyelid previously diagnosed as basal cell carcinoma: case report.
Sebaceous gland carcinoma (SGC) of the eyelid is a highly malignant neoplasm that arises from the meibomian glands, glands of Zeis, and sebaceous glands of the skin. The characteristics of this disease are high recurrence rate, significant metastatic potential, and notable mortality rate, which are quite different from basal cell carcinoma (BCC). We report the case of a 37-year-old woman with the history of left lower eyelid BCC (diagnosed 9 years ago), who had left parotid lymph nodes metastases and local recurrence twice. The chief complaint during visit was a left upper eyelid swelling mass noted for 3 months. She received salvage ablation surgery later. The final pathologic report is SGC. The diagnosis corresponds to the clinical presentation of this patient at last. The delay between initial examination and final diagnosis in this patient is about 9 years, but operation and concurrent chemotherapy and radiotherapy were performed after left parotid lymph nodes metastasis was noted. Although there was still local recurrence after concurrent chemotherapy and radiotherapy, the patient is still alive without distant metastasis. In this article, we would discuss the differences of the pathologic characters, treatment, and prognosis between SGC and BCC.


No evidence for presence of bacteria in modic type I changes.
Recent studies suggest an association between sciatica and Propionibacterium acnes. "Modic type I changes" in the vertebrae are closely associated with sciatica and lower back pain, and recent studies have questioned the ability of conventional magnetic resonance imaging (MRI) to differentiate between degenerative Modic type I changes and vertebral abnormalities caused by infection. To test whether bacteria could be cultured from biopsies of Modic type I changes. Twenty-four consecutive patients with Modic type I changes in lumbar vertebrae had a biopsy taken from the affected vertebra by a strict aseptic procedure. The biopsy was split into two specimens, which were inoculated into thioglycolate agar tubes in the surgical theatre and transported to the microbiology laboratory. In the laboratory, one specimen was streaked onto plates and analyzed for anaerobic and aerobic culture. The other tube was left unopened and incubated directly. Plates and tubes were incubated for 2 weeks and observed for visible growth. None of the biopsies yielded growth of anaerobic bacteria. In one patient, both biopsies yielded growth of Staphylococcus epidermidis, and in another patient coagulase-negative staphylococci were isolated from one biopsy. Both patients received oral antibiotics without convincing effect on symptoms. Our results showed no evidence of bacteria in vertebrae with Modic type I changes. The isolation of staphylococci from two patients probably represented contamination.


Contractile dysfunction and altered metabolic profile of the aging rat thyroarytenoid muscle.
The larynx and its muscles are important for ventilation, coughing, sneezing, swallowing, Valsalva's maneuver, and phonation. Because of their functional demands, the intrinsic laryngeal muscles have a unique phenotype: very small and fast fibers with high mitochondrial content. How aging affects their function is largely unknown. In this study, we tested the hypothesis that an intrinsic laryngeal muscle (thyroarytenoid muscle, a vocal fold adductor) would become weaker, slower, and fatigable with age. Muscles from Fischer 344 x Brown Norway F1 hybrid rats (6, 18, and 30 mo of age) were used for in vitro contractile function and histology. Thyroarytenoid muscles generated significantly lower twitch and tetanic forces at 30 mo vs. 6 and 18 mo. Maximal shortening velocity decreased by 20% at 30 mo (vs. 6 mo), and velocity of unloaded shortening was slower at 18 and 30 mo by 19 and 27% vs. 6 mo. There was no histochemical evidence of altered myosin ATPase activity at 18 or 30 mo of age. Fatigue resistance was significantly decreased at 18 and 30 mo. We also found abundant mitochondrial clusters and ragged red fibers in the muscles of 30-mo-old rats, and there was an age-related increase in glycogen-positive fibers. We conclude that rat thyroarytenoid muscles become weaker, slower, and more fatigable with age. These functional changes are not due to alterations in myosin ATPase activity, but a switch in the expression of myosin isoforms remains a possibility. Finally, the alterations in mitochondrial and glycogen content indicate a shift in the metabolic characteristics of these muscles with age.


Bone marrow-derived mesenchymal stem cells protect against lung injury in a mouse model of bronchopulmonary dysplasia.
The aim of the present study was to investigate the effect of bone marrow‑derived mesenchymal stem cells (BMSCs) in the treatment of lung injury in a mouse model of bronchopulmonary dysplasia (BPD) and examine the underlying mechanisms. A mouse model of BPD was created using continuous exposure to high oxygen levels for 14 days. BMSCs were isolated, cultured and then labeled with green fluorescent protein. Cells (1x106) were subsequently injected intravenously 1 h prior to high oxygen treatment. Animals were randomly divided into three groups (n=5 in each): Control group, BPD model group and BMSC injection group. At two weeks post‑treatment, the expression of transforming growth factor‑β1 (TGF‑β1), vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF) was detected using immunohistochemical staining and immunofluorescence. Compared with the BPD model group, the body weight, airway structure and levels of TGF‑β1 and VEGF were significantly improved in the BMSC‑treated group. Immunofluorescence observations indicated that BMSCs were able to differentiate into cells expressing vWF and VEGF, which are markers of vascular tissues. The present study demonstrated that intravenous injection of BMSCs significantly improved lung damage in a neonatal mouse model of BPD at 14 days following hyperoxia‑induced injury. This provides novel information which may be used to guide further investigation into the use of stem cells in BPD.


Dynamic Programming Based Segmentation in Biomedical Imaging.
Many applications in biomedical imaging have a demand on automatic detection of lines, contours, or boundaries of bones, organs, vessels, and cells. Aim is to support expert decisions in interactive applications or to include it as part of a processing pipeline for automatic image analysis. Biomedical images often suffer from noisy data and fuzzy edges. Therefore, there is a need for robust methods for contour and line detection. Dynamic programming is a popular technique that satisfies these requirements in many ways. This work gives a brief overview over approaches and applications that utilize dynamic programming to solve problems in the challenging field of biomedical imaging.


Coarse-grained simulations of DNA overstretching.
We use a recently developed coarse-grained model to simulate the overstretching of duplex DNA. Overstretching at 23 °C occurs at 74 pN in the model, about 6-7 pN higher than the experimental value at equivalent salt conditions. Furthermore, the model reproduces the temperature dependence of the overstretching force well. The mechanism of overstretching is always force-induced melting by unpeeling from the free ends. That we never see S-DNA (overstretched duplex DNA), even though there is clear experimental evidence for this mode of overstretching under certain conditions, suggests that S-DNA is not simply an unstacked but hydrogen-bonded duplex, but instead probably has a more exotic structure.


Superoxide anions in the paraventricular nucleus mediate the enhanced cardiac sympathetic afferent reflex and sympathetic activity in renovascular hypertensive rats.
An enhanced cardiac sympathetic afferent reflex (CSAR) is involved in the sympathetic activation in renovascular hypertension. The present study was designed to determine the role of superoxide anions in the paraventricular nucleus (PVN) in mediating the enhanced CSAR and sympathetic activity in renovascular hypertension in the two-kidney, one-clip (2K1C) model. Sinoaortic denervation and vagotomy were carried out, and renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded under anesthesia. The CSAR was evaluated by the response of RSNA to the epicardial application of capsaicin. Superoxide anion levels and NAD(P)H oxidase activity in the PVN increased in 2K1C rats and were much higher in 2K1C rats than in sham-operated (sham) rats after the epicardial application of capsaicin or PVN microinjection of ANG II. In both 2K1C and sham rats, PVN microinjection of the superoxide anion scavenger tempol or the NAD(P)H oxidase inhibitor apocynin abolished the CSAR, whereas the SOD inhibitor diethyldithiocarbamic acid (DETC) potentiated the CSAR. Tempol and apocynin decreased but DETC increased baseline RSNA and MAP. ANG II in the PVN caused larger responses of the CSAR, baseline RSNA, and baseline MAP in 2K1C rats than in sham rats. The effects of ANG II were abolished by pretreatment with tempol or apocynin in both 2K1C and sham rats and augmented by DETC in the PVN in 2K1C rats. These results indicate that superoxide anions in the PVN mediate the CSAR and the effects of ANG II in the PVN. Increased superoxide anions in the PVN contribute to the enhanced CSAR and sympathetic activity in renovascular hypertension.


Variability in gelatinase expression in the walls of vessels used as aortocoronary conduits may impact long-term graft patency.
An imbalance between the activity of matrix metalloproteinases (MMPs), particularly gelatinases, and tissue inhibitors of metalloproteinases (TIMPs) is considered as one of the mechanisms leading to aortocoronary graft failure. We aimed to assess the variability in gelatinase expression in the walls of aortocoronary conduits and to evaluate its impact on coronary artery bypass grafting (CABG) outcomes. The study included 101 consecutive patients (61 men and 40 women) who underwent CABG. An immunohisto-chemical analysis of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression was performed on the cross-sections of the internal thoracic artery (ITA), radial artery (RA), and saphenous vein (SV). The histological findings were compared between patients with SV graft disease (SVGD[+] group) and those without occlusions in the SV (SVGD[-] group). The median MMP and TIMP expression was the weakest in the ITA wall. MMP expression was comparable between the RA and SV cross-sections, whereas TIMP expression was stronger in the RA than in the SV wall (p < 0.05). In most SV segments, but not in the arteries, immunostaining intensity for MMP was comparable to or stronger than for TIMPs. In the veins harvested from the SVGD(+) group, MMP-2 and MMP-9 tissue expression was more pronounced than in the SVGD(-) group. TIMP levels were comparable between groups. Imbalance in the metalloproteinase-to-inhibitor tissue expression in the vessel wall might predispose to graft failure. A stronger expression of TIMPs than MMPs in the arterial grafts might explain favourable long-term outcomes.


T cells stimulated by CD40L positive leukemic blasts-pulsed dendritic cells meet optimal functional requirements for adoptive T-cell therapy.
Adoptive T-cell immunotherapy may provide complementary therapy for childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In this study, we have analyzed the functional characteristics of anti-BCP-ALL effector T cells generated by co-culturing T lymphocytes and dendritic cells (DC) from allogeneic human stem cell transplantation (HSCT) donors. After 21-day co-culture with DC pulsed with CD40L+ apoptotic BCP-ALL blasts, T cells presented with both effector and central memory phenotype, and showed high and specific cytotoxic activity against leukemic cells (average lysis = 77%), mostly mediated by CD8+ T cells. Noticeably, growth of CD4 T cells was maintained (45% of total cells), which actively produced Th1 cytokines (IFN-gamma, TNF-alpha, IL-2), but not IL-4, IL-5 and IL-10. Anti-BCP-ALL T cells expressed CD49d and CXCR4 (implicated in the recruitment to bone marrow), and CD62L and CCR7 (involved in the migration to lymphoid organs). In accordance with this profile, T cells significantly migrated in response to the chemokines CXCL12 and CCL19. In conclusion, stimulation of T cells with CD40L+BCP-ALL cells-loaded DC not only elicited the generation of potent and specific anti-leukemic cytotoxic effectors, but also the differentiation of specific and functional Th-1 CD4 lymphocytes. These effectors are fully equipped to reach leukemia-infiltrated tissues and have characteristics to support and orchestrate the anti-tumor immune-response.


Traumatic Brain Injury in a Community-Based Cohort of Homeless and Vulnerably Housed Individuals.
We characterized traumatic brain injury (TBI) and studied its associations with mental and physical health in a community cohort of homeless and vulnerably housed individuals. Detailed mental and physical health structured interviews, neuropsychological testing, and multimodal magnetic resonance imaging (MRI) were performed on 283 participants. Two TBI participant groups were defined for primary analyses: those with a self-reported history of TBI and those with MRI confirmation of TBI. By self-report, 174 participants (61.5%) reported a previous serious head or face injury (symptomatic or asymptomatic), with 100 (35.3%) experiencing symptoms consistent with TBI (any post-injury loss of consciousness, confusion, or memory loss). Persons self-reporting TBI had poorer current mental and physical health, more ongoing neurological symptoms, and a higher rate of mood disorders, compared to those with no TBI. The presence of a mood disorder, a TBI history, and an interaction between these factors contributed to lower mental health. There was evidence of TBI in 20 participants (6.9%) on clinical MRI sequences. These participants had globally lower cortical gray matter volumes and lower white matter fractional anisotropy (FA) values. Neurocognitive test scores positively correlated with both FA and cortical gray matter volumes in participants with MRI evidence of trauma. Previous TBI is associated with poorer mental and physical health in homeless and vulnerably housed individuals and interacts with mood disorders to exacerbate poor mental health. Focal traumatic lesions evident on MRI are associated with diffusely lower gray matter volumes and white matter integrity, which predict cognitive functioning.


Should transcobalamin deficiency be treated aggressively?
Transcobalamin (transcobalamin II, TC) transports plasma vitamin B(12) (cobalamin, Cbl) into cells. TC deficiency is a rare autosomal recessive disorder causing intracellular Cbl depletion, which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid, and methionine depletion. The clinical presentation reflects intracellular Cbl defects, with early-onset failure to thrive with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia, sometimes followed by neurological complications. We report the clinical, biological, and molecular findings and the outcome in five TC-deficient patients. The three treated early had an initial favorable outcome, whereas the two treated inadequately had late-onset severe neuro-ophthalmological impairment. Even if the natural course of the disease over time might also result in late-onset symptoms in the aggressively treated patients, these data emphasize that TC deficiency is a severe disorder requiring early detection and probably long-term aggressive therapy. Mutation analysis revealed six unreported mutations in the TCN2 gene. In silico structural analysis showed that these mutations disrupt the Cbl-TC interaction domain and/or the putative transcobalamin-transcobalamin receptor interaction domain.


Efficacy of a brief multifactorial adherence-based intervention in reducing blood pressure: a randomized clinical trial.
Lowering blood pressure (BP) by antihypertensive (AHT) drugs reduces the risks of cardiovascular events, stroke, and total mortality. However, poor adherence to AHT medications reduces their effectiveness and increases the risk of adverse events. To evaluate the effectiveness of a multifactorial adherence-based intervention in a primary care setting in lowering BP. Multicenter parallel randomized controlled trial. Thirty two nurses in 28 primary care centers of three Spanish regions. Patients aged 18-80 years, taking AHT drugs with uncontrolled BP (n=221) were randomized to a control group (usual care) or a multifactorial adherence-based intervention including nurse-led motivational interviews, pill reminders, family support, BP self-recording, and simplification of the dosing regimen by a pharmacist. The primary outcome was 12-month blinded measure of systolic BP (mean of three measurements). The secondary outcomes were 12-month diastolic BP and proportion of patients with adequately controlled BP. One hundred and fourteen patients were allocated to the intervention group and 109 to the control group. At 12 months, 212 (89%) participants completed the study. The systolic BP in the intervention group was 151.3 versus 153.7 in the control group (P=0.294). The diastolic BP did not differ between groups (83.4 versus 83.6). Of the patients in the control group, 9.2% achieved BP control versus a 15.8% in the intervention group. The relative risk for achieving BP control was 1.72 (95% confidence interval: 0.83-3.56). A multifactorial intervention based on improving adherence in patients with uncontrolled hypertension failed to find evidence of effectiveness in lowering systolic BP. ISRCTN21229328.


Particle Size of Milk Protein Concentrate Powder Affects the Texture of High-Protein Nutrition Bars During Storage.
Milk protein concentrate powder with 85% protein (MPC85) was jet-milled to give 2 particle size distributions (that is, JM-Coarse and JM-Fine) or freeze-dried (FD), in order to improve the functional properties of MPC85 for use in high-protein nutrition (HPN) bars. Volume-weighted mean diameter decreased from 86 μm to 49, 22, and 8 μm in FD, JM-Coarse, and JM-Fine, respectively (P < 0.05). The MPC85 powders modified by jet-milling and freeze-drying were significantly denser than the control MPC85 (P < 0.05). Volume of occluded air in the modified powders decreased (P < 0.05) by an order of magnitude, yet only FD possessed a lower volume of interstitial air (P < 0.05). Particle size reduction and freeze-drying MPC85 decreased its water holding capacity and improved its dispersibility by at least 20%. Contact angle measurements showed that these modifications increased initial hydrophobicity and did not improve wettability. HPN bars made from JM-Fine or FD were firmer by 40 or 17 N, respectively, than the control on day 0 (P < 0.05). HPN bar maximum compressive force increased by 38%, 33%, and 242% after 42 d at 32 °C when formulated with JM-Fine, FD, or control MPC85, respectively. HPN bars prepared with JM-Fine were less crumbly than those formulated with control or FD MPC85. Physically altering the particle structure of MPC85 improved its ability to plasticize within HPN bars and this improved their cohesiveness and textural stability.


Ecophysiology of riparian cottonwoods: stream flow dependency, water relations and restoration.
Cottonwoods (Populus spp.) are adapted to riparian or floodplain zones throughout the Northern Hemisphere; they are also used as parents for fast-growing hybrid poplars. We review recent ecophysiological studies of the native cottonwoods Populus angustifolia James, P. balsamifera L., P. deltoides Marsh., P. fremontii S. Watson and P. trichocarpa T. & G. in North America, and P. nigra L. in Europe. Variation exists within and across species and hybrids; however, all riparian cottonwoods are dependent on shallow alluvial groundwater that is linked to stream water, particularly in semi-arid regions. This conclusion is based on studies of their natural occurrence, decline following river damming and dewatering (water removal), water relations, isotopic composition of xylem water, and by the establishment of cottonwoods along formerly barren natural channels after flow augmentation in response to the conveyance of irrigation water. When alluvial groundwater is depleted as a result of river dewatering or groundwater pumping, riparian cottonwoods exhibit drought-stress responses including stomatal closure and reduced transpiration and photosynthesis, altered 13C composition, reduced predawn and midday water potentials, and xylem cavitation. These physiological responses are accompanied by morphological responses including reduced shoot growth, altered root growth, branch sacrifice and crown die-back. In severe cases, mortality occurs. For example, severe dewatering of channels of the braided Big Lost River in Idaho led to mortality of the narrowleaf cottonwood, P. angustifolia, and adjacent sandbar willows, Salix exigua Nutt., within 5 years, whereas riparian woodlands thrived along flowing channels nearby. The conservation and restoration of cottonwoods will rely on the provision of river flow regimes that satisfy these ecophysiological requirements for survival, growth and reproduction.


A hypothetical explanation of congenital nystagmus.
Congenital nystagmus (CN) is a conjugate, rhythmic, eye movement disorder characterized by a wide variety of waveforms ranging from jerk to pendular types. No detailed mechanisms have been proposed to explain the generation of the CN waveform. This paper proposes a hypothetical mechanism for CN, and shows with computer simulations that a model based on this hypothesis can account for a variety of disparate waveforms. The basis of this model is a gaze-holding network, or neural integrator, that has both position and velocity feedback loops. The signals carried in these loops could arise from either afference or efference . In normal subjects, the position feedback would be positive and the velocity feedback would be negative. Both would help to increase the time constant of an imperfect neural integrator in the brain stem. We propose that in patients with CN the sign of the velocity pathway is reversed, making the neural integrator unstable. This instability could manifest as many different CN waveforms, depending on the direction and velocity of post-saccadic ocular drift and actions of nonlinearities within the position and velocity feedback loops. Thus a single underlying abnormality may be responsible for a variety of CN waveforms.


Information Architecture of Web-Based Interventions to Improve Health Outcomes: Systematic Review.
The rise in usage of and access to new technologies in recent years has led to a growth in digital health behavior change interventions. As the shift to digital platforms continues to grow, it is increasingly important to consider how the field of information architecture (IA) can inform the development of digital health interventions. IA is the way in which digital content is organized and displayed, which strongly impacts users' ability to find and use content. While many information architecture best practices exist, there is a lack of empirical evidence on the role it plays in influencing behavior change and health outcomes. Our aim was to conduct a systematic review synthesizing the existing literature on website information architecture and its effect on health outcomes, behavioral outcomes, and website engagement. To identify all existing information architecture and health behavior literature, we searched articles published in English in the following databases (no date restrictions imposed): ACM Digital Library, CINAHL, Cochrane Library, Google Scholar, Ebsco, and PubMed. The search terms used included information terms (eg, information architecture, interaction design, persuasive design), behavior terms (eg, health behavior, behavioral intervention, ehealth), and health terms (eg, smoking, physical activity, diabetes). The search results were reviewed to determine if they met the inclusion and exclusion criteria created to identify empirical research that studied the effect of IA on health outcomes, behavioral outcomes, or website engagement. Articles that met inclusion criteria were assessed for study quality. Then, data from the articles were extracted using a priori categories established by 3 reviewers. However, the limited health outcome data gathered from the studies precluded a meta-analysis. The initial literature search yielded 685 results, which was narrowed down to three publications that examined the effect of information architecture on health outcomes, behavioral outcomes, or website engagement. One publication studied the isolated impact of information architecture on outcomes of interest (ie, website use and engagement; health-related knowledge, attitudes, and beliefs; and health behaviors), while the other two publications studied the impact of information architecture, website features (eg, interactivity, email prompts, and forums), and tailored content on these outcomes. The paper that investigated IA exclusively found that a tunnel IA improved site engagement and behavior knowledge, but it decreased users' perceived efficiency. The first study that did not isolate IA found that the enhanced site condition improved site usage but not the amount of content viewed. The second study that did not isolate IA found that a tailored site condition improved site usage, behavior knowledge, and some behavior outcomes. No clear conclusion can be made about the relationship between IA and health outcomes, given limited evidence in the peer-reviewed literature connecting IA to behavioral outcomes and website engagement. Only one study reviewed solely manipulated IA, and we therefore recommend improving the scientific evidence base such that additional empirical studies investigate the impact of IA in isolation. Moreover, information from the gray literature and expert opinion might be identified and added to the evidence base, in order to lay the groundwork for hypothesis generation to improve empirical evidence on information architecture and health and behavior outcomes.


PDTRT Special Section: Methodological issues in personality disorder research.
Introduces Personality Disorders: Theory, Research, and Treatment ongoing Special Section concerned with methodological issues in personality disorder research. This second edition includes two papers, one which discusses the value and advantages of sampling the views, opinions, and perceptions of clinicians in personality disorder research, and the other which takes a critical look at the ways in which structural equation modeling techniques have been used in the study of personality disorders, symptoms, and traits. (PsycINFO Database Record


Interleukin 37 promotes angiogenesis through TGF-β signaling.
IL-37 is a novel pro-angiogenic cytokine that potently promotes endothelial cell activation and pathological angiogenesis in our previous study, but the mechanisms behind the pro-angiogenic effect of IL-37 are less well understood. Extending our observations, we found that TGF-β interacts with IL-37, and potently enhances the binding affinity of IL-37 to the ALK1 receptor complex, thus allowing IL-37 to signal through ALK1 to activate pro-angiogenic responses. We further show that TGF-β and ALK1 are required in IL-37 induced pro-angiogenic response in ECs and in the mouse model of Matrigel plug and oxygen-induced retinopathy. The result suggests that IL-37 induces pro-angiogenic responses through TGF-β, which may act as the bridging molecule that mediates IL-37 binding to the TGF-β receptor complex.


Quality of life after the menopause in Iran: a population study.
Quality of life (QoL) decreases after the menopause as it has been assessed by several designed tools. The aim of the present research was to assess QoL and determine factors related to its impairment among postmenopausal Iranian women. This cross-sectional study was conducted through cluster sampling among 480 postmenopausal women in Yazd, Islamic Republic of Iran, in 2008. Data were collected using the menopause quality of life questionnaire (MENQOL) by interviewing. Content validity and Cronbach's alpha were used, respectively, to ensure the validity and reliability of the questionnaires. Inferential and descriptive statistics via SPSS.15 software was used for data analysis. The results showed that the menopausal women have worse QoL scores in vasomotor dimension and higher QoL scores in physical dimension. Univariate analysis showed that there were significant differences in the MENQOL scores by age, number of children, education, postmenopausal stage, employment status, and BMI. Women aged 60-65 (P < 0.05), with a university level of education (P < 0.01), who had employment (P < 0.01), who had postmenopausal stage 5 or more years (P < 0.05), with a body mass index <or=18.5 kg m(-2) (P < 0.05), and who had significantly lower scores indicating better quality of life. Logistic regression determined that vasomotor score decreased with age. Employment and number of children decreased the risk of having psychosocial scores above the median. Postmenopausal stage >or=5 increased the risk for higher scores within the sexual domain, respectively. Menopause causes a decrease in quality of life, which is dependent to work and other socio-demographic variables. Therefore, it is necessary to develop effective intervention programs to improve quality of life after menopause.


Genetics and conservation biology.
Conservation genetics encompasses genetic management of small populations, resolution of taxonomic uncertainties and management units, and the use of molecular genetic analyses in forensics and to understanding species' biology. The role of genetic factors in extinctions of wild populations has been controversial, but evidence now shows that they make important contributions to extinction risk. Inbreeding has been shown to cause extinctions of wild populations, computer projections indicate that inbreeding depression has important effects on extinction risk, and most threatened species show signs of genetic deterioration. Inappropriate management is likely to result if genetic factors are ignored in threatened species management.


Interindividual differences in the activation of two hepatic carcinogens to mutagens by human liver.
The possibility that the presence of malignant disease can influence the metabolic activation of two carcinogens, 2-acetylaminofluorene and aflatoxin B1, has been investigated in a group of patients with secondary carcinoma of the liver. Mutagenic activation by subcellular fractions from biopsy samples from the patients was determined in the Ames/Salmonella test and the results compared with those obtained from a group of control patients. No significant differences were observed between the groups of patients in their ability to activate the two compounds to mutagenic metabolites. A tenfold range in ability to activate aflatoxin B1 was observed whereas only a threefold range was obtained with 2-acetylaminofluorene. Human liver activates aflatoxin B1 approximately 100 times more efficiently than 2-acetylaminofluorene, a proven carcinogen in many species. This raises the question of the true risk to man from hepatocarcinogenicity from aflatoxin B1.


Inhibitory effects of FKBP14 on human cervical cancer cells.
The FK506-binding protein 14 (FKBP14), which belongs to a subfamily of immunophilins, has been implicated in various biochemical processes. However, its effects on human cervical cancer remain to be elucidated. The present study aimed to determine the exact role of FKBP14 in human cervical cancer cell proliferation, cell cycle progression, apoptosis, invasion and migration. Cell proliferation was measured by Cell Counting Kit‑8 assay. Flow cytometry was conducted to determine the effects of FKBP14 on cell cycle progression and apoptosis. Cell invasion and migration were determined by Transwell assay. The results of the present study demonstrated that silencing FKBP14 expression using short hairpin (sh)RNA suppressed proliferation, invasion and migration of HeLa and C‑33A cells, and also induced apoptosis and cell cycle arrest. Furthermore, silencing FKBP14 expression decreased the protein expression levels of B‑cell lymphoma 2 (Bcl‑2), matrix metalloproteinase (MMP)2 and MMP9, and increased the levels of caspase‑3 and Bcl‑2‑associated X protein in FKBP14 shRNA‑infected HeLa and C‑33A cells. In conclusion, FKBP14 may act as an oncogene through suppressing apoptosis and promoting motility in human cervical carcinogenesis; therefore, it may be considered a potential therapeutic target for the treatment of cervical cancer.


[Simulation of alpha-helix and beta-hairpin formation in water-soluble proteins by the code physics method].
One of the possible ways for complete and final solution of the problem of determination of three-dimensional structure of proteins on amino acid sequence is simulation of protein three-dimensional structure formation. The use of the code physics method developed by the author has been suggested to fulfill this task. The simulation of alpha-helix and beta-hairpin formation in water-soluble proteins as a start of realization of the plan is described here. The results of the simulation were compared with the experimental data for 14 proteins of no more than 50 amino acids and therefore with little number of alpha-helices and beta-strands (to meet limits of simulation process) and with secondary structure predictions by the best to data methods of protein secondary structure prediction, PSIpred, PORTER and PROFsec. Secondary structure of the proteins, obtained as a result of the simulation of alpha-helix and beta-hairpin formation using the code physics method, corresponded completely to experimental data while the secondary structure predicted by the PSIpred, PORTER and PROFsec methods differed from these data significantly.


Characterization of a community cluster of group a streptococcal invasive disease in Maui, Hawaii.
A community cluster of severe group A streptococcal skin infections occurred in Maui, Hawaii with 3 fatal cases of necrotizing fasciitis in 2002. emm types 1, 12, 58, 74, 85 and 109 were identified from 8 patients. emm types 74 and 109 have not been previously described in the United States according to the Centers for Disease Control and Prevention database. The identification of uncommon emm types suggested that group A streptococcal sero-types in Hawaii are different from those in the continental United States and can result in serious disease.


Phasic changes in human nasal and skin blood flow: relationship with autonomic tone.
To assess the autonomic control of the microcirculation in human skin and nasal mucosa, the spontaneous fluctuations of a laser Doppler signal recorded on forearm skin and nasal mucosa were compared with heart rate fluctuations and the respiratory signal in 11 healthy subjects by means of spectral analysis. Possible direct mechanical-thermal effects of airflow on the nasal mucosa were evaluated by comparing recordings obtained when the subjects were breathing through either the nose or the mouth. Comparison of the spectral analysis of the signal obtained for skin and nasal mucosa blood flow allowed us to define the characteristics of the autonomic tone of the microcirculation in these two areas. The skin is mainly influenced by sympathetic activity, and the nasal blood flow is regulated by both sympathetic and parasympathetic activity.


The evolution of flight in bats: narrowing the field of plausible hypotheses.
The evolution of flapping flight in bats from an arboreal gliding ancestor appears on the surface to be a relatively simple transition. However, bat flight is a highly complex functional system from a morphological, physiological, and aerodynamic perspective, and the transition from a gliding precursor may involve functional discontinuities that represent evolutionary hurdles. In this review, I suggest a framework for a comprehensive treatment of the evolution of complex functional systems that emphasizes a mechanistic understanding of the initial state, the final state, and the proposed transitional states. In this case, bats represent the final state and extant mammalian gliders are used as a model for the initial state. To explore possible transitional states, I propose a set of criteria for evaluating hypotheses about the evolution of flight in vertebrates and suggest methods by which we can advance our understanding of the transition from gliding to flapping flight. Although it is impossible ever to know with certainty the sequence of events landing to flapping flight, the field of possibilities can be narrowed to those that maintain the functional continuity of the wing and result in improved aerodynamic performance across this transition. The fundamental differences between gliding and flapping flight should not necessarily be seen as evidence that this transition could not occur; rather, these differences point out compelling aspects of the aerodynamics of animal wings that require further investigation.


Exercise-induced stridor due to abnormal movement of the arytenoid area: videoendoscopic diagnosis and characterization of the "at risk" group.
We evaluated 4 patients who developed severe, symptomatic stridor during maximal cardiopulmonary exercise testing, all referred due to exercise-related dyspnea. All underwent resting, unsedated transnasal fiberoptic laryngoscopy and had normal findings. Four patients performed repeat maximal exercise testing with fiberoptic laryngoscopy, and they form the basis of this report. They had normal vocal cord motion during exercise, but developed abnormal anterior motion of the arytenoid and aryepiglottic folds only at peak exercise, leading to partial airway obstruction and severe stridor. This report details the workup and characterizes patients at risk for this unusual phenomenon.


Is there a therapeutic window of opportunity in early inflammatory bowel disease? Early stage inflammatory bowel disease: the actual management.
Traditionally therapy for inflammatory bowel disease (IBD) encompassed a sequential approach with subjects treated with 5-ASA products and/or corticosteroids initially, and only where failing such treatment, moving on to immunomodulator or biologic therapy. In the rheumatologic literature the importance of the early introduction of immunosuppressive therapies for inflammatory arthropathies has been increasingly recognized, however this concept remains much debated in IBD with no clear consensus on the optimal therapeutic approach. In this review we discuss how the natural history of IBD provides a rationale for the early introduction of the most effective therapy. We outline how the experience of early immunosuppressive therapy in rheumatoid arthritis informs therapeutic decision making in IBD. We review the evolving treatment strategies in IBD and the current evidence supporting the introduction of immunosuppressive treatment soon after IBD diagnosis. Finally we discuss the importance of selecting appropriate therapeutic endpoints in IBD and review the potential risks and benefits of early immunosuppressive treatment strategies in IBD.


Quadratus Lumborum Block as a Cornerstone for Neonatal Intestinal Surgery Enhanced Recovery (ERAS): A Case Series.
Neonates present unique challenges for pediatric surgical teams. To optimize outcomes, it is imperative to standardize perioperative care by using early extubation and multimodal analgesic techniques. The quadratus lumborum (QL) block provides longer duration and superior pain relief than other single-injection abdominal fascial plane techniques. The purpose of this case series was to report our initial experience with QL blocks in neonatal patients treated with intestinal ERAS. Ten neonates requiring intestinal surgery at a single tertiary care center who received QL blocks between December 2019 and April 2022 for enhanced recovery were studied. Bilateral QL blocks were performed with 0.5 mL/kg of 0.25% ropivacaine per side with an adjuvant of 1 mcg/kg of dexmedetomidine. Gestational age at birth ranged from 32.2 to 41 weeks. The median age, weight, and American Society of Anesthesiologists (ASA) score at the time of surgery was 5 days [range 7.5 hours, 60 days], 2.84 kg [range 1.5, 4.5], and 3, respectively. Bilateral QL blocks were performed without complications in all patients. Two patients were outside the neonatal range from birth to surgery, but were under 42 weeks gestational age when corrected for prematurity. All patients were extubated with well-controlled pain, and no patient required reintubation within the first 24 hours. Postoperatively, median cumulative morphine equivalents were 0.16 mg/kg [range 0, 0.79] and six patients received scheduled acetaminophen. Morphine (0.1 mg/kg) was administered to patients with a modified neonatal infant pain scale (NIPS) score greater than or equal to 4, and pain was reassessed 1 hour after administration (Appendix). When developing intestinal ERAS protocols, Bilateral QL blocks may be considered for postoperative analgesia in the neonatal population. Further prospective studies are required to validate this approach in neonates.


Deep brain stimulation: potential for neuroprotection.
Over the last two decades there has been an exponential rise in the number of patients receiving deep brain stimulation (DBS) to manage debilitating neurological symptoms in conditions such as Parkinson's disease, essential tremor, and dystonia. Novel applications of DBS continue to emerge including treatment of various psychiatric conditions (e.g. obsessive-compulsive disorder, major depression) and cognitive disorders such as Alzheimer's disease. Despite widening therapeutic applications, our understanding of the mechanisms underlying DBS remains limited. In addition to modulation of local and network-wide neuronal activity, growing evidence suggests that DBS may also have important neuroprotective effects in the brain by limiting synaptic dysfunction and neuronal loss in neurodegenerative disorders. In this review, we consider evidence from preclinical and clinical studies of DBS in Parkinson's disease, Alzheimer's disease, and epilepsy that suggest chronic stimulation has the potential to mitigate neuronal loss and disease progression.


Upregulation of human CYP2C9 expression by Bisphenol A via estrogen receptor alpha (ERα) and Med25.
Bisphenol A (BPA) is an important industrial chemical, mainly used in the manufacture of polycarbonate plastic and epoxy resins. Due to its widespread use, humans have a high risk of exposure to BPA. BPA has been found to have adverse health effects such as interfering with hormone-related pathways and is well-known to act as an endocrine disruptor. The present study is the first to show the induction effect of BPA on gene expression and enzyme activity of CYP2C9, an important hepatic drug metabolizing enzyme in human. We further identify the mechanism of BPA upregulation of CYP2C9 expression. We show that BPA is able to transcriptionally activate CYP2C9 promoter through ERα and ERE site within the CYP2C9 promoter region in HepG2 cells, and can induce CYP2C9 gene expression and enzyme activity in human primary hepatocytes. Moreover, we demonstrate that Med25, a variable member of the Mediator complex, is a coactivator of ligand-activated ERα that interacts with ERα through its C-terminal LXXLL motif after BPA exposure, and is functionally involved in BPA-induced transcriptional regulation of CYP2C9 expression and enzyme activity. Our findings suggest that BPA exposure has a potential risk for adverse health effects in human liver metabolism by upregulation of CYP2C9 expression. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 970-978, 2017.


[Dynamics of ultrastructural morphology of the nucleolar apparatus in bovine preimplantation embryos collected in an area of chronic irradiation].
Ultrastructural morphology and immunoelectron microscopy of the nucleus and nucleologenesis in early preimplantation cow embryos were applied in an attempt to demonstrate a possible radiation injury to that early stage of development due to chronical irradiation of the animals in the Tchernobyl area. Mostly eight cell embryos as well as morulae were collected from superovulated cows which were previously constantly kept in zones of different levels of radioactive irradiation. In addition to the normometric status of reproductive organs in no case was it possible to detect an apparent deviation in the nuclear morphology or in the process of nucleologenesis as compared to the physiological situation (Kopecný et al., 1989b, 1991, 1996). This observation was supported by an immunoelectron microscope study of DNA association and penetration in the differentiated nucleolus in the late 8-cell stage. These observations show that the otherwise demonstrated radiation injury localized in the genome does not probably influence markedly the early events of the developing embryo and that the aberrant cytoplasmic command of the nuclear events known in other types of oocyte/early cow embryo impairment (review Kopecný and Nicmann, 1993; Kanka et al. 1991; Pavlok et al., 1993) is not seen in early embryos collected from chronically irradiated animals.


Incidence of Prediabetes/Diabetes among Women with Prior Gestational Diabetes and Non-Alcoholic Fatty Liver Disease: A Prospective Observational Study.
This prospective longitudinal study aims to evaluate and compare the incidence of prediabetes/diabetes among women stratified at the baseline postpartum visit according to the prior GDM and NAFLD status. Of the 309 women with baseline postpartum assessment at a median of 16 months following the index delivery, 200 (64.7%) [GDM: 137 (68.5%), normoglycaemia: 63 (31.5%)] were available for the follow-up analysis (performed at median of 54 months following the index delivery) and were participants for this study. We obtained relevant demographic, medical and obstetric details and performed a 75 g OGTT with glucose estimation at 0 and 120 min. NAFLD status was defined by ultrasonography at the baseline visit. Participants were divided into four groups: no NAFLD and no prior GDM (group 1), NAFLD but no prior GDM (group 2), prior GDM but no NAFLD (group 3), and NAFLD and prior GDM (group 4). The mean age of study participants (n = 200) was 32.2 ± 5.1 years, and the mean interval between the two visits was 34.8 ± 5.5 months. A total of 74 (37%) women had progression to prediabetes/diabetes [incidence rate of 12.8/100 woman-years]. The incidence rates (per 100 woman-years) were 8.6, 8.9, 13.4 and 15.3 in groups 1, 2, 3 and 4, respectively. The adjusted hazard ratio for incident (new-onset) prediabetes/diabetes in group 4 (reference: group 1) was 1.99 (95% CI 0.80, 4.96, P = 0.140). Among women with baseline NAFLD (irrespective of GDM status), the risk of incident prediabetes/diabetes increased with an increase in the duration of follow-up (3.03-fold higher per year of follow-up, P = 0.029) and was significantly higher in women who were not employed (6.43, 95% CI 1.74, 23.7, P = 0.005) and in women with GDM requiring insulin/metformin during pregnancy (4.46, 95% CI 1.27, 15.64, P = 0.019). NAFLD and GDM increased the risk for glycaemic deterioration in young Indian women. Future studies should focus on evaluating the effectiveness of lifestyle and behavioural interventions in such high-risk women.