The animal nuclear factor Y: an enigmatic and important heterotrimeric transcription factor.
Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor with the ability to bind to CCAAT boxes in nearly all eukaryotes and has long been a topic of interest since it is first identified. In plants, due to each subunit of NF-Y is encoded by multiple gene families, there are a wide variety NF-Y complex combinations that fulfill many pivotal functions. However, the animal NF-Y complex usually has only one type of combination, as each subunit is generally encoded by a single gene. Even though, mounting evidence points to that the animal NF-Y complex is also essential for numerous biological processes involved in proliferation and apoptosis, cancer and tumor, stress responses, growth and development. Therefore, a relatively comprehensive functional dissection of animal NF-Y will enable a deeper comprehension of how lesser combinations of the NF-Y complex regulate diverse aspects of biology processes in animal. Here, we focus mainly on reviewing recent advances related to NF-Y in the animal field, including subunit structural characteristics, expression regulation models and biological functions, and we also discuss future directions.


Mechanisms of primordial follicle activation and new pregnancy opportunity for premature ovarian failure patients.
Primordial follicles are the starting point of follicular development and the basic functional unit of female reproduction. Primordial follicles are formed around birth, and most of the primordial follicles then enter a dormant state. Since primordial follicles are limited in number and can't be renewed, dormant primordial follicles cannot be reversed once they enter the growing state. Thus, the orderly occurrence of primordial follicles selective activation directly affects the rate of follicle consumption and thus determines the length of female reproductive lifespan. Studies have found that appropriately inhibiting the activation rate of primordial follicles can effectively slow down the rate of follicle consumption, maintain fertility and delay ovarian aging. Based on the known mechanisms of primordial follicle activation, primordial follicle in vitro activation (IVA) technique has been clinically developed. IVA can help patients with premature ovarian failure, middle-aged infertile women, or infertile women due to gynecological surgery treatment to solve infertility problems. The study of the mechanism of selective activation of primordial follicles can contribute to the development of more efficient and safe IVA techniques. In this paper, recent mechanisms of primordial follicle activation and its clinical application are reviewed.


None of the above: A Bayesian account of the detection of novel categories.
Every time we encounter a new object, action, or event, there is some chance that we will need to assign it to a novel category. We describe and evaluate a class of probabilistic models that detect when an object belongs to a category that has not previously been encountered. The models incorporate a prior distribution that is influenced by the distribution of previous objects among categories, and we present 2 experiments that demonstrate that people are also sensitive to this distributional information. Two additional experiments confirm that distributional information is combined with similarity when both sources of information are available. We compare our approach to previous models of unsupervised categorization and to several heuristic-based models, and find that a hierarchical Bayesian approach provides the best account of our data. (PsycINFO Database Record


Initial attachment of principal fibers to the root dentin surface in rat molars.
The initial attachment of principal fibers to the root dentin surface was investigated in developing rat molars by light and electron microscopy. Ruthenium red was used to intensely stain the first deposited material on the root dentin surface. Observations suggested that when the principal fibers became embedded in the ruthenium red-positive material, there was no complicated interweaving between the principal fibers and the root dentinal matrix fibers. Therefore, it is likely that the initial principal fiber attachment to the root dentinal matrix fibers is mediated by the ruthenium red-positive material.


Strategies to encourage physical activity in patients with hemophilia to improve quality of life.
Hemophilia is a bleeding disorder caused by a congenital abnormality of blood coagulation. Until the mid-1970s, patients with hemophilia (PWH) were advised to refrain from physical activity (PA) because of a perceived increased risk of bleeding. Since then, PA, which is recognized as being essential for health maintenance, is now recommended by the World Federation of Hemophilia. Moreover, a number of studies reported that PA can improve treatment efficacy and prevent bleeding in PWH. Physical assessment and intervention in PA are currently used in clinical practice. However, the necessity of PA is not emphasized, and many PWH generally have low- to- no PA. Therefore, a behavior change approach to encourage patient motivation is becoming ever more important. In this article, we review articles addressing PA in PWH and discuss strategies to encourage PA through a behavior change approach by focusing on factors relevant to hemophilia, such as benefits and bleeding risk of PA, risk management of bleeding, PA characteristics, and difficulty with exercise adherence. The trust relationship between clinicians and patients, a transtheoretical model of behavior change, and motivation theory as approaches to promote PA are introduced. Finally, we review a case report of the clinical success of a behavior change approach to promote PA. Many PWH find it difficult to continue PA because of aging, fear of bleeding, insufficient recognition of PA benefits, and psychological problems. Therefore, it is essential and important to perform prophylaxis with PWH and to heighten their understanding of the benefits and risks of PA, before initiating the exercise regimen. For those patients who find it difficult to participate in PA, it is necessary to plan individual-based behavior change approach and encourage self-efficacy.


On Medicaid and the Affordable Care Act in Connecticut: the problem with subspecialty services.
Medicaid is the federal program, administered by states, for health care for the poor. The Affordable Care Act (ACA) has added a large number of new recipients to this program. Medicaid programs in some, if not many, states do not provide patients uniform access to subspecialty care guaranteed by the federal statutes. Insofar as the ACA does not address this pre-existing "sub-specialty gap" and more patients are now covered by Medicaid under the ACA, the gap is likely to increase and may contribute to disparities of health care access and outcomes. A brief description of previous studies demonstrating or suggesting a subspecialty gap in Medicaid services is accompanied by perspectives of the authors, using published literature - most notably the Denver, Colorado health care system - to propose various solutions that may be deployed to address gaps in subspecialty coverage. All published studies describing the Medicaid subspecialty gap are qualitative, survey designs. There are no authoritative objective data regarding the exact prevalence of gaps for each subspecialty in each state. However, surveys of caregivers suggest that gaps were prevalent in the United States prior to initiation of the ACA. Even fewer papers have addressed solutions (in light of the paucity of data describing the magnitude of the problem), and proposed solutions remain speculative and not grounded in objective data. There is reason to believe that a substantial proportion of U.S. citizens - those who are guaranteed a full complement of health services through Medicaid - have difficult or no access to some subspecialty services, many of which other citizens take for granted. This problem deserves greater attention to verify its existence, quantify its magnitude, and develop solutions.


Developing key performance indicators for adult critical care transfer services: Scoping review and Delphi technique.
In 2021 NHS England commissioned regional Adult Critical Care Transfer Services. These services will replace a historically predominant ad hoc approach to adult critical care transfers nationally. It is anticipated that these new formal services will provide a system of robust regional & national governance previously acknowledged to be deficient. As part of this process, it is important that an agreed set of transfer service quality indicators are developed to drive equitable improvement in patient care. We used a Delphi technique to develop a set of key performance indicators through consensus for a recently established London critical care transfer service. We believe this may be the first-time key performance indicators have been developed for adult critical care transfer services using a consensus method. We hope services will consider tracking similar measures to enable benchmarking and drive improvements in patient care.


Rapid cine MRI of the human heart using reconstruction by estimation of lines and inhibition of fold-in.
A fast imaging method is described that yields an approximately six-fold acquisition time reduction relative to conventional techniques. The method involves: 1) acquisition of every sixth k-space line; 2) shifting of acquired k-space lines between odd and even frames; and 3) a single-frame correction image. Reconstruction is achieved by temporal interpolation for k-space lines not acquired combined with subtraction of stationary fold-in artifacts. Seven patients with heart disease and one volunteer were evaluated. SNR was measured in myocardium and the ventricular cavity for both the conventional and new technique. The method is best suited for fast imaging of moving objects confined to a small region within a larger stationary object, such as the heart within the thoracic cavity. It can be implemented in cine and functional imaging sequences and, in principle, in perfusion sequences.


[Family burden of patients receiving inpatient treatment or alternative forms of psychiatric care].
Professionals working with chronic patients are usually aware of vast deficitis in what is called in the literature "natural support networks". The deficits generally increase over time, as is the case with broadly defined social skills. Although the efficacy of biological treatment was similar in all the three forms of care, nevertheless, patients and their families, when left without psychotherapeutic support provided to them by the day hospital or community treatment team, at one-year follow-up indicated lack of any satisfactory improvement in many dimensions of their functioning, and in some aspects-even a progressive deterioration.


Does N-terminal pro-brain natriuretic peptide add prognostic value to the Mehran risk score for contrast-induced nephropathy and long-term outcomes after primary percutaneous coronary intervention?
To evaluate the prognostic value of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) in relation to Mehran risk score (MRS) for contrast-induced nephropathy (CIN) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We prospectively enrolled 283 consecutive patients treated with PPCI for STEMI. NT-proBNP was measured, and the MRS was calculated. The primary end point was CIN, defined as an absolute increase in serum creatinine ≥0.5 mg/dL from baseline within 48-72 h after contrast medium exposure. The incidence of CIN was 9.2 %. Patients with CIN had higher NT-proBNP and MRS than those without CIN. The value of NT-proBNP was similar to MRS for CIN (C statistics 0.760 vs. 0.793, p = 0.689). After adjustment for MRS, elevated NT-proBNP (defined as the best cutoff point) was significantly associated with CIN. The addition of elevated NT-proBNP to MRS did not significantly improve the C statistics, over that with the original MRS model (0.833 vs. 0.793, p = 0.256). In addition, similar results were observed for in-hospital and long-term major adverse clinical events. Although NT-proBNP did not add any prognostic value to the MRS model for CIN, NT-proBNP, as a simple biomarker, was similar to MRS, and may be another useful and rapid screening tool for CIN and death risk assessment, identifying subjects who need therapeutic measures to prevent CIN.


A manipulative instrument with simultaneous gesture and end-effector trajectory planning and controlling.
To operate a redundant manipulator to accomplish the end-effector trajectory planning and simultaneously control its gesture in online programming, incorporating the human motion is a useful and flexible option. This paper focuses on a manipulative instrument that can simultaneously control its arm gesture and end-effector trajectory via human teleoperation. The instrument can be classified by two parts; first, for the human motion capture and data processing, marker systems are proposed to capture human gesture. Second, the manipulator kinematics control is implemented by an augmented multi-tasking method, and forward and backward reaching inverse kinematics, respectively. Especially, the local-solution and divergence problems of a multi-tasking method are resolved by the proposed augmented multi-tasking method. Computer simulations and experiments with a 7-DOF (degree of freedom) redundant manipulator were used to validate the proposed method. Comparison among the single-tasking, original multi-tasking, and augmented multi-tasking algorithms were performed and the result showed that the proposed augmented method had a good end-effector position accuracy and the most similar gesture to the human gesture. Additionally, the experimental results showed that the proposed instrument was realized online.


Complications of gastrostomy.
Despite its simplicity, gastrostomy has been associated with a relatively high incidence of complications. We have described two unusual complications: inadvertent duodenostomy, resulting in gastric outlet obstruction, and the migration of a gastrostomy feeding tube into the midportion of the jejunum, resulting in obstruction of the small bowel.


Use of an Electronic Medical Record (EMR) to Identify Glycemic Intensification Strategies in Type 2 Diabetes.
Current treatment guidelines for type 2 diabetes (T2D) recommend individualized intensification of therapy for glycated hemoglobin (A1C) ≥ 7% in most patients. The purpose of this investigation was to explore the ability of an electronic medical record (EMR) to identify glycemic intensification strategies among T2D patients receiving pharmacologic therapy. Patient records between 2005 and 2011 with documentation of A1C and active prescriptions for any diabetes medications were queried to identify potential candidates for intensification based on A1C ≥ 7% while on 1-2 oral diabetes medications (ODM). Patients with follow-up A1C values within 1 year of index A1C were grouped according to intensification with insulin, GLP-1 receptor agonists (GLP-1RA), a new class of ODM, or no intensification. Changes in A1C and continuation of intensification therapy were determined. A total of 4921 patients meeting inclusion criteria were intensified with insulin (n = 416), GLP-1RA (n = 68), ODM (n = 1408), or no additional therapy (n = 3029). Patients receiving insulin had higher baseline (9.3 ± 2.0 vs 8.3 ± 1.2 vs 8.3 ± 1.3 vs 7.6 ± 1.0%, P < .0001) and follow-up A1C (8.1 ± 1.6 vs 7.5 ± 1.2 vs 7.6 ± 1.3 vs 7.2 ± 1.1%, P < .0001) despite experiencing larger absolute A1C reductions (-1.2 ± 2.1 vs -0.8 ± 1.4 vs -0.7 ± 1.4 vs -0.3 ± 1.1%, P < .0001). Patients receiving GLP-1RA were more obese at baseline (BMI: 33.6 ± 7.1 vs 37.7 ± 6.1 vs 33.7 ± 6.8 vs 32.9 ± 7.1 kg/m(2), P < .0001) and follow-up (BMI: 33.9 ± 7.3 vs 36.6 ± 6.1 vs 33.8 ± 7.0 vs 32.4 ± 7.0 kg/m(2), P < .0001) despite experiencing more absolute weight reduction. Insulin was the most and GLP-1RA the least likely therapy to be continued. An EMR allows identification of prescribing practices and compliance with T2D treatment guidelines. Patients receiving intensification of glycemic medications had baseline A1C >8% suggesting that treatment recommendations are not being followed.


Multidisciplinary Antenatal Management of a Late Pregnancy Complicated With Advanced Stage Breast Burkitt Lymphoma - Case Report and a Review of the Literature.
The multidisciplinary team (MDT) plays a pivotal role in establishing the diagnosis and tailoring treatment for challenging, complicated, rare obstetrical cases. At 28 weeks of gestation, a lady presented with an unresolved unilateral proptosis and sustained severe mastitis. MDT managed the patient at a tertiary care hospital for primary breast Burkitt lymphoma (PBBL). It is a rare and highly malignant condition requiring an aggressive therapeutic approach. Antenatal chemotherapy (ANC) with an aggressive regimen of R-hyper-CVAD/MA was started. A healthy baby was vaginally delivered after completing the second therapy cycle at 32+ weeks, weighing 1.6kg with a good Apgar score. Postnatally, the central nervous system (CNS) prophylaxis was added; after completing eight chemo cycles, our patient remained stabilized for nine months. Unfortunately, due to the refractory and aggressive nature of malignancy, it relapsed, giving an overall survival (OS) of two years. MDT care should be considered at the earliest possible period to expedite the entire process. Positive results can be achieved with timely aggressive treatment and early management of such cases.


The readability of online patient information about laser resurfacing therapy.
Because there are important distinctions between ablative and non-ablative laser resurfacing, accurate and effective patient education is paramount. However, as more patients use the internet as a resource for medical information, little is known about the content and readability of these sources. Thus, we sought to evaluate the readability of major online resources about laser resurfacing while recognizing the recommendations by the American Medical Association and National Institutes of Health. An internet search for the term "Laser Resurfacing" was performed. The first 9 results were identified, patient information from each of these 9 sites were downloaded, and a total of 25 articles were examined. Readability was analyzed using 7 different established tests. Analysis demonstrated an average grade level of at least 9th grade, with all articles exceeding the recommended 6th grade reading level, emphasizing that these resources are too challenging for many patients to read and comprehend. Such materials may hamper appropriate decision-making in patients considering the use of a laser for their dermatologic conditions. The potential detrimental effect on the opinion, participation, and satisfaction of laser resurfacing should spur dermatologists to be more critical of online patient materials and motivated to produce more appropriate resources.


Shunting between the CVC and both the azygos vein and thoracic duct in a dog with CTD.
A 5 mo old female rottweiler was referred for evaluation of a suspected congenital heart disease. Clinical signs included anorexia, exercise intolerance, and severe loss of body condition. Clinical examination revealed dyspnea, pale mucous membranes, and weak femoral pulses. Pleural and abdominal effusions and iron deficiency anemia were identified. A distended intrathoracic caudal vena cava (CVC) visible on thoracic radiographs suggested that the modified transudate abdominal effusion was the result of improper venous return to the right side of the heart. Cor triatriatum dexter (CTD) was diagnosed via echocardiography but did not explain all the anomalies detected during a contrast echocardiography. Abnormal communications between the CVC and azygos vein and the CVC and thoracic duct were subsequently identified by abdominal ultrasonography and angiography. Medical management with diuretics, iron supplements, and surgical treatment of CTD resulted in normalization of the respiratory rate, the exercise intolerance, and the anemia. To the authors' knowledge, this is the first reported case of CTD associated with shunts between the CTV and both the azygos vein and thoracic duct in dogs. This report emphasizes the importance of presurgical assessment of concurrent thoracic and abdominal congenital vascular abnormalities.


Coupled-mode equation of polarization modes of twisted birefringent fibers in a unified coordinate.
A coupled-mode equation (CME) of twisted birefringent fiber is presented in this paper, which uses the degenerate polarization modes of single-mode fibers as eigenmodes in a unified coordinate. The inconsistency between the coordinate and the rotating principal axis, existing in the previous CME, is solved by conversion to the lab coordinate. The CME gives self-consistent results for fibers with high birefringence or low birefringence and for single-mode fibers as well. Analyses and simulations show the CME gives characteristics of twisted birefringent fiber coincident with the property of polarization-maintaining fibers.


Long-term follow-up and serological study after triple therapy of Helicobacter pylori-associated duodenal ulcer.
The purpose of this study was to monitor the change of IgG antibodies to Helicobacter pylori during the course of a long-term follow-up after the eradication of H. pylori, as well as to evaluate the efficacy of triple therapy in preventing the recurrence of duodenal ulcer (DU). Twenty-three DU patients with positive H. pylori were studied; among those patients, 20 ulcers healed after initial treatment of triple therapy. Each patient received a follow-up endoscopy and biopsy examination every 3 months for 1 yr, or whenever the ulcer symptoms recurred. Serological tests for IgG antibodies were performed with a commercial ELISA. Of the 20 patients with healed ulcers, one dropped out of this study; the recurrence rate of DU at 1 yr was 5% (1/19). There was no recurrence of ulcer in 17 H. pylori-negative patients and only one recurrence out of two H. pylori-positive patients. After the eradication of H. pylori, the seroconversion rates of IgG were 5%, 21%, 42%, 76%, and 94% at 0, 3, 6, 9, and 12 months, respectively. After 6 months, 95% (18/19) of the patients in which H. pylori was eradicated had at least a one-grade fall in IgG titers (p < 0.001). One patient had a relapse of H. pylori which was accompanied with re-elevating IgG titers. We conclude that seroconversion, which usually occurs after 1 yr, indicates complete eradication of H. pylori. Furthermore, we suggest that the success of the eradication of H. pylori can be judged without endoscopic examination, 8 months after treatment by triple therapy, according to the fall of IgG titers or seroconversion. Re-elevating IgG titers may be a warning of the possibility of relapse or reinfection of H. pylori.


Interferometric image reconstruction through the turbulent atmosphere.
A high-resolution image of an incoherent object can be recovered in spite of the atmospheric turbulence. The spatial frequency spectrum of object radiance is calculated from digitized interference patterns obtained by a computer-controlled wave front folding interferometer. The reconstruction technique and its application to a laboratory-generated turbulence are presented.


Prevalence, localization, perception and management of pain in dance: an overview.
Background and aims Pain is a highly complex bio-psychosocial phenomenon that may present a (potential) health risk and either occurs as a warning sign or a symptom of injury. It cannot be ruled out that these rising or changing requirements in dance of all styles, are reflected in health-related outcomes such as pain. The aim of this narrative review article is to outline an overview of prevalence and localization, concepts of performance pain and injury pain, pain perception and pain management in dance. At that consequences of pain and influencing factors focusing on different dance styles or forms of professionalism are discussed. Methods The databases CINAHL, Cochrane, Google Scholar, Medline, MeSH and Web of Science were screened for relevant articles. Results Pain prevalence in dance is very high. Pain localizations can be related to high dance-specific mechanical stress on the musculoskeletal system. Depending on the pain characteristics, dancers perceive pain as "positive" (performance pain) or "negative" (injury pain). Concerning pain attitudes and management, dancers show an increasing pain tolerance. Pain seems to be accepted as a necessity, often ignored and dancing is continued despite pain. Conclusions The findings of this article suggest that occurrence of pain, pain perception, coping with pain and pain history appear to be connected to dance-specific mechanical stress as well as to socialization in dance culture. In dance, effects of pain on health seem to be associated with characteristics of pain and pain behavior. Implications The results highlight the high relevance of pain in dance and the need to take into account preventive as well as rehabilitative measures.


Phytochemical analysis, antioxidant, antistress, and nootropic activities of aqueous and methanolic seed extracts of ladies finger (Abelmoschus esculentus L.) in mice.
Abelmoschus esculentus L. (ladies finger, okra) is a well-known tropical vegetable, widely planted from Africa to Asia and from South Europe to America. In the present study, we investigated the in vitro antioxidant capacity and in vivo protective effect of the aqueous and methanolic seed extracts of Abelmoschus esculentus against scopolamine-induced cognitive impairment using passive avoidance task and acute restraining stress-induced behavioural and biochemical changes using elevated plus maze (EPM) and forced swimming test (FST) in mice. Our results demonstrated that the pretreatment of mice with aqueous and methanolic seed extracts of Abelmoschus esculentus (200 mg/kg, p.o.) for seven days significantly (P < 0.01) attenuated scopolamine-induced cognitive impairment in the passive avoidance test. In addition, these extracts significantly reduced the blood glucose, corticosterone, cholesterol, and triglyceride levels elevated by acute restraint stress and also significantly increased the time spent in open arm in EPM and decreased the immobility time in FST. It has also been revealed that these extracts showed a significant antioxidant activity and no signs of toxicity or death up to a dose of 2000 mg/kg, p.o. These results suggest that the seed extracts of Abelmoschus esculentus L. possess antioxidant, antistress, and nootropic activities which promisingly support the medicinal values of ladies finger as a vegetable.


Emergence of Leaf Spot Disease on Leafy Vegetable and Ornamental Crops Caused by Paramyrothecium and Albifimbria Species.
The genera Paramyrothecium and Albifimbria have been established from the former genus Myrothecium and they generally comprise common soil-inhabiting and saprophytic fungi. Within these genera, only two fungi have been recognized as phytopathogenic thus far: P. roridum and A. verrucaria, both of which cause necrotic leaf spots and plant collapse. Severe leaf necrosis and plant decay have been observed in Northern and Southern Italy on leafy vegetable crops. Thirty-six strains of Paramyrothecium- and Albifimbria-like fungi were isolated from affected plants belonging to eight different species. Based on morphological characteristics, 19 strains were assigned to A. verrucaria, whereas the remaining strains, which mostly resembled Paramyrothecium-like fungi, could not be identified precisely. Molecular characterization of six loci (internal transcribed spacer [ITS], β-tubulin [tub2], calmodulin [cmdA], translation elongation factor 1-alpha [tef1], large subunit ribosomal RNA [LSU], and mitochondrial ATP 6synthase 6 [ATP6]) of the 36 new isolates and three previously ITS-characterized isolates assigned all strains to four species: A. verrucaria, P. roridum, P. foliicola, and P. nigrum. Single and concatenated phylogenetic analyses were conducted, and they clearly distinguished the isolated fungi into four different groups. A. verrucaria, P. roridum, P. foliicola, and P. nigrum were able to induce leaf necrosis singly, and they were confirmed to be the causal agents of the leaf spot disease through pathogenicity assays. The involvement of fungi previously considered saprophytic (i.e., P. foliicola and P. nigrum) in the development of plant disease for the first time deserves particular attention because of the possibility of their transmission by seeds and the limited knowledge of their management with chemicals.


The Effect of Local Hydration Environment on the Mechanical Properties and Unloaded Temporal Changes of Isolated Porcine Annular Samples.
Preventing dehydration during in vitro testing of isolated layers of annulus fibrosus tissue may require different test conditions than functional spine units. The purpose of the study was twofold: (A) to quantify changes in mass and thickness of multilayer annulus samples in four hydration environments over 120 min; and (B) to quantify cycle-varying biaxial tensile properties of annulus samples in the four environments. The environments included a saline bath, air, relative humidity control, and misting combined with controlled humidity. The loading protocol implemented 24 cycles of biaxial tensile loading to 20% strain at a rate of 2%/s with 3-, 8-, and 13-min of intermittent rest. Specimen mass increased an average (standard deviation) 72% (11) when immersed for 120 min (p < 0.0001). The air condition and the combined mist and relative humidity conditions reduced mass by 45% (15) and 25% (23), respectively, after 120 min (p < 0.0014). Stress at 16% stretch in the air condition was higher at cycle 18 (18 min of exposure) and cycle 24 (33 min of exposure) compared to all other environments in both the axial and circumferential directions (p < 0.0460). There was no significant change in mass or thickness over time in the relative humidity condition and the change in circumferential stress at 16% stretch between cycles 6 and 24 was a maximum of 0.099 MPa and not statistically significant. Implementation of a controlled relative humidity environment is recommended to maintain hydration of isolated annulus layers during cyclic tensile testing.


The Pediatric AIDS Severity Score (PASS): a multidimensional AIDS-severity adjustment for pediatric HIV infection.
A severity staging system predictive of mortality for perinatally HIV-infected children is needed for clinical and research purposes. A pediatric AIDS severity score (PASS) was developed using baseline sociodemographic, clinical, immunologic, and functional measures obtained from 786 perinatally HIV-infected children enrolled into a prospective cohort study (PACTG 219) in the pre-highly active antiretroviral therapy (HAART) era (pre-1996). PASS was then validated among 392 perinatally HIV-infected children randomly sampled from the original source population (n = 1178). Survival estimates and hazard ratios (HRs) were obtained using the Kaplan-Meier method and proportional hazards models, respectively. The most predictive models were determined using Harrell's "C" statistic. Overall survival was 95% and 90% at 1 and 2 years of follow-up, respectively. The most comprehensive model for predicting mortality, termed the "Full" PASS, included CD4% <15 (HR = 3.9), CDC category C (HR = 2.6), BMI <10% (HR = 2.4), a low (<70) neuropsychological score (HR = 2.6), a general health rating <5 (HR = 2.4), and an elevated symptoms score (HR = 1.9). These determinants were highly predictive of mortality (C statistic = 0.841). PASS will be helpful in assessing the effectiveness of ART among children with HIV infection, particularly when randomized clinical trials are not possible due to ethical and feasibility concerns.


Influences of dietary starch structure on intestinal morphology, barrier functions, and epithelium apoptosis in weaned pigs.
The objective of the present study was to evaluate the effects of dietary starch structure (amylose/amylopectin ratio, AR) on intestinal health of weaned pigs by determining the intestinal morphology, barrier functions, epithelium apoptosis and digestive enzymes. A total of one hundred and eight pigs (initial body weight 7.51 ± 0.05 kg) were randomly allotted on the basis of their body weight (BW) and litters to one of the six experimental diet treatments with six replicates per treatment and three pigs per replicate. The six diets included a control (corn-soybean meal basal diet, CON) diet and five experimental diets with AR being 2.90, 1.46, 0.68, 0.31 and 0.14, respectively. The diets and water were provided ad libitum for 21 d. Results showed that pigs fed CON and AR 2.90 diets had higher (P < 0.05) villus height and ratio of villus height : crypt depth in the jejunum and ileum compared with the other four starch groups. Pigs of CON and AR 0.14 groups had greater (P < 0.05) activities of sucrase (SA) and maltase (MA) than the pigs of other groups. Additionally, compared with the high amylopectin (AR 0.31 and 0.14) groups, the total apoptotic percentage was significantly decreased in (P < 0.01) CON and high amylose (AR 2.90) groups. Ingestion of CON and high amylose diets upregulated (P < 0.05) the levels of B-cell lymphoma-2 (Bcl-2) and occludin (OCLN) gene expression in duodenum and jejunum. However, no significant differences in the level of zonula occludens 1 (ZO-1) gene expression were observed in pigs fed with different AR diets. Interestingly, CON and high amylose groups enhanced the localization of ZO-1 protein in apical intercellular region of jejunal epithelium. Together, these results suggest that diets with high amylose can influence the intestinal health of young pigs by improving their intestinal barrier functions and reducing the epithelial cell apoptosis.


Safety and efficacy of modified FOLFOX6 plus high-dose bevacizumab in second-line or later treatment of patients with metastatic colorectal cancer.
The aim of this retrospective study was to show the efficacy and safety of modified FOLFOX6 plus high-dose bevacizumab (10 mg/kg/2 weeks) in the second-line or later treatment of metastatic colorectal cancer. A total of 24 consecutive patients treated between August 2007 and August 2009 were included in this retrospective study. None of the patients had received bevacizumab as part of prior treatment. All 24 patients received modified FOLFOX6 plus high-dose bevacizumab and were followed for a median of 36.9 months. Overall response rate was 29%. Median progression-free survival was 7.5 months, and median overall survival was 17.3 months. Grade 3/4 adverse events were: neutropenia (54.2%), leukopenia (25.0%), neuropathy (12.5%), hypertension (12.5%), thrombocytopenia (8.3%), and decreased haemoglobin, gastrointestinal haemorrhage, wound complications, nausea, diarrhoea, mucositis and fatigue (each 4.2%). Modified FOLFOX6 plus high-dose bevacizumab may be useful in the second-line treatment of patients with metastatic colorectal cancer who have not received bevacizumab.


Ureteral pacemaker potentials recorded with the sucrose gap technique.
Ureteral contractions occur at intervals which are integral multiples of the period of pacemaker potentials recorded in vitro from the renal pelvis with a sucrose gap, suggesting that a gating mechanism in the pyeloureter regulates the rate at which the pacemaker initiates contractions.


Pulmonary segmentectomy by thoracotomy or thoracoscopy: reduced hospital length of stay with a minimally-invasive approach.
Previous studies have discouraged limited pulmonary resection for primary lung cancer, but pulmonary segmentectomy has advantages for some patients. Furthermore, while thoracoscopic lobectomy has been increasingly applied with well-demonstrated advantages compared with thoracotomy, few data exist regarding thoracoscopic approaches to pulmonary segmentectomy. This study compares thoracoscopic segmentectomy (TS) with open segmentectomy (OS). This is a retrospective review of prospectively collected data for 77 consecutive segmentectomy patients treated between 2000 and 2006 at a single center. Preoperative, intraoperative, and postoperative variables for patients undergoing TS (n = 48) were compared with those undergoing OS (n = 29). Student's t tests were used for continuous data and Fisher's exact tests for dichotomous data. Baseline demographics were similar between groups. Indications for pulmonary resection included non-small cell lung cancer (n = 39), metastatic disease (n = 30), and other diagnoses (n = 8). All common segmentectomies were represented. No thoracoscopic cases required conversion to open procedures. Operative times, estimated blood loss, and chest tube duration were similar between groups. Outcomes were similar except that hospital length of stay was significantly less among TS patients (length of stay 6.8 +/- 6 days OS versus 4.3 +/- 3 days TS; p = 0.03). Thirty-day mortality was 6.9% (2 of 29) for the OS group compared with 0% for the TS group. Long-term survival rates were significantly better in the TS group (p = 0.0007). Thoracoscopic segmentectomy is a safe and feasible procedure, comparing favorably with OS by reducing hospital length of stay. For experienced thoracoscopic surgeons, TS appears to be a sound option for lung-sparing, anatomic pulmonary resections.


Expression of cord blood cytochrome P450 1A1 gene according to the air pollution level of the maternal residence area.
This study aimed to compare the cytochrome P450 1A1 (CYP1A1) gene expression in the cord blood of infants born from mothers living in low- and high-air polluted areas. The study was conducted in Spring 2012 in Isfahan, the second large and air-polluted city in Iran. The study comprised 60 neonates, consisting of 30 infants born from mothers residing in areas with high levels of air pollution and an equal number of infants born in areas with a lower air pollution level. The umbilical cord blood sample was taken immediately after birth. The relative gene expression levels of CYP1A1 were examined using real time-polymerase chain reaction method. CYP1A1 gene expression level was 3.3-fold higher in the group living in areas with higher pollution level than in the other group (P = 0.01). No significant difference existed in the mean values of maternal age, gestational age, the newborns' birth weight, and the gender distribution between the two groups. This study provides confirmatory evidence of prenatal health hazards of ambient air pollution and highlights the need for pollution prevention programs to protect women of childbearing age and their children. The clinical implications of this study finding should be confirmed in future longitudinal studies.


User-Accessible Machine Learning Approaches for Cell Segmentation and Analysis in Tissue.
Advanced image analysis with machine and deep learning has improved cell segmentation and classification for novel insights into biological mechanisms. These approaches have been used for the analysis of cells in situ, within tissue, and confirmed existing and uncovered new models of cellular microenvironments in human disease. This has been achieved by the development of both imaging modality specific and multimodal solutions for cellular segmentation, thus addressing the fundamental requirement for high quality and reproducible cell segmentation in images from immunofluorescence, immunohistochemistry and histological stains. The expansive landscape of cell types-from a variety of species, organs and cellular states-has required a concerted effort to build libraries of annotated cells for training data and novel solutions for leveraging annotations across imaging modalities and in some cases led to questioning the requirement for single cell demarcation all together. Unfortunately, bleeding-edge approaches are often confined to a few experts with the necessary domain knowledge. However, freely available, and open-source tools and libraries of trained machine learning models have been made accessible to researchers in the biomedical sciences as software pipelines, plugins for open-source and free desktop and web-based software solutions. The future holds exciting possibilities with expanding machine learning models for segmentation via the brute-force addition of new training data or the implementation of novel network architectures, the use of machine and deep learning in cell and neighborhood classification for uncovering cellular microenvironments, and the development of new strategies for the use of machine and deep learning in biomedical research.


Spontaneous Intracranial Hypotension Occurring after Craniotomy for Brain Tumor Biopsy Mimicking Postoperative Bleeding.
In this study, we report on a previously healthy 44-year-old man who underwent an open biopsy under general anesthesia for a tumorous lesion found in his left frontal lobe via a small supratentorial craniotomy. While both postoperative course and brain computed tomography (CT) scans had been considered unremarkable, the patient became stuporous on postoperative day (POD) 4. A brain CT obtained on that day showed a subdural hematoma with marked brain shift which we thought might have been due to postoperative bleeding; he was immediately brought to an operating theater for hematoma removal. However, no bleeding source was found, and the brain remained depressed after hematoma evacuation. Furthermore, the brain shift remained unchanged on postoperative CT. While spontaneous intracranial hypotension (SIH) was considered, imaging studies to search for possible cerebrospinal fluid (CSF) leakage in the spinal column were not performed as the patient's condition has improved. However, he became stuporous again on POD 8, which urged us to perform CT myelogram. The CT myelogram showed a massive CSF leakage at the L1-L2 level. Subsequent autologous blood patch has successfully terminated the CSF leakage, and he became fully oriented shortly after the blood patch therapy. Thus, it should be noted that SIH may occur during postoperative period of intracranial surgery, and it may manifest radiographically as a subdural hematoma indistinguishable from postoperative bleeding. SIH should also be included in a differential diagnosis of postoperative headache, regardless of its characteristics, because headache associated with SIH may not always be orthostatic.


Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells.
Bupivacaine is a local anesthetic compound belonging to the amino amide group. Its anesthetic effect is commonly related to its inhibitory effect on voltage-gated sodium channels. However, several studies have shown that this drug can also inhibit voltage-operated K(+) channels by a different blocking mechanism. This could explain the observed contractile effects of bupivacaine on blood vessels. Up to now, there were no previous reports in the literature about bupivacaine effects on large conductance voltage- and Ca(2+) -activated K(+) channels (BK(Ca)). Using the patch-clamp technique, it is shown that bupivacaine inhibits single-channel and whole-cell K(+) currents carried by BK(Ca) channels in smooth muscle cells isolated from human umbilical artery (HUA). At the single-channel level bupivacaine produced, in a concentration- and voltage-dependent manner (IC(50) 324 µM at +80 mV), a reduction of single-channel current amplitude and induced a flickery mode of the open channel state. Bupivacaine (300 µM) can also block whole-cell K(+) currents (~45% blockage) in which, under our working conditions, BK(Ca) is the main component. This study presents a new inhibitory effect of bupivacaine on an ion channel involved in different cell functions. Hence, the inhibitory effect of bupivacaine on BK(Ca) channel activity could affect different physiological functions where these channels are involved. Since bupivacaine is commonly used during labor and delivery, its effects on umbilical arteries, where this channel is highly expressed, should be taken into account.


Ecophysiological Characterization of Rhizosphere Bacterial Communities at Different Root Locations and Plant Developmental Stages of Cucumber Grown on Rockwool.
Bacterial communities from the rhizosphere of cucumber were characterized with respect to growth rates and carbon source utilization, in order to develop a selection strategy for biocontrol agents against Pythium aphanidermatum. Rhizosphere samples were collected from different root regions (root tips, the root base, and the intermediate region where lateral roots emerge) and developmental stages (the seedling, vegetative, and generative stage) from plants cultivated on reused rockwool. By colony counts on 1/10 strength TSA on subsequent days after plating, percentages of fast- and slow-growing isolates (i.e., forming visible colonies within 2 days, or after 3 or more days, respectively) were determined for each rhizosphere sample. At all plant developmental stages, root tips had the highest percentages of fast growing isolates, and root bases the lowest. During plant growth, the relative amounts of slowly growing bacteria increased. Community-level carbon source utilization was determined for the different rhizosphere samples with Biolog GN plates. Principal component analysis showed that rhizosphere samples from different developmental stages and root locations had distinct carbon source utilization patterns. Communities from root tips of seedlings showed the highest utilization of several monosaccharides. Communities from tips and intermediate regions of plants in the vegetative stage utilized relatively many amino acids and several organic acids, and in the generative stage, more di- and polysaccharides were used. Root base samples scored low with respect to carbon source utilization, except for some disaccharides. From the different rhizosphere samples, 826 bacteria, randomly collected from 1/10 strength TSA plates, were screened on the utilization of 9 carbon sources. The 9 selected carbon sources were chosen because they are reported to occur in the rhizosphere, to be used by the zoospores of Pythium in the infection process, or appeared to be discriminant in the analysis of community-level carbon source utilization performed in this study. It appeared that monosaccharides (glucose and fucose), amino acids (alanine and asparagine), and organic acids (galacturonic, succinic, and linoleic acid) were used for growth mainly by bacteria from the root tips, and to a lesser extent from the intermediate region, of young plants. Disaccharides were predominantly utilized by isolates from plants in the vegetative stage. Overall, the results indicated that growth rates and carbon source utilization reflect the adaptation of bacteria to the rhizosphere environment. The possibility of using these characteristics to screen for rhizosphere competent biocontrol agents that compete for substrates with P. aphanidermatum is discussed.


Nuclear import of transcription factor BR-C is mediated by its interaction with RACK1.
The transcription factor Broad Complex (BR-C) is an early ecdysone response gene in insects and contains two types of domains: two zinc finger domains for the activation of gene transcription and a Bric-a-brac/Tramtrack/Broad complex (BTB) domain for protein-protein interaction. Although the mechanism of zinc finger-mediated gene transcription is well studied, the partners interacting with the BTB domain of BR-C has not been elucidated until now. Here, we performed a yeast two-hybrid screen using the BTB domain of silkworm BR-C as bait and identified the receptor for activated C-kinase 1 (RACK1), a scaffolding/anchoring protein, as the novel partner capable of interacting with BR-C. The interaction between BR-C and RACK1 was further confirmed by far-western blotting and pull-down assays. Importantly, the disruption of this interaction, via RNAi against the endogenous RACK1 gene or deletion of the BTB domain, abolished the nuclear import of BR-C in BmN4 cells. In addition, RNAi against the endogenous PKC gene as well as phosphorylation-deficient mutation of the predicted PKC phosphorylation sites at either Ser373 or Thr406 in BR-C phenocopied RACK1 RNAi and altered the nuclear localization of BR-C. However, when BTB domain was deleted, phosphorylation mimics of either Ser373 or Thr406 had no effect on the nuclear import of BR-C. Moreover, mutating the PKC phosphorylation sites at Ser373 and Thr406 or deleting the BTB domain significantly decreased the transcriptional activation of a BR-C target gene. Given that RACK1 is necessary for recruiting PKC to close and phosphorylate target proteins, we suggest that the PKC-mediated phosphorylation and nuclear import of BR-C is determined by its interaction with RACK1. This novel finding will be helpful for further deciphering the mechanism underlying the role of BR-C proteins during insect development.


One-dimensional tunneling calculations in the imaginary-frequency, rectilinear saddle-point normal mode.
We present tunneling calculations using the reaction path Hamiltonian in the zero-curvature approximation and a one-dimensional Hamiltonian in the imaginary-frequency, rectilinear normal mode of a saddle point, neglecting the vibrational angular momentum terms. This latter Hamiltonian was recently introduced and applied to the tunneling splitting in full-dimensional malonaldeyde [Y. Wang et al., J. Chem. Phys. 128, 224314 (2008)]. The results using the latter method are shown to be much more accurate than those using the former one for the ground-state tunneling splittings for H and D-transfer in malonaldehyde and for the D+H(2) reaction in three dimensions for zero total angular momentum.


Effects of dietary protein and energy levels on cow manure excretion and ammonia volatilization.
Adjusting dietary composition is considered an effective way to reduce nutrient losses to the environment. The effects of various dietary protein and energy levels on manure composition (Ca, Mg, K, Na, N, P, and pH) were studied by determining total and direct available (free) nutrient concentrations in 8 slurries obtained from a feeding trial. Furthermore, the effects of dietary changes on NH(3) volatilization from manure slurries were studied. Increasing the crude protein (CP) content of the feed (108 to 190 g/ kg of dry matter) resulted in an average increase in total N and P content of the slurries of 56 and 48%, respectively. Feeding the cows more energy (5,050 to 6,840 kJ/kg of dry matter) increased total N and P content of the slurries by 27 and 39%, respectively. Total ammoniacal nitrogen (TAN) amounted to 52 to 77% of the total N content present in manure slurries. A low protein content or a low energy content of the diets reduced TAN concentrations in the slurries by 43% (CP) or 25% (energy). Changes in the protein content or the energy content of the feed did not significantly affect the free:total ratios of Na, Ca, and Mg content of the slurries. In agreement with the calculated NH(3,aq) (aqueous) content, the total amount of NH(3) volatilized from manure slurries was much greater (on average 10 times greater) when the cows were fed greater levels of CP. Although the slurries contained more TAN when cows were fed diets richer in energy, NH(3) volatilization from the slurries was lower.


First case of robotic laparoendoscopic single-site radical prostatectomy with single-site VesPa platform.
This study aimed at reporting our first experience with robotic laparoendoscopic single-site radical prostatectomy (R-LESS-RP) with single-site VesPa platform (Intuitive Surgical Inc.). A 68-year-old-man presenting with a cT1c adenocarcinoma Gleason Score 3 + 4 = 7 in 4/12 bilateral cores underwent a transperitoneal robotic LESS-RP with a single-site Vespa platform. Initial PSA, prostate weight, and body mass index (BMI) were 4.4 ng/ml, 45 g, and 25, respectively. Instruments and camera cross within the Single-Site port; the da Vinci System software detects and reassigns the user's hands with the instruments position. The single-site port is inserted through a 2-cm intraumbilical incision. The robotic 8.5 mm scope and two surgical curved instruments (fenestrated bipolar forceps and cautery hook) are introduced through the ports and used for most of the procedure, whereas a wristed needle driver on the right hand is used for the reconstructive steps. An additional 12 mm port (Air Seal, SurgiQuest) is placed in a midline between the umbilicus and the right iliac spine in order to facilitate table assistance during surgery and to place a drain at the end of the procedure.Operative time and blood loss were 300 min and 400 mL, respectively. The postoperative course was uneventful. The drain and the catheter were removed on days 1 and 6, respectively. The patient experienced a temporary mild stress incontinence (one pad at sixth month) and erectile dysfunction.Our first robotic laparoendoscopic single-site radical prostatectomy (R-LESS-RP) with the single-site VesPa platform was associated with acceptable operative times and perioperative outcome. This procedure is feasible without complications, provided that a proper patient selection has occurred. Limited movements together with the lack of the fourth robotic arm require a considerable expertise in robotic surgery. Some tricks can help overcome technical limitations. The Robotic LESS-RP reduces in some measure the limitations of conventional LESS RP, although further refinement of the robotic instruments is necessary.


The effects of intracerebroventricular administration of tonin on water drinking and blood pressure in rats.
Intraventricular administration of tonin, an enzyme which forms angiotensin II directly from a natural protein substrate (angiotensinogen), stimulated water drinking and increased systemic blood pressure in rats. These responses were abolished by the simultaneous administration of an angiotensin II analogue, but unaffected by an angiotensin I- converting enzyme inhibitor. We confirmed, in vitro, that angiotensin II was generated when the brain homogenate was incubated with tonin in the presence of DFP and EDTA. These results indicate that the central effects of tonin on water drinking and systemic blood pressure are mediated via the direct formation of angiotensin II in the brain, and suggest the possibility that the tonin-angiotensin II system in the central nervous system might be important in controlling water balance and blood pressure.


Race/ethnicity modifies the association between school prevalence of e-cigarette use and student-level use: Results from the 2014 US National Youth Tobacco Survey.
This study assessed racial/ethnic moderation of the association between school prevalence of lifetime e-cigarette use and students' use. Using multilevel regression methods and data from the 2014 US National Youth Tobacco Survey, we found attending schools with high rates of e-cigarette use was positively associated with students' lifetime use of e-cigarettes, especially for white students. A cross-level interaction term indicated a weaker association between non-Hispanic black race and attending high-use schools (odds ratio [OR] =0.61, 95% confidence interval [CI] =0.39, 0.95). Results implicate race/ethnicity as an important effect modifier in the link between school contexts and teenage e-cigarette use.


CT demonstration of colovesical fistulae secondary to diverticulitis.
Colovesical fistula, a not infrequent complication of diverticulitis, can be difficult to demonstrate by commonly used diagnostic imaging modalities. We present four cases in which computed tomography was used to detect the presence of such a fistula. Computed tomography readily detected air within the bladder earlier and without equivocation when compared with other imaging techniques. It was useful also in the assessment of the extent and the degree of pericolonic inflammation, thus playing an important role in preoperative surgical planning and postoperative follow-up.


Biochemistry and functional aspects of human glandular kallikreins.
Human urinary kallikrein was purified by gel filtration on Sephacryl S-200 and affinity chromatography on aprotinin-Sepharose, followed by ion exchange chromatography on DEAE-Sepharose. In dodecylsulfate gel electrophoresis two protein bands with molecular weights of 41,000 and 34,000 were separated. The amino acid composition and the carbohydrate content of the kallikrein preparation were determined; isoleucine was identified as the only aminoterminal amino acid. The bimolecular velocity constant for the inhibition by diisopropyl fluorophosphate was determined as 9 +/- 2 1 mol-1 min-1. The hydrolysis of a number of substrates was investigated and AcPheArgOEt was found to be the most sensitive substrate for human urinary kallikrein. Using this substrate an assay method for kallikrein in human urine was developed. It was shown by radioimmunoassay that pig pancreatic kallikrein can be absorbed in the rat intestinal tract. Furthermore, in dogs the renal excretion of glandular kallikrein from blood was demonstrated by radioimmunological methods.


Patterns of relapse following radiotherapy for differentiated thyroid cancer: implication for target volume delineation.
Post-operative residual disease in differentiated thyroid cancer is an indication for external beam radiotherapy (EBRT) especially if there is poor radioiodine uptake by the residual disease. There are no standardized guidelines or consensus in target delineation for radiotherapy in thyroid cancer. To determine the pattern of recurrence in patients with well differentiated thyroid cancer who received adjuvant or definitive radiotherapy as well as radioiodine ablation following surgery or biopsy with a view to better defining future target volume delineation for radiotherapy. Forty-nine patients with differentiated thyroid cancer received radical external beam radiotherapy and radioiodine ablation (3.5GBq) following thyroidectomy or biopsy between 1990 and 2000. Nineteen patients had macroscopic residual (11) or inoperable disease (8), whilst 30 patients had clear (5) or microscopic positive resection margin (24), and 1 patient the resection margin status was unknown. All the patients were deemed high risk for local recurrence or progressive disease. The thyroid bed and regional nodes were irradiated using two radiotherapy techniques: (1) non co-planar lateral fields (NCLF) in coronal plane using 6MV photons to a dose of 45-50Gy in 16 fractions over 22 days and (2) anterior-posterior parallel pair of 6MV photons to a dose of 40-42.5Gy in 16 fractions over 22 days. There was no attempt to irradiate the lymph nodes in that part of the anterior and posterior mediastinum extending from the brachiocephalic veins to the carina. The median follow-up was 5.4 years (range 0.9-12.4 years). The actuarial 5-year cause-specific survival and local control for the whole group was 75.7% and 81.4%, respectively. Of the 4 patients with mediastinal recurrence, all had neck recurrences and two had distant metastases. All the medisastinal recurrences occurred in superior mediastinum (level VII) and all were treated with NCLF in coronal plane radiotherapy technique. Furthermore, mediastinal recurrences did not occur in isolation. The 5-years loco-regional control rate was 89.1% for those with clear or microscopic positive margins and 69.2% for those with macroscopic residual or inoperable disease. Five-year cause specific survival was 58.3% for patients with macroscopic residual or inoperable disease and 91.4% for those with clear or microscopic positive margins. The status of postoperative margin relating to bulk of disease influences local control and cause specific survival. Surgical resection in locally advanced thyroid cancer should be performed by an experienced surgeon to achieve macroscopic clearance where possible. The majority of recurrences were loco-regional. The few superior mediastinal recurrences did not occur in isolation. All the mediastinal recurrences occurred in the superior mediastinum (level VII). We recommend the target volume should encompass the thyroid bed and regional neck nodes and the superior mediastinum level VII excluding the lymph nodes on both sides of the trachea within the anterior and posterior mediastinum extending from the brachiocephalic veins to the carina (compartment 4). Thus, this should facilitate dose escalation to improve loco-regional control and avoiding radiation induced mediastinal toxicity.


Molecular screening and characterization of Legionella pneumophila associated free-living amoebae in domestic and hospital water systems.
Free-living amoebae are ubiquitous in the environment and cause both opportunistic and non-opportunistic infections in humans. Some genera of amoebae are natural reservoirs of opportunistic plumbing pathogens, such as Legionella pneumophila. In this study, the presence of free-living amoebae and Legionella was investigated in 140 water and biofilm samples collected from Australian domestic (n = 68) and hospital water systems (n = 72). Each sample was screened in parallel using molecular and culture-based methods. Direct quantitative polymerase chain reaction (qPCR) assays showed that 41% samples were positive for Legionella, 33% for L. pneumophila, 11% for Acanthamoeba, and 55% for Vermamoeba vermiformis gene markers. Only 7% of samples contained culturable L. pneumophila serogroup (sg)1, L. pneumophila sg2-14, and non-pneumophila Legionella. In total, 69% of samples were positive for free-living amoebae using any method. Standard culturing found that 41% of the samples were positive for amoeba (either Acanthamoeba, Allovahlkampfia, Stenamoeba, or V. vermiformis). V. vermiformis showed the highest overall frequency of occurrence. Acanthamoeba and V. vermiformis isolates demonstrated high thermotolerance and osmotolerance and strong broad spectrum bacteriogenic activity against Gram-negative and Gram-positive bacteria. Importantly, all Legionella positive samples were also positive for amoeba, and this co-occurrence was statistically significant (p < 0.05). According to qPCR and fluorescence in situ hybridization, V. vermiformis and Allovahlkampfia harboured intracellular L. pneumophila. To our knowledge, this is the first time Allovahlkampfia and Stenamoeba have been demonstrated as hosts of L. pneumophila in potable water. These results demonstrate the importance of amoebae in engineered water systems, both as a pathogen and as a reservoir of Legionella. The high frequency of gymnamoebae detected in this study from Australian engineered water systems identifies an issue of significant public health concern. Future water management protocols should incorporate treatments strategies to control amoebae to reduce the risk to end users.


Differential role for IL-7 in inducing lung Kruppel-like factor (Kruppel-like factor 2) expression by naive versus activated T cells.
Kruppel-like Factor 2 [KLF2, also called lung Kruppel-like factor (LKLF)] is a transcription factor shown to be necessary for the maintenance of naive T cells. KLF2 is expressed in both naive and memory cells, and is proposed to promote quiescence in these populations. During T cell stimulation, both KLF2 protein and mRNA are down-regulated, and loss of KLF2 appears to be critical for full T cell activation. It is unclear, however, how KLF2 expression is maintained in naive T cells. Recently it was proposed that IL-7, which is known to promote KLF2 re-expression in antigen-stimulated T cells, may also induce KLF2 expression in naive T cells. Here we address this issue by comparing the impact of IL-7 on KLF2 expression in naive and activated T cells. Use of bcl-2 transgenic T cells allowed us to uncouple the requirements for IL-7 in preserving naive T cell survival from its role in maintaining KLF2 expression. Our data demonstrates that IL-7 signals are not required for KLF2 maintenance in naive T cells, suggesting that this cytokine has distinct effects on KLF2 expression in naive versus activated T cells.


[Exploratory research on diagnostic essentials of pediatric tuberculous pleurisy].
Objective: To summarize the clinical diagnostic essentials of pediatric tuberculous pleurisy so as to reduce the misdiagnosis rate. Method: A retrospective study was conducted on 113 cases of tuberculous pleurisy who were seen from August 2006 to September 2014 in the second Department of Respiratory Medicine, Beijing Children's Hospital Affiliated to Capital Medical University. Meanwhile, another 113 cases of children over 5 years of age with mycoplasma pneumoniae pneumonia complicated with pleural effusion were randomly selected as control group. The following five items were analyzed in relation to the diagnosis: fever, cough, lung lesions, pleural effusion(unilateral or bilateral), adenosine deaminase (ADA) level in pleural effusion, tuberculin skin test(PPD). The sensitivity and specificity of single item and combined items in diagnosis were studied. Result: (1) Among two groups, the proportion of patients with persisting fever was 92.0% (104 cases) and 98.2% (111 cases), while the proportion of patients with cough was 47.8% (54 cases) and 99.1% (112 cases) (χ(2)=76.3, P<0.01), respectively. There were 25(22.1%) cases and 113(100.0%) cases with lung lesions (except for atelectasis) in two groups (χ(2)=144.1, P<0.01), respectively. The proportion of patients with unilateral pleural effusion was 94.7%(107 cases) and 71.7%(81 cases)(χ(2)=21.4, P<0.01) while the patients with positive PPD results was 93.8%(106 cases) and 3.5%(4 cases)(χ(2)=184.3, P<0.01). The level of ADA in pleural effusion in both groups are comparable[46.4(22.0-70.9)U/L]and[39.5(26.3-78.5)U/L]. (2)The sensitivity of the lack of cough, lack of lung lesions, unilateral pleural effusion and PPD test positive in diagnosis of tuberculous pleurisy were 52.2%, 77.9%, 94.7%, 93.8%, while the specificity was 99.1%, 100.0%, 28.3%, 96.5%, respectively. Among the four items, the specificity of unilateral pleural effusion was only 28.3%, so it needed to be added with other indicators to improve the specificity. The sensitivity of unilateral pleural effusion combined with positive PPD, lack of cough, lack of lung lesions were 88.5%, 50.4% and 73.5%, while the specificity was 96.5%, 99.1%, and 100.0%, respectively, which significantly improved the specificity so as to reduce misdiagnosis. Conclusion: In children aged over 5 years who present with persistent fever and pleural effusion, tuberculous pleurisy should be considered even in the absence of cough or lung lesions(except for atelectasis), or with positive PPD result, any of the three features is specific for the diagnosis. Unilateral pleural effusion is more meaningful for the diagnosis when it is combined with any of the above three features.


Hypoxia-inducible factor 1-α in chronic gastrointestinal ischemia.
Chronic gastrointestinal ischemia (CGI) is the result of decreased mucosal perfusion. Typical histological characteristics are lacking which hamper its early diagnosis. Hypoxia-inducible factor-1α (HIF-1α) is expressed under acute hypoxia. We investigated HIF-1α expression in chronic ischemic and inflammatory conditions of the human gastrointestinal (GI) tract. Immunohistochemical expression of HIF-1α was analyzed in 61 patients, including patients with CGI, Helicobacter pylori gastritis, ischemic colitis (IC), infectious colitis, and inflammatory bowel disease (IBD), and 22 controls. HIF-1α expression in >10 % of the cells was regarded as positive staining, and expression <10 % of the cells was considered as negative staining. In the upper GI tract, HIF-1α expression was found in 5/20 CGI patients, but not in controls (p = 0.08). The sensitivity and specificity of HIF-1α expression for diagnosing CGI were 25 and 84%, respectively. In the lower GI tract, HIF-1α was expressed in all patients with IC and infectious colitis and in a majority of IBD patients as well as in 7/12 controls. The sensitivity and specificity of HIF-1α for diagnosing IC were 100 and 51%, respectively. HIF-1α expression was more often (p = 0.02) observed in patients with histological signs of inflammation in the lower GI tract. HIF-1α is expressed in acute and chronic ischemic tissue, but also in normal colon tissue and inflammatory disorders.


Differential alteration in vascular structure of resistance arteries isolated from the cerebral and mesenteric vascular beds of transgenic [(mRen-2)27], hypertensive rats.
In this study we examined the structural properties of cerebral and mesenteric resistance arteries isolated from normotensive, Sprague-Dawley (SD) rats (mean arterial pressure [MAP], 110 +/- 3 mm Hg) and hypertensive, transgenic (TG) rats (MAP, 167 +/- 4 mm Hg), which express the mouse Ren-2 renin gene. Vessels were set up in a pressure myograph, and ID and vascular wall thickness were determined at increasing intraluminal pressures. Arteries were subsequently pressurized to the MAP of the animal from which they were isolated and were fixed with glutaraldehyde before being embedded in araldite, sectioned, and examined histologically. The middle cerebral artery (MCA) isolated from SD rats and TG rats had similar media cross-sectional areas. There was no difference in MCA diameter at 10 mm Hg in vessels from TG rats compared with SD rats. However, at higher distending pressures, the diameter of the MCA from TG rats was significantly smaller than that of vessels from SD rats. This reduced ID at the higher pressures was a consequence of a decreased distensibility of the MCA from TG rats (as shown by a leftward shift of the stress-strain relationship in arteries from TG rats) and was not caused by an increase in wall thickness. First- and second-order mesenteric resistance arteries isolated from TG rats displayed an increased wall thickness and media content compared with vessels from SD rats. However, this alteration in mesenteric artery structure did not impinge on the ID of arteries from TG rats; there was no difference in the IDs of mesenteric resistance arteries between the two strains at any distending pressure. These observations show that there are distinct regional alterations in vascular structure in hypertensive TG rats expressing the mouse Ren-2 renin gene. Mesenteric resistance arteries isolated from TG rats display signs of vascular growth, although this structural alteration does not produce a reduction in the ID of these arteries per se. In contrast, cerebral arteries from TG rats do not show increased growth but have a reduced vascular distensibility, which results in a smaller ID compared with vessels from SD rats.


EP4 Receptor Conformation Sensor Suited for Ligand Screening and Imaging of Extracellular Prostaglandins.
Prostaglandins are important lipid mediators with a wide range of functions in the human body. They act mainly via plasma membrane localized prostaglandin receptors, which belong to the G-protein coupled receptor class. Due to their localized formation and short lifetime, it is important to be able to measure the distribution and abundance of prostaglandins in time and/or space. In this study, we present a Foerster resonance energy transfer (FRET)-based conformation sensor of the human prostaglandin E receptor subtype 4 (EP4 receptor), which was capable of detecting prostaglandin E2 (PGE2)-induced receptor activation in the low nanomolar range with a good signal-to-noise ratio. The sensor retained the typical selectivity for PGE2 among arachidonic acid products. Human embryonic kidney cells stably expressing the sensor did not produce detectable amounts of prostaglandins making them suitable for a coculture approach allowing us, over time, to detect prostaglandin formation in Madin-Darby canine kidney cells and primary mouse macrophages. Furthermore, the EP4 receptor sensor proved to be suited to detect experimentally generated PGE2 gradients by means of FRET-microscopy, indicating the potential to measure gradients of PGE2 within tissues. In addition to FRET-based imaging of prostanoid release, the sensor allowed not only for determination of PGE2 concentrations, but also proved to be capable of measuring ligand binding kinetics. The good signal-to-noise ratio at a commercial plate reader and the ability to directly determine ligand efficacy shows the obvious potential of this sensor interest for screening and characterization of novel ligands of the pharmacologically important human EP4 receptor. SIGNIFICANCE STATEMENT: The authors present a biosensor based on the prostaglandin E receptor subtype 4, which is well suited to measure extracellular prostaglandin E2 (PGE2) concentration with high temporal and spatial resolution. It can be used for the imaging of PGE2 levels and gradients by means of Foerster resonance energy transfer microscopy, and for determining PGE2 release of primary cells as well as for screening purposes in a plate reader setting.


Cytarabine and its effect on cerebellum of suckling mouse.
Suckling mice were injected with 30 mg/kg or 50 mg/kg body weight of cytarabine subcutaneously two, three, and four days after birth. Twenty-four hours after the final injection, these mice showed extensive necrosis of undifferentiated cells in the external granular layer of cerebellum. One or two weeks later, a new external granular layer regenerated but it did so only incompletely and regionally. The mice allowed to live longer showed impaired cerebellar function, cerebellar hypoplasia, and other malformations, including heterotopic granule cells in the molecular layer, irregularly arranged Purkinje cells, and scanty cellularity in the internal granular layer.


Clinical use of laboratory tests for the identification of secondary forms of arterial hypertension.
The prevalence of secondary hypertension can be underestimated if appropriate tests are not performed. The importance of selecting patients with a high pre-test probability of secondary forms of hypertension is first discussed. The laboratory tests currently used for seeking a cause of hypertension are critically reviewed, with emphasis on their operative features and limitations. Strategies to identify primary aldosteronism, the most frequent form of secondary hypertension, and to determine its unilateral or bilateral causes are described. Treatment entails adrenalectomy in unilateral forms, and mineralocorticoid receptor blockade in bilateral forms. Renovascular hypertension is also a common, curable form of hypertension, that should be identified as early as possible to avoid the onset of cardiovascular target organ damage. The tests for its confirmation or exclusion are discussed. The various tests available for the diagnosis of pheochromocytoma, which is much rarer than the above but extremely important to identify, are also described, with emphasis on recent developments in genetic testing. Finally, the tests for diagnosing some rarer monogenic forms and other renal and endocrine causes of arterial hypertension are explored.


Periapical cemento-osseous dysplasia: a case report with twelve-year follow-up and review of literature.
To present a case report describing the long-term behaviour of periapical cemento-osseous dysplasia by observing the radiographic changes that took place over a period of 12 years. A review of the pertinent literature is also presented. A healthy 26-year-old white female was referred to the Wilford Hall USAF Medical Center Endodontic Department for evaluation of an asymptomatic radiolucency at the apex of the right mandibular lateral incisor. Following a clinical evaluation that included pulp testing, a diagnosis of periapical cemento-osseous dysplasia (PCOD) was made. No treatment was rendered but follow-up visits were recommended. The patient was subsequently re-evaluated 8 times over a period of 12 years. During that time the lesion changed in appearance, displaying the various phases of PCOD. At the same time, lesions affecting the three adjoining incisors appeared and behaved in a similar manner. At the 12-year recall, the right lateral and both central incisors revealed no evidence of PCOD and an almost normal trabecular pattern of bone could be seen. Misdiagnosis and unnecessary treatment of PCOD may be avoided with careful pulp testing and knowledge of its most common locations of occurrence, radiographic appearances (phases) and benign behaviour.


Dynamic processes in biological membrane mimics revealed by quasielastic neutron scattering.
Neutron scattering is a powerful tool to study relaxation processes in biological membrane mimics in space and time. Combining different inelastic and quasielastic neutron scattering techniques, a large dynamic range can be covered: from atomic to mesoscopic lengths and from femto- to some hundreds of nanoseconds in time. This allows studies on e.g. the diffusion of lipids, the membrane undulation motions, the dispersion of sound waves in membranes as well as the mutual interactions of membrane constituents such as lipids, proteins, and additives. In particular, neutron scattering provides a quite direct experimental approach to the inter-atomic and inter-molecular potentials on length and time scales which are perfectly accessible by molecular dynamics (MD) simulations. Neutron scattering experiments may thus substantially support the further refinement of biomolecular force fields for MD simulations by supplying structural and dynamical information with high spatial and temporal resolution. In turn, MD simulations support the interpretation of neutron scattering data. The combination of both, neutron scattering experiments and MD simulations, yields an unprecedented insight into the molecular interactions governing the structure and dynamics of biological membranes. This review provides an overview of the molecular dynamics in biological membrane mimics as revealed by neutron scattering. It focuses on the latest findings such as the fundamental molecular mechanism of lateral lipid diffusion as well as the influence of additives and proteins on the short-time dynamics of lipids. Special emphasis is placed on the comparison of recent neutron scattering and MD simulation data with respect to molecular membrane dynamics on the pico- to nanosecond time scale.


Immunoglobulin therapy of neonatal group B streptococcal infections: an overview.
Group B streptococci (GBS) are a major cause of sepsis and meningitis in newborn babies. Neonatal GBS infections are often rapidly progressive, suggesting that the immunity to GBS is deficient. Studies have shown that opsonic antibody is required for efficient phagocytosis and killing of GBS, and neonatal GBS infections have been associated with diminished levels of anti-GBS antibody. Intravenous immunoglobulin (IVIG) has been shown to provide protective immunity in experimental GBS infection models. However, lot to lot variation in opsonic antibody levels occurs in standard IVIG preparations. Recently hyperimmune anti-GBS IVIG has been prepared with high levels of opsonic and protective antibody to GBS. Hyperimmune IVIG preparations will allow physicians to give higher quantities of specific anti-GBS antibody without having to administer large fluid volumes or large amounts of nonspecific immunoglobulin. In addition specific immunoglobulin preparations will ensure that the IVIG contains reliable antibacterial activity. Although human studies are limited they suggest that IVIG therapy in neonates may be safe and effective in treating neonatal sepsis. However, further studies are necessary to determine the role of IVIG in preventing or treating neonatal infections.


Turtle interacts with borderless in regulating glial extension and axon ensheathment.
Proper recognition between axons and glial processes is required for the establishment of axon ensheathment in the developing nervous system. Recent studies have begun to reveal molecular events underlying developmental control of axon-glia recognition. In our previous work, we showed that the transmembrane protein Borderless (Bdl) is specifically expressed in wrapping glia (WG), and is required for the extension of glial processes and the ensheathment of photoreceptor axons in the developing Drosophila visual system. The exact mechanism by which Bdl mediates axon-glia recognition, however, remains unknown. Here, we present evidence showing that Bdl interacts with the Ig transmembrane protein Turtle (Tutl). Tutl is specifically expressed in photoreceptor axons. Loss of tutl in photoreceptors, like loss of bdl in WG, disrupts glial extension and axon ensheatment. Epistasis analysis shows that Tutl interacts genetically with Bdl. Tutl interacts with Bdl in trans in cultured cells. We propose that Tutl interacts with Bdl in mediating axon-glia recognition for WG extension and axon ensheathment.


Factors associated with dietary habits and mood states affecting taste sensitivity in Japanese college women.
We conducted a cross-sectional survey to evaluate the factors associated with dietary habits and mood states affecting taste sensitivity in 127 Japanese college women with a mean age of 19.2 y. Differential thresholds for the four basic tastes on the tongue were determined by the filter paper disc method, while dietary intake was assessed using a food frequency questionnaire. Psychological mood states were evaluated by the Profile of Mood State (POMS) questionnaire. Differential thresholds for saltiness and bitterness in alcohol drinkers were higher than those in alcohol non drinkers, whereas differential thresholds for the other tastes did not differ significantly between any of the stratified groups. Canonical correlation analysis revealed that among the five POMS mood states, POMS fatigue scores showed relatively stronger association with combined variables of taste thresholds. Logistic regression analysis revealed significant involvement of zinc and iron intake, and that POMS fatigue and anger scores affected the differential threshold for sourness. Specific mood and dietary factors were shown to be associated with sensitivity to sourness and bitterness. Among the five POMS mood states, high POMS fatigue scores and low POMS anger scores appeared to be associated with decreased taste sensitivity.


[Integration of new nurses in nursing units in a university hospital].
The study presented in this article raises the problems of the integration of recently graduated nurses in the hospital from the point of view of a culture difference between the two socialisation worlds: more reflexive standards of behaviour and culture in the schools (emphasis on analysis, knowledge, care actions argumentation...) and more instrumental ones in the hospitals (emphasis on efficiency, work organisation, operationality...). An enquiry by means of interviews with recent graduates from different schools (open, semi-open and closed questions) enables to successively analyse the skills they consider to have acquired at school, the ones they consider as required by the hospital and the differences they feel between hospital and school concerning the enhanced skills. The results show a significant discrepancy between the ideal of the interviewed nurses and the reality of their work within the institutional constraints of the hospital.


Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.
The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8,823 age-associated differentially methylated CpG probes. Notably, these age-associated changes tended to level off after the age of 60, as confirmed by Horvath's clock. Using stringent selection criteria, we further identified a DNA methylation signature of aging liver including 75 genomic regions. We demonstrated that this signature is specific for liver compared to other tissues and that it is able to detect biological age-acceleration effects associated with obesity. Finally, we combined DNA methylation measurements with available expression data. Although the intersection between the two omic characterizations was low, both approaches suggested a previously unappreciated role of epithelial-mesenchymal transition and Wnt-signaling pathways in the aging of human liver.


Supportive Care Needs of Iranian Cancer Survivors and Relationships with Social Support.
Assessment of supportive care needs of cancer survivors and identifying factors affecting such needs is important for implementation of any supportive care programs. So, the aims of present study were to investigate the supportive care needs of Iranian cancer survivors and relationships with social support. In this descriptive-correlational study two hundred and fifty cancer survivors participated via convenient sampling methods. The Supportive Care Needs Survey (SCNS-SF34) and Multidimensional Scale of Perceived Social Support (MSPSS) were used for data collection. SPSS software was applied and univariate regression was used for examine relationships of supportive care needs with social support. Participants demonstrated many unmet supportive care needs, especially in health system and information and psychological domains. In addition, participants reported that family members and significant others were their main source of support. Also, social support has a significant correlation with all domains of supportive care needs. There is an indispensable need for establishment of supportive care programs for Iranian cancer survivors. In addition, family members of family members of such survivors are an important resource to help develop such programs.


Hyponatremia, hyperkalemia and hypercalcemia after ileal conduit diversion.
In all types of urinary diversion interchange of electrolytes between blood and the urine in the lumen of the conduit may occur, resulting in electrolyte abnormalities. We describe a 67-year-old woman who developed hyponatremia, hyperkalemia and hypercalcemia following ureteroileocutaneostomy. The hyperkalemia and hypercalcemia were successfully treated with sodium polystyrene sulfonate.


Rey Auditory-Verbal Learning Test performance of patients with and without memory impairment.
Investigated performance on the Rey Auditory Verbal Learning Test (AVLT) of 92 psychiatric and neurological patients classified as memory-impaired (N = 45) or non-memory-impaired (N = 47). The groups were comparable on age and education. Relative to the non-memory-impaired Ss, performance of the memory-impaired patients was significantly lower on all AVLT scores, ps less than .01. The AVLT appears to hold promise as a quick screening measure for the clinical evaluation of patients with suspected verbal learning and memory impairments.


Tranexamic acid for the management of uterine fibroid tumors: A systematic review of the current evidence.
To conduct a detailed systematic review of the current evidence on the administration and efficacy of tranexamic acid in patients with menorrhagia due to uterine fibroids. We conducted an electronic search on the following databases PubMed and Medline (1950-2013); (1980-2013); Cochrane library (1993-2013). A total of 36 articles were retrieved after the initial electronic search. Careful assessment of the retrieved studies led to the final selection of 5 articles for inclusion in the review. Tranexamic acid may reduce blood loss perioperatively in myomectomies. It may reduce the menorrhagia in patients with fibroids, however a stratification of fibroids by size and location is required to define the responses. It is safe in general, with mild adverse effects observed in some cases. More studies with a double-blind randomized design and larger numbers of participants are necessary to reach more precise and safe conclusions.


A photo-Favorskii ring contraction reaction: the effect of ring size.
The effect of ring size on the photo-Favorskii induced ring-contraction reaction of the hydroxybenzocycloalkanonyl acetate and mesylate esters (7a-d, 8a-c) has provided new insight into the mechanism of the rearrangement. By monotonically decreasing the ring size in these cyclic derivatives, the increasing ring strain imposed on the formation of the elusive bicyclic spirocyclopropanone 20 results in a divergence away from rearrangement and toward solvolysis. Cycloalkanones of seven or eight carbons undergo a highly efficient photo-Favorskii rearrangement with ring contraction paralleling the photochemistry of p-hydroxyphenacyl esters. In contrast, the five-carbon ring does not rearrange but is diverted to the photosolvolysis channel avoiding the increased strain energy that would accompany the formation of the spirobicyclic ketone, the "Favorskii intermediate 20". The six-carbon analogue demonstrates the bifurcation in reaction channels, yielding a solvent-sensitive mixture of both. Employing a combination of time-resolved absorption measurements, quantum yield determinations, isotopic labeling, and solvent variation studies coupled with theoretical treatment, a more comprehensive mechanistic description of the rearrangement has emerged.


[Role of intracellular zinc in programmed cell death].
Apoptosis is a type of cell death involved in several biological events during tissue development, remodelling or involution. It could be induced by several extracellular or intracellular stimuli with an important role for metals like zinc or calcium. Cellular zinc is described as an inhibitor of apoptosis, while its depletion induces death in many cell lines. Using different chemical tools like specific zinc-chelators or ionophores, it is possible to study and understand the mechanisms of programmed cell death induction. The decrease in intracellular zinc concentration induces a characteristic apoptosis with apoptotic bodies formation and nuclear DNA condensation and fragmentation. This zinc depletion activates the caspases-3, -8 and -9, responsible for the proteolysis of several target proteins like poly(ADP-ribose) polymerase or transcription factors. Zinc addition in cell culture medium prevents the apparition of morphological and biochemical signs induced by intracellular zinc chelation, but also by other apoptosis inducers like etoposide or tumour necrosis factor alpha (TNF alpha). However, excess of zinc can also be cytotoxic. The balance between life and cell death is maintained by several zinc channels, controlling the intracellular zinc movements and the free amount of the metal.


Malocclusion after open reduction of midfacial fracture: a case report.
Malocclusion is a serious complication of open reduction surgery for facial fractures. It is often caused by the lack of adequate consideration for the occlusal relationship before the trauma and intermaxillary fixation during the operation. This is a case report of postoperative malocclusion that occurred in a patient with a midfacial complex fracture.


The Lack of Dopamine Transporter Is Associated With Conditional Associative Learning Impairments and Striatal Proteomic Changes.
Dopamine (DA) is critically involved in different functions of the central nervous system (CNS) including control of voluntary movement, affect, reward, sleep, and cognition. One of the key components of DA neurotransmission is DA reuptake by the DA transporter (DAT), ensuring rapid clearance of DA from the synaptic cleft. Thus, lack of DAT leads to persistent high extracellular DA levels. While there is strong evidence for a role of striatal dopaminergic activity in learning and memory processes, little is known about the contribution of DAT deficiency to conditional learning impairments and underlying molecular processes. DAT-knockout (DAT-KO) rats were tested in a set of behavioral experiments evaluating conditional associative learning, which requires unaltered striatal function. In parallel, a large-scale proteomic analysis of the striatum was performed to identify molecular factors probably underlying behavioral patterns. DAT-KO rats were incapable to acquire a new operant skill in Pavlovian/instrumental autoshaping, although the conditional stimulus-unconditional stimulus (CS-US) association seems to be unaffected. These findings suggest that DAT directly or indirectly contributes to the reduction of transference of incentive salience from the reward to the CS. We propose that specific impairment of conditional learning might be caused by molecular adaptations to the hyperdopaminergic state, presumably by dopamine receptor 1 (DRD1) hypofunction, as proposed by proteomic analysis. Whether DRD1 downregulation can cause cognitive deficits in the hyperdopaminergic state is the subject of discussion, and further studies are needed to answer this question. This study may be useful for the interpretation of previous and the design of future studies in the dopamine field.


Quantitative assessment of differential sensory blockade after lumbar epidural lidocaine.
A cutaneous current perception threshold (CPT) sensory testing device measures both large and small diameter sensory nerve fiber function and may be useful in evaluating differential neural blockade. Eight subjects received both lumbar epidural saline and lumbar epidural lidocaine. Five milliliters of normal saline was administered and the CPTs were measured. After the saline, 10 mL of 2% plain lidocaine was administered. CPTs, and sensation to touch, pinprick, and cold were subsequently measured. Saline had no effect on any measurements. Lidocaine caused an increase in all CPTs at the umbilicus and the knee reaching a statistical significance at 5 Hz for the umbilicus only. The great toe showed a slight increase of the 5 Hz stimulus and no increase of the 2000 or 250 Hz stimulus. There was a significant decrease in touch, pinprick, and cold sensation at the umbilicus and knee and a significant decrease in the cold sensation at the great toe. There was no effect on any measurements made at the mastoid. Epidural lidocaine resulted in a differential neural blockade as measured by a CPT monitor but not with crude sensory measurements.


Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats.
Effect of Gymnema sylvestre, R.Br. (G. sylvestre; GS4) on glucose homeostasis was studied in rats. In the first set of experiments, the acute effect of GS4 was examined in both non-diabetic and streptozocin (30 mg/kg)-induced mildly diabetic rats. Administration of 1 g/kg body weight of GS4 to 18-h fasted non-diabetic rats significantly attenuated the serum glucose response to oral administration of 1 g/kg glucose. The immunoreactive insulin (IRI) response in GS4-administered rats was lower, but not significantly, than that in control rats. In mildly diabetic rats, a 60 min increment in serum glucose concentrations was significantly reduced by GS4 administration. No IRI response was observed in these diabetic rats irrespective of GS4 administration. In the second set of experiments, the chronic effect of GS4 was examined in mildly diabetic rats. Two weeks after the induction of diabetes, the rats were divided into two groups that had similar impairment of glucose tolerance assessed by an oral glucose loading test. The rats were fed for 32-35 days with either a control diet or a diet supplemented with GS4. After 4 weeks, GS4 showed a tendency to reduce the serum glucose concentrations in the fed state and to improve the glucose tolerance. Gain in body weight, food intake, pancreas weight and the pancreatic contents of IRI, protein, amylase and trypsinogen were unaltered in the GS4-treated group compared with the control. These results suggest the usefulness of G. sylvestre in the treatment of certain classes of non-insulin-dependent diabetes mellitus.


Impact of hyperventilation and apnea on myocardial oxygenation in patients with obstructive sleep apnea - An oxygenation-sensitive CMR study.
Oxygenation-sensitive cardiovascular magnetic resonance imaging (OS-CMR) is an emerging technique that can monitor changes in myocardial oxygenation in vivo. Obstructive sleep apnea syndrome (OSAS) is associated with endothelial and microcirculatory dysfunction and increased cardiovascular morbidity and mortality. Little is known about myocardial responses to apnea in patients with OSAS. We hypothesized that the coronary vascular response to hyperventilation and long breath-hold is diminished in patients with OSAS when compared to healthy volunteers. Twenty-nine OSAS patients and 36 healthy volunteers were prospectively enrolled. All CMR scans were performed on a clinical 3T system. Participants performed a breathing maneuver with 60s of hyperventilation followed by a maximal breath-hold. During the breath-hold, OS-CMR images were continuously acquired and signal intensity changes were measured by a blinded reader. Patients with OSAS were older than healthy volunteers (p<0.01) and presented more co-morbidities; 66% were currently treated with nocturnal positive airway pressure. Compared to healthy participants, the expected increase of myocardial oxygenation during the first 15s of the breath-hold was significantly lower in patients with OSAS (2.6±8.3% vs. 6.7±5.6%; p<0.05), and remained reduced at all time points during the breath-hold. Importantly this result was mainly driven by patients under continuous positive airway pressure (CPAP), suggesting that CPAP might have a greater impact on increase of myocardial oxygenation rather than OSAS itself. The myocardial vascular response to combined breathing maneuvers of hyperventilation followed by voluntary apnea is blunted in patients with obstructive sleep apnea. Clinical studies should now further define the clinical role of oxygenation-sensitive CMR in patients with respiratory disorders.