Clinical study on laparoscopic minimally invasive surgery and transumbilical single-port laparoscopic surgery in the treatment of benign ovarian tumours and its influence on ovarian functions.
The objective of this study was to explore the influence of traditional laparoscopic surgery and transumbilical single-port laparoscopic surgery on ovarian function in patients with benign ovarian tumours. Forty-four patients with benign ovarian tumours who were treated in our hospital from January 2020 to June 2021 were selected and randomly divided into two groups, with 22 cases in each group according to random number table. The conventional group was treated with conventional laparoscopic surgery, while the modified group was treated with transumbilical single-port laparoscopic surgery. The measurement method was t-test, and the enumeration method was two tests. The clinical operation-related indicators, ovarian function (follicle-stimulating hormone, E2 and luteinising hormone), complication incidence, Visual Analogue Scale (VAS) and landscaping satisfaction scores of the two groups were compared. There were no significant differences in complications and operation duration between the two groups (P > 0.05). After treatment, the ovarian function indexes and beautification satisfaction scores of the modified group were significantly superior to those of the conventional group (P < 0.05). Besides, the intraoperative bleeding volume, post-operative exhaust time, hospital stay and three-dimensional VAS scores on day 1 and day 3 after surgery of the modified group were lower than those of the conventional group (P < 0.05). Transumbilical single-port laparoscopic surgery for benign ovarian tumours has a significant clinical effect, which can effectively reduce bleeding during the operation, improve ovarian function, relieve surgical pain, promote rapid post-operative recovery and improve patients' satisfaction with landscaping. It is worthy of clinical application.


Diffuse alveolar hemorrhage in childhood-onset systemic lupus erythematosus: a severe disease flare with serious outcome.
To evaluate prevalence, clinical manifestations, laboratory abnormalities and treatment in a multicenter cohort study including 847 childhood-onset systemic lupus erythematosus (cSLE) patients with and without diffuse alveolar hemorrhage (DAH), as well as concomitant parameters of severity. DAH was defined as the presence of at least three respiratory symptoms/signs associated with diffuse interstitial/alveolar infiltrates on chest x-ray or high-resolution computer tomography and sudden drop in hemoglobin levels. Statistical analysis was performed using Bonferroni correction (p < 0.0022). DAH was observed in 19/847 (2.2%) cSLE patients. Cough/dyspnea/tachycardia/hypoxemia occurred in all cSLE patients with DAH. Concomitant parameters of severity observed were: mechanical ventilation in 14/19 (74%), hemoptysis 12/19 (63%), macrophage activation syndrome 2/19 (10%) and death 9/19 (47%). Further analysis of cSLE patients at DAH diagnosis compared to 76 cSLE control patients without DAH with same disease duration [3 (1-151) vs. 4 (1-151) months, p = 0.335], showed higher frequencies of constitutional involvement (74% vs. 10%, p < 0.0001), serositis (63% vs. 6%, p < 0.0001) and sepsis (53% vs. 9%, p < 0.0001) in the DAH group. The median of disease activity score(SLEDAI-2 K) was significantly higher in cSLE patients with DAH [18 (5-40) vs. 6 (0-44), p < 0.0001]. The frequencies of thrombocytopenia (53% vs. 12%, p < 0.0001), intravenous methylprednisolone (95% vs. 16%, p < 0.0001) and intravenous cyclophosphamide (47% vs. 8%, p < 0.0001) were also significantly higher in DAH patients. This was the first study to demonstrate that DAH, although not a disease activity score descriptor, occurred in the context of significant moderate/severe cSLE flare. Importantly, we identified that this condition was associated with serious disease flare complicated by sepsis with high mortality rate.


A review of the physiological and immunological functions of biliary epithelial cells: targets for primary biliary cirrhosis, primary sclerosing cholangitis and drug-induced ductopenias.
Our understanding of biliary epithelial cells (BEC) in physiobiology and immunology has steadily expanded. BEC transports IgA as well as IgM into bile, synthesizes and secretes various chemokines, cytokines, and expresses adhesion molecules involved in cell interaction and signal transduction. These then suggest a myriad of potential roles for BEC in defense from invading microorganisms as well as the pathogenesis of diverse immunologically driven diseases such as primary biliary cirrhosis (PBC), graft-versus-host disease, and primary sclerosing cholangitis (PSC). Despite the progress, there still remain many areas of BEC biology that require further investigation. Most importantly, it remains to be clarified that the extent to which the immunologic activities observed in BEC represent a BEC response to tissue injury or whether BEC themselves are the active participants in the pathogenesis of various cholestatic immunological diseases, including PBC and PSC.


Early detection of protein energy malnutrition in Sharkia Governorate.
The objective of this cross-sectional study was to assess the nutritional status of children, aged 6 to 36 months, in Sharkia Governorate aiming for early detection of malnourished cases. the present study was carried out on 1000 children aged 6 to 36 months, selected by a multistage random sample from 6 villages in two districts in Sharkia Governorate. Data were gathered by an interview questionnaire to the child's mother or care giver at their homes. Anthropometric measurements as height, weight, mid-arm, head circumference and skin fold thickness were assessed. Body mass index was calculated. Dietary evaluation was done by a 24 hours recall for amounts and frequencies of food and was transferred to their recommended daily allowance (RDA). The studied children were classified into three groups according to their weight for age percentiles, underweight children, borderline malnourished children and normal weight children. Serum hemoglobin, pre-albumin and albumin were assessed for a randomly selected number of the studied group. the study showed that all anthropometric measurements were lower than normal in underweight and borderline subjects. The prevalence rates of wasting, stunting and underweight were 15%, 24.4% and 15.4% in the studied infants in Sharkia Governorate, respectively. The study revealed that nutrient intake of the study subjects was lower than the RDA for the energy intake from carbohydrates, vitamin D, and iron, while it was higher than the RDA for the energy intake from lipids and vitamin A and equal to the lower level of the normal range of RDA for the energy intake from proteins. Most of the protein intake was of plant origin. Caloric intake was less than RDA in underweight and border line children, but more than RDA in normal children (86%, 90% and 102%). The ratios of caloric intake to the required calories according to weight were 90%, 98% and 108% in the three groups respectively. Chronic cough and chronic and recurrent diarrhea were more complained by underweight and borderline children. Underweight children were more infested with oxyurius and entamoeba histolitica than the other 2 groups. Serum hemoglobin, albumin and plasma pre-albumin levels were within normal range with significantly lower values in underweight and borderline infants compared to normal children. By multiple linear regression analysis, the most important factors affecting BMI were carbohydrate, lipid and caloric intake, serum albumin, plasma pre-albumin, vitamin A and D intake and protein intake. There is a high prevalence of wasting ,stunting and underweight among infants and children of the studied sample in Sharkia governorate explained by the low socioeconomic status, unbalanced diet. Early changes of protein energy malnutrition were detected, in spite of the fact that serum hemoglobin, albumin and plasma pre-albumin levels were within normal range, they were significantly lower in underweight and borderline infants compared to normal children.


Catalytic Asymmetric Conjugate Addition of Indolizines to α,β-Unsaturated Ketones.
A catalytic enantioselective conjugate addition of indolizines to enones is described. The chiral phosphoric acid (S)-TRIP activates α,β-unsaturated ketones, thereby promoting an enantioface-differentiating attack by indolizines. Using this reaction, several alkylated indolizines were synthesized in good yields and with enantiomeric ratios of up to 98:2.


Maternal thyroid hormone before the onset of fetal thyroid function regulates reelin and downstream signaling cascade affecting neocortical neuronal migration.
Though aberrant neuronal migration in response to maternal thyroid hormone (TH) deficiency before the onset of fetal thyroid function (embryonic day [E] 17.5) in rat cerebral cortex has been described, molecular events mediating morphogenic actions have remained elusive. To investigate the effect of maternal TH deficiency on neocortical development, rat dams were maintained on methimazole from gestational day 6 until sacrifice. Decreased number and length of radial glia, loss of neuronal bipolarity, and impaired neuronal migration were correctible with early (E13-15) TH replacement. Reelin downregulation under hypothyroidism is neither due to enhanced apoptosis in Cajal-Retzius cells nor mediated through brain-derived neurotrophic factor-tyrosine receptor kinase B alterations. Results based on gel shift and chromatin immunoprecipitation assays show the transcriptional control of reelin by TH through the presence of intronic TH response element. Furthermore, hypothyroidism significantly increased TH receptor α1 with decreased reelin, apolipoprotein E receptor 2, very low-density lipoprotein receptor expression, and activation of cytosolic adapter protein disabled 1 that compromised the reelin signaling. Integrins (α(v) and β₁) are significantly decreased without alteration of α₃ indicating intact neuroglial recognition but disrupted adhesion and glial end-feet attachment. Results provide mechanistic basis of essentiality of adequate maternal TH levels to ensue proper fetal neocortical cytoarchitecture and importance of early thyroxine replacement.


Minimally invasive keyhole approaches for removal of tumors of the third ventricle.
In recent years, keyhole microsurgery has become an important subject of modern minimally invasive neurosurgery. In this study, minimally invasive techniques avoiding unnecessary tissue injuries were applied to refine traditional approaches for the removal of third ventricular tumors within a limited operative filed. Individualized keyhole approaches were designed according to the characteristics of third ventricular tumors and their growth patterns. A series of keyhole approaches such as supraorbital subfrontal approach, infratentorial supracerebellar approach, interhemispheric transcallosal approach, pterional approach were taken to enter the third ventricle anteriorly, posteriorly, superiorly or laterally, respectively. A total of 34 removed tumors in or extended into the third ventricle included 11 craniopharyngiomas, 10 pituitary adenomas, 2 pinealomas, 1 cholesteatoma, 3 germinomas, and 7 gliomas. Total tumor resection was done in 27 (79.4%) of the patients, and subtotal resection in 7 patients (20.6%). Residual tumor was due to tight adherence of germinoma to the vein of Galen (1 patient), craniopharyngioma to the pituitary stalk (3), supratentorial extension of pineal region gliomas (1), suprasellar extension of gliomas (1) and giant pituitary adenoma (1). Complications such as brain contusion, postoperative hemorrhage and infection were not associated with keyhole approaches. Extended incision or enlarged bone flap was not made because of episode during operation or inadequate exposure. Keyhole approaches are safe, effective and minimally invasive in the surgical treatment of tumors deeply seated in the third ventricle. Individualized keyhole approach ensures a successful treatment. Tumors in the upper middle part of the third ventricle can be exposed by the interhemispheric transcallosal keyhole approach. Tumors of the posterior third ventricle may be well exposed by the infratentorial supracerebellar keyhole approach. Tumors of the anterior third ventricle can be entered by either a supraorbital subfrontal keyhole approach or a pterional keyhole approach.


Chronic corticosterone-induced impaired cognitive flexibility is not due to suppressed adult hippocampal neurogenesis.
Hippocampal neurogenesis has been implicated in the etiology of depression. Recent studies suggest new neurons add flexibility to hippocampal-dependent learning and memory. We hypothesized that suppressed hippocampal neurogenesis may contribute to impaired cognitive flexibility associated with depression. The chronic corticosterone (CORT)-induced animal model of depression was used. In Experiment 1, rats received either CORT (40mg/kg) or vehicle injections for 21days and were subjected to Water maze during the last six days of drug treatment. No group differences were found during the spatial learning phase; however, cognitive flexibility, measured by reversal training, was significantly impaired in the CORT-treated rats. The probe test revealed enhanced memory of the new platform location for the CORT-treated rats. Given the time newborn neurons require to mature, we presumed if impaired cognitive flexibility seen in Experiment 1 were due to suppressed neurogenesis, terminating CORT treatment 3days prior to behavioural testing should still induce the impairment. Therefore, Experiment 2 was similar to Experiment 1, except that CORT injections were terminated 3days prior to behavioural assessment. However, not only was spatial learning significantly enhanced in the CORT-treated rats, but there were also no group differences during reversal or probe tests. Bromodeoxyruidine, administered a day after the first drug treatments in both experiments, was quantified and revealed the number of new neurons were the same in both groups in both experiments. Results suggest cognitive flexibility is impaired in the CORT-induced animal model of depression; an effect that is reversible and independent of suppressed hippocampal neurogenesis.


Depressive symptoms amongst adolescent primary care attenders. Levels and associations.
Background High rates of depressive disorder have been documented amongst adolescents attending general practitioners (GPs) in urban areas. However, little is known about the associations of adolescent depression in primary care. We completed a cross-sectional questionnaire survey of adolescents, their parents and general practitioners, following adolescent attendance at the surgery. We found high levels of depressive symptoms to be present in adolescent attenders of a broad range of social backgrounds. Depressive symptoms were associated with the following demographic and contextual factors: older age, female gender and parental psychiatric symptoms. They were also associated with the presence of physical symptoms causing psychosocial impairment, with health risks (use of cannabis and exposure to drugs) and with use of services (both primary care and mental health services). Levels of depressive symptoms were similar in urban and suburban groups. However, associations of depressive symptoms with smoking, exposure to drugs, cannabis use and primary care attendance were demonstrated in the suburban group and not the urban group. Adolescent GP attenders have high levels of depressive symptomatology. GP recognition and intervention should have the potential to impact on adolescent depression and on associated risks.


Design and preparation of matrine surface-imprinted material and studies on its molecule recognition selectivity.
A matrine molecule surface-imprinted material was designed and prepared using an effective surface-imprinting technique developed by our group, and its molecular recognition performance and mechanism were investigated in depth. Monomer glycidyl methacrylate (GMA) was first graft-polymerized on the surfaces of micron-sized silica gel particles in surface-initiated graft polymerization manner, obtaining the grafted particles PGMA/SiO(2) with high grafting degree. Subsequently, the ring-opening reaction of the epoxy groups of the grafted macromolecules PGMA with 5-aminosalicylic acid (5-ASA) was carried out, resulting in the functional grafted particle SA-PGMA/SiO(2), on whose surfaces salicylic acid as functional group was chemically bonded. By right of the mutual strong secondary bond forces, electrostatic interaction and hydrogen bonding, SA-PGMA/SiO(2) particles produced strong adsorption for matrine. Finally, with this strong adsorption, matrine molecule surface imprinting was carried out on the surfaces of SA-PGMA/SiO(2) particles with ethylene glycol diglycidyl ether as cross-linking agent, resulting in the matrine molecule surface-imprinted material MIP-SAP/SiO(2). The binding characteristic of MIP-SAP/SiO(2) toward matrine was investigated in depth with both batch and column methods and using oxymatrine and cytisine as two contrast alkaloids. The experimental results show that MIP-SAP/SiO(2) has special recognition selectivity and excellent binding affinity for matrine. Relative to oxymatrine and cytisine, the selectivity coefficients of MIP-SAP/SiO(2) for matrine are 5.66 and 11.17, respectively.


The role of ultrasound in the evaluation of acute pelvic pain in pregnancy and postpartum period: a review.
Acute pelvic pain in pregnant and postpartum patients presents diagnostic and therapeutic challenges. Ultrasound remains the primary imaging modality of choice for assessing pregnant and postpartum women. The purpose of this review is to help practitioners ensure a correct diagnosis of acute pelvic pain in pregnancy and the postpartum period. This review describes the various causes and highlights the sonographic features and characteristics of acute pelvic pain in pregnancy and the postpartum period. Evaluation of acute pelvic pain in pregnancy and the postpartum period is challenging. Knowledge of the clinical settings and sonographic features of acute pelvic pain in pregnancy and the postpartum period can lead to accurate diagnosis and appropriate management of the condition.


[Acute hemorrhagic ulcer in a 3-month-old child].
A case of the acute haemorrhaging ulcus in a three-months old infant with lethal outcome is presented in this paper. The unclear proximal gastrointestinal haemorrhage didn't indicate the possibility of the presence of ulcer, due to the absence of frequent etiologic factors of the inception at this age.


Management of epilepsy in MERRF syndrome.
Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is a rare syndromic mitochondrial disorder (MID) with a broad phenotypic but narrow genotypic heterogeneity. One of the predominant phenotypic features in addition to myopathy is epilepsy. The most frequent seizure type in MERRF is generalised myoclonic seizure but also focal myoclonic, focal atonic, generalised tonic-clonic, generalised atonic, generalised myoclonic-atonic, typical absences, or tonic-clonic seizures of unknown onset have been reported. There are no guidelines available for the management of epilepsy in MERRF syndrome but several expert opinions and general recommendations for the treatment of mitochondrial epilepsy have been published. According to these recommendations the antiepileptic drugs (AEDs) of choice are levetiracetam, topiramate, zonisamide, piracetam, and benzodiazepines. Perampanel has not been applied in MERRF patients but is promising in non-mitochondrial myoclonic epilepsy. Mitochondrion-toxic agents, including mitochondrion-toxic AEDs, such as valproate, carbamazepine, phenytoin, and barbiturates, should be avoided as well as AEDs potentially enhancing the frequency of myoclonus, such as phenytoin, carbamazepine, lamotrigine, vigabatrin, tiagabine, gabapentin, pregabalin, and oxcarbazepine.


Sample size calculation of clinical trials published in two leading endodontic journals.
The purpose of this article was to evaluate the quality of sample size calculation reports in published clinical trials in Journal of Endodontics and International Endodontic Journal in years 2000-1 and 2009-10. Articles fulfilling the inclusion criteria were collected. The criteria were: publication year, research design, types of control group, reporting sample size calculation, the number of participants in each group, study outcome, amount of type I (α) and II (β) errors, method used for estimating prevalence or standard deviation, percentage of meeting the expected sample size and considering clinically importance level in sample size calculation. Data were extracted from all included articles. Descriptive analyses were conducted. Inferential statistical analyses were done using independent T-test and Chi-square test with the significance level set at 0.05. There was a statistically significant increase in years between 2009 and 10 compared to 2000-1 in terms of reporting sample size calculation (P=0.002), reporting clinically importance level (P=0.003) and in samples size of clinical trials (P=0.01). But there was not any significant difference between two journals in terms of reporting sample size calculation, type of control group, frequency of various study designs and frequency of positive and negative clinical trials in different time periods (P>0.05). Sample size calculation in endodontic clinical trials improved significantly in 2009-10 when compared to 2000-1; however further improvements would be desirable.


Within- and between-session reliability of medial gastrocnemius architectural properties.
This study aimed to determine the within- and between-session reliability of medial gastrocnemius (MG) architecture (e.g. muscle thickness (MT), fascicle length (FL) and pennation angle (PA)), as derived via ultrasonography followed by manual digitization. A single rater recorded three ultrasound images of the relaxed MG muscle belly for both legs of 16 resistance trained males, who were positioned in a pronated position with their knees fully extended and the ankles in a neutral (e.g. 90°) position. A subset of participants (n = 11) were retested under the same conditions ~48-72 hours after baseline testing. The same rater manually digitized each ultrasound image on three occasions to determine MG MT, FL and PA before pooling the data accordingly to allow for within-image (n = 96), between-image (n = 32) and between-session reliability (n = 22) to be determined. Intraclass correlation coefficients (ICCs) demonstrated excellent within-image (ICCs = 0.99-1.00, P < 0.001) and very good between-image (ICCs = 0.83-0.95, P < 0.001) and between-session (ICCs = 0.89-0.95, P < 0.001) reliability for MT, FL and PA. Between-session coefficient of variation was low (≤ 3.6%) for each architectural parameter and smallest detectible difference values of 10.6%, 11.4% and 9.8% were attained for MT, FL and PA, respectively. Manually digitizing ultrasound images of the MG muscle at rest yields highly reliable measurements of its architectural properties. Furthermore, changes in MG MT, FL and PA of ≥ 10.6%, 11.4% and 9.8% respectively, as brought about by any form of intervention, should be considered meaningful.


Advanced endovascular training for vascular residents: what more do we need?
In the 25 years that formalized vascular surgery training and certification has been, in effect, the treatment of patients with peripheral vascular disease has undergone dramatic changes, largely due to the emergence of a wide variety of endoluminal techniques and devices that enable minimally invasive treatment of conditions that formerly required operative intervention. Unfortunately, vascular surgeons, for the most part, were painfully slow to embrace these new and evolving technologies, which became increasingly complex as they expanded to treat virtually all vascular maladies in all peripheral vascular territories. Not surprisingly, this left vascular surgeons disadvantaged relative to other disciplines for whom these techniques were more familiar, and we have spent the better part of the last decade playing catch-up to master them and regain our role as the only specialty qualified to offer all types of therapies to our patients with vascular disease. This has caused some to question what changes need to be made in our vascular surgery training paradigm for our new trainees to attain and maintain a preeminent role in the evaluation and treatment of patients with peripheral vascular disease. While the knee-jerk response is to consider special or supplemental training programs for these advanced techniques, or even certificates of added qualifications for the more challenging of them, such as carotid stenting, we believe that all that is really needed is for the vascular surgical community as a whole, and particularly those faculty in training programs, to truly embrace these new technologies and apply them to the patients they are already rendering care to. Given the prevalence of vascular disease and overall wealth of clinical material already present in most training programs, the simple willingness to apply endoluminal therapies to our existing patient populations is all that would really be needed to insure that all future graduates of vascular surgery training programs are fully competent in all of the current endoluminal therapies and well-positioned to continue to evolve with the field. The real question to be considering, which is beyond the focus of this article, is how we are to maintain our open surgical skills in the era of minimally invasive treatment of vascular disease.


Base-Anchored Model for Highly Scalable and Accessible Compression of Multiview Imagery.
We present a compression scheme for multiview imagery that facilitates high scalability and accessibility of the compressed content. Our scheme relies upon constructing at a single base view, a disparity model for a group of views, and then utilizing this base-anchored model to infer disparity at all views belonging to the group. We employ a hierarchical disparity-compensated inter-view transform where the corresponding analysis and synthesis filters are applied along the geometric flows defined by the base-anchored disparity model. The output of this inter-view transform along with the disparity information is subjected to spatial wavelet transforms and embedded block-based coding. Rate-distortion results reveal superior performance to the x.265 anchor chosen by the JPEG Pleno standards activity for the coding of multiview imagery captured by high-density camera arrays.


Congenital upper auricular detachment: Report of two unusual cases.
Two unusual cases of congenital bilateral ear deformity have been presented. The deformity is characterized by upper auricular detachment on the right side with anotia on the left side in the first case and upper auricular detachment on the left side with normal ear on the right side in the second case. An attempt has been made to correlate the presented deformity with the embryological - foetal development of the auricle. Satisfactory correction can be obtained by repositioning the auricle back in to its normal position.


Enhancement of serum-response factor-dependent transcription and DNA binding by the architectural transcription factor HMG-I(Y).
The mechanisms by which HMG-I proteins regulate cell growth are unknown, and their effects on gene expression have only been partially elucidated. We explored the potential interaction between HMG-I proteins and serum-response factor (SRF), a member of the MADS-box family of transcription factors. In cotransfection experiments, HMG-I(Y) potentiated SRF-dependent activation (by more than 5-fold) of two distinct SRF-responsive promoters, c-fos and the smooth muscle-specific gene SM22alpha. This effect was also observed with a heterologous promoter containing multiple copies of the CC(A/T)6GG (CArG) box. HMG-I proteins bound specifically to the CArG boxes of c-fos and SM22alpha in gel mobility shift analysis and enhanced binding of SRF to these CArG boxes. By chelating peptide-immobilized metal affinity chromatography, we mapped the domain of HMG-I(Y) that interacts with SRF to amino acids 50-81, a region that does not bind specifically to DNA in electrophoretic mobility shift assays even though it includes the third AT-hook DNA-binding domain. Surprisingly, HMG-I(Y) mutants that failed to bind DNA still enhanced SRF binding to DNA and SRF-dependent transcription. In contrast, deletion of the HMG-I(Y) 50-81 domain that bound SRF prevented enhancement of transcription. To our knowledge, this is the first report of an HMG-I protein interacting with a MADS-box transcription factor. Our observations suggest that members of the HMG-I family play an important role in SRF-dependent transcription and that their effect is mediated primarily by a protein-protein interaction.


Serological evidence of hantavirus infections in Malaysia.
Hantaviruses are primarily rodent-borne and transmission is by inhalation of virus-contaminated aerosols of rodent excreta, especially urine and saliva. The genus Hantavirus, family Bunyaviridae, comprises at least 14 serotypes and the symptoms of clinical illness range from mild fever to severe hemorrhagic manifestations with renal complications. Many countries in Southeast Asia are unaware of the importance of hantavirus infections and give them low priority. Malaysia, like other countries in the region, has conducted very few studies on the epidemiology of hantaviruses - and even these were conducted in the 1980s. Using a more extensive range of hantavirus antigens, we conducted a seroprevalence study of rodents and humans and found further evidence of hantavirus infections. Moreover, the data from the antibody profiles strongly suggest the presence of different hantaviruses at the study sites.


Halothane increases Ca2+ efflux via Ca2+ channels of sarcoplasmic reticulum in chemically skinned rat myocardium.
1. A method has been developed to study Ca2+ fluxes across the sarcoplasmic reticulum (SR) of chemically (saponin) skinned myocardium without interference from the SR Ca2+ pump. 2. Exposure of rat cardiac trabeculae to a solution containing 50 micrograms/ml saponin for 10 min or longer caused an SR Ca2+ efflux which was not blocked by Ruthenium Red (RRed) and did not require the presence of nucleotides. 3. Exposure of the saponin-treated cardiac preparation to 11 mM-AMP, when the SR Ca2+ pump was not active, enhanced Ca2+ release from the SR by a mechanism which was blocked by 10 microM-RRed. 4. The amount of Ca2+ loaded by the 10 min saponin-treated trabeculae was maintained constant for at least 3 min when the preparations were transferred to low [Ca2+] solutions (0.1 mM-EGTA; pCa greater than 7.5) containing ATP. This indicated that the Ca2+ pump can efficiently recycle Ca2+ lost from the SR under these conditions. 5. Halothane (0.47 and 1.89 mM) reversibly increased the rate of Ca2+ release from the SR regardless of whether or not the SR Ca2+ pump was active. This effect was more marked at 1.89 mM than at 0.47 mM. RRed (10 microM) completely blocked the Ca2+ release induced by both concentrations of halothane. 6. The presence of nucleotide (11 mM-AMP) did not affect the halothane-induced Ca2+ release when the Ca2+ pump was inactive. 7. Exposure of cardiac preparations to solutions containing more than 5 mM-halothane irreversibly damaged the ability of the SR to load Ca2+. 8. The results suggest that at lower doses (0.47 and 1.89 mM) halothane specifically and reversibly stimulates Ca2+ efflux via the RRed-sensitive SR Ca2(+)-release channel by a mechanism which does not require the presence of nucleotides or relatively high [Ca2+]. The results also suggest that AMP and halothane act independently and non-synergistically to increase Ca2+ efflux through the same SR Ca2(+)-release channel. At higher doses (greater than 5 mM) halothane irreversibly damages the SR membrane, presumably by disrupting the lipid bilayer.


Optronic convolutional neural networks of multi-layers with different functions executed in optics for image classification.
Although deeper convolutional neural networks (CNNs) generally obtain better performance on classification tasks, they incur higher computation costs. To address this problem, this study proposes the optronic convolutional neural network (OPCNN) in which all computation operations are executed in optics, and data transmission and control are executed in electronics. In OPCNN, we implement convolutional layers with multi input images by the lenslet 4f system, downsampling layers by optical-strided convolution and obtaining nonlinear activation by adjusting the camera's curve and fully connected layers by optical dot product. The OPCNN demonstrates good performance on the classification tasks in simulations and experiments and achieves better performance than other current optical convolutional neural networks by comparison due to the more complex architecture. The scalability of OPCNN contributes to building deeper networks when facing complicated datasets.


[Review and perspective of a long-term follow-up of two cohorts of workers heavily exposed to asbestos].
National screening programs for detection of breast, colon and cervical cancers have been set up in France. Occupational cancers are excluded from these programs. Surveillance is left to the initiative of former employees who can initiate post-professional medical monitoring. This study describes an experience of such monitoring organised by the health insurance in collaboration with "victims". The long term follow-up, every two years, of 324 workers directly and heavily exposed to asbestos confirms the high risk of developing lung cancer, mesothelioma or asbestosis, the latter at times rapidly evolving. The early discovery of 3 bronchopulmonary cancers points to the interest of an annual or biannual routine screening. While new imaging techniques reduce by a factor of 8 irradiation, without significantly affecting the diagnostic capacity, the health benefit provided by annual monitoring scanner in heavy smokers favors an early detection program for lung cancers. The population targeted for such a screening (active or former smoker with pleural plaques) should be defined in more detail. The increasingly frequent observation of lung or pleural changes besides the populations at risk should also be considered. Therefore the detecting procedures applied to those workers indirectly or discontinuously exposed should be reassessed (only 1 TDM at 60 y, or on retirement, for the relevant occupations). These data suggest that the recommendation HAS 2010 for post-professional screening of workers occupationally exposed to asbestos should be reconsidered, particularly in case of pleural plaques. An organized screening program needs to be overhauled.


Integrative genomic analysis identifies a role for intercellular adhesion molecule 1 in childhood asthma.
Childhood asthma is characterized by chronic airway inflammation. Integrative genomic analysis of airway inflammation on genetic and protein level may help to unravel mechanisms of childhood asthma. We aimed to employ an integrative genomic approach investigating inflammation markers on DNA, mRNA, and protein level at preschool age in relationship to asthma development. In a prospective study, 252 preschool children (202 recurrent wheezers, 50 controls) from the Asthma DEtection and Monitoring (ADEM) study were followed until the age of six. Genetic variants, mRNA expression in peripheral blood mononuclear cells, and protein levels in exhaled breath condensate for intercellular adhesion molecule 1 (ICAM1), interleukin (IL)4, IL8, IL10, IL13, and tumor necrosis factor α were analyzed at preschool age. At six years of age, a classification (healthy, transient wheeze, or asthma) was based on symptoms, lung function, and medication use. The ICAM1 rs5498 A allele was positively associated with asthma development (p = 0.02) and ICAM1 gene expression (p = 0.01). ICAM1 gene expression was positively associated with exhaled levels of soluble ICAM1 (p = 0.04) which in turn was positively associated with asthma development (p = 0.01). Furthermore, rs1800872 and rs1800896 in IL10 were associated with altered IL10 mRNA expression (p < 0.01). Exhaled levels of IL4, IL10, and IL13 were positively associated with asthma development (p < 0.01). In this unique prospective study, we demonstrated that ICAM1 is associated with asthma development on DNA, mRNA, and protein level. Thus, ICAM1 is likely to be involved in the development of childhood asthma.


Federal Employees Health Benefits Program and Federal Employees Dental and Vision Insurance Program: eligibility for Pathway Programs participants. Interim final rule with request for comments.
The U.S. Office of Personnel Management (OPM) is issuing an interim final regulation to update the Federal Employees Health Benefits Program (FEHBP) and the Federal Employees Dental and Vision Insurance Program (FEDVIP) regulations to reflect updated election opportunities for participants in the Pathways Programs. The Pathways Programs were created by Executive Order (E.O.) 13562, signed by the President on December 27, 2010, and are designed to enable the Federal Government to compete effectively for students and recent graduates by improving its recruitment efforts through internships and similar programs with Federal agencies. This interim final rule furthers these recruitment and retention efforts by providing health insurance, as well as dental and vision benefits, to eligible program participants and their families.


[Amplification and typing of Sta56 gene of Orientia tsutsugamushi from Shandong province].
To clarify the gene type of Orientia tsutsugamushi (Ot) from Shandong province. Nested-polymerase chain reaction (nPCR) was used to identify the gene type of 23 isolated Ot strains, 2 pools of homogenized leptotrombidium (L.) scutellare, 10 blood specimens of scrub typhus patients, and at the same time to compare with the international reference strains Gilliam, Karp, Kato. Sequencing analysis of the Sta56 gene was also used to further identify the precise gene types. Of the 35 samples, 33 had the same products in the amplification of template Ot-DNA. They all belonged to Kawasaki strains endemic in Japan while 2 (FXS4 and LHGM2 strain) belonged to Karp strains. The Sta56 gene sequence homologies to Japan Kawasaki strain of the 2 representative strains (B-16 and FXS2 strain) of the 33 samples were 94.22%, 95.21% respectively, but they were less than 75.87% to other prototype strains; The homologies to Karp strain of FXS4 and LHGM2 strain were 83.03%, 96.45% respectively. B-16 and FXS2 strain were designated as of types strain Japan Kawasaki, FXS4 and LHGM2 as Karp strain. The results indicated that the dominant Ot strains in Shandong Province were similar to Kawasaki strains, but Karp strains also existed.


Cellulose granulomatous peritonitis.
The case history of a patient developing granulomatous peritonitis due to cellulose is described. At a second laparotomy following an operation for intestinal obstruction due to adhesions, the peritoneum was found to be studded with multiple, yellow nodules, closely resembling tuberculous lesions, but shown on microscopy to be tuberculoid granulomata containing cellulose fibres. The main features of the condition, which is self-limiting, and probably more common than is generally realized, are discussed.


Investigation of sainfoin (Onobrychis viciifolia) cultivar differences on nitrogen balance and fecal egg count in artificially infected lambs.
Research in ruminant nutrition and helminth control with forages, which contain condensed tannins (CT), suggests that varying responses may depend not only on CT concentration but also on CT composition. An experiment was designed to test this by feeding 2 dried sainfoin cultivars (Visnovsky and Perly), which differed in CT properties, to lambs that were artificially infected with the abomasal blood-sucking nematode Haemonchus contortus. Twenty-four infected lambs received 1 of these 2 cultivars; the feeds were either untreated or treated with the CT-binding polyethylene glycol over 4 wk (n = 6). The 2 cultivars were also fed to 2 × 6 uninfected lambs. Nutrient digestibility, N balance, ADG, plasma urea, together with indicators of infection [fecal egg count (FEC), abomasal worm count, per capita female fecundity, erythrocytic indices, and serum protein], were determined. The specific effects of sainfoin cultivar, CT, and infection were evaluated by contrast analysis. Digestibility of both NDF and ADF were less (P < 0.001) with Perly compared with Visnovsky. The apparent nutrient digestibility was reduced (P < 0.001) by CT. However, no clear cultivar effects were evident on N excretion and retention. Condensed tannins reduced (P = 0.05) body N retention and shifted (P < 0.001) N excretion from urine to feces. Unlike cultivar and CT, infection decreased (P = 0.002) ADG. Plasma urea concentration was decreased (P = 0.007) in Perly- compared with Visnovsky-fed lambs and was decreased (P < 0.001) by CT. Plasma concentrations of essential and semiessential AA were increased (P < 0.001) by CT. The groups of infected lambs did not clearly differ in abomasal worm counts and erythrocytic indicators. In the last 2 to 3 wk of the experiment, FEC was decreased (P ≤ 0.01) when feeding CT. The lack of substantial cultivar effects suggests that the differences in CT properties may have been too small to result in nutritional and anthelmintic effects. The present results indicate that sainfoin CT had a mitigating effect on FEC and, consequently, pasture infectivity. However, the reduction was too small to expect any significant benefits in an Haemonchus-dominated system. Therefore, the use of sainfoin for controlling H. contortus should only be one component within an integrated worm control system.


Genome-Based Reclassification of Fusobacterium nucleatum Subspecies at the Species Level.
Fusobacterium nucleatum is classified as four subspecies, subsp. nucleatum, polymorphum, vincentii, and animalis, based on DNA-DNA hybridization (DDH) patterns, phenotypic characteristics, and/or multilocus sequence analysis (MLSA). The gold standards for classification of bacterial species are DDH and 16S ribosomal RNA gene (16S rDNA) sequence homology. The thresholds of DDH and 16S rDNA similarity for delineation of bacterial species have been suggested to be >70 and 98.65%, respectively. Average nucleotide identity (ANI) and genome-to-genome distance (GGD) analysis based on genome sequences were recently introduced as a replacement for DDH to delineate bacterial species with ANI (95-96%) and GGD (70%) threshold values. In a previous study, F. hwasookii was classified as a new species based on MLSA and DDH results. 16S rDNA similarity between F. hwasookii type strain and F. nucleatum subspecies type strains was higher than that between F. nucleatum subspecies type strains. Therefore, it is possible that the four F. nucleatum subspecies can be classified as Fusobacterium species. In this study, we performed ANI and GGD analyses using the genome sequences of 36 F. nucleatum, five F. hwasookii, and one Fusobacterium periodonticum strain to determine whether the four F. nucleatum subspecies could be classified as species using OrthoANI and ANI web-based softwares provided by ChunLab and Kostas lab, respectively, and GGD calculator offered by German Collection of Microorganisms and Cell Cultures. ANI values calculated from OrthoANI and ANI calculators between the type strains of F. nucleatum subspecies ranged from 89.80 to 92.97 and from 90.40 to 91.90%, respectively. GGD values between the type strains of F. nucleatum subspecies ranged from 42.3 to 46.0%. ANI and GGD values among strains belonging to the same F. nucleatum subspecies, subsp. nucleatum, subsp. polymorphum, subsp. vincentii, and subsp. animalis were >96 and >68.2%, respectively. These results strongly suggest that F. nucleatum subsp. nucleatum, subsp. polymorphum, subsp. vincentii, and subsp. animalis should be classified as F. nucleatum, F. polymorphum, F. vincentii, and F. animalis, respectively.


Laminin promotes proliferation of bone marrow-derived macrophages and macrophage cell lines.
We examined the effect of laminin on DNA synthesis or cell growth of bone marrow-derived macrophages (BMM) and five macrophage cell lines including two factor-dependent macrophage cell lines (BDM-1 and BDM-1W3) and three factor-independent ones (BAM3, J774.1, and P388D1). Laminin stimulated the M-CSF-dependent proliferation of BMM and BDM-1 cells in a dose-dependent manner, but it had no effect on the proliferation of BDM-1W3 cells. This stimulatory effect was modified by increasing the concentration of fetal calf serum in the culture medium. Laminin also stimulated the proliferation of BAM3 and J774.1 cells, whereas it could not stimulate that of P388D1 cells. Taken together, these results suggest that the differences in the response of these macrophage cell lines to the presence of laminin may be derived from the difference in the state of maturation of these cells. Although laminin acted as a potent mitogenic factor when it was added to the culture medium, the stimulation was two- to threefold lower when dishes were coated with equivalent amounts of laminin. When BDM-1 cells were cultured with laminin, they underwent drastic morphological changes. A monoclonal antibody that recognizes the integrin alpha 6 subunit only partially inhibited the mitogenic effect of laminin. The results in this report suggest that laminin may participate in the regulation of macrophage populations in vivo.


[Cytoarchitecture of the nucleus raphe dorsalis of the rat].
The nucleus raphe dorsalis of the rat was investigated by means of the Golgi rapid impregnation technique: a) Type 1 neurons: polygonal neurons with somatic spines. The axons which course towards the ventral tegmental area, there by giving off a few collaterals. b( Type 2 neurons: fusiform neurons the axons of which course in a latero-dorsal direction, emitting a few collaterals, too. c) Type 3 neurons: small pyriform neurons. The axons of these cells do not show any favoured route within the nucleus. The type 1 and type 2 neurons are considered to be efferent neurons having different modes of projection and termination. The type 1 neurons are supposed to represent the 5-HT ergic raphe dorsalis neurons. The type 3 neurons, are in probability, raphe interneurons. The findings presented here are indicative of the nucleus raphe dorsalis of the rat to have a more intricate cytoarchitecture as has been thought previously.


Effect of functional groups on the sensing properties of silicon nanowires toward volatile compounds.
Molecular layers attached to a silicon nanowire field effect transistor (SiNW FET) can serve as antennas for signal transduction of volatile organic compounds (VOCs). Nevertheless, the mutual relationship between the molecular layers and VOCs is still a puzzle. In the present paper, we explore the effect of the molecular layer's end (functional) groups on the sensing properties of VOCs. Toward this end, SiNW FETs were modified with tailor-made molecular layers that have the same backbone but differ in their end groups. Changes in the threshold voltage (ΔVth) and changes in the mobility (Δμh) were then recorded upon exposure to various VOCs. Model-based analysis indicates that the interaction between molecular layers and VOCs can be classified to three main scenarios: (a) dipole-dipole interaction between the molecular layer and the polar VOCs; (b) induced dipole-dipole interaction between the molecular layers and the nonpolar VOCs; and (c) molecular layer tilt as a result of VOCs diffusion. Based on these scenarios, it is likely that the electron-donating/withdrawing properties of the functional groups control the dipole moment orientation of the adsorbed VOCs and, as a result, determine the direction (or sign) of the ΔVth. Additionally, it is likely the diffusion of VOCs into the molecular layer, determined by the type of functional groups, is the main reason for the Δμh responses. The reported findings are expected to provide an efficient way to design chemical sensors that are based on SiNW FETs to nonpolar VOCs, which do not exchange carriers with the molecular layers.


Global mean first-passage times of random walks on complex networks.
We present a general framework, applicable to a broad class of random walks on complex networks, which provides a rigorous lower bound for the mean first-passage time of a random walker to a target site averaged over its starting position, the so-called global mean first-passage time (GMFPT). This bound is simply expressed in terms of the equilibrium distribution at the target and implies a minimal scaling of the GMFPT with the network size. We show that this minimal scaling, which can be arbitrarily slow, is realized under the simple condition that the random walk is transient at the target site and independently of the small-world, scale-free, or fractal properties of the network. Last, we put forward that the GMFPT to a specific target is not a representative property of the network since the target averaged GMFPT satisfies much more restrictive bounds.


Timing of Adjuvant Radiotherapy After Keloid Excision: A Systematic Review and Meta-Analysis.
No consensus exists regarding the appropriate timing of adjuvant radiotherapy administration after surgical excision of keloids. This study investigated the appropriate timing of adjuvant radiotherapy. A systematic review and meta-analysis of randomized controlled trials and observational cohort studies was performed. A pooled estimate of the incidence rate was performed using a random-effects model. Subgroup analyses based on different anatomic region, biologically effective dose, keloid length, and radiotherapy regimen were also conducted. Sixteen observational cohort studies (1,908 keloid lesions) met the inclusion criteria. The incidence rate was significantly lower in the group treated with electron beam therapy more than 24 hours after surgery (3.80%; 95% confidence interval [CI], 1.78%-8.13%) than that in the group treated with the same therapy within 24 hours of surgery (37.16%; 95% CI, 20.80%-66.37%; p < .0001), but no significant difference was observed between the groups regarding brachytherapy and x-ray treatments. Immediate adjuvant radiotherapy did not significantly reduce the incidence rate of recurrent keloids.


'Safe enough in here?': patients' expectations and experiences of feeling safe in an acute psychiatric inpatient ward.
To understand the experience of being a patient on an acute psychiatric inpatient ward. Acute psychiatric inpatient care is an integral part of the mental health system. A key driver for admission to acute wards is risk. Previous research indicates that people do not always feel safe when in an acute ward. Understanding the patient experience of safety can influence nursing practice, as well as policy and service development. A qualitative approach was used. Patient experience was conceptualised as represented through narrative as data. Sociolinguistic theories linking narrative structure with meaning informed the development of the analytic framework. Thirteen patients with a variety of diagnoses were recruited from an acute ward. Unstructured interviews were carried out in participants' homes two and six weeks postdischarge. Holistic analysis of each individual's data set was undertaken. Themes running across these holistic analyses were then identified and developed. Participant narratives were focused around themes of help, safety and power. This study presents findings relating to the experience of safety. Participants expected to be safe from themselves and from others. Initially, they experienced a sense of safety from the outside world. Lack of knowledge of their fellow patients made them feel vulnerable. Participants expected the nurses to keep them safe, and felt safer when there were male nurses present. Participants talk about safety in terms of psychological and physical safety. A key issue was the perception of threat from other patients, highlighting the need to consider patient safety as more than physical safety. Nurses need to be sensitive to the possibility that patients feel unsafe in the absence of obvious threat. Institutional structures that challenge patients' sense of safety must be examined.


Clinical evaluation of toric soft lens reproducibility.
The manufacturing variability of frequent replacement toric soft lenses is such that some resulting variation in clinical performance can be expected. The purpose of this study was to evaluate the effect of manufacturing variability on the clinical performance of three frequent replacement toric soft contact lenses. This was a three-part study in which 12 to 14 subjects were enrolled for each part. In each part, subjects were preadapted to the lens type 1 month prior to the assessment visits. Subjects wore a total of 12 test lenses in one eye and, in each case, the clinical performance was compared with a control lens of the same type worn in the other eye that was removed between assessments but not replaced. The study lenses were Acuvue Toric (Vistakon), Focus Toric (Ciba Vision) and FreshLook Toric (Wesley lessen). Two lens types (Focus Toric and FreshLook Toric) showed significantly greater variability with the test lenses compared with the nonreplaced control lenses with several variables: lens fit, visual acuity, and subjective vision quality. One lens (Focus Toric) also showed greater variability of orientation position, and another (Acuvue Toric) showed greater variability in subjective vision quality. The study demonstrated variability in aspects of clinical performance, which appear to be linked to variability of manufacturing output. With toric soft lenses used on a frequent replacement basis, better reproducibility is needed if consistent clinical performance is to be maintained.


Isolation and properties of polyribosomes and fragments of the endoplasmic reticulum from rat liver.
1. A centrifugation method for the fractionation of the postmitochondrial fraction from rat-liver homogenates is described. The technique, in which no detergent is used, may be used as a tool to discriminate between two classes of ribosomes. One class is firmly bound to membranes and the other consists either of free polysomes or of ribosomes attached by weaker forces to the membranes of the endoplasmic reticulum. 2. Electron-micrograph studies revealed that the polysomes were not contaminated with bound ribosomes or with membranous fragments. 3. The separated fractions were characterized by their RNA, protein, ribonuclease and phospholipid content. 4. The influence of starvation on the RNA and protein contents of the different fractions was investigated. 5. Labelling of the various centrifugal fractions in vivo revealed no difference in uptake of radioactive amino acid between the two classes of ribosomes. 6. Incorporation of radioactive leucine in vitro and the polyuridylic acid-directed phenylalanine incorporation were similar for both classes of ribosomes.


Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Phase 1 and Randomized Phase 2 Trial.
ERBB2 (HER2)-targeted therapy provides benefits in metastatic breast cancer (mBC) and gastric cancer, but additional treatments are needed to maximize efficacy and quality of life. To determine maximum tolerated doses (MTDs) of trastuzumab emtansine (T-DM1) plus capecitabine in patients with previously treated ERBB2-positive mBC and locally advanced/metastatic gastric cancer (LA/mGC) (phase 1) and the efficacy and safety of this combination vs T-DM1 alone in patients with mBC (phase 2). The MTD in phase 1 was assessed using a 3 + 3 design with capecitabine dose modification. Phase 2 was an open-label, randomized, international multicenter study of patients with mBC treated with T-DM1 plus capecitabine or T-DM1 alone. Eligible patients had previously treated ERBB2-positive mBC or LA/mGC with no prior chemotherapy treatment for advanced disease. Patients in the phase 1 mBC cohort received capecitabine (750 mg/m2, 700 mg/m2, or 650 mg/m2 twice daily, days 1-14 of a 3-week cycle) plus T-DM1 3.6 mg/kg every 3 weeks. Patients with LA/mGC received capecitabine at the mBC phase 1 MTD, de-escalating as needed, plus T-DM1 2.4 mg/kg weekly. In phase 2, patients with mBC were randomized (1:1) to receive capecitabine (at the phase 1 MTD) plus T-DM1 or T-DM1 alone. The phase 1 primary objective was to identify the MTD of capecitabine plus T-DM1. The phase 2 primary outcome was investigator-assessed overall response rate (ORR). In phase 1, the median (range) age was 54.0 (37-71) and 57.5 (53-70) years for patients with mBC and patients with LA/mGC, respectively. The capecitabine MTD was identified as 700 mg/m2 in 11 patients with mBC and 6 patients with LA/mGC evaluable for dose-limiting toxic effects. In phase 2, between October 2014 and April 2016, patients with mBC (median [range] age, 52.0 [28-80] years) were randomized to receive combination therapy (n = 81) or T-DM1 (n = 80). The ORR was 44% (36 of 81 patients) and 36% (29 of 80 patients) in the combination and T-DM1 groups, respectively (difference, 8.2%; 90% CI, -4.5 to 20.9; P = .34; clinical cutoff, May 31, 2017). Adverse events (AEs) were reported in 78 of 82 patients (95%) in the combination group, with 36 (44%) experiencing grade 3-4 AEs, and 69 of 78 patients (88%) in the T-DM1 group, with 32 (41%) experiencing grade 3-4 AEs. No grade 5 AEs were reported. Adding capecitabine to T-DM1 did not statistically increase ORR associated with T-DM1 in patients with previously treated ERBB2-positive mBC. The combination group reported more AEs, but with no unexpected toxic effects. ClinicalTrials.gov Identifier: NCT01702558.


[Nitric oxide is involved in the modulation of central respiratory rhythm].
This experiment was expected to test whether nitric oxide (NO) exerted significant effect on the central respiratory rhythm. Experiments were performed on in vitro brainstem slice preparations from neonatal rats. These preparations include the medial region of the nucleus retrofacialis (mNRF); a part of pre-Bötinger complex, ventral respiratory group (VRG) and dorsal respiratory group (DRG). Respiratory-related burst activities were recorded from hypoglossal nerve rootlets before and during superfusion of the slice preparation with L-Arginine (L-Arg), sodium nitroprusside (SNP) or 7-nitro indazole (7-NI, an inhibitor of NO synthase). After perfusion with L-Arg and SNP, there was no significant change in respiratory rhythmical discharge activity (RRDA), but 7-NI decreased the integral amplitude of burst and inspiratory time. These results indicate that NO may take part in the inspiratory off-switching mechanism and that it also modulates the amplitude of respiratory-related bursts.


The Roles of Prevention Messages, Risk Perception, and Benefit Perception in Predicting Binge Drinking among College Students.
To account for the effect of prevention-message exposure on binge drinking among college students, I hypothesized a conceptual model outlining potential mechanisms including perceived probability of negative consequences (PPNC), perceived severity of negative consequences (PSNC), perceived probability of positive consequences (PPPC), and perceived beneficiality of positive consequences (PBPC) from binge drinking, based on the two-step process model. I conducted an online survey at a public university in the US (N = 278). Findings suggested only PBPC was significantly related to binge drinking and the relationship was positive; prevention-message exposure was not directly associated with binge drinking, but was positively associated with PPNC, PSNC, PPPC, and PBPC; none of the mediational paths was significant; higher risk perception (interaction between PPNC and PSNC) was significantly related to less binge drinking, while benefit perception (interaction between PPPC and PBPC) was not predictive of binge drinking. Implications of findings were discussed.


Electrocardiographic and transmembrane potential effects of 5-iminodaunorubicin in the rat.
5-Iminodaunorubicin (5-ID) is a quinone-modified anthracycline that retains antitumor activity but lacks the usual redox-cycling effects of quinoid agents. As a test for decreased cardiotoxicity, we have compared the dose- and time-dependent effects of multiple doses of 5-ID and doxorubicin (DXR) on the rat electrocardiogram (ECG) using a signal-averaging process and have related the ECG changes induced by 5-ID to transmembrane potential alterations in myocardial preparations isolated from treated rats. 5-ID was studied at dose levels of 16, 4, and 1 mg/kg, while DXR was given at 4, 2, and 1 mg/kg. At the high- and medium-dose levels, both agents produced widening of the QRS complex, increased R- and S-wave voltage, and prolonged the Q alpha T interval. The QRS widening reversed in all surviving rats, whereas Q alpha T prolongation was reversible with 5-ID but irreversible with DXR. At the lowest dose, 5-ID had no effect on the ECG until the end of treatment. Microelectrode studies on single cells showed that QRS widening occurring with 5-ID treatment was related to a decrease in the maximum rate of depolarization (Vmax) and that Q alpha T prolongation resulted from an increase in the duration of the action potential. Electron microscopic examination showed that although these toxic changes could not be related to specific morphological alterations, in general, the more severe the electrophysiological change, the greater the ultrastructural change. The most consistent ECG change was Q alpha T prolongation. Using this parameter as a marker for cardiotoxicity, 5-ID was about 4 to 5 times less cardiotoxic than was DXR at high- and medium-dose levels and was noncardiotoxic (i.e., below a threshold for cardiotoxicity) compared with DXR at 1 mg/kg over 20 (DXR) to 35 (5-ID) treatments. The decrease in cardiotoxicity relative to DXR is consistent with previous findings that quinone redox cycling is suppressed in 5-ID. However, the ECG and transmembrane potential effects that we identified at elevated doses of 5-ID can be associated with toxic changes in cardiac cell membranes. Therefore, membrane changes other than those due to quinone redox cycling and, presumably, lipid peroxidation must underlie the electrophysiological changes and structural modifications observed with 5-ID in this study. We believe that 5-ID is a useful mechanistic probe in anthracycline cardiotoxicity studies as well as being of obvious interest for clinical trials.


Down-regulation of nerve growth factor expression in the bladder by antisense oligonucleotides as new treatment for overactive bladder.
Nerve growth factor over expression in the bladder has a role in overactive bladder symptoms via the mediation of functional changes in bladder afferent pathways. We studied whether blocking nerve growth factor over expression in bladder urothelium by a sequence specific gene silencing mechanism would suppress bladder overactivity and chemokine expression induced by acetic acid. Female Sprague-Dawley® rats anesthetized with isoflurane were instilled with 0.5 ml saline, scrambled or TYE™ 563 labeled antisense oligonucleotide targeting nerve growth factor (12 μM) alone or complexed with cationic liposomes for 30 minutes. The efficacy of nerve growth factor antisense treatments for acetic acid induced bladder overactivity was assessed by cystometry. Bladder nerve growth factor expression levels and cellular distribution were quantified by immunofluorescence staining and enzyme-linked immunosorbent assay. Effects on bladder chemokine expression were measured by Luminex® xMAP® analysis. Liposomes were needed for bladder uptake of oligonucleotide, as seen by the absence of bright red TYE 563 fluorescence in rats instilled with oligonucleotide alone. At 24 hours after liposome-oligonucleotide treatment baseline bladder activity during saline infusion was indistinct in the sham and antisense treated groups with a mean ± SEM intercontraction interval of 348 ± 55 and 390 ± 120 seconds, respectively. Acetic acid induced bladder overactivity was shown by a decrease in the intercontraction interval to a mean of 33.2% ± 4.0% of baseline in sham treated rats. However, the reduction was blunted to a mean of 75.8% ± 3.4% of baseline in rats treated with liposomal antisense oligonucleotide (p <0.05). Acetic acid induced increased nerve growth factor in the urothelium of sham treated rats, which was decreased by antisense treatment, as shown by enzyme-linked immunosorbent assay and reduced nerve growth factor immunoreactivity in the urothelium. Increased nerve growth factor in bladder tissue was associated with sICAM-1, sE-selectin, CXCL-10 and 1, leptin, MCP-1 and vascular endothelial growth factor over expression, which was significantly decreased by nerve growth factor antisense treatment (p <0.01). Acetic acid induced bladder overactivity is associated with nerve growth factor over expression in the urothelium and with chemokine up-regulation. Treatment with liposomal antisense suppresses bladder overactivity, and nerve growth factor and chemokine expression. Local suppression of nerve growth factor in the bladder could be an attractive approach for overactive bladder. It would avoid the systemic side effects that may be associated with nonspecific blockade of nerve growth factor expression.


Immunohistochemical profile and differential diagnosis of microglandular adenosis.
Twelve examples of microglandular adenosis (MA) were evaluated immunohistochemically using a panel of antibodies directed against actin, S-100 protein, collagen type IV, the c-erb-B2 gene product, and the progesterone receptor, as well as antibodies BER-EP4 and B72.3. The results were compared with the reactions observed in 15 cases of tubular carcinoma and 11 examples of sclerosing adenosis. Three examples of secretory adenosis were also evaluated, but only for S-100 protein and actin. The results confirmed the absence of a myoepithelial cell layer and the presence of basal laminar investiture in MA. Tubular carcinoma lacked a myoepithelial cell layer and basal laminar investiture. Sclerosing adenosis, in contrast, had both a myoepithelial cell layer and displayed basement membrane around the tubules. Secretory adenosis also had a myoepithelial cell layer; the presence of basement membrane could be confirmed easily using periodic acid-Schiff reaction in the three cases of secretory adenosis. An interesting and unexpected finding was the presence of an intensely positive reaction in the epithelial lining cells of the tubules in microglandular adenosis for S-100 protein. A far less intense positivity for S-100 protein was observed sporadically in many normal myoepithelial and some epithelial cells in the adjacent breast lobules. The intensely positive reaction suggests that the proliferating cells in MA correspond to an S-100-positive epithelial cell type that is often present in a small number and in a sporadic manner in the normal breast. The epithelial cells in tubular carcinoma, sclerosing and secretory adenosis were negative for S-100 protein.(ABSTRACT TRUNCATED AT 250 WORDS)


Ocular and orbital metastases presenting as a first sign of gastric adenocarcinoma.
The authors report a case of simultaneous choroidal and orbital metastases with optic nerve involvement presenting as an initial manifestation of gastric adenocarcinoma. To our knowledge, this is the first case of its kind reported in the literature where a 60 years male presented with 6 months history of progressive painful diminution of vision in his left eye associated with inward and upward rotation of the same globe. Examination of left eye revealed displacement of the globe superomedially by an inferolateral mass with restriction of ocular motility in levoversion. Fundus examination showed exudative retinal detachment with a subretinal mass which was supported by the ocular ultrasonography. Intraocular and orbital tumour was demonstrated by CT. Endoscopic biopsy revealed adenocarcinoma of the stomach. The left orbit was exenterated and specimen was sent for histopathological examination which confirmed the presence of same metastatic tumour cells in the eye and orbit. The patient underwent chemotherapy and radiotherapy for gastric carcinoma but the patient died after 6 months.


G-banding and molecular cytogenetic analyses of marginal zone lymphoma.
We analysed the acquired chromosomal aberrations of 22 marginal zone lymphoma (MZL) patients by various genome-wide cytogenetic techniques, such as G-banding, multicolour fluorescence in situ hybridisation (M-FISH), cross-species colour banding (RxFISH), and comparative genomic hybridisation (CGH), as well as FISH with locus-specific probes. Patients with an abnormal chromosome 3 (n = 11), the most frequently rearranged chromosome, showed a shorter median survival than patients with a normal chromosome 3 (n = 11, 74 months vs. 219 months, P < 0.03). Four of five patients with nodal MZL had chromosome 3 abnormalities and patients with nodal MZL had a shorter median survival than patients in the other morphological subgroups of MZL (P < 0.003). CGH analysis showed only gains of chromosome material, namely of chromosome regions 3p12-25, 3q12-21, 3q23-28, 12q13-15, 12q22-24, 19p13 and 19q13 in two to four cases each (20-40%). In two MZL, the novel unbalanced translocation der(13)t(3;13)(q24;p11) was detected as the sole karyotypic rearrangement, indicating that gain of 3q24-qter could be an important event in the pathogenesis of these lymphomas. Another two cases showed, in addition to other abnormalities, a t(4;14)(p13;q32). Both these lymphomas had involvement of the IGH gene at 14q32, and one of them also of the RHOH/TTF gene at 4p13, which encodes a new member of the RHO protein subfamily.


Granulation, control of bacterial contamination, and enhanced lipid accumulation by driving nutrient starvation in coupled wastewater treatment and Chlorella regularis cultivation.
Bacterial contamination and biomass harvesting are still challenges associated with coupling of microalgae and wastewater treatment technology. This study investigated aggregation, bacterial growth, lipid production, and pollutant removal during bacteria contaminated Chlorella regularis cultivation under nutrient starvation stress, by supposing the C/N/P ratios of the medium to 14/1.4/1 (MB₂.₅) and 44/1.4/1 (MB₄.₀), respectively. Granules of 500-650 μm were formed in the bacteria contaminated inoculum; however, purified C. regularis were generally suspended freely in the medium, indicating that bacterial presence was a prerequisite for granulation. Extracellular polymeric substance (EPS) analysis showed that polysaccharides were dominant in granules, while protein mainly distributed in the outer layer. Denaturing gradient gel electrophoresis (DGGE) results revealed Sphingobacteriales bacterium and Sphingobacterium sp. are vital organisms involved in the flocculation of microalgae, and nitrifiers (Stenotrophomonas maltophilia) could co-exist in the granular. Both EPS and DGGE results further supported that bacteria played key roles in granulation. C. regularis was always dominant and determined the total biomass concentration during co-cultivation, but bacterial growth was limited owing to nutrient deficiency. Starvation strategy also contributed to enhancement of lipid accumulation, as lipid content in MB₄.₀ with a greater C/N/P led to the greatest increase in the starvation period, and the maximum lipid productivity reached 0.057 g/(L·day). Chemical oxygen demand and nitrogen removal in MB₄.₀ reached 92 and 96%, respectively, after 3 days of cultivation. Thus, cultivation of microalgae in high C/N/P wastewater enabled simultaneous realization of biomass granulation, bacterial overgrowth limitation, enhanced lipid accumulation, and wastewater purification.


Effect of increased milking frequency in early lactation with or without recombinant bovine somatotropin.
Multiparous Holstein cows (n = 300) were assigned to 1 of 2 milking frequency treatments at parturition. Cows were either milked 6 times (6x) or 3 times (3x) daily to determine effects on early lactation milk yields and subsequent lactation persistency with or without use of recombinant bST (rbST). Treatments included a control group milked 3x and 3 groups milked 6x for either the first 7, 14, or 21 days in milk (DIM). Those 4 groups of cows all received rbST starting at 63 DIM. The fifth treatment group was also milked 6x for the first 21 DIM but those cows received no rbST during the entire lactation. All cows returned to 3x milking after their respective treatment periods ended. Cows milked 3x tended to produce more milk (43.2 vs. 41.5 and 41.0 +/- 1.1 kg/d) during the first 9 wk of lactation compared with cows milked 6x for 7 or 21 DIM, respectively. Group milk yields after wk 9 averaged 38.3 +/- 0.7 kg/d and did not differ among various groups assigned to an increased milking frequency in early lactation. Percentages of milk fat (3.8 +/- 0.12%) and protein (2.9 +/- 0.06%) did not differ among treatments during the first 9 wk after calving. Early lactation milk yield (41.9 +/- 1.2 kg/d) did not differ between the 2 groups of cows milked 6x for 21 DIM. However, cows subsequently administered rbST (at 63 DIM) produced more milk (38.8 vs. 34.2 +/- 0.9 kg/d) from wk 10 to 44. The number of cows sent to the hospital during the 305-d trial for mastitis (97), digestive disorders (14), respiratory issues (9), lameness (22), or retained placenta (16), were not affected by treatments (chi(2) = 0.49). Under the conditions of this commercial dairy herd in Arizona, increasing milking frequency to 6 times daily for 7 to 21 d at the start of lactation conditions did not increase milk yield nor improve lactation persistency.


Forces applied during classical touch assays for Caenorhabditis elegans.
For decades, Caenorhabditis elegans roundworms have been used to study the sense of touch, and this work has been facilitated by a simple behavioral assay for touch sensation. To perform this classical assay, an experimenter uses an eyebrow hair to gently touch a moving worm and observes whether or not the worm reverses direction. We used two experimental approaches to determine the manner and moment of contact between the eyebrow hair tool and freely moving animals and the forces delivered by the classical assay. Using high-speed video (2500 frames/second), we found that typical stimulus delivery events include a brief moment when the hair is contact with the worm's body and not the agar substrate. To measure the applied forces, we measured forces generated by volunteers mimicking the classical touch assay by touching a calibrated microcantilever. The mean (61 μN) and median forces (26 μN) were more than ten times higher than the 2-μN force known to saturate the probability of evoking a reversal in adult C. elegans. We also considered the eyebrow hairs as an additional source of variation. The stiffness of the sampled eyebrow hairs varied between 0.07 and 0.41 N/m and was correlated with the free length of hair. Collectively, this work establishes that the classical touch assay applies enough force to saturate the probability of evoking reversals in adult C. elegans in spite of its variability among trials and experimenters and that increasing the free length of the hair can decrease the applied force.


Adapting the Vulnerable Elders Survey-13 to Predict Mortality Using Responses to the Medicare Health Outcomes Survey.
To use items from the Medicare Health Outcomes Survey (HOS) to adapt or validate a simple method for identifying community-dwelling older adults at greater risk of death and to extend the method to identify a very high-risk group. Analysis of longitudinal data. National sample of beneficiaries from Medicare Advantage plans with 500 or more enrollees. Medicare beneficiaries aged 65 and older responding to 2009 baseline and 2011 follow-up HOS (N = 238,687). Bivariate and multivariate analyses of the HOS; adaptation and validation of a previously validated Vulnerable Elders Survey-13 (VES-13) scoring system that uses age and self-reported function to predict mortality. A modified predictive model, that uses substitutes for several items in the previously validated VES-13, predicted 2-year mortality; 10.6% of those scoring 3 or more, and 2.4% of those scoring less than 3 died within 2 years (relative risk of death 4.4, similar to 4.2 for the original VES-13 sample), and 15.5% of those scoring 7 or more died within 2 years (relative risk of death (relative to scores <3) of 6.5). Sixteen percent of HOS beneficiaries were missing some data; 2-year mortality for those with missing items was 9.5%, versus 7.1% for those with no missing items (P < .001). Imputation of median values for missing VES-13 items results in valid predictions of mortality for those with partially missing data. The VES-13 algorithm is robust to substitution of functional items and can be used to identify very high-risk older adults. Multiple imputation of missing items reduces loss-to-follow-up bias and increases sample size.


Sexually transmitted infections: old foes on the rise.
Sexually transmitted infections (STIs) are commonly spread via sexual contact. It is estimated that one million STIs are acquired every day worldwide. Besides their impact on sexual, reproductive and neonatal health, they can cause disastrous and life-threatening complications if left untreated. In addition to this personal burden, STIs also represent a socioeconomic problem, deriving in treatment costs of tremendous proportions. Despite a substantial progress in diagnosis, treatment and prevention, the incidence of many common STIs is increasing, and STIs continue to represent a global public health problem and a major cause for morbidity and mortality. With this Special Issue, Microbial Cell provides an in-depth overview of the eight major STIs, covering all relevant features of each infection.


A Short Boredom Proneness Scale.
It has been evident for some time that the Boredom Proneness Scale (BPS), a commonly used measure of trait boredom, does not constitute a single scale. Factor analytic studies have identified anything from two to seven factors, prompting Vodanovich and colleagues to propose an alternative two factor, short form version Boredom Proneness Scale-Short Form (BPS-SR). The present study further investigates the factor structure and validity of both the BPS and the BPS-SR. The two-factor solution obtained for the BPS-SR appears to be an artifact of item wording of reverse-scored items. These same items may also have contributed to the earlier complexity and inconsistency of results for the full BPS. An eight-item scale of only consistently worded items (i.e., those not requiring reverse scoring) was developed. This new scale demonstrated unidimensionality and the scale score had good internal consistency and construct validity comparable to the original BPS score.


Molecular interaction fingerprint approaches for GPCR drug discovery.
Protein-ligand interaction fingerprints (IFPs) are binary 1D representations of the 3D structure of protein-ligand complexes encoding the presence or absence of specific interactions between the binding pocket amino acids and the ligand. Various implementations of IFPs have been developed and successfully applied for post-processing molecular docking results for G Protein-Coupled Receptor (GPCR) ligand binding mode prediction and virtual ligand screening. Novel interaction fingerprint methods enable structural chemogenomics and polypharmacology predictions by complementing the increasing amount of GPCR structural data. Machine learning methods are increasingly used to derive relationships between bioactivity data and fingerprint descriptors of chemical and structural information of binding sites, ligands, and protein-ligand interactions. Factors that influence the application of IFPs include structure preparation, binding site definition, fingerprint similarity assessment, and data processing and these factors pose challenges as well possibilities to optimize interaction fingerprint methods for GPCR drug discovery.


Brain amyloid accumulation possibly exacerbates concurrent mild cognitive impairment with subthreshold depression in older adults: A 1-year follow-up study.
This study aimed to investigate the 1-year changes in neuropsychological test results in older adults with concomitant late-life depression (LLD) and mild cognitive impairment (MCI) according to the presence or absence of brain amyloidopathy. All subjects underwent 18F-florbetaben-positron emission tomography and a standardized neuropsychological battery. The subjects were divided based on brain amyloidopathy and severity of depressive symptoms into the following groups: LLD-MCI-A(+), subthreshold depression (STD)-MCI-A(+), major depressive disorder (MDD)-MCI-A(+), LLD-MCI-A(-), STD-MCI-A(-), and MDD-MCI-A(-). After one year, follow-up neurocognitive tests were conducted. Fifty-nine participants completed both the baseline and 1-year follow-up neurocognitive tests. In the LLD-MCI-A(+) group, the word list recall and word list recognition scores decreased during the follow-up period. The STD-MCI-A(+) group also showed a significant decrease in word list recall score and the score/Z-score of word list recognition. On the other hand, the word list recall Z-score improved at the 1-year follow-up in the LLD-MCI-A(-) group. In particular, the MDD-MCI-A(-) group showed significant increases in word list memory score/Z-score and word list recall Z-score during the follow-up period. Considering that AD progresses slowly, a longer follow-up period may be required. Our findings showed differences in the extent of change of neuropsychological test results depending on the severity of depressive symptoms and presence or absence of brain amyloidopathy. Our results suggest that clinicians might explore the underlying neuropathology when assessing older adults with concomitant depression and cognitive impairment, even if the symptoms of depression are not severe.


Organogels from a vitamin C-based surfactant.
A new double chained surfactant, 2-octyl-dodecanoyl-6-O-ascorbic acid (8ASC10), with a L-ascorbic acid unit as the polar headgroup was synthesized for the first time. The behavior of the compound in the dry solid state has been characterized through DSC, XRD, and SAXS measurements. The surfactant forms stable viscous organogels in the presence of suitable organic solvents and also water-induced organogels upon addition of water to the organogel. These mixtures show shear-thinning properties and are birefringent. The behavior and properties of the organogels have been studied through rheology, DSC, and SAXS experiments. The organogels possess the same antioxidant properties of the original L-ascorbic acid ring and can be used to solubilize and protect valuable organic molecules.


Anti-cancer iron(II) complexes of pentadentate N-donor ligands: cytotoxicity, transcriptomics analyses, and mechanisms of action.
Two cytotoxic iron(II) complexes [Fe(L)(CH3 CN)n ](ClO4 )2 (L=qpy for Fe-1 a, Py5 -OH for Fe-2 a) were synthesized. Both complexes are stable against spontaneous demetalation and oxidation in buffer solutions. Cyclic voltammetry measurements revealed the higher stability of Fe-2 a (+0.82 V vs Fc) against Fe(II) to Fe(III) oxidation than Fe-1 a (+0.57 V vs Fc). These two complexes display potent cytotoxicity at micromolar level against a panel of cancer cell lines (Fe-1 a=0.8-3.1 μM; Fe-2 a=0.6-3.4 μM), and induce apoptosis that involves caspase activation. Transcriptomic and Connectivity Map analyses revealed that the changes of gene expression induced by Fe-1 a and Fe-2 a are similar to that induced by ciclopirox, an antifungal compound whose mode of action involves formation of intracellular cytotoxic iron chelates. Both Fe-1 a and Fe-2 a caused cellular nuclear DNA damage, as revealed by Comet assay and H2 AX immunofluorescence experiments. The cytotoxicity is associated with production of reactive oxygen species (for Fe-1 a), cell cycle regulation, and stress kinase pathways. The relative contributions of these to the overall cytotoxic mechanism is significantly affected by the structure of penta-N-donor ligand.


Sensory, chemical, and electronic tongue assessment of micro-oxygenated wines and oak chip maceration: assessing the commonality of analytical techniques.
Micro-oxygenation (MOX) was conducted in the presence and absence of oak chips at rates to mimic oxygen ingress during barrel maturation of red wine. Following MOX, wines were analyzed for chemical attributes pertaining to phenolic composition and assessed by a trained sensory panel. An electronic tongue (ET) was also used to assess the wines. Variations in chemical attributes were found to be mostly influenced by vintage, followed by oak chip maceration accounting for 48% and 16% of variation within the data set, respectively. MOX treatment accounted for 11% of variability within the physiochemical data set, with attributes pertaining to anthocyanin polymerization and levels of sulfur dioxide in the finished wine being most significantly influenced. A generalized Procrustes rotation and alignment of the chemical, electronic tongue, and sensory data sets followed by PLS1 regressions showed good prediction of the sensory characters oak, pencil shavings, stewed plum, vegetal, and spice over the range of sensory scores from the ET data; bitterness and astringency could also be predicted from the physicochemical data with good precision.


TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic?
In 2005 a newly discovered T helper cell subset that secreted interleukin (IL)-17 became the center of attention in immunology. Initial studies painted Th17 cells as the culprit for destruction in many different autoimmune and auto-inflammatory diseases. Subsequently, the discovery of patients with primary immunodeficiencies in the IL-17 pathway taught us that Th17 cells have a critical role in defense against certain fungal and bacterial infections. Moreover, the paradoxical exacerbation of Crohn's disease in the clinical trials of a Secukinumab (AIN457), a fully human neutralizing antibody to IL-17A, has cast into doubt a universal pro-inflammatory and harmful role for Th17 cells. Evidence now suggests that depending on the environment Th17 cells can alter their differentiation program, ultimately giving rise to either protective or pro-inflammatory cells. In this review we will summarize the evidence from patients with immunodeficiencies, autoimmune, or auto-inflammatory diseases that teaches us how the pro-inflammatory versus protective function of Th17 cells varies within the context of different human diseases.


[Giant esophageal fibrovascular polyp].
Fibrovascular polyps are extremely rare benign neoplasias of the esophagus, which usually originate in the lower cricoid area. They do not produce any discomfort in the patient for a long time, however it may make itself evident by the patient's regurgitation of the polyp, producing asphyxia or, more frequently, dysphagia. The case of a 58 year old male patient is presented herein, with a 9 month record of dysphagia, weight loss and intermittent melena. The barium x-ray showed a distended esophagus, with a tumor running from the upper esophageal sphincter to the cardia. The endoscopy confirmed the presence of a pediculated tumor, implanted in the cervical esophagus. Surgeons suspected the potential malignancy of the tumor and performed a transhiatal esophagectomy. The final pathologic diagnosis was giant fibrovascular esophageal polyp.


Invited review: Rumen modifiers in today's dairy rations.
Our aim was to review feed additives that have a potential ruminal mechanism of action when fed to dairy cattle. We discuss how additives can influence ruminal fermentation stoichiometry through electron transfer mechanisms, particularly the production and usage of dihydrogen. Lactate accumulation should be avoided, especially when acidogenic conditions suppress ruminal neutral detergent fiber digestibility or lead to subclinical acidosis. Yeast products and other probiotics are purported to influence lactate uptake, but growing evidence also supports that yeast products influence expression of gut epithelial genes promoting barrier function and resulting inflammatory responses by the host to various stresses. We also have summarized methane-suppressing additives for potential usage in dairy rations. We focused on those with potential to decrease methane production without decreasing fiber digestibility or milk production. We identified some mitigating factors that need to be addressed more fully in future research. Growth factors such as branched-chain volatile fatty acids also are part of crucial cross-feeding among groups of microbes, particularly to optimize fiber digestibility in the rumen. Our developments of mechanisms of action for various rumen-active modifiers should help nutrition advisors anticipate when a benefit in field conditions is more likely.


Risk factors for injury and severe injury in youth ice hockey: a systematic review of the literature.
To identify risk factors for injury in youth ice hockey (ie, body checking, age, player position, player experience and level of play). Systematic review and meta-analysis. A systematic review of the literature, including a meta-analysis component was completed. Ten electronic databases and the American Society for Testing and Materials Safety in Ice Hockey series (volumes 1-4) were systematically searched with strict inclusion and exclusion criteria to identify articles examining risk factors for injury in youth ice hockey. Participation in games, compared with practices, was associated with an increased risk of injury in all studies examined. Age, level of play and player position produced inconsistent findings. Body checking was identified as a significant risk factor for all injuries (summary rate ratio: 2.45; 95% CI 1.7 to 3.6) and concussion (summary odds ratio: 1.71; 95% CI 1.2 to 2.44). Findings regarding most risk factors for injury remain inconclusive; however, body checking was found to be associated with an increased risk of injury. Policy implications regarding delaying body checking to older age groups and to only the most elite levels requires further rigorous investigation.


Burden of Constipation: Looking Beyond Bowel Movements.
Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) are associated with significant social and economic burdens. To address these burdens, a deeper understanding of their root causes is required. A discrepancy exists between patients' and healthcare providers' (HCPs) perceptions of constipation symptoms and the impact of symptoms associated with CIC and IBS-C. Compared with the HCPs' perceptions of patients' symptoms, a greater percentage of patients report acceptance and feeling in control of their CIC or IBS-C symptoms. Unfortunately, only one-third of individuals with CIC or IBS-C formally consult an HCP about their constipation. Fewer than half take medications, and these are generally over-the-counter therapies rather than prescription therapies. For those who seek help, only one-fifth feel that their constipation symptoms are well managed. Notable sex and cultural differences exist regarding individuals consulting their HCP about constipation. Many individuals with CIC and IBS-C remain inadequately managed and unduly affected, contributing to the high social and economic burden of these conditions.


Eating Disorder Specialist Views on Gender Competency and Education for Treating Gender Minority Patients.
Studies exploring patient experience with eating disorder specialists have reported poor gender competency among clinicians, as revealed through patient-clinician interactions. Through interviews with eating disorder specialists, the authors sought to (1) clarify how and why current practice and clinical training may not meet the needs of transgender and gender-diverse patients, (2) assess where and how clinicians received education on gender identity, and (3) how changes can be made to meet educational and patient needs. Specialists were recruited, and semi-structured interviews were conducted. Narratives were coded by two independent coders, using thematic analysis. Four key themes emerged from 19 completed interviews: Training and education received, importance of receiving training or education, self-education, and improvements recommended by clinicians. Only ~ 16% (n = 3) of clinicians reported sufficient training both in graduate school and through their place of employment. Most with sufficient education received it at their clinic/practice. Despite lacking formal training, all clinicians engaged in some form of self-education on gender. These findings support the need for standardized and comprehensive graduate curricula, in-service training, and continuing education requirements. Advocacy is required to encourage accrediting organizations to mandate training on gender among mental health clinicians.


Evaluation of the antitumor effects of rilotumumab by PET imaging in a U-87 MG mouse xenograft model.
Dysregulation of the hepatocyte growth factor (HGF)/MET pathway has been implicated in various cancers. Rilotumumab is an investigational, fully human monoclonal antibody that binds and neutralizes HGF. The purpose of this study was to evaluate the efficacy of rilotumumab in a U-87 MG mouse xenograft tumor model using (18)F-FDG and (18)F-FLT PET. U-87 MG tumor-bearing nude mice received rilotumumab or control IgG2. In the dose response study, increasing doses of rilotumumab (10, 30, 100, 300, or 500 μg) were administered, and mice were evaluated with (18)F-FDG PET at baseline and 7 days post-treatment. In the time course study, 300 μg of rilotumumab twice per week was used for the treatment, and mice were evaluated over 7 days using (18)F-FDG and (18)F-FLT PET. In the dose response study, rilotumumab at doses of 300 and 500 μg was similarly effective against tumor growth. Treatment with 300 and 500 μg rilotumumab inhibited (18)F-FDG accumulation with significant decreases of -37% and -40% in the percent injected dose per gram of tissue (%ID/g), respectively. In the time course study, treatment with 300 μg rilotumumab inhibited (18)F-FDG and (18)F-FLT accumulation with a maximum %ID/g of -41% and -64%, respectively. No apparent differences between the use of either tracer to evaluate rilotumumab efficacy were observed. Rilotumumab inhibited (18)F-FDG and (18)F-FLT accumulation as early as 2 and 4 days after treatment, respectively, in a mouse tumor model. Further studies to evaluate (18)F-FDG PET imaging as an early tumor response marker for rilotumumab are warranted. Rilotumumab is currently being tested in patients with MET-positive, advanced gastric and gastroesophageal cancer.


[Evaluation of low-flow sevoflurane anesthesia using modified Engström Elsa Anesthesia System].
Engström Elsa Anesthesia System (Engström Elsa) was modified to make sevoflurane administration possible, and low-flow sevoflurane anesthesia using this modified anesthesia machine was administered to 10 surgical patients. Among the breakdown products of sevoflurane, CF2 = C (CF3) OCH2F (compound A) was 14.0 +/- 7.8 ppm after the first hour of anesthesia, and remained at this level until 7 hours. CH3OCF2CH(CF3)OCH2F (compound B) was detected in 3 of 10 patients, and these concentrations were below 0.5 ppm. No patient had clinical or laboratory evidence of organ toxicity. Low-flow sevoflurane anesthesia using modified Engström Elsa can be performed safely and easily. Although low levels of two breakdown products were detected, clinical laboratory tests showed no abnormality in hepatic or renal function.


Electron cyclotron beam measurement system in the Large Helical Device.
In order to evaluate the electron cyclotron (EC) heating power inside the Large Helical Device vacuum vessel and to investigate the physics of the interaction between the EC beam and the plasma, a direct measurement system for the EC beam transmitted through the plasma column was developed. The system consists of an EC beam target plate, which is made of isotropic graphite and faces against the EC beam through the plasma, and an IR camera for measuring the target plate temperature increase by the transmitted EC beam. This system is applicable to the high magnetic field (up to 2.75 T) and plasma density (up to 0.8 × 10(19) m(-3)). This system successfully evaluated the transmitted EC beam profile and the refraction.


Host modulation: conceptualization to clinical trials and integration into clinical practice.
A better understanding of the pathogenesis of periodontitis has resulted in pharmacotherapeutic advancements, addressing both the microbes and the host response, leading to improved management of this chronic progressive disease by the dental practitioner. The adjunctive use of host-modulatory agents can enhance therapeutic responses, slow the progression of the disease, and allow for more-predictable management of patients. This article will review the pathogenesis and risk factors associated with periodontitis and address in detail the concept and clinical utility of host modulation as a therapeutic strategy.