Schizophrenia-Mimicking Layers Outperform Conventional Neural Network Layers.
We have reported nanometer-scale three-dimensional studies of brain networks of schizophrenia cases and found that their neurites are thin and tortuous when compared to healthy controls. This suggests that connections between distal neurons are suppressed in microcircuits of schizophrenia cases. In this study, we applied these biological findings to the design of a schizophrenia-mimicking artificial neural network to simulate the observed connection alteration in the disorder. Neural networks that have a "schizophrenia connection layer" in place of a fully connected layer were subjected to image classification tasks using the MNIST and CIFAR-10 datasets. The results revealed that the schizophrenia connection layer is tolerant to overfitting and outperforms a fully connected layer. The outperformance was observed only for networks using band matrices as weight windows, indicating that the shape of the weight matrix is relevant to the network performance. A schizophrenia convolution layer was also tested using the VGG configuration, showing that 60% of the kernel weights of the last three convolution layers can be eliminated without loss of accuracy. The schizophrenia layers can be used instead of conventional layers without any change in the network configuration and training procedures; hence, neural networks can easily take advantage of these layers. The results of this study suggest that the connection alteration found in schizophrenia is not a burden to the brain, but has functional roles in brain performance.


Beyond 'charting outcomes' in the radiation oncology match: analysis of self-reported applicant data.
The Charting Outcomes resource is useful in gauging an applicant's competiveness for a given specialty. However, many variables are not reported in Charting Outcomes that may influence an applicant's ability to match. A significant proportion of applicants record their experiences in an anonymous, self-reported applicant spreadsheet. We analyzed factors associated with a successful match using this dataset to test the hypothesis that research productivity and high academic performance correlates with success rates. A retrospective analysis of "RadOnc Interview Spreadsheet" for the 2015, 2016, and 2017 radiation oncology match was performed. Data were accessed via studentdoctor.net. Board scores, research characteristics, Sub-I participation, and interview invitation rates were available. Mann-Whitney U, Kruskal-Wallis, and chi-square tests were used for statistical analysis. When possible, results were compared to those reported in the National Residency Match Program's "Charting Outcomes" report. A total of 158 applicants were examined for the applicant characteristics. Applicants applied to a median of 61 programs and received a median of 14 interviews. The mean step 1 score was 248 (range: 198 to 272) and most were in the highest grade point average quartile (68.3%). 21.7% participated in additional research year(s), and 19% obtained a PhD. The majority of applicants took three radiation oncology electives (48.7%). On multivariate analysis, alpha-omega-alpha (AOA) honors society status (p=0.033), participating in a research year (p=0.001) and number of journal publications (p=0.047) significantly correlated with higher interview invitation rates. In summary, this study identifies important considerations for radiation oncology applicants that have not been previously reported, such as induction into AOA and number of journal publications.


Inactivation of Aspergillus species in real water matrices using medium pressure mercury lamps.
The aim of this work is to understand the inactivation efficiency of medium pressure mercury lamps, measured in terms of growth inhibition as well as cell death, damage and response, using three strains from three different Aspergillus species (A. fumigatus, A. niger and, A. terreus) spiked in filtered surface water. A complete characterization of the effect of the treatment on each strain of the fungal species was assessed considering spores' morphology, cell wall integrity and enzymatic activity, the formation of pyrimidine dimers in the DNA and proteome analysis. Results showed that, when subjected to medium pressure mercury lamps, A. niger is the most resistant to inactivation, that both A. fumigatus and A. niger suffer more morphological changes and present a higher number of damaged spores and A. terreus presented more dead spores. DNA damages detected in A. niger were able to be repaired to some extent, under both light and dark conditions. Finally, proteome analysis showed that the UV radiation treatment triggered different types of stress response, including cell wall reorganization and DNA repair in A. fumigatus and A. terreus, and oxidative stress responses like the increase in production of citric acid and itaconic acid in A. niger and A. terreus, respectively.


Acupuncture for stable angina pectoris: a systematic review protocol.
Previous reviews indicate that the effect of acupuncture on stable angina pectoris (SAP) remains controversial. The results of trials published in the past 5 years may possibly change this situation, but an updated systematic review is not available. We therefore designed this study to systematically assess the efficacy and safety of acupuncture for treating SAP. Nine online databases will be searched without language or publication status restrictions from their inception to September 2017. Randomised controlled trials that include patients with stable angina receiving acupuncture therapy versus a control group will be deemed eligible. The selection of studies, data extraction and risk of bias assessment will be carried out by two independent reviewers. Data synthesis will be performed using RevMan V.5.3 software with either a fixed effects model or random effects model, depending on the heterogeneity test. Evidence quality will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. The efficacy-effectiveness spectrum for each included trial will be rated using the Rating of Included Trials on the Efficacy-effectiveness Spectrum tool. Outcomes of interest include the improvement of weekly angina attacks and reduction of nitroglycerin medication use after receiving acupuncture treatment, the incidence of cardiovascular events, heart rate variability, pain intensity measured on a visual analogue scale, total workload and exercise duration at peak exercise, safety and adverse events. A meta-analysis will be conducted if no considerable heterogeneity is detected. The results will be presented as risk ratios with 95% CIs for dichotomous data and weighted mean differences or standardised mean differences with 95% CIs for continuous data. This systematic review will not involve private information from individuals or endanger their rights, and therefore does not necessarily require ethical approval. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. CRD42015016201.


Outcome of laryngeal manual therapy in four Dutch adults with persistent moderate-to-severe vocal hyperfunction: a pilot study.
A relatively new management strategy for the treatment of voice disorders is the use of laryngeal manual therapy. The main purpose of the present pilot study is to document the outcome of vocal quality after a well-defined laryngeal manual therapy (LMT) program. Four Dutch professional voice users with a persistent moderate or severe muscle tension dysphonia were studied pretreatment (1 week before LMT) and posttreatment (1 week) after completion of manual therapy (25 sessions). These subjects had received several months of traditional voice therapy, without any success. To measure and compare, the effect of LMT objective and subjective assessment techniques were used. Perceptual voice assessment included a perceptual rating of the voice using the GRBAS scale. Furthermore, the vocal quality in this population was modeled by means of the Dysphonia Severity Index (DSI). All of the subjects selected for LMT showed improvement in perceptual vocal quality and DSI values. As the DSI is a weighted variable including aerodynamic and acoustic measures, small improvements (closer to 5) are very indicative of vocal quality improvement. The use of LMT in professional voice users with persistent moderate-to-severe muscle tension dysphonia, especially in some subjects who have not responded to traditional voice therapy, is supported by this pilot study.


Ward rounds: can an aide-memoire help new doctors?
Ward rounds are fundamental to the care of medical inpatients, and newly graduated doctors may be expected to conduct them alone. There are no studies exploring the frequency with which this occurs, however, or how prepared they feel for this task. Newly graduated (Foundation Year-1, FY1) doctors in Northern Lincolnshire and Goole (NLaG) National Health Service Foundation Trust were surveyed at the end of their FY1 year. An online survey asked: how often they conducted medical ward rounds alone; how prepared they felt to do so; and how often they considered 13 important aspects of care. An aide-memoire outlining aspects to consider on ward rounds was introduced during induction for a second cohort of FY1s, and the survey was repeated. In the initial survey (2015), 42% (n = 19) of the 45 FY1s in NLaG responded: 84% (n = 16) reported conducting ward rounds alone twice or more each week, with 5% (n = 1) feeling prepared and 89% (n = 17) feeling unprepared to do so. In the second survey (2016), following the introduction of the aide-memoire, 52% (n = 25) of the 48 FY1s responded: 32% (n = 7) reported feeling prepared with the aide-memoire (a 27% increase from 2015). There was also a statistically significant increase in the frequency with which they reported considering three of 13 important aspects of care: nutrition, mobility and discharge planning. There are no studies exploring the frequency with which newly graduated doctors conduct ward rounds alone DISCUSSION: The FY1s were regularly conducting ward rounds alone, and felt unprepared for this. An aide-memoire is a low-cost intervention with some value in improving preparedness, and could be further developed and used elsewhere.


Can mHealth Improve Risk Assessment in Underserved Populations? Acceptability of a Breast Health Questionnaire App in Ethnically Diverse, Older, Low-Income Women.
Use of mobile health (mHealth) tools has expanded rapidly but little research has been done on its acceptability by low-income, diverse, older patient populations. To assess the attitudes of a diverse group of underserved women on the acceptability and usability of mHealth tools in a clinical setting using a breast health questionnaire application (app) at a public hospital mammography clinic. Semi-structured interviews were conducted in a breast-imaging center of an urban safety net institution from July-August 2012. Interviews included pre- and post-questions. Women completed the Athena breast health questionnaire app on an iPad and were asked about their experience and ways to improve the tool. Fifteen women age 45-79 years from diverse ethnic and educational backgrounds were interviewed. The majority of women, 11 of 15, preferred the Athena app over a paper version and all the women thought the app was easy to use. Two Spanish-speaking Latinas preferred paper; and two women, with limited mobile phone use, did not have a preference. Many women indicated that it would be necessary to have staff available for instruction and assistance if the app were to be implemented. mHealth tools are an acceptable, if not preferred, method of collecting health information for diverse, older, low-income women. Further studies are required to evaluate the reliability and accuracy of data collection using mHealth tools in underserved populations. mHealth tools should be explored as a novel way to engage diverse populations to improve clinical care and bridge gaps in health disparities.


Iliopsoas Disorder in Athletes with Groin Pain: Prevalence in 638 Consecutive Patients Assessed with MRI and Clinical Results in 134 Patients with Signal Intensity Changes in the Iliopsoas.
Although iliopsoas disorder is one of the most frequent causes of groin pain in athletes, little is known about its prevalence and clinical impact. We retrospectively reviewed the cases of 638 consecutive athletes who had groin pain. Each athlete was assessed with magnetic resonance imaging (MRI). First, we identified the prevalence of changes in signal intensity in the iliopsoas. Then we classified the changes in signal intensity in the iliopsoas, as visualized on short tau inversion recovery MRI, into 2 types: the muscle-strain type (characterized by a massive high-signal area in the muscle belly, with a clear border) and the peritendinitis type (characterized by a long and thin high-signal area extending proximally along the iliopsoas tendon from the lesser trochanter, without a clear border). Finally, we compared the time to return to play for the athletes who had these signal intensity changes. Changes in signal intensity in the iliopsoas were detected in 134 (21.0%) of the 638 athletes. According to our MRI classification, 66 athletes had peritendinitis changes and 68 had muscle-strain changes. The time from the onset of groin pain to return to play was significantly shorter for the patients with muscle-strain changes on MRI than for those with peritendinitis changes (8.6 ± 8.3 versus 20.1 ± 13.9 weeks, respectively; p < 0.0001). Changes in MRI signal intensity in the iliopsoas were observed in 21.0% of 638 athletes who had groin pain. Distinguishing between muscle-strain changes and peritendinitis changes could help to determine the time to return to play.


Assessment of musculoskeltal system pain complaints reported by forestry workers.
According to the European Occupational Diseases Statistics (EODS-2005) diseases related with musculoskeletal disorders occupy the first position on the obligatory list of occupational diseases. These disorders most frequently occur in the agriculture-hunting-forestry sector in such countries as: Finland, Holland, Germany, France and Spain (data: EU-OSHA). The study included a selected group of males - 414 forestry workers, employees of the State Forests, aged 25-65, mean age 48. The control group were 119 office workers aged 23-64, mean age 45.8. The basic research instrument was a questionnaire designed by specialists concerning pain complaints occurring in 7 areas of the motor system: neck, arms, upper and lower back, hips, knees and feet. The results of the survey showed that in the selected group of forestry workers, among 7 investigated areas of the motor system, the most frequently reported pain complaints involved the lower part of the spine (272 persons, 65.7% of the total number of respondents). In the control group such pain complaints occurred in 55.5% (66) of office workers (p = 0.04). Forestry workers most often described this pain as permanent, radiating to the leg, or as an acute pain. According to the frequency of reporting pain, the area of the knees was placed on the second position (214 foresters; 51.7%). The work of a forester which consist, among other things, in relocation on foot or by vehicle over long distances along an uneven terrain and in various weather conditions, is a risk factor of the occurrence of musculosceletal disorders concerning the low back and knees.


[Research on maize multispectral image accurate segmentation and chlorophyll index estimation].
In order to rapidly acquire maize growing information in the field, a non-destructive method of maize chlorophyll content index measurement was conducted based on multi-spectral imaging technique and imaging processing technology. The experiment was conducted at Yangling in Shaanxi province of China and the crop was Zheng-dan 958 planted in about 1 000 m X 600 m experiment field. Firstly, a 2-CCD multi-spectral image monitoring system was available to acquire the canopy images. The system was based on a dichroic prism, allowing precise separation of the visible (Blue (B), Green (G), Red (R): 400-700 nm) and near-infrared (NIR, 760-1 000 nm) band. The multispectral images were output as RGB and NIR images via the system vertically fixed to the ground with vertical distance of 2 m and angular field of 50°. SPAD index of each sample was'measured synchronously to show the chlorophyll content index. Secondly, after the image smoothing using adaptive smooth filtering algorithm, the NIR maize image was selected to segment the maize leaves from background, because there was a big difference showed in gray histogram between plant and soil background. The NIR image segmentation algorithm was conducted following steps of preliminary and accuracy segmentation: (1) The results of OTSU image segmentation method and the variable threshold algorithm were discussed. It was revealed that the latter was better one in corn plant and weed segmentation. As a result, the variable threshold algorithm based on local statistics was selected for the preliminary image segmentation. The expansion and corrosion were used to optimize the segmented image. (2) The region labeling algorithm was used to segment corn plants from soil and weed background with an accuracy of 95. 59 %. And then, the multi-spectral image of maize canopy was accurately segmented in R, G and B band separately. Thirdly, the image parameters were abstracted based on the segmented visible and NIR images. The average gray value of each channel was calculated including red (ARed), green (AGreen), blue (ABlue), and near-infrared (ANIR). Meanwhile, the vegetation indices (NDVI (normalized difference vegetation index), RVI (ratio vegetation index); and NDGI(normalized difference green index)) which are widely used in remote sensing were applied. The chlorophyll index detecting model based on partial least squares regression method (PLSR) was built with detecting R2=0. 5960 and predicting R2= 0. 568 5. It was feasible to diagnose chlorophyll index of maize based on multi-spectral images.


Beyond glycemic control: treating the entire type 2 diabetes disorder.
The prevalence of type 2 diabetes mellitus, which is directly associated with overweight/obesity and increased cardiovascular disease risk, is projected to continue to increase during the next few decades. Traditionally, treatment has focused primarily on glycemic control, but accumulating evidence suggests that the clinical management of patients with type 2 diabetes requires a more comprehensive approach to minimize associated morbidity and mortality. Because the majority (80%-90%) of patients with type 2 diabetes are overweight or obese, effective glucose control and weight loss are the cornerstones of initial management. Both effective glucose control and therapy to reduce cardiovascular risk factors, including overweight/obesity, are needed to prevent the complications of type 2 diabetes. Most conventional antidiabetes agents, including sulfonylureas, thiazolidinediones, and insulin, improve glycemic control but are associated with weight gain or, as with metformin, are weight-neutral or weight-sparing. The incretin-based therapies, such as the glucagon-like peptide-1 (GLP-1) receptor agonists and the dipeptidyl peptidase-4 inhibitors, have been shown to be safe and effective in lowering glucose while eliciting favorable effects on weight (ie, weight-reducing and weight-neutral, respectively). The effects of these agents on other parameters of cardiovascular risk are also being studied. Advances in GLP-1 receptor agonist therapy include development of agents with longer durations of activity allowing for more convenient dosing of therapies for patients with type 2 diabetes, which should lead to better patient compliance, adherence, and overall clinical outcomes.


Megamitochondria formation - physiology and pathology.
Mitochondria undergo structural changes simultaneously with their functional changes in both physiological and pathological conditions. These structural changes of mitochondria are classified into two categories: simple swelling and the formation of megamitochondria (MG). Data have been accumulated to indicate that free radicals play a crucial role in the mechanism of the MG formation induced by various experimental conditions which are apparently various. These include ethanol-, chloramphenicol- and hydrazine-induced MG formation. Involvement of free radicals in the mechanism of MG formation is showed by the fact that MG formation is successfully suppressed by free radical scavengers such as alpha-tocopherol, coenzyme Q(10), and 4-OH-TEMPO. Detailed mechanisms and pathophysiological meanings of MG formation still remain to be investigated. However, a body of evidence strongly suggests that enormous changes in physicochemical and biochemical properties of the mitochondrial membranes during MG formation take place and these changes are favorable for membrane fusion. A recent report showed that continous exposure of cells with MG to free radicals induces apoptosis, finding which suggests that MG formation is an adaptative process to unfavorable environments at the level of intracellular organelles. Mitochondria try to decrease intracellular reactive oxygen species (ROS) levels by decreasing the consume of oxygen via MG formation. If mitochondria succeed to suppress intracellular ROS levels, MG return to normal both structurally and functionally, and they restore the ability to actively synthesize ATP. If cells are additionally exposed to excess amounts of free radicals, MG become swollen, membrane potential of mitochondria (DeltaPsim) decreases, cytochrome c is released from mitochondria, leading to activation of caspases and apoptosis is induced.


Non-surgical complications in oncological colorectal surgery: a comparison between open and laparoscopic techniques.
Most of the studies on laparoscopic surgery in the treatment of colorectal cancer analyzed the oncological or surgical outcome. It remains to be clarified, if laparoscopic surgery leads to a significant reduction in the incidence of systemic complications in the postoperative period. We undertook a quantitative and qualitative assessment of non-surgical complications arising in our patients during the postoperative stay ,in relation to laparoscopic surgery compared to open surgery for colorectal cancer. In the study, 426 patients were recruited. The interventions were performed by an open technique for 225 patients, in VL for 145 patients and 56 patients were subjected to intraoperative conversion. The correlation between surgical technique and onset cardiac complications showed a higher rate of onset of these in open (11.7%) than the VL technique (5.5%). Same result for pulmonary complications (open 13.2%, VL 3.4%) and renal (open 5.7%, VL 1.4%). Average age of patients treated with open surgery 75 years, average operating time duration 169 minutes. Average age patients treated in VL 69 years, average operating time duration 175 minutes. A possible benefit of videolaparoscopic rectal surgery on non-surgical complications has also been investigated, but a significant conclusion has not been reached due to the small number of adverse events found in the reference sample. The evaluation of the duration of the operating session in relation to non-surgical complications showed an increase in the occurrence of pulmonary, renal and systemic adverse events. There was also a significantly greater risk of pulmonary complications in male patients (M 12.7%, F 6.8%). Finally, by stratifying patients by age, a significant positive correlation emerged in the onset of pulmonary complications in the subgroup of patients aged ≥ 70 years, operated with open technique (open 14.6%, vl 3.8). The data analysed shows a reduction of pulmonary and renal cardiac adverse events after laparoscopic oncological surgery, it has not come to a conclusion for rectal cancer. There is also an increase in adverse events related to the duration of the operating session, the male sex and the age ≥ 70 years, thus enhancing the hypothesis that elderly patients are actually the population who can ultimately benefit more of minimally invasive surgical techniques. Adverse eventColectomy, Colorectal cancer, Laparoscopy, Open surgery.


Discovering exceptional diversifications at continental scales: the case of the endemic families of neotropical suboscine passerines.
The study of continental adaptive radiations has lagged behind research on their island counterparts in part because the mere identification of adaptive radiations is more challenging at continental scales. Here, I demonstrate a new method based on simulations for discovering clades that show exceptionally high phenotypic diversity. The method does not require a phylogeny but accounts for differences in age and species richness among clades and incorporates effects of the phylogenetic structure of data. In addition, I developed a new multivariate measure of phenotypic diversity, which has the advantage over other measures of disparity in that it takes covariation into account. I applied these methods to a clade of endemic Neotropical suboscine passerines, within which the family Furnariidae has been considered an adaptive radiation. I found that the families Thamnophilidae, Furnariidae, and Dendrocolaptidae have experienced a higher rate of cladogenesis than have other clades. Although Thamnophilidae is exceptionally diverse in body size, only Furnariidae and Dendrocolaptidae are exceptionally diverse in shape. The combination of high rates of cladogenesis and high morphometric diversity in traits related to feeding and locomotion suggest that the clade Furnariidae-Dendrocolaptidae represent an authentic continental adaptive radiation.


Clinical Effectiveness of SARS-CoV-2 Booster Vaccine Against Omicron Infection in Residents and Staff of Long-term Care Facilities: A Prospective Cohort Study (VIVALDI).
Successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused severe disease in long-term care facility (LTCF) residents. Primary vaccination provides strong short-term protection, but data are limited on duration of protection following booster vaccines, particularly against the Omicron variant. We investigated the effectiveness of booster vaccination against infections, hospitalizations, and deaths among LTCF residents and staff in England. We included residents and staff of LTCFs within the VIVALDI study (ISRCTN 14447421) who underwent routine, asymptomatic testing (December 12, 2021-March 31, 2022). Cox regression was used to estimate relative hazards of SARS-CoV-2 infection, and associated hospitalization and death at 0-13, 14-48, 49-83, 84-111, 112-139, and 140+ days after dose 3 of SARS-CoV-2 vaccination compared with 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex, LTCF capacity, and local SARS-CoV-2 incidence. A total of 14 175 residents and 19 793 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0-111 days after the first booster, but no protection was apparent after 112 days. Additional protection following booster vaccination waned but was still present at 140+ days for COVID-associated hospitalization (adjusted hazard ratio [aHR], 0.20; 95% CI, 0.06-0.63) and death (aHR, 0.50; 95% CI, 0.20-1.27). Most residents (64.4%) had received primary course vaccine of AstraZeneca, but this did not impact pre- or postbooster risk. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalizations and no deaths. Our findings suggest that booster vaccination provided sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 4 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial.


Measuring sucrose in blood after oral administration to detect abomasal ulcers in calves.
Abomasal ulcers are common in cattle, especially in calves, and to date, there is no reliable antemortem method for diagnosis, to our knowledge. We assessed if measuring sucrose in blood after oral administration in calves could be used to identify animals with abomasal ulcers. Terminally ill calves (n = 12; part A) and calves designated for slaughter (n = 123; part B) were given a sucrose solution per os, and blood samples were taken 15, 30, 60, 90, and 120 min (part A) or 30 and 60 min (part B) after administration. The calves were then euthanized or slaughtered, and their abomasa were examined. Serum samples were analyzed using highperformance liquid chromatography-mass spectrometry, and data were analyzed using general linear mixed models. Calves both with and without affected abomasa had increasing sucrose values over time without significant differences. Also, there was no relationship between the size of the mucosal lesion and sucrose values.


[Thoracoscopic repair of esophageal atresia with and without tracheoesophageal fistula].
Esophageal atresia (EA) is the interruption of the continuity of the esophagus, with or without persistent communication with the trachea. Recent advances in surgical techniques have made possible correction with minimally invasive surgery (MIS). To evaluate the management of thoracoscopic technique in the treatment of EA. Retrospective analysis of medical records in two centers was carried out between 2007 and 2012. Variables such as gestational age, gender, weight, type of esophageal atresia, malformations, surgery and postoperative complications were recorded. Twenty patients, 15 of them with type III EA, 4 with type I and one unclassifiable, were part of the study. 13 patients underwent ligation, cut of tracheoesophageal fistula and end to end anastomosis. Two underwent laparoscopic gastrostomy and fistula ligation. One patient required conversion and underwent esophagostomy plus gastrostomy. 4 patients without fistula required laparoscopic gastrostomy and aspiration of the proximal esophagus to be able to perform esophageal anastomosis. In the postoperative period, pleural drainage and a transanastomotic feeding tube were installed. Seven patients required esophageal dilations and 4 patients developed stenosis due to reflux. Two had recurrent fistula, one with spontaneous resolution and another with endoscopic resolution. Three children died: two of them due to pathologies not related to surgery and one as a result of limitation of therapeutic effort after fistula patency. Esophageal atresia repair with MIS is a safe and effective option with excellent exposure and visualization of anatomic landmarks and little associated morbidity.


Effects of moderate caffeine intake on the calcium economy of premenopausal women.
We examined directly the effects of a moderate dosage of caffeine (400 mg/d) on the calcium economy in 16 healthy premenopausal women in a double-blind, placebo-controlled crossover design. The subjects took divided doses of caffeine (100 mg/tablet) or identical-appearing placebos with decaffeinated coffee on personalized schedules for treatment periods lasting 19 d each and with 37-d interstudy intervals. We randomized the treatment sequence among subjects and studied them as inpatients under metabolic-balance conditions. We found no significant effects of caffeine on fractional calcium absorption, endogenous fecal calcium, or urine calcium, whether examined day by day or cumulatively. Although the mean balance shift was negative, the change was not significantly different from zero. There was evidence of altered bone remodeling, with slight decreases in bone accretion, bone resorption, and calcium pool turnover.


Origin of the oocyte shell membrane of a dasyurid marsupial: an immunohistochemical study.
Polyclonal antibodies were raised against the extracellular coats (mucoid and shell membrane) of unfertilized oocytes and early embryos of a dasyurid marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata). Indirect immunofluorescence was used to test the specificity of the antibodies to the shell membrane. Streptavidin/biotin immunoperoxidase cytochemistry revealed that precursors of the tertiary egg membranes are secreted by the luminal epithelium of the ampulla, isthmus (including the crypts), utero-tubal junction, and adjacent endometrial glands. Histochemistry distinguished between the sites of mucoid and shell membrane precursor secretion. The mucoid coat stained positively with Alcian blue at pH 1.0 and 2.5, with Alcian blue at pH 0.2 after performic acid oxidation, and with PAS which was amylase resistant. Some of the luminal epithelial cells of the ampulla and isthmus, as well as its crypts, also stained positively by these histochemical methods but the luminal epithelium of the utero-tubal junction and endometrial glands were negative for all methods. The shell membrane did not stain with any of the above methods nor with dihydroxy-dinapthyl-disulphide (DDD) or ferric ferricyanide but it was eosinophilic and stained positively with the red cytoplasmic stain of Masson's trichrome. Therefore, it is concluded that shell membrane precursors are secreted by the luminal epithelium of the utero-tubal junction, adjacent glands, and by scattered glands in the anterior region of the uterus but not by any cell population of the oviduct.


Bilateral atticoantral chronic suppurative otitis media presenting as bilateral cutaneous mastoid fistulas.
Postauricular cutaneous mastoid fistula secondary to chronic suppurative otitis media (CSOM) is an unusual complication. Bilateral manifestation along with primary acquired cholesteatoma and atelectasis of the pars tensa as an end-stage complication in the natural course of atticoantral CSOM is rare. This kind of complication has a very morbid effect on the ear, and it poses a therapeutic challenge in terms of eradicating disease and restoring function. In this article, we describe the unusual course of an atticoantral CSOM that (1) began as a primary acquired cholesteatoma simultaneously in both ears, (2) proceeded to automastoidectomy and a severe mixed hearing loss bilaterally, and (3) ended with the development of bilateral cutaneous mastoid fistulas that served to arrest the further progression of the disease process on its own. This case serves as a good demonstration of how a ventilating mastoid fistula can change the natural course of atticoantral CSOM and abort the occurrence of deadly complications.


Convenience of Adding a Needle Grasper in Single-Incision Laparoscopic Distal Gastrectomy With Billroth I Anastomosis for Clinical Early Gastric Cancer.
To overcome the technical difficulties of single-incision laparoscopic distal gastrectomy (SILDG), needle grasper (Endo ReliefTM)-assisted SILDG (NASILDG) was developed. Here, we compared the operative convenience and postoperative outcomes between SILDG and NASILDG. A needle grasper was inserted into the right upper abdomen and used in the NASILDG. We retrospectively reviewed patients who underwent D1 + dissection and delta-shaped Billroth I anastomosis with SILDG or NASILDG performed by a single surgeon between September 2015 and August 2018. The SILDG (male, 50.0%) and NASILDG (male, 60.0%) groups included 10 and 15 patients, respectively. The operative time without combined operation and anastomosis was significantly shorter in the NASILDG group. Early complications and scar characteristics were not significantly different between the two groups. By adding a needle grasper, SILDG became more convenient without decreasing cosmetic results. NASILDG could be a recommended method to reduce the technical difficulty of SILDG.


Structural variation of the human genome.
There is growing appreciation that the human genome contains significant numbers of structural rearrangements, such as insertions, deletions, inversions, and large tandem repeats. Recent studies have defined approximately 5% of the human genome as structurally variant in the normal population, involving more than 800 independent genes. We present a detailed review of the various structural rearrangements identified to date in humans, with particular reference to their influence on human phenotypic variation. Our current knowledge of the extent of human structural variation shows that the human genome is a highly dynamic structure that shows significant large-scale variation from the currently published genome reference sequence.


The risk of multiple primary malignancies with colorectal carcinoma.
With advances in diagnostic techniques and treatment modalities, the number of patients identified with colorectal carcinoma who develop multiple primary malignancy during long-term follow-up has been increasing. We investigated multiple primary malignancies occurring in a large number of colorectal carcinoma patients who had undergone surgery in the 1980s at our institution. A total of 1,304 Japanese patients with colorectal carcinoma treated between January 1980 and December 1989 were prospectively followed to investigate the situations in which multiple primary malignancies occurred. To determine whether the incidence of multiple primary malignancies in this series was higher than expected, we calculated the expected numbers of carcinoma occurrences and evaluated these findings by exact binomial test. The median follow-up period was 95 months. The incidence of multiple primary malignancy was 18.7 percent (143/765) among males and 14.7 percent (79/539) among females. The most common site of multiple primary malignancy among males was the stomach, followed by the lung, prostate, larynx, liver, esophagus, and urinary bladder. The most common site among females was the uterus, followed by the stomach, breast, and liver. The sites that showed a higher incidence of multiple primary malignancy than the expected value were: the prostate, larynx, urinary bladder, oral cavity/pharynx and thyroid among males, and the uterus and oral cavity/pharynx among females. Fifteen to 20 percent of Japanese colorectal carcinoma patients experienced multiple primary malignancies. Postoperative long-term screening methods should be established considering the actual occurrence numbers and risk rate of multiple primary malignancies in addition to metachronous colorectal carcinoma.


Community based study to estimate prevalence, burden of illness and help seeking behavior in rheumatic diseases in Mexico City. A COPCORD study.
To estimate the prevalence, burden of illness and help seeking behavior of musculoskeletal complaints and provide point prevalence estimates of osteoarthritis, low back pain, fibromyalgia, rheumatoid arthritis and gout among adult population in a suburban community in Mexico city. Home survey of adults in a balanced and stratified sample validated against physical exam. Three trained interviewers applied a validated COPCORD core questionnaire. Subjects with pain (in the last seven days or ever) > or = 4 (0-10) and no trauma; or with current or past disability were evaluated preferably the same day by a trained clinician in a structured interview. A diagnosis using ACR criteria when available, recommendation or referral was provided as required. Analysis was based on descriptive statistics of participant characteristics, pain site and distribution, patterns of help seeking behavior. Point prevalence with 95% confidence intervals of most common diseases and associated disability rate. 1169 men and 1331 women were included. Pain in the last 7 days not associated with trauma was reported in 419 (17%) participants. The most common sites of involvement were knee (12.3%); low back (6.3%); ankles (6%) and shoulders (5.3%). The mean/SD pain score was 4.8/2.5. Thirteen percent of the total sample had some treatment. The general practitioner treated 72% of those; 75% perceived good efficacy with medications. Point prevalence estimates and 95% CI were: disability: 1.4% (0.0-1.9); osteoarthritis: 2.3% (1.7-2.9); fibromyalgia: 1.4 (1.0-2.0); low back pain: 6.3% (5.4-7.3); rheumatoid arthritis: 0.3% (0.1-0.6) and gout 0.4% (0.1-0.7). Pain in the last 7 days due to musculoskeletal disorders is 17% in this community. Medications were commonly prescribed. Point prevalence estimates of most common diagnoses was similar to other community surveys using COPCORD methodology but very different help seeking behavior.


Bugs and irritable bowel syndrome: The good, the bad and the ugly.
Recently, there has been strong interest in the therapeutic potential of probiotics for irritable bowel syndrome (IBS). At the same time, there is a rapidly growing body of evidence to support an etiological role for gastrointestinal infection and the associated immune activation in the development of post-infectious IBS. In a more controversial area, small intestinal bacterial overgrowth has been associated with a subset of patients with IBS; the issue of whether it is appropriate to treat a subset of IBS patients with antibiotics and probiotics is currently a matter for debate. Thus, it appears that the gastrointestinal microbial flora may exert beneficial effects for symptoms of IBS under some circumstances, while in other situations gut microbes could give rise to symptoms of IBS. How do we make sense of the apparently diverse roles that 'bugs' may play in IBS? To address this question, we have conducted an in-depth review, attempting where possible to draw lessons from Asian studies.


Antioxidant value addition in human diets: genetic transformation of Brassica juncea with gamma-TMT gene for increased alpha-tocopherol content.
Alpha-tocopherol, the most biologically active form of vitamin E, is implicated in decreasing the risk of several types of cancers, coronary heart disease and a number of degenerative human conditions, when taken in excess of the recommended daily allowance. Natural alpha-tocopherol has twice the bioavailability of the synthetic isomer. This study describes a successful attempt at fortifying human diets with natural alpha-tocopherol by taking recourse to genetic engineering of an important oilseed crop, Brassica juncea. Gamma-tocopherol methyl transferase cDNA from Arabidopsis thaliana, coding for the enzyme catalysing the conversion of the large gamma-tocopherol pool to alpha-tocopherol, was overexpressed in B. juncea plants. The successful integration of the transgene was confirmed by PCR and Southern blot analysis, while the enhanced transcript level was evident in the northern blot analysis. HPLC analysis of the seeds of the T1 transgenic lines showed a shift in tocopherol profile with the highest over-expressors having alpha-tocopherol levels as high as sixfold over the non-transgenic controls. This study discusses the production of a transgenic oilseed crop with high alpha-tocopherol levels, which can provide a feasible, innocuous, and inexpensive way of taking the beneficial effects of high alpha-tocopherol intake to the masses.


Isoprene-Degrading Bacteria from Soils Associated with Tropical Economic Crops and Framework Forest Trees.
Isoprene, a volatile hydrocarbon emitted largely by plants, plays an important role in regulating the climate in diverse ways, such as reacting with free radicals in the atmosphere to produce greenhouse gases and pollutants. Isoprene is both deposited and formed in soil, where it can be consumed by some soil microbes, although much remains to be understood about isoprene consumption in tropical soils. In this study, isoprene-degrading bacteria from soils associated with tropical plants were investigated by cultivation and cultivation-independent approaches. Soil samples were taken from beneath selected framework forest trees and economic crops at different seasons, and isoprene degradation in soil microcosms was measured after 96 h of incubation. Isoprene losses were 4-31% and 15-52% in soils subjected to a lower (7.2 × 105 ppbv) and a higher (7.2 × 106 ppbv) concentration of isoprene, respectively. Sequencing of 16S rRNA genes revealed that bacterial communities in soil varied significantly across plant categories (framework trees versus economic crops) and the presence of isoprene, but not with isoprene concentration or season. Eight isoprene-degrading bacterial strains were isolated from the soils and, among these, four belong to the genera Ochrobactrum, Friedmanniella, Isoptericola and Cellulosimicrobium, which have not been previously shown to degrade isoprene.


Podocyte injury induces nuclear translocation of WTIP via microtubule-dependent transport.
Podocyte structural and transcriptional phenotype plasticity characterizes glomerular injury. Transcriptional activity of WT1 (Wilm's tumor 1) is required for normal podocyte structure and is repressed by the podocyte adherens junction protein, WTIP (WT1 interacting protein). Here we show that WTIP translocated into podocyte nuclei in lipopolysaccharide (LPS)-treated mice, a model of transient nephrotic syndrome. Cultured podocytes, which stably expressed an epitope-tagged WTIP, were treated with LPS. Imaging and cellular fractionation studies demonstrated that WTIP translocated from podocyte cell contacts into nuclei within 6 h and relocalized to cell contacts within 24 h after LPS treatment. LPS-stimulated WTIP nuclear translocation required JNK activity, which assembled a multiprotein complex of the scaffolding protein JNK-interacting protein 3 and the molecular motor dynein. Intact microtubule networks and dynein activity were necessary for LPS-stimulated WTIP translocation. Podocytes expressing sh-Wtip change morphology and demonstrate altered actin assembly in cell spreading assays. Stress signaling pathways initiate WTIP nuclear translocation, and the concomitant loss of WTIP from cell contacts changes podocyte morphology and dynamic actin assembly, suggesting a mechanism that transmits changes in podocyte morphology to the nucleus.


Effect of static magnetic field on some enzymes activities in rats.
The magnetic field of 0.008 T and 0.15 T inductions influence lasting 7 weeks (7 days a week), 1 h daily determines the increase of the activity of cytoplasmatic enzymes (glutamic pyruvic transaminase, glutamic oxalacetic transaminase, lactic dehydrogenase), the decrease of cholinesterase activity and the growth of alkaline phosphatase activity in the plasma of the examined animals. The observed changes were reversible. 2 months after the exposure had been stopped, the tested parameters were back to normal.


Role of routine oesophago-gastroduodenoscopy before cholecystectomy.
A proportion of patients do not get symptomatic relief after cholecystectomy because there is an overlap in the symptomology of biliary and gasroduodenal pathologies. In our unit all the patients are offered gastroscopy prior to Cholecystectomy. Aim of this study was to evaluate the efficacy of gastroscopy in all patients with upper abdominal pain irrespective of ultrasound findings. This retrospective study was carried out, between Jan 2001-Oct 2003. All the patients undergoing laparoscopic cholecystectomy by a single surgeon were studied. Group 1 (n = 61) were not endoscoped before the operation (Jan 2001-May 2002). Group 2 (n = 60) had routine endoscopy carried out before surgery (June 2002-October 2003). The results were entered in a database and analyzed. Total of 240 laparoscopic cholecystectomies were carried out. Female to male ratio was 4:1. In Group 1, the recurrence or persistence of symptoms was 20/61 (32.78%) patients who were not scoped. In Group 2, all patients were scoped with positive findings in 35% of the patients. All were treated for the pathology and only 2(3.3%) had recurrence or persistence of symptoms. The routine use of gastroscopy before laparoscopic cholecystectomy helps to reduce persistence of symptoms and is recommended.


Molecular characterization of postnatal development of testicular steroidogenesis in luteinizing hormone receptor knockout mice.
We recently demonstrated that the sexual development of LH receptor (LHR) knockout mice is normal until birth, but is totally arrested thereafter. To study further the functional defects of LHR knockout mice, the expression of selected Leydig cell-specific genes was studied in (-/-) and control (+/+) mice between birth and adulthood. Testis weights were similar at birth in both types of mice, but after about 3 wk, the (-/-) testes remained significantly lighter, weighing only 18% of (+/+) testes on d 70. Testicular testosterone (T) content on d 1 was also similar in (-/-) and (+/+) testes, but it was 97% reduced by d 70 in the former. Likewise, testicular T production in vitro was similar in neonatal (-/-) and (+/+) testes, but became undetectable in adult (-/-) testes. The mRNA expression of cytochrome P450 side-chain cleavage, 17 alpha-hydroxylase cytochrome P450, 17 beta-hydroxysteroid dehydrogenase type III, 3 beta-hydroxysteroid dehydrogenase I (3 beta HSDI), steroidogenic acute regulatory protein, and relaxin-like factor were similar in newborn (-/-) and (+/+) testes, but became gradually very low/undetectable in (-/-) mice. The only exception was the persistently high expression of 3 beta HSDI in peritubular Leydig precursor and mesenchymal cells of the (-/-) testes at all ages. Immunohistochemistry and Western hybridization studies confirmed the above findings. In conclusion, LH action is not essential for the differentiation and function of mouse fetal Leydig cells, but, with the exception of 3 beta HSDI, the expression of the key genes of endocrine function of adult Leydig cells is dependent on LH signaling.


Endovascular treatment of complex abdominal and thoracoabdominal type IV aortic aneurysms with fenestrated technology.
The establishment use of fenestrated and branched devices to treat complex aortic aneurysms as a first-line management option has been previously reported. This article reviews the current literature of the use of fenestrated devices to treat complex abdominal and thoracoabdominal type IV aortic aneurysms as a first-line management option. A literature search was performed. This review particularly focuses on all the aspects of the use and results of fenestrated stent-grafts (SGs) in patients with complex abdominal and type IV thoracoabdominal aortic aneurysms and summarizes the available evidence. The use of fenestrated SGs for complex aortic aneurysm disease has grown enormously the last years. SGs with fenestrations, scallops and occasionally branches have to be customized to each patient's anatomy and precisely deployed in vivo. Bridging covered stents between the main graft and the target vessels eventually exclude the aneurysm preserving blood flow to vital organs. Multiple device morphologies have been used incorporating the visceral arteries in various combinations. High technical success rates and satisfactory perioperative outcomes are described as well as mid- and long-term success and durability including target vessel and branch stent perfusion, data emerging mainly from high volume specialized centers. Percentage of target vessel successfully perfused was reported between 90.5 and 100%. 30-day mortality is reported between 0% and 4.1% while the lowest type 1 or type 3 endoleak rates were 2.5% and 1.3% respectively. Migration rates are kept below 3%. Renal failure was the most frequent complication reported. Advances in SG technology have reduced but not eliminated secondary interventions. Outcomes depend mostly on proximal extension of the disease which increases also the complexity of the repair. High level of expertise and organizational facilities are required for better mid- and long-term outcomes. Fenestrated EVAR (fEVAR) has been shown to be safe and effective in the short and mid-term follow-up. Remaining issues including secondary interventions and the need for follow-up are still within the range of those reported for EVAR. These, continue to plague fEVAR for complex abdominal or type IV thoracoabdominal aortic aneurysms.


[Echocardiographic diagnosis of Valsalva's sinus aneurysm].
Valsalva's sinus aneurysm is a congenital heart disease that may occur both as isolated abnormality or combined with other ailments. The present paper summarizes the results of the use in 20 patients of non-invasive research methods, namely ultrasound cardiography and Doppler's cardiography, in the diagnosis of Valsalva's sinus aneurysms and concomitant heart diseases. Analysis of the findings has shown that the use of ultrasound cardiography in conjunction with pulse Doppler's cardiography permits demonstration with a high accuracy of the direct signs of Valsalva's sinus aneurysm without use of invasive methods, identification of the rupture of its wall and the pathological diastolic blood flow to the cavity corresponding to the rupture. In addition, the application of the above techniques makes it possible to diagnose with a high degree of significance the concomitant abnormalities such as the defects of the interventricular and interatrial septa, aortal valve failure and, in some cases, the signs of concomitant bacterial endocarditis.


Cell Type-Specific TGF-β Mediated EMT in 3D and 2D Models and Its Reversal by TGF-β Receptor Kinase Inhibitor in Ovarian Cancer Cell Lines.
Transcriptome profiling of 3D models compared to 2D models in various cancer cell lines shows differential expression of TGF-β-mediated and cell adhesion pathways. Presence of TGF-β in these cell lines shows an increased invasion potential which is specific to cell type. In the present study, we identified exogenous addition of TGF-β can induce Epithelial to Mesenchymal Transition (EMT) in a few cancer cell lines. RNA sequencing and real time PCR were carried out in different ovarian cancer cell lines to identify molecular profiling and metabolic profiling. Since EMT induction by TGF-β is cell-type specific, we decided to select two promising ovarian cancer cell lines as model systems to study EMT. TGF-β modulation in EMT and cancer invasion were successfully depicted in both 2D and 3D models of SKOV3 and CAOV3 cell lines. Functional evaluation in 3D and 2D models demonstrates that the addition of the exogenous TGF-β can induce EMT and invasion in cancer cells by turning them into aggressive phenotypes. TGF-β receptor kinase I inhibitor (LY364947) can revert the TGF-β effect in these cells. In a nutshell, TGF-β can induce EMT and migration, increase aggressiveness, increase cell survival, alter cell characteristics, remodel the Extracellular Matrix (ECM) and increase cell metabolism favorable for tumor invasion and metastasis. We concluded that transcriptomic and phenotypic effect of TGF-β and its inhibitor is cell-type specific and not cancer specific.


Treatment of pressure ulcers with topical negative pressure versus traditional wound management methods: a research sampler.
The treatment of pressure ulcers is still a matter of debate. The pros and cons of topical negative pressure versus traditional saline wet-to-moist dressings, platelet-derived growth factor, and surgical debridement are discussed in the literature review. This article examines literature that relates to the mechanism of action and efficacy of topical negative pressure.


Investigating calcification-related candidates in a non-symbiotic scleractinian coral, Tubastraea spp.
In hermatypic scleractinian corals, photosynthetic fixation of CO2 and the production of CaCO3 are intimately linked due to their symbiotic relationship with dinoflagellates of the Symbiodiniaceae family. This makes it difficult to study ion transport mechanisms involved in the different pathways. In contrast, most ahermatypic scleractinian corals do not share this symbiotic relationship and thus offer an advantage when studying the ion transport mechanisms involved in the calcification process. Despite this advantage, non-symbiotic scleractinian corals have been systematically neglected in calcification studies, resulting in a lack of data especially at the molecular level. Here, we combined a tissue micro-dissection technique and RNA-sequencing to identify calcification-related ion transporters, and other candidates, in the ahermatypic non-symbiotic scleractinian coral Tubastraea spp. Our results show that Tubastraea spp. possesses several calcification-related candidates previously identified in symbiotic scleractinian corals (such as SLC4-γ, AMT-1like, CARP, etc.). Furthermore, we identify and describe a role in scleractinian calcification for several ion transporter candidates (such as SLC13, -16, -23, etc.) identified for the first time in this study. Taken together, our results provide not only insights about the molecular mechanisms underlying non-symbiotic scleractinian calcification, but also valuable tools for the development of biotechnological solutions to better control the extreme invasiveness of corals belonging to this particular genus.


A Pilot Study Exploring the Effects of Sleep Deprivation on Analogue Measures of Pilot Competencies.
Sleep loss can result in cognitive, motor, and neurobehavioral impairments. In an aviation context, this can cause a serious threat to flight safety. Therefore, the study aimed to investigate the effects of 24-h sleep deprivation on mood, fatigue, and airline pilot competencies. Seven subjects attended two 24-h testing periods, one with an 8-h sleep opportunity, and the other with no sleep opportunity (i.e., sleep deprivation). Subjects were required to complete a battery of mood, fatigue, and analogue measures of pilot competency tasks every 8 h (0 h, 8 h, 16 h, 24 h) throughout each testing period. While total mood disturbance was found to significantly increase (83.42, SD = 25.7), both objective (352.71, SD = 42.00) and subjective (34.85, SD = 8.82) fatigue were found to significantly decrease following 24-h sleep deprivation. Cognitive flexibility (757.45, SD = 58.48) and hand-eye coordination (dominant hand only) (60.28, SD = 3.86) were also negatively impacted following 24-h sleep deprivation. However, working memory and situation awareness were not significantly negatively impacted by the bout of sleep deprivation. Some pilot-specific task-related factors such as subjective fatigue, cognitive flexibility, and working memory were found to be particularly susceptible to sleep loss, with significant declines in performance observed following 16-h continuous wakefulness, suggesting reductions in optimal functioning following this period of wakefulness. Further investigation using more regular testing time points, employing additional pilot competencies, and using more aviation-specific tasks is warranted.O'Hagan AD, Issartel J, McGinley E, Warrington G. A pilot study exploring the effects of sleep deprivation on analogue measures of pilot competencies. Aerosp Med Hum Perform. 2018; 89(7):609-615.


Development of metacyclic Leishmania promastigotes is associated with the increasing expression of GP65, the major surface antigen.
Using immunofluorescence techniques and flow microfluorometry analysis, we have demonstrated that the binding of a monoclonal antibody (VD5/25) produced against GP65, the major surface antigen of Leishmania braziliensis, increased on the surface of stationary-phase promastigotes from all the New World Leishmania species causing mucocutaneous or cutaneous disease as compared with the log-phase parasites. In addition, a sequential development of Leishmania amazonensis promastigotes from a non-infective to an infective stage was demonstrated. Indeed, promastigotes in the stationary phase (days 6-7) were found to be far more infective than those in the logarithmic phase of growth (day 3) both in vitro for mouse peritoneal macrophages and in vivo for BALB/c mice. The intracellular survival and multiplication of L. amazonensis were significantly inhibited when infective promastigotes were treated with the VD5/25 monoclonal antibody. The increasing expression of GP65 on the promastigote surface may thus contribute to Leishmania infectivity. This seems to represent a characteristic mechanism applicable to all New World Leishmania species studied.


[Possibilities and indications for application of laparoscopic technology in diagnostics and treatment of acute appendicitis.
The diagnosis and the treatment of patients with suspected acute appendicitis remains a challenge before clinicians. Acute appendicitis is the most frequently urgent abdominal condition imposing operative therapy [1]. Its application as a diagnostic instrument in unclear or difficult cases seems logical in the era of laparoscopy. The treatment of acute appendicitis consists of removal of the inflamed appendix. As preoperative diagnostic accuracy is never 100 %, the operation itself also includes a diagnostic element. Nearly a century passed prior to laparoscopic appendectomy extending a challenge to the operation of McBurney. The new technology combines a secure manner for removal of the inflamed appendix with a smaller trauma of the abdominal wall and the possibility for inspections of the entire abdominal cavity.


Recurrent miscarriage.
On epidemiological evidence, the definition of recurrent miscarriage should be three or more consecutive pregnancy losses. Data should be collected to 28 weeks' gestation but analysis up to 20-22 weeks' or 500 g fetal weight should also be possible. General practitioners and gynaecologists should do what they feel is suitable for couples whose history does not meet these criteria but a diagnosis of recurrent miscarriage should not be made. Women meeting the definition can be subdivided into primary and secondary groups, respectively consisting of those who have lost all previous pregnancies and those who have had one successful pregnancy followed by consecutive losses.


Metal Contents in Fish from the Bay of Bengal and Potential Consumer Exposure-The EAF-Nansen Programme.
Fish represent an important part of the Sri Lankan and Bangladeshi diet. However, fish is also a source of contaminants that may constitute a health risk to consumers. The aim of this study was to analyse the contents of arsenic, cadmium, mercury, and lead in 24 commonly consumed marine fish species from the Bay of Bengal and to assess the potential health risk associated with their consumption. Mercury and lead contents did not exceed the maximum limits for any of the sampled species, and consumer exposure from estimated daily consumption was assessed to be minimal for adults and children. Numerous samples exceeded the maximum limit for cadmium (58%), particularly those of small size (≤25 cm). However, consumer exposure was insignificant, and health assessment showed no risk connected to consumption. These data represent an important contribution to future risk/benefit assessments related to the consumption of fish.


Quality of life and relationships in sex offenders with intellectual disability.
Hayes (1991) and Day (1994) have developed hypotheses about the importance of social and developmental variables in the aetiology of sexual offences in offenders with intellectual disability. The present study is the first of its kind to investigate the perceived quality of life and relationships of sex offenders in comparison to an appropriate control group. A group of 28 sex offenders with intellectual disability (ID) were compared with 28 members of a control group of individuals with ID. All participants completed the Significant Others Scale (SOS) which assesses self-perceptions of potential and ideal support from significant others in the individual's life, and the Life Experience Checklist (LEC) which assesses experiences and opportunities across 5 living domains: home, leisure, freedom, relationships and opportunities. There were no differences between the groups on age and IQ. On the SOS there were no differences between the groups on the number of times each significant other was reported. Actual and ideal levels of support from both mother and father were lower for sex offenders than the control group. On the LEC, sex offenders reported lower scores on the relationships and leisure sections. Poorer relationships and little indication of any wish to change that state of affairs suggests lower levels of integration and identification with society for sex offenders compared with the control group.


[Prevention of fall and fracture].
Many programs to prevent falls were designed for intervention in fall risk factors. Several meta-analyses, based on many randomized, controlled trials and conducted for the purpose of evaluating the efficacy of these interventions, have been published recently. According to these studies, multifactorial fall risk assessment and management, as well as muscle strengthening and balance retraining, succeeded in reducing falls by approximately 10-38%. Only New Zealand trials were found to decrease even injurious falls, with reduction of moderate or serious injuries by 35% using fall prevention. However, there was no significant difference between the two groups when looking at only serious injuries such as fractures. Thus, fall prevention can prevent falls, but not fractures at present.


Renoprotective effects of benazepril: current perspective.
Cardiovascular (CV) disease, its associated risk factors and continued progression run in parallel with renal deterioration (cardio-renal syndrome). Most guidelines promote early treatment, including the use of ACE inhibitors to control CV risk in patients with chronic renal failure. The renoprotective effects of the ACE inhibitor, benazepril, independent of blood pressure control, have been demonstrated, as monotherapy or in combination with amlodipine or hydrochlorothiazide, in large clinical trials: Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) and Gauging Albuminuria Reduction with Lotrel in Diabetic Patients with Hypertension (GUARD) in patients with mild-to-severe chronic kidney disease. In the ACCOMPLISH trial, CV outcomes and renoprotective effects were greater in patients receiving benazepril in combination with amlodipine; the GUARD trial demonstrated that combined benazepril/hydrochlorothiazide was more effective than amlodipine combined with benazepril in reducing baseline urinary albumin:creatinine ratio and normalizing urinary albumin:creatinine ratio in patients with baseline microalbuminuria, although this effect was accompanied with a greater decrease in glomerular filtration rate than with benazepril/amlodipine. While this is not a study in patients with overt renal disease (patients had severe CV diseases), the ACCOMPLISH trial is the first large study to date to show the added benefit of combining ACE inhibitors and calcium-channel blockers in renal protection. Future large, well-controlled trials, designed to evaluate hard renal outcomes, are required to identify which patients will benefit most from particular combination treatment strategies in renoprotection.


The Multifunctional Fungal Ergosterol.
The roles of ergosterol in the regulation of membrane fluidity and structure, as well its role as a target for the activity of antifungals, have been known for decades. Two recent studies, however, demonstrated that ergosterol is an immunologically active lipid that induces pyroptosis and that virtually all steps of its biosynthetic process are potential drug targets. In combination, those two reports strongly indicate that the biological relevance of ergosterol is broader than the current literature suggests.


Anesthetic Implications in Alternating Hemiplegia of Childhood: A Case Report.
The following case report describes a 13-year-old child with alternating hemiplegia of childhood (AHC) who underwent magnetic resonance imaging MRI with general anesthesia and experienced a hemiplegic spell, seizure, apnea, and sudden cardiac arrest with successful resuscitation. AHC is a rare neurodevelopmental disorder characterized by repeated episodes of weakness or paralysis affecting one or both sides of the body and multiple other neurologic problems. The challenges associated with this disorder include management of developmental delay, dystonia, hemiplegia, cerebrovascular dysfunction, apnea, and autonomic dysfunction. The current literature is extremely limited in describing the effects of general anesthesia for a patient with AHC. While the neurologic manifestations of AHC are well described, autonomic dysfunction and the potential for sudden cardiac arrest have not been widely reported. To our knowledge, this is the first case report to emphasize anesthetic considerations in a pediatric patient with AHC, specifically the unrecognized potential for cardiac arrhythmia and sudden cardiac arrest.


A Dynamic Directional Model for Effective Brain Connectivity using Electrocorticographic (ECoG) Time Series.
We introduce a dynamic directional model (DDM) for studying brain effective connectivity based on intracranial electrocorticographic (ECoG) time series. The DDM consists of two parts: a set of differential equations describing neuronal activity of brain components (state equations), and observation equations linking the underlying neuronal states to observed data. When applied to functional MRI or EEG data, DDMs usually have complex formulations and thus can accommodate only a few regions, due to limitations in spatial resolution and/or temporal resolution of these imaging modalities. In contrast, we formulate our model in the context of ECoG data. The combined high temporal and spatial resolution of ECoG data result in a much simpler DDM, allowing investigation of complex connections between many regions. To identify functionally segregated sub-networks, a form of biologically economical brain networks, we propose the Potts model for the DDM parameters. The neuronal states of brain components are represented by cubic spline bases and the parameters are estimated by minimizing a log-likelihood criterion that combines the state and observation equations. The Potts model is converted to the Potts penalty in the penalized regression approach to achieve sparsity in parameter estimation, for which a fast iterative algorithm is developed. The methods are applied to an auditory ECoG dataset.


Glycosyltransferase functions of E. coli O-antigens.
ECODAB (the E. coli O-antigen database) has been expanded to include information about glycosyltransferases (GTs) involved in the assembly of the O-antigen polysaccharide. Similarity searches have been performed to be able to determine GT functions that have not been reported prior to this work. In addition to suggesting the function of 179 GTs, the approach leads to the prediction of part of the O-antigen structures of a number of serogroups. The procedure suggests a novel way of combining genetic information with experimental techniques in structural analysis of oligo- and polysaccharides.


Hemoglobin level is positively associated with blood pressure in a large cohort of healthy individuals.
It has been hypothesized that an increased hemoglobin level elevates blood pressure. The present study investigated the association between hemoglobin level and systolic blood pressure and diastolic blood pressure in healthy persons. The study population was composed of 101 377 whole blood and plasma donors, who made 691 107 visits to the blood bank. At each visit, hemoglobin level and blood pressure were measured as part of the standard procedure before a blood donation. We used repeated measurement analysis to analyze the data. We used generalized estimating equation models to assess the between-person effect and linear mixed models to assess the within-person effect. All of the analyses were done separately for men and women. In the study population, 50% were men. The mean age in men was 49.3 years (±12.5 years), and in women it was 42.4 years (±13.7 years). Hemoglobin level was positively associated with both systolic and diastolic blood pressures. With respect to the between-person effect, regression coefficients for systolic blood pressure were 1.3 mm Hg per millimole per liter increase in hemoglobin level for men and 1.8 mm Hg per millimole per liter increase in hemoglobin level for women. With respect to the within-person effect, regression coefficients for systolic blood pressure were 0.7 mm Hg and 0.9 mm Hg per millimole per liter increase in hemoglobin level, for men and women, respectively. For diastolic blood pressure, results were comparable. The results show that hemoglobin level is positively associated with both systolic and diastolic blood pressures in healthy individuals. We observed consistent effects between persons but also within persons.


[Risk factors for breast cancer. Do epidemiologic findings provide a basis for primary prevention?].
In Norway, approximately one in every 13 women will develop breast cancer. Epidemiological studies show rather consistent results regarding associations with some risk factors. Lowest risk is found in women with many children, early first birth, late menarche and early menopause. Recent studies indicate that a full-term pregnancy, after a short-lasting adverse effect, results in a risk-reduction of lifelong duration. The authors review the present knowledge of these and other risk factors of possible importance in the etiology; lactation, diet, body weight, physical activity, use of oral contraceptives and hormone replacement therapy. Primary preventive measures may potentially lead to substantial reduction in risk of breast cancer. However, it is difficult to suggest any feasible intervention strategy which would have a high probability of reducing occurrence of breast cancer in the general population.


Conservation of genes and culture: historical and contemporary issues.
The paper examines the reasons for and consequences of lost domestic animal biodiversity. The origin of domestic poultry and livestock diversity is reviewed from the first center of domestication in the Middle East during the Neolithic Revolution. Accompanied by domestic animals and birds, mankind spread worldwide over the last 12,000 yr, thereby increasing domestic animal biodiversity via adaptation to many environmental challenges, resulting in about 6,000 breeds within only a small number of species used for food. During the last 50 yr of the 20th century, about 20% of these livestock and poultry breeds have become extinct, and the remainder is at risk. This erosion of unique biodiversity is due to changes in farm practices developed in the West that involve mono-breed, intensive farming systems that are unsustainable. The close symbiotic relationship of Homo sapiens and domestic animals and birds over millennia is changing, resulting in a lost understanding of sustainability among urban communities. The single-minded focus on profit is resulting in the loss of the historic European and Western culture based on Judeo-Christian values. Respect for biological boundaries, community, and quality of life are disappearing in Western society. Concurrently, farming is now only a business. The principal decision makers are no longer farmers but business executives, who are remote from the farm. The emphasis on cheap food is the principal driver that leads to increased competition and unsustainable practices. Farmers as well as their breeds are disappearing. The advent of gene technology and transgenic livestock is reviewed with the prospect of extensive manipulation of animal form and function and abuse of genotypes as animals are redesigned, suffer, and lose all dignity. By handling its animals in this manner, high Western civilization is losing its culture and values and becoming simply the top animal species by using its power selfishly. The case is presented that the extinction of animals indicates an urgent need to conserve historic Western culture before it, too, is lost.


PTS is activated by ATF4 and promotes lung adenocarcinoma development via the Wnt pathway.
The effects and mechanism of 6-pyruvoyl-tetrahydropterin synthase (PTS) on lung adenocarcinoma (LUAD) were studied in LUAD cells and mice with subcutaneously transplanted tumors. PTS level in tissues and cells was tested by immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). The impacts of PTS on cell viability, proliferation, apoptosis, invasion, and migration were determined by Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry, transwell assay, and wound healing assay, respectively. The Cancer Genome Atlas (TCGA) analysis and dual luciferase assay were conducted to predict and verify the relationship between PTS and activating transcription factor 4 (ATF4). A mouse model was established by subcutaneous injection with cancer cells. Tumor volume was calculated as V = ab2/2. Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to measure cell proliferation and apoptosis in tumors. PTS was highly expressed in LUAD. Higher PTS level was correlated with late clinical stages and poor survival of patients. Down-regulation of PTS inhibited the viability and proliferation and induced apoptosis of LUAD cells. PTS was activated by ATF4, and up-regulation of ATF4 reversed the inhibitory effect of PTS silencing on LUAD cells. Silencing of PTS inhibited the Wnt pathway. Down-regulation of PTS inhibited tumor growth in mice. PTS was highly expressed in LUAD. PTS was activated by ATF4 and promoted LUAD development via the Wnt pathway.


Beta1-adrenoceptor blockade mitigates excessive norepinephrine release into cardiac interstitium in mitral regurgitation in dog.
Mitral regurgitation (MR) is associated with increased neuronal release of norepinephrine (NE) and epinephrine (EP) into myocardial interstitial fluid (ISF) that may be necessary in sustaining left ventricular (LV) function via activation of cardiomyocyte beta-adrenergic receptors (ARs). However, activation of neuronal beta-ARs on cardiac neurons may lead to further catecholamine release, with an attendant risk of functional deterioration. We hypothesize that a beneficial effect of beta-AR blockade may therefore mitigate excessive catecholamine release from cardiac adrenergic neurons in dogs with MR. We measured the effects of chronic beta-receptor blockade (beta-RB) on ISF NE and EP release using in vivo microdialysis in open-chest anesthetized dogs after 4 wk of MR with or without extended release of metoprolol succinate (100 mg/day) as well as in control dogs. Fractional shortening increased by 30% in both MR and MR + beta-RB dogs after 4 wk of MR. In MR + beta-RB dogs, stellate-stimulated heart rate change was attenuated compared with control and MR dogs, whereas peak change of LV pressure over time (+dP/dt) increased equally in all groups. Stellate-stimulated ISF NE increased fivefold over baseline in MR versus twofold in control dogs (< 0.05), but the NE release was significantly attenuated in MR + beta-RB dogs. In contrast, stellate-stimulated increases in ISF EP did not differ in control, MR, and MR + beta-RB dogs. This study demonstrates that beta-RB attenuates ISF NE release from cardiac neurons and that the LV functional response to MR is not dependent on an excess increase in ISF NE. Thus beta1-RB may exert a beneficial effect by attenuating untoward effects of excessive sympathetic efferent neural NE release while sustaining early LV functional adaptation to MR.


Behavior of college baseball players in a virtual batting task.
A baseball batting simulation was used to investigate the information used to hit a baseball. Measures of spatial and temporal swing accuracy were used to test whether batters (a) use speed to estimate pitch height, (b) initiate a constant swing duration at a fixed time to contact, (c) are influenced by the history of previous pitches and pitch count, and (d) use rotation direction. Batters were experienced college players. Pitch speed variance led to predictable spatial errors, and spatial accuracy was worse than temporal accuracy. Swing duration was generally variable. The history of the previous 3 pitches and the pitch count had significant effects on accuracy, and performance improved when rotation cues were added. There were significant effects of expertise on hitting strategy.


Outcomes in women receiving low-molecular-weight heparin during pregnancy.
To assess the rate and type of maternal and infant complications among pregnant women receiving low-molecular-weight heparin (LMWH). Retrospective study of pregnant women on LMWH referred to two university hematology clinics from January 2001 to December 2010. We recorded the number of pregnancies, indication, dose and dose adjustments for LMWH, pregnancy outcomes (live births, maternal and infant complications) and side effects of LMWH. There were 89 pregnancies in 76 women. The most common indication for LMWH was a history of adverse outcome of pregnancy associated with thrombophilia. LMWH was adjusted in 75 and 45% of pregnancies in women on therapeutic and prophylactic doses, respectively. Live birth rate was 97%. There were 25 maternal and 11 infant complications. Side effects were minimal and included decreased bone mineral density and bleeding. LMWH use among pregnant women is associated with successful pregnancy outcomes. Although side effects were minimal, maternal and infant complications occurred in 28 and 12% of cases, respectively.


Organophosphate flame retardants in household dust before and after introduction of new furniture.
Flame retardant compounds originating from household items collect in household dust, a reasonable proxy for human exposure. Contributions of specific items or behaviors to dust are difficult to separate. This study examined standardized college housing before and after the introduction of new, flame retardant couches in order to explore any effect that changing upholstered furniture may have on flame retardant concentrations in dust. Two contradictory hypotheses were posited: (1) that new furniture might increase flame retardant releases immediately after introduction due to initial off-gassing of new materials or (2) that older furniture would release more flame retardants due to mechanical breakdown of polyurethane foam. This study was designed to determine which of these processes dominated. Prior to the introduction of new furniture, TDCIPP was detected in 12/20 samples at a median concentration of 22 μg/g and TCEP was detected in 1/20 samples at a concentration of 16 μg/g. TDCIPP and TCEP were not detected in any samples (N = 29) after the introduction of new couches. TPHP was detected both before (in 11/20 samples) and after (in 5/29 samples) introduction of new couches; the median concentrations before and after were 63 ± 49 and 16 ± 11 μg/g (standard deviation shown). Introduced couches contained TDCIPP (and not TPHP) at ∼1.25% (w/w). These data support the second hypothesis and indicate that removal of older furniture decreases TDCIPP and TCEP concentrations in dust and may potentially reduce total flame retardant concentrations in dust, at least immediately after introduction of the new furniture.


Enhanced insect-resistance, UV protection, and antibacterial and antistatic properties exhibited by wool fabric treated with polyphenols extracted from mango seed kernel and feijoa peel.
The synthetic dyes, antimicrobial and insect-resistant agents, UV radiation absorbents, and antistatic agents that are used to introduce multifunctional properties to textiles are not only toxic to the environment but also require multi-step treatments to achieve them. Toxic antimicrobials are responsible for the growth of drug-resistant bacteria. Nature-derived polyphenols, such as tannin, could be a viable green alternative. In this work, wool fabrics were treated with a commercial tannic acid (PP-1), and also with gallotannin-rich polyphenols extracted from feijoa fruit peel (PP-2) and mango seed kernel (PP-3) to introduce multifunctional properties, i.e. to make the fabric antistatic, insect-resistant, hydrophilic, and able to absorb harmful UV radiation. The effect of the treatment on the colour, colour intensity, surface resistivity, UV radiation absorption, antibacterial activity, and insect-repellence was systematically evaluated. It was found that PP-3-treated fabric exhibited excellent surface hydrophilicity, antibacterial activity against Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and insect-resistant activity against the larvae of Tineola bisselliella. PP-3 treatment also provided comparable UV protection and antioxidant activity but was marginally inferior to the UV protection and antioxidant activity exhibited by the PP-1-treated fabric. The commercial tannic acid treated fabric provided the best antistatic properties but the lowest surface hydrophilicity. The developed treatment could provide a green and sustainable alternative to hazardous UV absorbing, antibacterial and insect-resistant agents used in the textile industry.


Level of empathy among dietitians: A pilot study.
The health-care providers' empathy has been linked to better patient outcomes. The increased demand for dietetics services has called for dietitians to examine their clinical practices and encounters with patients. To date, there are limited studies published on empathy among dietitians. Hence, this study aimed to determine the clinical dietitians' empathy level in Malaysia. Using a purposive sampling method, this study was conducted on dietitians practising in the Malaysian hospitals (government and private). The Toronto Empathy Questionnaire (TEQ), a validated 16-item questionnaire was self-administered, either by online survey method or face-to-face method. Additional information on gender, ethnicity, years of experience and percentage of working time spent on clinical, administrative and other areas were collected. A total of 69 dietitians participated in the study (private (n = 36) and government (n = 33)). The dietitians' mean total TEQ scores were 49.72 ± 5.62 (score ranged between 35 and 63). Significant difference of mean total TEQ scores was found between dietitians from private (51.06 ± 5.26) and government hospitals (48.27 ± 5.72). There was no significant difference in the level of empathy by gender, ethnicity, years of experience and percentage of time spent on clinical consultations, administration or others while at work. Results from this study showed that there were differences in empathy level of Malaysian dietitians by work setting. This preliminary finding serves as a baseline for future studies and could facilitate the development of dietetics education in Malaysia.


[Coronary artery disease in women – how to prevent heart failure after myocardial infarction?].
Cardiovascular disease has been the most common cause of death and disability in women. The prevelence of cardiovascular diseases in women increases dramatically with age as the population ages and women's life expectancy inareases. Compared with men, women with coronary artery diseases are older and more likely to have hyprtension, diabetes and congestive heart failure. Principles of diagnostic and therapeutic management of women are similar to those in men. Clinical trials focusing on treatment alternatives in women have demonstrated improvements in outcomes with advances in technologies and contemporary therapies. All efforts should be focused on the proper screening, prevention and referral for treatment of women with coronary artery disease in order to impact the increasing mortality from heart failure.


Adrenomedullin is increased in alveolar macrophages and released from the lungs into the circulation in severe heart failure.
Adrenomedullin (AM) is a potent vasorelaxing peptide with natriuretic, diuretic, and growth inhibitory properties. Plasma concentrations and myocardial AM expression are increased in heart failure (HF). Since AM and AM binding sites are abundantly expressed in the lungs, we investigated to what extent pulmonary AM and AM receptor subtypes [CRLR/RAMP2 (AM1) and CRLR/RAMP3 (AM2)] are changed in HF and whether the lungs contribute to the increased plasma concentrations of AM reported in HF. Pulmonary AM mRNA and protein expression were increased by 2.8- and 2.6-fold, respectively, whereas mRNA expression of RAMP2 and CRLR was decreased in rats with HF 7 days after induction of MI compared to sham-operated rats (P < 0.05). Pulmonary AM receptor density was substantially decreased in HF rats compared to sham (3.7 +/-0.6 vs. 29.9 +/- 1.1 fmol/mg membrane protein; P < 0.05). Immunoreactivities against AM and the AM receptor components CRLR, RAMP2, and RAMP3 in the pulmonary tissue were seen in vascular smooth muscle cells, vascular endothelial cells, and in alveolar macrophages. AM mRNA expression in alveolar macrophages obtained from HF rats by bronchoalveolar lavage was 2.9-fold higher than in sham-operated rats (P < 0.05). An even more substantial increase of AM mRNA expression was found in alveolar macrophages from patients with HF (10-fold, P < 0.05), and this increase displayed a negative correlation to left ventricular systolic function (P < 0.05). Furthermore, a net release of AM from the lungs into the circulation was only found in HF patients with the most severe left ventricular systolic dysfunction. Thus, our data demonstrate increased expression and decreased receptor binding of AM in the lungs in severe HF. Furthermore, our data indicate that alveolar macrophages are an important source of pulmonary AM in both experimental and clinical HF. Finally, a net release of AM from the lungs into the circulation was only found in patients with severe systolic dysfunction.


Patient reports of lifestyle advice in primary care.
Patients' perceptions of preventive lifestyle in primary care practice were examined. Practice was assessed with a modified version of the Primary Care Assessment Survey (PCAS). This was mailed to random samples of patients twice, using practice mailing lists from three Ontario Family Health Networks (FHNs). Family Health Networks are physician-based group practices, with additional nurse-led telephone advisory services to provide care 24 hours a day, seven days a week. The PCAS questionnaire consisted of nine scales (ranging from 0 to 100). For preventive counselling, additional questions on diet and exercise counselling were included to determine how the physician delivered the intervention. Of the 2184 survey questionnaires mailed to patients, 22% were undeliverable. The response rate was 62% at valid addresses (49% of all mailed questionnaires). Of the nine scales, scores (± standard deviation) for preventive counselling were lowest at 33 ± 25. In particular, rates of diet (37%) and exercise (24%) counselling were low in the FHNs. For most other aspects of primary care services, patients generally rated FHNs highly. The majority of patients advised about diet and exercise were given verbal advice or pamphlets. In these primary health care organizations, considerable room exists for increased preventive counselling, especially about diet and exercise.


Fecundity and size in the housefly: investigations of some environmental sources and genetic correlates of variation.
Environmental sources and genetic correlates of variation in fecundity and size were studied in field and laboratory housefly populations in central Iowa, U.S.A. Electrophoresis of enzymatic proteins was used to monitor genotypes and heterozygosity. In the field, mean fecundity declined as adult densities increased. Fecundity varied greatly within breeding seasons. Fly body size varied spatially and temporally during summer and winter. Fecundity and size were positively correlated. Size was independent of genotypes at the six loci studied. No relationship was observed between heterozygosity and the magnitude or variability of body size.


Characterization of membrane potential dependency of mitochondrial Ca2+ uptake by an improved biophysical model of mitochondrial Ca2+ uniporter.
Mitochondrial Ca(2+) uniporter is the primary influx pathway for Ca(2+) into respiring mitochondria, and hence plays a key role in mitochondrial Ca(2+) homeostasis. Though the mechanism of extra-matrix Ca(2+) dependency of mitochondrial Ca(2+) uptake has been well characterized both experimentally and mathematically, the mechanism of membrane potential (ΔΨ) dependency of mitochondrial Ca(2+) uptake has not been completely characterized. In this paper, we perform a quantitative reevaluation of a previous biophysical model of mitochondrial Ca(2+) uniporter that characterized the possible mechanism of ΔΨ dependency of mitochondrial Ca(2+) uptake. Based on a model simulation analysis, we show that model predictions with a variant assumption (Case 2: external and internal Ca(2+) binding constants for the uniporter are distinct), that provides the best possible description of the ΔΨ dependency, are highly sensitive to variation in matrix [Ca(2+)], indicating limitations in the variant assumption (Case 2) in providing physiologically plausible description of the observed ΔΨ dependency. This sensitivity is attributed to negative estimate of a biophysical parameter that characterizes binding of internal Ca(2+) to the uniporter. Reparameterization of the model with additional nonnengativity constraints on the biophysical parameters showed that the two variant assumptions (Case 1 and Case 2) are indistinguishable, indicating that the external and internal Ca(2+) binding constants for the uniporter may be equal (Case 1). The model predictions in this case are insensitive to variation in matrix [Ca(2+)] but do not match the ΔΨ dependent data in the domain ΔΨ≤120 mV. To effectively characterize this ΔΨ dependency, we reformulate the ΔΨ dependencies of the rate constants of Ca(2+) translocation via the uniporter by exclusively redefining the biophysical parameters associated with the free-energy barrier of Ca(2+) translocation based on a generalized, non-linear Goldman-Hodgkin-Katz formulation. This alternate uniporter model has all the characteristics of the previous uniporter model and is also able to characterize the possible mechanisms of both the extra-matrix Ca(2+) and ΔΨ dependencies of mitochondrial Ca(2+) uptake. In addition, the model is insensitive to variation in matrix [Ca(2+)], predicting relatively stable physiological operation. The model is critical in developing mechanistic, integrated models of mitochondrial bioenergetics and Ca(2+) handling.


Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation.
Cinnamon bark is a very popular herb used in traditional medicine to treat various disorders such as chronic gastric symptoms, arthritis, and the common cold. The immunomodulatory effect of water extract of cinnamon bark (CWE) on cytokine secretion and involvement of intracellular signaling molecules in activated T cells have been examined. Mice were orally administered CWE for 7 days. Serum was obtained 90 min after intravenous injection of anti-CD3 antibody (Ab). Splenocytes were cultured with anti-CD3 Ab and CWE for cytokine expression, cell cycle, apoptotic/necrotic changes, and viability. IκBα, p38, JNK, ERK1/2, STAT4, and STAT6 were analyzed using western blotting. Administration of CWE decreased systemic levels of IFN-γ, but not the levels of IL-4 or IL-2. In vitro, CWE inhibited anti-CD3 Ab-stimulated IFN-γ and IL-4 at the mRNA and secreted protein levels. Despite its inhibition of IL-2 transcript, CWE enhanced IL-2 secretion. CWE treatment caused a reduction in the sub-G1 phase, accompanied by an increased ratio of apoptotic cells to necrotic cells. The increased IL-2 secretion by CWE was not mediated by its direct effect on CD4 T cells. CWE inhibited the activation of p38, JNK, ERK1/2, and STAT4, but not IκBα degradation or STAT6. These observations provided evidence that CWE was able to down-regulate IFN-γ expression in activated T cells without altering IL-2 production, involving inhibition of p38, JNK, ERK1/2, and STAT4. Our results contribute to a better understanding of the immunomodulatory action of cinnamon bark for the application of inflammatory disorders.


90% Extraordinary optical transmission in the visible range through annular aperture metallic arrays.
We demonstrate what we believe to be the first experimental extraordinary optical transmission (EOT) of up to 90%, thanks to a well-identified guided mode that propagates through annular apertures engraved into an optically thick silver layer. In spite of the metal losses, high transmission can be obtained by adjusting the geometrical parameters of the fabricated structure, as was already theoretically demonstrated. To our knowledge, this is the first study showing such a large transmission in the visible range.


Real-time Indocyanine Green Videolymphography Navigation for Lymphaticovenular Anastomosis.
Indocyanine green (ICG) lymphography is a useful imaging modality for evaluation of lymphedema and detection of lymphatic vessels. It also allows us to ensure patency of the anastomosed vessels intraoperatively. However, strong light from the operating microscope usually disturbs ICG fluorescence imaging. Only some built-in ICG camera systems with specific operating microscopes make real-time ICG lymphography possible in lymphaticovenular anastomosis (LVA). We applied a new high-resolution ICG videolymphography system, which is separated from the operating microscope. Because the system can divide near-infrared fluorescence light of ICG from visible light of the operating microscope, real-time ICG videolymphography-navigated LVA under operating microscope illumination is possible regardless types of operating microscopes. The study involved 10 patients with upper extremity lymphedema characterized by International Society of Lymphology stage 2 and treated by 3 lymphaticovenular anastomoses at the forearm (30 lymphaticovenular anastomoses incorporating 30 lymphatic vessels) under real-time ICG videolymphography. The rate of intraoperative detection of lymphatic vessels using real-time ICG videolymphography was 86.7% (0.25-0.85 mm in diameter), and that of lymph flow through the lymphaticovenular anastomoses was 76.7%. None of lymphatic vessels and no flow were detected under the microscope light by means of another non-built-in ICG lymphography camera. Real-time ICG videolymphography in LVA is beneficial, because the surgeon could find lymphatic vessels easily by checking dual images of original view and ICG fluorescent view and ensure accuracy of the LVA in a suture by a suture without any pauses of the surgical procedures.