Preconception folate status and reproductive outcomes among a prospective cohort of folate-replete women.
Most studies of folate metabolism and reproduction have been conducted after pregnancy and in folate-deficient populations. However, measurement of maternal folate status preconceptionally may be most relevant to certain folate-linked early processes preceding a successful pregnancy, and there has been a major increase in folate concentrations in women of childbearing age in high resource settings. To examine associations between preconceptional biomarkers of maternal folate status (folate and homocysteine) and reproductive outcomes in folate-replete women. Cohort nested within the Effects of Aspirin in Gestation and Reproduction trial, a block-randomized, double-blind, placebo-controlled trial whereby women were randomized to daily low-dose aspirin (81 mg/day) or placebo and all women received folic acid (400 μg/day). In total, 1228 women with 1-2 previous pregnancy losses and no documented infertility were recruited from 4 clinical sites in the United States (2006-2012) and were attempting pregnancy for up to 6 menstrual cycles. Log-binomial regression models were used to estimate relative risks and 95% confidence intervals between preconception serum folate and plasma homocysteine for anovulation, pregnancy, and pregnancy loss. Greater plasma homocysteine was nonlinearly associated with greater risks of pregnancy loss only among women with 2 previous losses: a relative risk of 1.43 (95% confidence interval, 1.08-1.89) was found for plasma homocysteine concentrations at the study median of 8.0 μmol/L compared with a US population median of 6.0 μmol/L. No meaningful relationships were found between serum folate and any reproductive outcome or between plasma homocysteine and anovulation or becoming pregnant. These data justify further study of the role of folate and homocysteine metabolism in normal and abnormal early pregnancy.


Patient-reported outcomes from a phase IV study of aflibercept in patients with refractory retinal vein occlusions.
To determine the patient-centered effectiveness of switching patients with persistent macular edema due to retinal vein occlusion (RVO) to aflibercept using the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). Prospective study of eyes with persistent cystoid macular edema due to RVO despite regular treatment with bevacizumab or ranibizumab switched to aflibercept. Three loading doses of intravitreal aflibercept were administered every 4 weeks and thereafter every 8 weeks until week 48. Vision-related quality of life (VRQoL) using NEI-VFQ-25 was measured at baseline, 24 weeks, and 48 weeks following the switch. Baseline scores were compared to week 24 and 48 using paired t-test. Relationship between best-corrected visual acuity (BCVA) in the study eye and the NEI-VFQ-25 composite and subscale scores was investigated. Eighteen patients with RVO were enrolled in the study with a mean age of 70.3 ± 8.6 years. The mean change in BCVA and central macular thickness (CMT) from baseline to 48 weeks was +20.6 ± 5.2 Early Treatment of Diabetic Retinopathy Score letters and -109.2 ± 82.8 µm, respectively. VRQoL improved significantly, with an increase of mean NEI-VFQ composite score of 11.5 ± 9.5; the corresponding improvements in near and distant activities were 13.3 ± 19.4 and 8.4 ± 10.4, respectively (P < 0.001 for both). Logistic regression analysis demonstrated that BCVA gain of >15 letters and CMT < 300 µm at the end of the study predicted a higher change in VFQ-25. Switching eyes with persistent macular edema due to RVO to aflibercept resulted in significant improvement in visual function and patient satisfaction.


7 Tesla imaging of cerebral radiation necrosis after arteriovenous malformations treatment using amide proton transfer (APT) imaging.
Arteriovenous malformations (AVM) can be treated with stereotactic radiosurgery. An infrequent, but important complication of this treatment is radionecrosis, which can be detected by MRI. However, the imaging characteristics of necrosis are unspecific in conventional MRI. Here, we report a case of necrosis after radiotherapy of an AVM to illustrate the potential of 7 Tesla MRI including amide proton transfer (APT) for necrosis imaging.


Cyclic AMP-elevating agents prolong or inhibit eosinophil survival depending on prior exposure to GM-CSF.
1. Purified human eosinophils survived for up to 7 days when cultured in vitro in the presence of 1 ng ml-1 granulocyte-macrophage colony stimulating factor (GM-CSF) with a viability of 73%. In the absence of GM-CSF, eosinophil viability decreased after one day in culture, and only 4% of cells were viable by day 4. 2. Culture of eosinophils with cholera toxin produced a concentration-dependent decrease in GM-CSF-induced survival at 7 days (IC50 = 7 ng ml-1) which was associated with a 6 fold increase in the intracellular cyclic AMP concentration. This inhibition of cell survival could be prevented by the addition of the protein kinase A inhibitor, H89 (10(-6)M). 3. When eosinophils were cultured with dibutyryl cyclic AMP, there was a concentration-dependent inhibition of GM-CSF-induced survival at 7 days with an IC50 of 200 microM. The related cyclic nucleotide analogue, dibutyryl cyclic GMP did not inhibit GM-CSF-induced eosinophil survival over the same concentration range. 4. Culture of eosinophils with forskolin, or with the phosphodiesterase inhibitors, rolipram and SK&F94120, had no effect on GM-CSF-induced eosinophil survival at any concentration examined. 5. After 7 days' culture in the absence of GM-CSF, fractionation of eosinophil DNA on agarose gels demonstrated a 'ladder' pattern characteristic of apoptosis. GM-CSF prevented DNA fragmentation and this protection could be overcome by both cholera toxin and dibutyryl cyclic AMP. 6. GM-CSF did not affect intracellular cyclic AMP concentrations in unstimulated eosinophils or in cells stimulated by cholera toxin. Thus, GM-CSF does not apparently increase eosinophil survival by affecting cyclic AMP levels. 7. In the absence of GM-CSF both cholera toxin and dibutyryl cyclic AMP decreased the rate of eosinophil death, when compared to cells cultured with medium alone. The t1/2 values for cell death were 1.63 +/- 0.3, 2.46 +/- 0.3 and 4.62 +/- 1.0 days for cells cultured in the presence of medium, cholera toxin and dibutyryl cyclic AMP respectively. 8. In conclusion, cyclic AMP exerts opposing effects on eosinophil survival depending on prior exposure of the cells to GM-CSF.


[Nomographs for determination of sedimentation constants of nucleic acids by means of centrifugation in sucrose gradients using the "Sinco" ultracentrifuge].
A set of nomographs for determination of standard sedimentation constant values for DNA and RNA directly from the results of centrifugation without any marker is calculated and plotted for 9 Spinco bucket-rotors, 5 temperatures, and two commonly used sucrose gradients (5--20 and 15--30%).


Minilaparoscopy with Interchangeable, Full 5-mm End Effectors: First Human Use of a New Minimally Invasive Operating Platform.
The most common paradigm in minimally invasive surgery is entry of a single trocar through separate incisions in the abdomen. However, in an effort to decrease postoperative pain and minimize scarring, alternative techniques have been described. Needlescopic surgery uses instruments that are 3 mm or less in diameter. Prior uses of needlescopic instruments have been hindered somewhat by diminished shaft strength and small end-effector size. The Percuvance™ (Teleflex, Wayne, PA) system uses a 2.9-mm shaft with interchangeable 5-mm end effectors in order to minimize abdominal wall trauma while maintaining the functionality of traditional laparoscopic instruments. All patients evaluated for laparoscopic surgery by two surgeons with a foregut and general surgery practice at the Cleveland Clinic (Cleveland, OH) were included in the study. Fifteen consecutive patients were enrolled in the study. Patient demographics and operative results were reviewed. In March 2015, 15 patients underwent surgery using the Percuvance surgical system at the Cleveland Clinic. There was one conversion to open surgery due to extensive intraabdominal adhesions and unclear anatomy. There was one re-exploration for presumed anastomotic leak, which was negative. Operative time and length of hospital stay were similar to those of standard laparoscopic procedures. There were no deaths in this series. Subjective surgeon experience was overall positive, and functionality of the Percuvance system seemed equal to that of standard 5-mm laparoscopic instrumentation. This initial experience with the Percuvance system demonstrated effective exchange of 5-mm port sites for needlescopic instruments with similar handling to traditional laparoscopic instruments. This interchangeable system may allow performance similar to standard laparoscopic port instrument orientation and principles in the setting of decreased-caliber access.


Effects of cyclical etidronate with alfacalcidol on lumbar bone mineral density, bone resorption, and back pain in postmenopausal women with osteoporosis.
The purpose of the present open-labeled, randomized, prospective study was to compare the effects of cyclical etidronate combined with alfacalcidol with those of cyclical etidronate alone on lumbar bone mineral density (BMD), bone resorption, and back pain in postmenopausal women with osteoporosis. Forty postmenopausal women with osteoporosis, 60-86 years of age, without any vertebral fractures in the lumbar spine, were randomly divided into two groups with 20 patients in each group. One group was treated with cyclical etidronate (oral etidronate 200 mg daily for 2 weeks every 3 months) and the other was given cyclical etidronate combined with alfacalcidol (cyclical etidronate plus alfacalcidol 1 Ig daily continuously). The BMD of the lumbar spine (L1-L4) measured by dual-energy X-ray absorptiometry, urinary crosslinked N-terminal telopeptides of type I collagen (NTX) measured by an enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Both treatments significantly reduced the urinary NTX level and back pain. Cyclical etidronate combined with alfacalcidol significantly increased the lumbar BMD with a more significant reduction in the urinary NTX level than cyclical etidronate alone, but cyclical etidronate alone did not significantly increase the lumbar BMD. Alleviation of back pain was similar in the two groups. These results suggest that cyclical etidronate combined with alfacalcidol appears to be more useful than cyclical etidronate alone for increasing the lumbar BMD by more markedly suppressing bone resorption in postmenopausal women with osteoporosis.


Dysregulation of systemic iron metabolism in alcoholic liver diseases.
Alcoholic liver diseases (ALD) are frequently associated with iron overload. Until recently, the effects of ethanol in hepatic iron uptake and intestinal iron absorption have not been clarified in detail. Two possible mechanisms for iron overload are the uptake of iron into hepatocytes in a specific manner through the increased expression of transferrin receptor (TfR) 1; and increased intestinal iron absorption by the lowering of hepcidin. It is worthwhile to examine whether a similar mechanism is present in the development of steatosis and non-alcoholic steatohepatitis (NASH). Hepatocytes have several iron uptake pathways. Ethanol increases transferrin (Tf)-mediated uptake via a receptor-dependent manner, but downregulates the non-Tf-bound iron uptake. According to immunohistochemical study, TfR1 was increased in hepatocytes in 80% of hepatic tissues of patients with ALD, but was not detected in normal hepatic tissues. In an experimental model, ethanol exposure to the primary cultured-hepatocytes in the presence of iron increased TfR1 expression and (59)Fe-labeled Tf uptake. In patients with ALD, intestinal iron absorption is increased by oral iron uptake assay. The regulatory hormone for iron homeostasis, hepcidin is downregulated in ethanol-loaded mice liver. As well as ALD, a similar mechanism was present in the mouse model fed with a high-fat diet, a model of the initial phenomenon of steatosis. The common mechanism for hepatic iron deposition and the triggering role of iron may be present in the development of ALD and non-alcoholic fatty liver disease/NASH.


On the use of chemotaxonomy, a phytoplankton identification and quantification method based on pigment for quick surveys of subtropical reservoirs.
Traditionally, composition and biomass of phytoplankton communities are determined by microscopy, but this method is time-consuming and so does not allow for high-frequency data acquisition across space and time. Pigment-based chemotaxonomy (CHEMTAX) is now widely applied to study of phytoplankton community structure on broader spatial and temporal scales of oceans, but the ability of this approach to provide estimates of phytoplankton assemblage in freshwater ecosystems is yet underdeveloped. To investigate the efficiency of the high-performance liquid chromatography (HPLC)-CHEMTAX in quantifying the different phytoplankton groups in inland freshwater, we present a comparison between phytoplankton pigment analyses by HPLC with CHEMTAX and microscopic counting of phytoplankton samples from four subtropical reservoirs in January and July 2014, respectively. The correlation between pigment and phytoplankton abundance detected by microscopy was stronger than that between pigment and phytoplankton biomass. The published marker pigments and their revised ratios can be used to describe phytoplankton abundances in a mixed community of freshwater phytoplankton, and pigment-based CHEMTAX can successfully describe the overall pattern of phytoplankton community dynamics during different seasons. The use of pigment-based CHEMTAX for quick surveys of phytoplankton communities can be recommended as a useful supplement or alternative tool to microscopy for freshwater ecosystem management.


Evaluating the cytotoxic doses of narrowband and broadband UVB in human keratinocytes, melanocytes, and fibroblasts.
No comparative and simultaneous in vitro studies have been performed to determine the cytotoxic dose of narrowband UVB (NBUVB) and broadband UVB (BBUVB) for keratinocytes, melanocytes, and fibroblasts. Culture medium was often replaced with phosphate-buffered saline (PBS) before UV irradiation; however, its amount differed across studies. We determined the cytotoxic doses of NBUVB and BBUVB and tested for changes in viability according to the amount of PBS. We exposed cultured human keratinocytes, melanocytes, and fibroblasts to ultraviolet light in the range 12.5-1000 mJ/cm(2) for NBUVB and 1.25-100 mJ/cm(2) for BBUVB. The viability was assessed after 24 h. We also determined changes in viability at cytotoxic doses according to the amount of PBS (40, 80, and 120 microl/well in a 96-well plate). Cytotoxicity was observed at doses of 100, 200, and 400 mJ/cm(2) for NBUVB and 5, 10, and 25 mJ/cm(2) for BBUVB in keratinocytes, melanocytes, and fibroblasts, respectively. At cytotoxic doses, there was no change in viability according to the amount of PBS. Fibroblasts are more resistant to UVB irradiation, irrespective of the amount of NBUVB and BBUVB, than keratinocytes and melanocytes. The amount of PBS during irradiation had no effect on viability.


Association of IL-13 gene polymorphisms with airway hyperresponsiveness in a Japanese adult asthmatic population.
A single nucleotide polymorphism (SNP; rs20541) in the IL-13 gene has been recognized as a risk factor for asthma. This SNP causes Arg to Gln (Q) substitution at position 110 in the mature IL-13 protein. We have recently showed that FEV1 in asthmatics with the Q110 variant of IL-13 declined faster, and progressive airway remodeling was observed in these subjects (Wynn, 2003 [1]). However, the effects of the IL-13 variant on airway hyperresponsiveness (AHR) remain to be elucidated. We analyzed the relationship between SNP rs20541 in IL-13 and AHR in asthmatics. We recruited 182 asthmatics who visited the asthma outpatient clinic at Iwate Medical University Hospital from 2006 to 2011. Subjects were genotyped for rs20541. Asthma severity, atopic status, age of asthma onset, serum IgE concentration, AHR, and pulmonary function were studied in these subjects. AHR was measured using the continuous methacholine inhalation method (Astograph; Chest; Tokyo, Japan). Genotyping of rs20541 revealed 26 A/A, 77 A/G, and 79 G/G patient genotypes. The D min (U) of the 3 genotypes was 1.17±0.300 in A/A, 1.99±0.35 in A/G, and 2.85±0.39 in G/G. The D min in the 3 genotypes was significantly different. Spirometric data revealed that % FEV1 and % FEF75 were significantly different among the 3 groups of IL-13 genotypes, whereas no significant differences were observed in therapeutic steps, atopic status, house dust mite sensitization, or serum IgE concentration. The SNP rs20541 in IL-13 was associated with AHR in Japanese adult asthmatics.


Multiple Reaction Monitoring for Direct Quantitation of Intact Proteins Using a Triple Quadrupole Mass Spectrometer.
Methods that can efficiently and effectively quantify proteins are needed to support increasing demand in many bioanalytical fields. Triple quadrupole mass spectrometry (QQQ-MS) is sensitive and specific, and it is routinely used to quantify small molecules. However, low resolution fragmentation-dependent MS detection can pose inherent difficulties for intact proteins. In this research, we investigated variables that affect protein and fragment ion signals to enable protein quantitation using QQQ-MS. Collision induced dissociation gas pressure and collision energy were found to be the most crucial variables for optimization. Multiple reaction monitoring (MRM) transitions for seven standard proteins, including lysozyme, ubiquitin, cytochrome c from both equine and bovine, lactalbumin, myoglobin, and prostate-specific antigen (PSA) were determined. Assuming the eventual goal of applying such methodology is to analyze protein in biological fluids, a liquid chromatography method was developed. Calibration curves of six standard proteins (excluding PSA) were obtained to show the feasibility of intact protein quantification using QQQ-MS. Linearity (2-3 orders), limits of detection (0.5-50 μg/mL), accuracy (<5% error), and precision (1%-12% CV) were determined for each model protein. Sensitivities for different proteins varied considerably. Biological fluids, including human urine, equine plasma, and bovine plasma were used to demonstrate the specificity of the approach. The purpose of this model study was to identify, study, and demonstrate the advantages and challenges for QQQ-MS-based intact protein quantitation, a largely underutilized approach to date.


Neuronal-immune interactions in mediating stress effects in the etiology and course of schizophrenia: role of the amygdala in developmental co-ordination.
Stress, in its many forms, is long associated with the etiology and course of schizophrenia. The mechanisms mediating the impacts of stress are not fully elucidated. Here it is proposed that stress induced cortisol alters kynurenic acid (KA) and quinolinic acid (QA) in the cortex and amygdala/striatum, respectively. These effects are significantly modulated by BAG-1 (bcl-2 associated anthanogene) and involve ROS, IL-18, and the induction of IDO (indoleamine 2,3-dioxygenase). The kynurenine pathway (KP) products response to stress seems to mediate both prenatal etiology and symptom course in adulthood. It is suggested that the effects of cortisol and quinolinic acid in the amygdala, coupled to an increase in dopamine efflux, mediate amygdala driven developmental changes in the cortex and VTA/N.Accumbens junction. This change in patterned brain activity co-ordinates alterations in motivated behaviour and thought outputs. Such developmental alterations determine changes in sensory-amygdala interactions, readily allowing developmental links to changes in lateral inhibition and pre-pulse inhibition. Decreases in vitamin D3 and melatonin further potentiate such stress induced changes. The likely involvement of glia in mediating increases in the KP products suggests that adaptation to stress is driven by neuronal activity as a form of glia to glia communication.


The relationship between mineral contents, particle matter and bottom ash distribution during pellet combustion: molar balance and chemometric analysis.
This paper aims to identify the correlation between the mineral contents in agropellets and particle matter and bottom ash characteristics during combustion in domestic boilers. Four agrifood residues with higher mineral contents, namely grape marc (GM), tomato waste (TW), exhausted olive mill solid waste (EOMSW) and olive mill wastewater (OMWW), were selected. Then, seven different pellets were produced from pure residues or their mixture and blending with sawdust. The physico-chemical properties of the produced pellets were analysed using different analytical techniques, and a particular attention was paid to their mineral contents. Combustion tests were performed in 12-kW domestic boiler. The particle matter (PM) emission was characterised through the particle number and mass quantification for different particle size. The bottom ash composition and size distribution were also characterised. Molar balance and chemometric analyses were performed to identify the correlation between the mineral contents and PM and bottom ash characteristics. The performed analyses indicate that K, Na, S and Cl are released partially or completely during combustion tests. In contrast, Ca, Mg, Si, P, Al, Fe and Mn are retained in the bottom ash. The chemometric analyses indicate that, in addition to the operating conditions and the pellet ash contents, K and Si concentrations have a significant effect on the PM emissions as well as on the agglomeration of bottom ash.


Role of electrical activity in axotomy-induced increased glucose use.
Glucose use as demonstrated by 2-deoxyglucose autoradiography increases in the hypoglossal nucleus after axotomy of the hypoglossal nerve. There are several possible explanations for this increase, including increased energy metabolism to support increased protein, RNA, and lipid synthesis during regeneration or, alternatively, increased electrical activity associated with the site of nerve transection or alterations in the neurolemma. To evaluate the possible role of electrical activity, we recorded spike activity in the hypoglossal nucleus after axotomy and evaluated glucose uptake in the hypoglossal nucleus after xylocaine application to the proximal nerve stump. There was no evidence from these experiments that an increased number of action potentials is responsible for the increased glucose use after axotomy.


Intramural ectopic pregnancy following pelvic adhesion: case report and literature review.
Intramural pregnancy is an uncommon type of ectopic pregnancy, where the gestational sac is completely encircled by myometrium and unconnected with endometrial cavity, fallopian tubes or round ligament. Owing to its potentially life-threatening hemorrhage and uterine rupture, early diagnosis and management are urgently required. We present a case of a woman undergoing zigzag medical procedures, which featured non-consensus preoperative diagnosis of intramural and interstitial pregnancy and an intramural ectopic pregnancy ultimately confirmed and successfully removed by emergency laparoscopy. Additionally, we present a review of the related literature and discuss its varied clinical features, imageological characters, diagnosis, differential diagnosis and multiple treatments. A comprehensive bibliographic search through PubMed, using keywords: intramural ectopic pregnancy. Relevant literatures published from January 2013 to April 2019 were reviewed. Twenty-four cases in total for intramural ectopic pregnancy including this report were reviewed. Diagnoses were mainly made by ultrasound images. Most patients had a history of uterine surgery or intrauterine operation and had been surgically resected. None of the mothers were in danger, but only one case had live birth at 37 weeks of gestation. Non-specific clinical presentation and non-uniform ultrasound criteria pose a challenge for us to make timely and accurate management. Integrated radiological examinations and communication and cooperation between sonographers and gynecologists play a vital role in diagnostic accuracy and selecting the optimal therapeutic method of an intramural pregnancy.


Improved solubilization of activated sludge by ozonation in pressure cycles.
The generation of a large volume of activated sludge (AS) from wastewater treatment has increasingly become a great burden on the environment. Anaerobic digestion is routinely practiced for excess waste sludge; however, the process retention time is long because of kinetic limitation in the hydrolysis step. We tested the feasibility of applying ozone in pressure cycles to enhance the disintegration and solubilization of AS with the goal to prepare them for digestion using reduced ozone dose and contact time. The AS was subjected to repetitive pressure cycles in a closed vessel in which an ozone gas mixture was compressed into the slurry to reach 1040 kPa in the headspace to be followed by rapid venting. For a returned AS with total COD (tCOD) of 8200 mg L(-1), a dose of 0.01 gO(3)g(-1) total suspended solids (TSS) delivered via 20 pressure cycles within 16 min resulted in a 37-fold increase of the sCOD/tCOD ratio (due to increased soluble COD, i.e. sCOD) and a 25% reduction of TSS, in comparison to a dose of 0.08 gO(3)g(-1) TSS via bubbling contact over 15 min that resulted in a 15-fold increase of the sCOD/tCOD ratio and a 12% reduction of TSS. Sludge solubilization was evidenced by increased dissolved contents of total phosphorous (from 10 to 64 mg L(-1)), total nitrogen (from 14 to 120 mg L(-1)), and protein (from <15 to 39 mg L(-1)) in the sludge suspension after treatment, indicating significant solubilization of AS.


Mitigating fall risk: A community fall reduction program.
One fourth of all American's over 65 years of age fall each year. Falls are a common and often devastating event that can pose a serious health risk for older adults. Healthcare providers are often unable to spend the time required to assist older adults with fall risk issues. Without a team approach to fall prevention the system remains focused on fragmented levels of health promotion and risk prevention. The specific aim of this project was to engage older adults from the community in a fall risk assessment program, using the Stopping Elderly Accidents, Deaths & Injuries (STEADI) program, and provide feedback on individual participants' risks that participants could share with their primary care physician. Older adults who attended the risk screening were taking medications that are known to increase falls. They mentioned that their health care providers do not screen for falls and appreciated a community based screening.


The identification of a repeated DNA sequence involved in the karyotype polymorphism of the human Y chromosome.
We show that individual men are polymorphic for the amount of two different repeated DNA sequences. The amount of one of these sequences is proportional to the length of the brightly fluorescent heterochromatin on the Y chromosome. There are no detectable alterations in sequence between polymorphic individuals. Female DNA contains sequences complementary to those found on the Y, but at a much reduced level.


Water-electrolyte balance in overmature fetuses.
The water and electrolyte contents of various fetal and maternal tissues were studied at the final stage of embryogeny and during prolonged pregnancy. The data indicate that the placenta in prolonged pregnancy can act as a depot organ for water and sodium.


A prospective clinical audit to evaluate postoperative quality of recovery in adults at New Somerset Hospital, Cape Town, South Africa.
Recent developments in perioperative medicine increasingly emphasise patient-centred approaches to quality of care metrics. To this end, the 15-item Quality of Recovery (QoR-15) scale is a well-validated and widely applied patient-centred measure of perioperative service quality. To assess quality of recovery in a South African (SA) population by applying the QoR-15 and to identify the local contributors to poor quality of recovery. A prospective observational study was performed in all adults undergoing elective and emergency surgery during daytime hours over a 2-week period in February 2019 at New Somerset Hospital, Cape Town, SA. Patients were approached by a qualitative interviewer on day 1 post surgery for consented recruitment, collection of demographic information and application of the QoR-15 questionnaire. Of 193 patients who had surgery, 154 fulfilled our criteria and completed the questionnaire. The median QoR-15 score was 123 out of 150, which is classified as 'good', although most patients (35%) fell into the 'moderate' category (90 - 121); 59% achieved the patient acceptable symptom state score (≥118). The median scores of the most poorly reported QoR-15 items were 5 for 'moderate pain' and 6 for 'able to return to work or usual home activities'. Poor scoring was not related to anaesthetic modality (p=0.088), surgical discipline (p=0.237), timing of surgery (p=0.717) or obstetric as opposed to non-obstetric patients (p=0.472). Construct validity was supported by a negative correlation with duration of anaesthesia (rho=-0.286; p<0.001) and lack of correlation with age (rho=-0.034; p=0.674). We found the QoR-15 to be a valid, feasible and acceptable tool for clinical auditing of perioperative service quality in SA. The median QoR-15 score was 123, with the majority of patients reflecting a moderate QoR. We have highlighted areas with potential for improvement and provided recommendations to address these aspects.


Network-based stage-specific drug repurposing for Alzheimer's disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common type of dementia. With no disease-curing drugs available and an ever-growing AD-related healthcare burden, novel approaches for identifying therapies are needed. In this work, we propose stage-specific candidate repurposed drugs against AD by using a novel network-based method for drug repurposing against different stages of AD severity. For each AD stage, this approach a) ranks the candidate repurposed drugs based on a novel network-based score emerging from the weighted sum of connections in a network resembling the structural similarity with failed, approved or currently ongoing drugs b) re-ranks the candidate drugs based on functional, structural and a priori information according to a recently developed method by our group and c) checks and re-ranks for permeability through the Blood Brain Barrier (BBB). Overall, we propose for further experimental validation 10 candidate repurposed drugs for each AD stage comprising a set of 26 elite candidate repurposed drugs due to overlaps between the three AD stages. We applied our methodology in a retrospective way on the known clinical trial drugs till 2016 and we show that we were able to highly rank a drug that did enter clinical trials in the following year. We expect that our proposed network-based drug-repurposing methodology will serve as a paradigm for application for ranking candidate repurposed drugs in other brain diseases beyond AD.


Risk factors for vertical incomplete resection in endoscopic submucosal dissection as total excisional biopsy for submucosal invasive colorectal carcinoma.
Endoscopic submucosal dissection (ESD) for colorectal tumor is a minimally invasive treatment. Histologic information obtained from the entire ESD specimen is important for therapy selection in submucosal invasive colorectal carcinoma (SMca). This study aimed to identify risk factors for vertical incomplete resection (vertical margin-positive [VM+]) when ESD was performed as total excisional biopsy for SMca. From June 2003 through December 2011, 78 SMca cases were resected by ESD at Hiroshima University Hospital. Patient and tumor characteristics, intraoperative variables, and histopathology were compared between the VM+ group and the vertical complete resection (vertical margin-negative) group. The ability of magnifying endoscopy (ME) and endoscopic ultrasonography (EUS) to predict VM+ was assessed. ESD resulted in VM+ in eight cases (10.3 %), with a greater percentage invading to a depth of ≥2,000 vs. <2,000 μm (P = 0.047). Severe submucosal fibrosis was found in five of the eight cases (62.5 %, P = 0.017). Poor differentiation was seen at the deepest invasive portion in six cases (75.0 %), and two of six cases had an invasion depth <2,000 μm. Of 39 EUS cases, 36 not showing deep invasion close to the muscularis propria were completely resected by ESD. Submucosal fibrosis and poor differentiation at the deepest invasive portion may be risk factors for VM+ in colorectal ESD for tumors with submucosal deep invasion. ME plus EUS is more likely to help determine whether ESD is indicated as complete total excisional biopsy for SMca.


Impact of proactive of infliximab monitoring using the Bayesian approach in the maintenance phase in patients with inflammatory bowel disease.
There is increasing evidence that proactive monitoring is useful in improving the control of inflammatory bowel disease, although it remains controversial. The aim of this study was to evaluate the efficacy of proactive TDM based on the Bayesian approach to optimise the IFX dose compared with the standard of care dosing in patients with IBD. Retrospective observational cohort of inflammatory bowel disease patients>18 years. Patients were classified into two groups according to the strategy used to optimise the dose of IFX: a standard therapy group (ST-group) with clinically based dose adjustment and therapeutic drug monitoring group (TDM-group), with estimation of pharmacokinetic parameters calculated by Bayesian prediction. A total of 153 patients were included. Of these, 75 were in the TDM-group. Clinical response at week 52 was evaluated in 114 patients. The proportion of patients who achieved clinical remission was higher in the TDM than in the ST-group (80.7% vs 61.4%, respectively, p=0.023). A total of 28 patients (24.6%) met the parameters for the composite variable 'poor clinical outcome' at week 52. The proportion of patients who reached this outcome was lower in the TDM-group than in the ST-group (12.3% vs 36.8%, respectively, p=0.002). Proactive therapeutic drug monitoring using Bayesian approach is associated with higher secondary response and fewer long-term complications.


High-resolution stereoscopic digital fundus photography versus contact lens biomicroscopy for the detection of clinically significant macular edema.
The purpose of this study was to compare high-resolution stereoscopic digital photography to contact lens biomicroscopy (CLBM) for the diagnosis of clinically significant macular edema. Comparative, prospective, observational case series. One hundred twenty diabetic patients. Patients underwent clinical retinal examination with CLBM by a retinal specialist. On the same day as clinical grading, patients received high-resolution stereoscopic digital imaging of the macula. The stereoscopic digital images were viewed using liquid crystal shutter goggles at least 2 months after clinical examination by a single masked grader for the presence or absence of diabetic retinopathy. Presence or absence of the Early Treatment of Diabetic Retinopathy Study criteria for clinically significant macular edema (CSME) overall, CSME 1, CSME 2, CSME 3, macular edema, microaneurysms, intraretinal hemorrhage, and hard exudate. Two hundred seven eyes of 105 patients had complete data sets from both diagnostic modalities. Exact agreement was high for all identified pathologic conditions: CSME overall, 83.6%; CSME 1, 83.6%; CSME 2, 96.1%; CSME 3, 88.5%; macular edema, 75.0%; microaneurysms, 77.9%; intraretinal hemorrhage, 83.7%; and hard exudate, 73.1%. Sensitivity ranged from 50.0% (CSME 2) to 90.6% (CSME overall). Specificity ranged from 90.0% (macular edema) to 99.0% (CSME 2). High-resolution stereoscopic digital photography is both sensitive and specific when identifying CSME and correlates well with the accepted standard of CLBM for the diagnosis of CSME.


Automated extraction of auditory brainstem response latencies and amplitudes by means of non-linear curve registration.
Animal results have suggested that auditory brainstem responses (ABRs) to transient sounds presented at supra-threshold levels may be useful for measuring hearing damage that is hidden to current audiometric tests. Evaluating such ABRs requires extracting the latencies and amplitudes of relevant deflections, or "waves". Currently, this is mostly done by human observers manually picking the waves' peaks and troughs in each individual response - a process that is both time-consuming and requiring of expert experience. Here, we propose a highly automated procedure for extracting individual ABR wave latencies and amplitudes based on the well-established methodology of non-linear curve registration. First, the to-be-analysed individual ABRs are temporally aligned - either with one another or, if available, with a pre-existing template - by locally compressing or stretching their time axes with smooth and invertible time warping functions. Then, the individual latencies and amplitudes of relevant ABR waves are obtained by picking the latencies of the waves' peaks and troughs on the common (aligned) time axis and combining these with the individual aligned responses and inverse time warping functions. Using an example ABR data set with a wide range of response latencies and signal-to-noise ratios (SNRs), we test different choices for fitting the time warping functions. We cross-validate the warping results using independent response replicates and compare automatically and manually extracted latencies and amplitudes for ABR waves I and V. Using a Bayesian approach, we show that, for the best registration condition, automatic and manual data were statistically similar. Non-linear curve registration can be used to temporally align individual ABRs and extract their wave latencies and amplitudes in a way that closely matches results from manual picking.


Impact of nonlinear distortion on acoustic radiation force elastography.
High-intensity focused ultrasound (HIFU) produces an acoustic radiation force that induces tissue displacement, which can be measured by monitoring time shifts in the backscattered signals from interrogation pulses. If the pulse occurs simultaneously with the HIFU, the arrival time of the backscatter will be biased because nonlinearity associated with the HIFU changes the local sound speed. Measurements of the pressure field using 1.1 MHz HIFU and a 7.5 MHz pulse in water exhibited a nonlinearly induced apparent displacement (NIAD) that varied with the HIFU pressure, propagation distance and the timing of the pulse relative to the HIFU. Nonlinear simulations employing the KZK equation predicted NIADs that agreed with measurements. Experiments with chicken breast demonstrated a NIAD with magnitude similar to that expected from the radiation force. Finally it was shown that if two pulses were fired with different phases relative to the HIFU, then upon averaging, the NIAD could be mitigated.


Klotho Protein: Its Role in Aging and Central Nervous System Pathology.
This review is devoted to Klotho protein and recent evidences for its functions in the brain. Information on transcriptional regulation of the klotho gene and posttranslational modifications of the protein resulting in multiple forms of Klotho is reviewed. Evidence is summarized that Klotho regulates the activity of protein factors, enzymes, and receptors, including data suggesting the importance of its glycosidase activity. Effects of Klotho on components of the glutamatergic neurotransmitter system, signal cascades involving protein kinases and protein phosphorylation, as well as oligodendrocyte differentiation and myelination are discussed. A possible contribution is proposed for Klotho levels in the development of central nervous system pathologies including mental disorders.


Cyclometalated (boroxinato)gold(III) complexes from arrested transmetalation.
Organic boroxines are ubiquitous, but metallaboroxine analogues remain rare. A new class of (boroxinato)gold species are demonstrated here, as are observations of phosphorescence from boroxinato complexes. Four new compounds are crystallographically characterized.


Overweight and obesity in adults and risk of renal cell carcinoma in Canada.
To assess the role of overweight and obesity in renal cell carcinoma (RCC) risk in Canada. Mailed questionnaires were used to obtain data on 1,279 (691 male and 588 female) newly diagnosed, histologically confirmed RCC cases and 5,370 population controls, between 1994 and 1997, in eight Canadian provinces. Data were collected on socio-economic status, height, weight, smoking habits, alcohol use, diet, and residential and occupational histories. Weight was expressed as body mass index (BMI). Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using unconditional logistic regression. The study found an increased risk of RCC associated with overweight and obesity among both male and female adults; the test for trend was statistically significant (p < 0.0001 for both sexes). Compared with normal BMI, the adjusted ORs for obese class III (BMI > or = 40.00) were 3.7 (95% CI = 1.5-9.4) and 3.8 (95% CI = 2.3-6.4) among males and females, respectively. These findings indicate that overweight and obesity play an important role in the etiology of renal cell among both males and females.


Stereo-imaging made easy.
A new stereo-imaging technique is described. This new technique uses both secondary electron and back scatter electron detectors simultaneously for imaging the fracture surfaces, pictures of which are used in stereo-imaging.


Structure of chromatin in spermatozoa.
The specialized structure of the sperm chromatin has a dual function - first to protect the DNA from damage during storage and transport to the oocyte, and then to enable a rapid and complete unpacking of the undamaged paternal genome in the ooplasm. It is evident that zinc has a pivotal role in maintaining the structural stability and in enabling a rapid decondensation at the appropriate time. It is important for the sperm chromatin structure that the spermatozoa are ejaculated together with the zinc-rich prostatic secretion. Early exposure to zinc-binding seminal vesicular fluid can deplete the sperm chromatin of zinc and most likely induce surplus formation of disulfide bridges, likely to cause incomplete and delayed decondensation of the sperm chromatin in the oocyte. A premature decrease in sperm chromatin structure stability is likely to increase the risk for damage to the DNA due to increased access to the genome for DNA damaging compounds. The status of the sperm chromatin structure can vary in vitro depending on the exposure to zinc-depleting conditions when spermatozoa are stored in semen after ejaculation. When sperm DNA damage tests are evaluated and validated, it is therefore essential to also take into account the dynamics of zinc-dependent and zinc-independent sperm chromatin stability.


The effects of fiberoptic bronchoscopy with and without atropine premedication on pulmonary function in humans.
Pulmonary function studies, including arterial blood gas analysis, were performed in 21 patients undergoing fiberoptic bronchoscopy. Eight received premedication with atropine and 13 did not. In the atropine-treated group there was no significant deterioration in pulmonary function immediately after bronchoscopy compared with baseline. Compared with the values obtained after topical lidocaine anesthesia, however, there was a decrease in peak expiratory flow rate (PEFR) (20 +/- 20%), forced expiratory volume in one second (FEV1.0) (11 +/- 12%), forced expiratory flow between 25 and 75% of vital capacity (FEF25-75) (22 +/- 16%), and forced expiratory flow at 75% of exhaled vital capacity (FEF75) (28 +/- 38%) and an increase in residual volume (RV) (16 +/- 19%). In the no-atropine group, postbronchoscopy values showed a decrease in PEFR (13 +/- 19%), forced vital capacity (FVC) (13 +/- )9%), FEV1.0 (14 +/- 16%), and oxygen partial pressure (Pa02) (11 +/- 9%) and an increase in RV (19 +/- 31%) and alveolar-arterial oxygen pressure gradient (deltaAaPO2) (91 +/- 129%) compared with baseline values. In this group also, topical lidocaine anesthesia resulted in a decrease in FVC compared with baseline. We conclude that the deleterious effect of bronchoscopy on pulmonary function is counterbalanced by the beneficial effect of atropine and that atropine is therefore a useful premedication for fiberoptic bronchoscopy.


Antibody recognition of substituted ammonium ions. Modulation by the counterion.
Antibodies directed against elliptinium acetate, a quaternary ammonium compound with antineoplastic activity in man, were obtained in rabbits, after conjugation of the drug with haemocyanin. These antibodies are specific for the quaternary ammonium structure. However, the recognition of the drug can be markedly decreased (ten-fold) by changing the associated counterion. These observations were extended to other ellipticine derivatives that exist in two forms: acetate and chloride. In each case, the recognition of the acetate form was 7-11-fold higher than that of the chloride form. These results could be explained by high-energy strengths existing between the cation and the anion, resulting in a paired-ion antigen. This represents the first identification of antibodies directed to a paired-ion structure, with specificity for both the cation and anion used for immunization. Such results are relevant in the construction of immunoassays for quaternary ammonium compounds.


Chronic ethanol exposure potentiates muscarinic receptor and alpha 2-adrenoceptor-mediated inhibition of cAMP accumulation in PC 12 cells.
The effects of ethanol on receptor-mediated inhibition of cAMP production were investigated in PC 12 cells. The in vitro addition of ethanol enhanced N-ethylcarboxyadenosine (NECA)-stimulated cAMP production without altering the inhibitory action of carbachol or epinephrine. A 4 day exposure of PC 12 cells to ethanol decreased the stimulation of cAMP production by NECA, but increased the inhibition of NECA-stimulated cAMP production by carbachol and epinephrine.


Younger women are more susceptible to inflammation: A longitudinal examination of the role of aging in inflammation and depressive symptoms.
The degree to which effects of inflammation on mood and behavior vary across the lifespan remains relatively unexplored despite well-established, age-related alterations in both the immune and central nervous systems. Further, the implications of this developmental process within different symptom domains warrants careful consideration. Women diagnosed with breast cancer (n = 188; ages 27-89) provided blood samples and reported depressive symptoms prior to adjuvant treatment, at the end of adjuvant treatment, and 6-, 12-, and 18-months after completing adjuvant treatment via the CES-D. Blood was assayed for C-reactive Protein (CRP) and interleukin (IL)-6. We used mixed linear effect models to estimate within- and between-person effects of CRP or IL-6 on 4 domains of depressive symptoms: depressed affect, low positive affect, somatic complaints, and interpersonal problems. High average inflammation was associated with elevated somatic complaints (CRP p = .009, IL-6: p = .05), interpersonal problems (CRP p = .002, IL-6 p < .001), and positive affect (IL-6 p = .03), but only among the youngest women in the sample (age 50 or younger). Younger women also reported more depressed affect at assessments when inflammation was higher (CRP p = .045, IL-6 p = .09). The association between inflammation and specific depressive symptoms is dynamic and varies across the lifespan, which may help clarify apparent inconsistencies in the extant literature as well as inform more precise interventions targeting this pathway.


Bee venom-derived antimicrobial peptide melectin has broad-spectrum potency, cell selectivity, and salt-resistant properties.
Antimicrobial peptides have attracted attention as alternatives to conventional antibiotics. Previously, a novel antimicrobial peptide, melectin, consisting of 18 amino acids was isolated from the venom of a bee, Melecta albifrons. Here, we investigated the antibacterial activity of melectin against drug-resistant bacteria. Melectin showed broad-spectrum antimicrobial activity but low cytotoxicity and no hemolytic activity. Melectin maintained its antimicrobial activity at physiological salt concentrations. Melectin is an α-helical structure that binds to the bacterial membrane via electrostatic interactions and kills bacteria in a short time by bacterial membrane targeting. Collectively, our results suggest that melectin has antibacterial activity and anti-inflammatory activity.


Integrating Children's Mental Health into Primary Care.
Children's mental health problems are among global health advocates' highest priorities. Nearly three-quarters of adult disorders have their onset or origins during childhood, becoming progressively harder to treat over time. Integrating mental health with primary care and other more widely available health services has the potential to increase treatment access during childhood, but requires re-design of currently-available evidence-based practices to fit the context of primary care and place a greater emphasis on promoting positive mental health. While some of this re-design has yet to be accomplished, several components are currently well-defined and show promise of effectiveness and practicality.


The Use of Translational Research Platforms in Clinical and Biomedical Data Exploration.
The rise of precision medicine combined with the variety of biomedical data sources and their heterogeneous nature make the integration and exploration of information that they retain more complicated. In light of these issues, translational research platforms were developed as a promising solution. Research centers have used translational tools for the study of integrated data for hypothesis development and validation, cohort discovery and data-exploration. For this article, we reviewed the literature in order to determine the use of translational research platforms in precision medicine. These tools are used to support scientists in various domains regarding precision medicine research. We identified eight platforms: BRISK, iCOD, iDASH, tranSMART, the recently developed OncDRS, as well as caTRIP, cBio Cancer Portal and G-DOC. The last four platforms explore multidimensional data specifically for cancer research. We focused on tranSMART, for it is the most broadly used platform, since its development in 2012.


Addenbrooke's cognitive examination test for brief cognitive assessment of adolescents suffering from migraine with aura.
The aim of this study was to assess the role of the Addenbrooke's cognitive examination test (ACE-R) in the evaluation of cognitive status in migraineurs interictally. A total of 44 adolescent patients and 44 healthy controls, matched by age and gender, have undergone ACE-R testing. Migraineurs were additionally questioned about migraine aura features and presence of higher cortical dysfunctions (HCD) during an aura. According to the questionnaire results, patients were subsequently divided into HCD and Non-HCD group. ACE-R scores of migraine patients were significantly lower than in healthy controls (93.68 ± 3.64 vs 96.91 ± 2.49; t = 4.852, p < 0.001). Also, subscores of memory and verbal fluency were significantly higher in the control population. There was no correlation of HCD occurrence with cognitive examination score, although Non-HCD subgroup achieved better score (93.13 ± 3.91 vs 94.29 ± 3.30; t = 1.053, p = 0.298). Findings have shown that migraineurs get lower ACE-R test scores, with a tendency to have a poorer outcome in more complex aura. Also, our study has revealed that the ACE-R test is an easily administered test for brief assessment of cognitive status in migraineurs. Future perspectives could be further evaluation of ACE-R test in larger sample size and the impact of migraine with aura on cognitive function in adolescents.


Long-term evaluation of safety and biological effects of Korean Red Ginseng (Panax Ginseng): a long-term in vivo study.
Although Korean Red Ginseng (KRG) is safe, this finding was only evaluated in 3-mo-long studies. Its safety was verified through a 6-mo KRG administration clinical study, but long-term studies beyond 6 mo are insufficient. This study investigated the safety and efficacy of 12-mo KRG administration. In this study, 300 mg/kg of KRG was administered to male and female Sprague Dawley rats for 4, 8, and 12 mo to evaluate its efficacy and safety. Clinical signs, including pathological examination and haematological analyses, were observed. Flow cytometric analyses were utilised to analyse spleen and thymus immune cell counts after 12 mo. Proteomic analysis of the sera was performed using a nanospray-interfaced mass spectrometer with an 11-plex Tandem Mass Tag (TMT) labelling system. Bioinformatic analysis was then performed using Ingenuity Pathway Analysis and PANTHER. Data are available via ProteomeXchange with identifier PXD032036. No significant body and organ weight changes were observed, and haematological and serum biochemical analyses did not show clinical significance. The effectiveness of long-term KRG administration was confirmed through increased immune cell distribution and activity. Changes in proteins correlated with viral infection reduction were confirmed through proteomic analysis. The results suggested that 12-mo KRG intake is safe, improves immune system activity, and reduces viral infections with no significant changes in toxicological aspects.


Primary pulmonary artery sarcoma: intra-operative similarity to pulmonary embolus.
An infarcted right lower lobe, thought to be due to a thrombotic pulmonary embolus, was resected in a 48 year old man. Subsequent examination of the lobe unexpectedly showed the infarction to be secondary to a primary sarcoma of the pulmonary artery.


Highly Tough, Stretchable, Self-Adhesive and Strain-Sensitive DNA-Inspired Hydrogels for Monitoring Human Motion.
Hydrogels used as strain sensors often rely on splicing tapes to attach them to surfaces, which causes much inconvenience. Therefore, to develop strain sensor hydrogels that possess both good mechanical properties and self-adhesion is still a great challenge. Inspired by the multiple hydrogen bonding interactions of nucleobases in DNA, we designed and synthesized a series of hydrogels PAAm-GO-Aba/Tba/Aba+Tba comprising polyacrylamide (PAAm), graphene oxide (GO), acrylated adenine and thymine (Aba and Tba). The introduction of nucleobases helps hydrogels to adhere to various substrates through multiple hydrogen-bonding interactions. It has also been found that the adhesive strength of hydrogels with nucleobases for hogskin increased to 2.5 times that of those without nucleobases. Meanwhile, these hydrogels exhibited good dynamic mechanical and self-recovery properties. They can be directly attached to human skin as strain sensors to monitor the motions of finger, wrist, and elbow. Electrical tests indicate that they give precise real-time monitoring data and exhibit good strain sensitivity and electrical stability. This work provides a promising basis from which to explore the fabrication of tough, self-adhesive, and strain-sensitive hydrogels as strain sensors for applications in wearable devices and healthcare monitoring.


Infectious complications in survivors of cardiac arrest admitted to the medical intensive care unit.
To describe the incidence, associated factors and outcome of infectious complications in patients admitted to the medical intensive care unit (MICU) after cardiopulmonary resuscitation (CPR). We identified a retrospective cohort of 56 patients consecutively admitted to MICU after CPR. We collected data on demographics, the first MICU day APACHE III score, mode and location of cardiac arrest, CPR duration, witnessed aspiration, prior antibiotics, the lowest first MICU day Glasgow coma score (GCS), new infections, duration of mechanical ventilation and mortality. Seventy-nine percent of the arrests occurred in the hospital. Pulseless electrical activity was the most common rhythm (52%). New infections developed in 46%. The most common infection was pneumonia (65%) and the most common pathogen Staphylococcus aureus (31%). Blood cultures were obtained in 40 patients during the first 48 h and pathogens were isolated in five (12.5%). Patients with infection were younger (53.7 vs. 70.4 years, P<0.001). Median first day GCS was eight in-patients with infection compared with ten in those without (P=0.032). Patients with infection had longer duration of mechanical ventilation (median 9 vs. 2 days, P=0.001) and MICU length of stay (median 8 vs. 3 days, P<0.001). Hospital mortality was 54% in-patients with infection versus 37% without (P=0.197). Infectious complications are common in survivors of cardiac arrest and are associated with increased morbidity.


Neural networks, nativism, and the plausibility of constructivism.
Recent interest in PDP (parallel distributed processing) models is due in part to the widely held belief that they challenge many of the assumptions of classical cognitive science. In the domain of language acquisition, for example, there has been much interest in the claim that PDP models might undermine nativism. Related arguments based on PDP learning have also been given against Fodor's anti-constructivist position--a position that has contributed to the widespread dismissal of constructivism. A limitation of many of the claims regarding PDP learning, however, is that the principles underlying this learning have not been rigorously characterized. In this paper, I examine PDP models from within the framework of Valiant's PAC (probably approximately correct) model of learning, now the dominant model in machine learning, and which applies naturally to neural network learning. From this perspective, I evaluate the implications of PDP models for nativism and Fodor's influential anti-constructivist position. In particular, I demonstrate that, contrary to a number of claims, PDP models are nativist in a robust sense. I also demonstrate that PDP models actually serve as a good illustration of Fodor's anti-constructivist position. While these results may at first suggest that neural network models in general are incapable of the sort of concept acquisition that is required to refute Fodor's anti-constructivist position, I suggest that there is an alternative form of neural network learning that demonstrates the plausibility of constructivism. This alternative form of learning is a natural interpretation of the constructivist position in terms of neural network learning, as it employs learning algorithms that incorporate the addition of structure in addition to weight modification schemes. By demonstrating that there is a natural and plausible interpretation of constructivism in terms of neural network learning, the position that nativism is the only plausible model of acquisition can no longer be defended. Indeed, I briefly discuss a number of learning-theoretic reasons indicating that constructivist models so characterized uniquely possess a number of important learning characteristics.


The use of growth charts for assessing and monitoring growth in Canadian infants and children.
Recent changes to commonly used growth charts, including the addition of charts for body mass index, have raised questions on which growth charts to use for Canadian children and how to apply body mass index in the paediatric population. This statement, developed collaboratively by key organizations in paediatric health care, is intended for use as a practice guideline for medical practitioners and clinical and community health (public health, home health) professionals. The desired outcome is the provision of recommendations that will promote consistent practices in monitoring growth and assessing atypical patterns of linear growth and weight gain in infants, children and adolescents.


Improved lensometry with a programmed calculator-lensometer combination.
The arithmetic associated with prescription calculation seems to be the major source of error and inefficiency in the performance of traditional lensometry. We have found that a programmed calculator used in combination with a lensometer achieves greater accuracy in less time than does the lensometer alone. This approach may be a useful alternative to the physician who does not wish to make a substantial investment in a fully automatic device.


[Coordination of health vigilances: for a global management of hospital risks].
The sanitary vigilances represent a permanent sanitary surveillance. They signal, enregister, treat and investigate the adverse events occurring through the use of health products. They assure the traceability of these health products and the management of the sanitary alerts. The sanitary vigilances are part of the sanitary security. They are optimized when coordinated and integrated to the global risk management process of the health care establishments.


Defects in rutile and anatase polymorphs of TiO2: kinetics and thermodynamics near grain boundaries.
The direct consequence of irradiation on a material is the creation of point defects-typically interstitials and vacancies, and their aggregates-but it is the ultimate fate of these defects that determines the material's radiation tolerance. Thus, understanding how defects migrate and interact with sinks, such as grain boundaries, is crucial for predicting the evolution of the material. We examine defect properties in two polymorphs of TiO(2)-rutile and anatase-to determine how these materials might respond differently to irradiation. Using molecular statics and temperature accelerated dynamics, we focus on two issues: how point defects interact with a representative grain boundary and how they migrate in the bulk phase. We find that grain boundaries in both polymorphs are strong sinks for all point defects, though somewhat stronger in rutile than anatase. Further, the defect kinetics are very different in the two polymorphs, with interstitial species diffusing quickly in rutile while oxygen defects-both interstitials and vacancies-are fast diffusers in anatase. These results allow us to speculate on how grain boundaries will modify the radiation tolerance of these materials. In particular, grain boundaries in rutile will lead to a space charge layer at the boundary and a vacancy-rich damage structure, while in anatase the damage structure would likely be more stoichiometric, but with larger defects consisting primarily of Ti ions.


Development of new 1, 3-dihydroxyacridone derivatives as Akt pathway inhibitors in skeletal muscle cells.
In the present work, four new compounds based on the privileged structure acridone were efficiently synthesized following simple operational techniques and biologically tested on proliferative skeletal muscle cells (C2C12) and rhabdomyosarcoma cells (RD) showing no significant changes in the number of dead or viable cells at 1 µM during 24 or 48 h of treatment. Of relevance, acridone derivatives 3a-3d at 0.5 µM for 24 h effectively inhibited Akt activation in C2C12, while at 1 µM only compounds 3a and 3b have effect. RD cells showed a different response pattern. These cells treated with 3a (0.5 µM), 3b (0.5 µM) or 3d (0.5 or 1 µM) for 24 h shown significant Akt inhibition. In addition, 3a-3d assayed at 1 µM for 48 h were highly successful in inhibiting Akt phosphorylation. Finally, based on molecular docking and molecular dynamics simulations, we rationalize the experimental results mentioned above and propose that 3-phosphoinositide-dependent kinase-1 (PDK1) could be one of the molecular targets of this new series of 1, 3-dihydroxyacridone derivatives. Biological and in silico studies revealed that 3b could be considered as the most promising prototype for the development of new antitumor agents.


Wedge resection in the cone after failed refractive surgery in a patient with keratoconus.
A 30-year-old man with keratoconus in the right eye had radial keratotomy in the left eye. Two pairs of corneal relaxing incisions (CRIs) were made in the right eye to flatten the central cornea and reduce high astigmatism. The right eye required an enhancement, and two additional arcuate CRIs were made. A corneal ulcer developed in the right eye, with infiltrates in the incision and corneal thinning. Although the second set of CRIs resulted in more regular astigmatism, the corneal thinning and ulcer caused regression at two months postoperatively. A wedge resection was performed to even the irregular astigmatism. The results are presented.


Effects of interrupting sitting with different activity bouts on postprandial lipemia: A randomized crossover trial.
To determine whether interrupting prolonged sitting with three different activity breaks has both acute and chronic effects on postprandial lipid metabolism immediately after the activity-break period and on the following day, this study is a secondary analysis of an experimental research, which included 16 sedentary healthy adults (7 men, 24 ± 3 years, BMI 22.2 ± 2.3 kg/m2 ) who completed four 26-h laboratory trials. Participants spent 22.5 hours in a whole room calorimeter for testing energy expenditure (EE), including a 9-h activity-break period: (a) 9-h prolonged sitting (SIT); (b) 3 minutes of brisk walking (60% VO2max ) in between every 30-min sitting bout (WALK3), (c) 5 minutes every 45-min (WALK5), and (d) 8 minutes every 60-min (WALK8). Total area under the curve (tAUC) and incremental AUC (iAUC) for 2-h postprandial serum triglyceride (TG) levels and non-esterified fatty acid (NEFA) levels were examined immediately after the 9-h trial (post-dinner) and the next morning (post-breakfast). WALK8 reduced the post-breakfast TG tAUC by 11% (P = .041) relative to SIT, and the effect was attenuated after adjustment for EE. The tAUC and iAUC indicated no significant treatment effects on post-dinner TG and NEFA, and post-breakfast NEFA in any of the activity-break trials. EE was positively associated with the post-breakfast NEFA iAUC (unstandardized β = 0.17 µmol/L/MJ [0.05-0.28], P = .006). There was a chronic effect of interrupting sitting with short bouts (8 minutes) of brisk walking every 60 minutes on postprandial lipemia the following morning after intervention, and higher activity bout-induced EE may be more effective in sedentary, healthy adults.


The US Affordable Care Act: Reflections and directions at the close of a decade.
In this month's Editorial, PLOS Medicine Academic Editor Zirui Song and his colleague Adrianna McIntyre discuss outcomes and possible futures for the United States Affordable Care Act as it nears the ten year mark.


Fcgamma receptor signaling in primary human microglia: differential roles of PI-3K and Ras/ERK MAPK pathways in phagocytosis and chemokine induction.
Cryptococcus neoformans monoclonal antibody immune complex (IC) induces beta-chemokines and phagocytosis in primary human microglia via activation of Fc receptor for immunoglobulin G (FcgammaR). In this report, we investigated microglial FcgammaR signal-transduction pathways by using adenoviral-mediated gene transfer and specific inhibitors of cell-signaling pathways. We found that Src inhibitor PP2 and Syk inhibitor piceatannol inhibited phagocytosis, macrophage-inflammatory protein-1alpha (MIP-1alpha) release, as well as phosphorylation of extracellular-regulated kinase (ERK) and Akt, consistent with Src/Syk involvement early in FcgammaR signaling. Constitutively active mitogen-activated protein kinase kinase (MEK) induced MIP-1alpha, and Ras dominant-negative (DN) inhibited IC-induced ERK phosphorylation and MIP-1alpha production. These results suggest that the Ras/MEK/ERK pathway is necessary and sufficient in IC-induced MIP-1alpha expression. Neither Ras DN nor the MEK inhibitor U0126 inhibited phagocytosis. In contrast, phosphatidylinositol-3 kinase (PI-3K) inhibitors Wortmannin and LY294002 inhibited phagocytosis without affecting ERK phosphorylation or MIP-1alpha production. Conversely, Ras DN or U0126 did not affect Akt phosphorylation. Together, these results demonstrate distinct roles played by the PI-3K and Ras/MEK/ERK pathways in phagocytosis and MIP-1alpha induction, respectively. Our results demonstrating activation of functionally distinct pathways following microglial FcgammaR engagement may have implications for human central nervous system diseases.


GeoBioMed perspectives on kidney stone recurrence from the reactive surface area of SWL-derived particles.
Shock wave lithotripsy (SWL) is an effective and commonly applied clinical treatment for human kidney stones. Yet the success of SWL is counterbalanced by the risk of retained fragments causing recurrent stone formation, which may require retreatment. This study has applied GeoBioMed experimental and analytical approaches to determine the size frequency distribution, fracture patterns, and reactive surface area of SWL-derived particles within the context of their original crystal growth structure (crystalline architecture) as revealed by confocal autofluorescence (CAF) and super-resolution autofluorescence (SRAF) microscopy. Multiple calcium oxalate (CaOx) stones were removed from a Mayo Clinic patient using standard percutaneous nephrolithotomy (PCNL) and shock pulse lithotripsy (SPL). This produced approximately 4-12 mm-diameter PCNL-derived fragments that were experimentally treated ex vivo with SWL to form hundreds of smaller particles. Fractures propagated through the crystalline architecture of PCNL-derived fragments in a variety of geometric orientations to form rectangular, pointed, concentrically spalled, and irregular SWL-derived particles. Size frequency distributions ranged from fine silt (4-8 μm) to very fine pebbles (2-4 mm), according to the Wentworth grain size scale, with a mean size of fine sand (125-250 μm). Importantly, these SWL-derived particles are smaller than the 3-4 mm-diameter detection limit of clinical computed tomography (CT) techniques and can be retained on internal kidney membrane surfaces. This creates clinically undetectable crystallization seed points with extremely high reactive surface areas, which dramatically enhance the multiple events of crystallization and dissolution (diagenetic phase transitions) that may lead to the high rates of CaOx kidney stone recurrence after SWL treatment.


Treatment of delayed union and non-union of the carpal scaphoid with a compression staple and cancellous bone grafting--new method and preliminary results.
Scaphoid non-union (eight cases) and delayed union (three cases) were treated by compression staple and inlay of cancellous bone from iliac crest between the bony fragments. Union was achieved in ten of the cases (91 per cent). The consolidation time was 8-12 weeks in seven cases and 24 weeks or more in three cases. The compression stable fixation connected with bone grafting is a new and simple method to treat chronic fractures of the carpal scaphoid which is a difficult problem. The early results appear promising.


Urine heme dipsticks are useful in monitoring the impact of praziquantel treatment on Schistosoma haematobium in sentinel communities of Delta State, Nigeria.
Nigeria is highly endemic for infection with Schistosoma haematobium, which most commonly manifests itself with blood in urine. To monitor the impact of annual mass drug administration (MDA) with Praziquantel for S. haematobium in Delta State, Nigeria, cross-sectional hematuria surveys of school children were conducted in 8 sentinel villages (SVs) at baseline (n=240) and after two annual doses (n=402). We assessed the comparability of three assessments of hematuria (child's reported history, nurse visual diagnosis (NVD) and dipstick) to determine the need for mass treatment. Dipstick was considered to be the gold standard. Prior to treatment, history and NVD each identified only the 3 most highly prevalent SVs, and overall this represented just 37.5% of the 8 SVs in need of treatment. Following treatment, after dipstick prevalence decreased by 88.5% (p<0.001), and history and NVD identified only one of two villages still needing treatment. The study suggests that dipsticks should be the recommended method for launching and monitoring mass treatment for S. haematobium.


Biomechanical concepts of forefoot surgery.
There are many types of compensations that occur in the foot. The body is a unique organism that does what "it" does best, not what it "should" do. The compensatory motions that occur to balance the abnormal structural or positional problems that we see must be neutralized for surgery to be successful. The complete process includes evaluation and observation of what is mechanically happening, which leads to correcting the anatomic deformity that is present, and finally treating the biomechanical forces so surgical correction is long lasting and satisfying.


No decrease in clindamycin susceptibility despite increased use of clindamycin for pediatric community-associated methicillin-resistant Staphylococcus aureus skin infections.
A previous study at our institution revealed 98% of methicillin-resistant Staphylococcus aureus (MRSA) isolates were susceptible to clindamycin; however, beta-lactams were then the predominant empiric treatment. This follow-up chart review study examined subsequent staphylococcal skin and soft tissue infection treatment and susceptibility patterns over a 2-year period. Of 296 S. aureus skin and soft tissue infections, 73% were MRSA, of which 87% were community-associated-MRSA; MRSA infections peaked in warm summer months. Despite a significant increase in empiric clindamycin use, 97% of community-associated-MRSA isolates retained susceptibility to clindamycin.


Financial literacy, behavioral traits, and ePayment adoption and usage in Japan.
This study investigates how financial literacy and behavioral traits affect the adoption of electronic payment (ePayment) services in Japan. We construct a financial literacy index using a representative sample of 25,000 individuals from the Bank of Japan's 2019 Financial Literacy Survey. We then analyze the relationship between this index and the extensive and intensive usage of two types of payment services: electronic money (e-money) and mobile payment apps. Using an instrumental variable approach, we find that higher financial literacy is positively associated with a higher likelihood of adopting ePayment services. The empirical results suggest that individuals with higher financial literacy use payment services more frequently. We also find that risk-averse people are less likely to adopt and use ePayment services, whereas people with herd behavior tend to adopt and use ePayment services more. Our empirical results also suggest that the effects of financial literacy on the adoption and use of ePayment differ among people with different behavioral traits. The online version contains supplementary material available at 10.1186/s40854-023-00504-3.


Feasibility of using a tailored mesh in laparoscopic Sugarbaker parastomal hernia repair.
In parastomal hernia (PH) repair, laparoscopic Sugarbaker technique (LS) is considered the best practice; however, meshes specific for LS repairs ceased to be available. The aim of the study was to evaluate feasibility of using a physician-modified mesh (tailored mesh: TM) in LS. Thirty-three patients who underwent LS for PH between June 2012 and September 2021 were examined to compare surgical outcomes between LS with TM (n = 11) and with a ready-made specific mesh (SM, n = 22). All meshes were coated plastic meshes. Statistical analysis was performed with the Mann-Whitney U test and Fisher's exact test. P < .05 was considered to be statistically significant. We compared the outcomes of TM with SM in LS for similar hernia types during median follow-up periods of 23 (range, 2-29) and 74 (range, 36-110) months (P < .0001), respectively. The median operation times were 146 (range, 45-423) for TM and 193 (range, 65-386) minutes for SM (P = .2301). Perioperative complications were observed in one TM patient (9%) and two SM patients (9%) (P = 1.0000). The lengths of postoperative stay were similar. Recurrence was observed in two cases in the SM group (9%) within 1 year after the operation. In LS, TM seems to be a feasible mesh comparable to SM within short- and mid-term follow-up.


The effects of transpositions of functional I retrotransposons depend on the conditions and dose of parental exposure.
Transposable elements (TEs) cause destabilization of animal genomes. I retrotransposons of Drosophila melanogaster, as well as human LINE1 retrotransposons, are sources of intra- and interindividual diversity and responses to the action of internal and external factors. The aim of this study was to investigate the response to irradiation for the offspring of Drosophila melanogaster with the increased activity of inherited functional I elements. The material used was dysgenic Drosophila females with active I retrotransposons obtained as a result of crossing irradiated/non-irradiated parents of a certain genotype. Non-dysgenic females (without functional I elements) were used as controls. The effects of different conditions (irradiation of both parents simultaneously or separately) and doses (1-100 Gy) of parental irradiation have been assessed by analyzing SF-sterility, DNA damage and lifespan. The presence of full-size I retrotransposons was determined by PCR analysis. The maternal exposure and exposure of both parents are efficient in contrast with paternal exposure. Irradiation of mothers reduces the reproductive potential and viability of their female offspring which undergo high activity of functional I retrotransposons. Though I retrotranspositions negatively affect the female gonads, irradiation of the paternal line can increase the lifespan of SF-sterile females. Radiation stress in the range of 1-100 Gy increases DNA fragmentation in both somatic and germ cells of the ovaries with high I-retrotransposition. These results allow for the specificity of the radiation-induced behavior of I retrotransposons and their role in survival under conditions of strong radiation stress.


Destruction of catecholamine-containing neurons by 6-hydroxydopa, an endogenous amine oxidase cofactor.
The amino acid, 6-hydroxydopa (6-OHDOPA), found at the active site of amine oxidases, exists as a keto-enol. Exogenously administered 6-OHDOPA is an excitotoxin like beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA), acting at the non-N-methyl-D-aspartate (non-NMDA) alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor. BMAA and BOAA are causal factors of neurolathyrism in humans. Much exogenously administered 6-OHDOPA is biotransformed by aminoacid decarboxylase (AADC) to the highly potent and catecholamine-(CA) selective neurotoxin, 6-hydroxydopamine (6-OHDA). 6-OHDOPA destroys locus coeruleus noradrenergic perikarya and produces associated denervation of brain by norepinephrine-(NE) containing fibers. Opiopeptides and opioids enhance neurotoxic effects of 6-OHDOPA on noradrenergic nerves, by a naloxone-reversible process. An understanding of mechanisms underlying neurotoxic effects of 6-OHDOPA can be helpful in defining actions of known and newfound amino acids and for investigating their potential neurotoxic properties.


Risk of renal stone formation induced by long-term bed rest could be decreased by premedication with bisphosphonate and increased by resistive exercise.
To clarify the influence of long-term bed rest on renal stone formation and to analyze the mechanism of bed-rest-induced stone formation and prevention by bisphosphonate and bed-rest exercise. Twenty-five men aged 26-48 years and divided into control (CON: n = 9), exercise (EX: n = 9), and pamidronate (PMD: n = 7) groups, rested on a 6 degrees head-down tilt bed for 90 days. The exercise group carried out resistive exercise every 3 days. Pamidronate (60 mg) was intravenously given 2 weeks before the initiation of bed rest. Abdominal X-ray examination and urine biochemistry were carried out during 90 days of bed rest and 90 days of reloading. Renal stone formation was observed in two (22.2%) and four (44.4%) subjects in the control and exercise groups, respectively. No stone was seen in the pamidronate group. In the exercise group, urinary oxalate and phosphate excretion were significantly higher than in the control group. In the pamidronate group, urinary calcium excretion and relative supersaturation of calcium oxalate and brushite were lower than in the control group throughout the bed-rest and recovery period. Long-term bed-rest-induced renal stone formation was found to be induced by increased urinary calcium and subsequent crystal formation of calcium oxalate and calcium phosphate. Exercise during bed rest for the prevention of bone mineral loss and contracture might increase the risk of renal stone formation. Pamidronate is useful for the prevention of renal stone formation during and after bed rest.


Factors related to the use of opioids as early treatment in patients with knee osteoarthritis.
To examine factors related to the use of opioids as an early treatment option for knee OA patients METHODS: Using the Korean nationwide claim database, we selected knee OA patients between 2013 and 2015. Among them, patients without any claim of knee OA for 2 years before the index date were included as our study population. We analyzed their first claim for prescriptions, including tramadol and stronger opioids, at the index date of each patient. Using a multinomial model, we identified factors associated with the early use of tramadol and stronger opioids in knee OA patients. Among a total of 2,857,999 knee OA patients, 12.2% (n = 348,516) were treated with opioids as their first treatment. However, the prevalence of stronger opioid use was only 0.07% (n = 1972). Male sex (OR 1.28 in tramadol, OR 1.13 in stronger opioids) and comorbidities with depression (OR 1.05, 1.46), low back pain (OR 1.13, 1.30), intervertebral disc disorder (OR 1.11, 1.40), and spinal stenosis (OR 1.27, 1.55) were the factors for the early use of tramadol or stronger opioids in knee OA patients. Patients in a tertiary referral hospital tended to use tramadol or stronger opioids than those in clinics (OR 1.04, 56.63, respectively). In Korea, 12.2% of knee OA patients were treated with opioids as an early treatment, and tramadol was used more commonly than stronger opioids. Male sex and having comorbidities such as depression or musculoskeletal disease are patient factors associated with the early use of opioids in knee OA patients.


Toward flexible regulation of polyhydroxyalkanoate composition based on substrate feeding strategy: Insights into microbial community and metabolic features.
The suitable feeding strategy considering both substrate preference (enrichment stage) and flexible regulation (PHA accumulation stage) were investigated, respectively, based on intracellular polymers synthesis peculiarities of the three types of cultures (M-Ac, M-Pr and M-Bu), which were enriched correspondingly using acetic type, propionic type and butyric type substrate. Compared to M-Ac and M-Bu cultures, maximum PHA content (PHAm) of M-Pr exhibited the most stable responses to varying fractions of propionic acid (fPr) of the substrate. The substrate composed of acetic acid and propionic acid (Mix-AP) demonstrated higher efficiency in regulation of polymer composition than that composed of butyric acid and propionic acid (Mix-BP). For the whole process of three-stage MC PHA production, propionic acid-dominated acidification products should be used for the long-term enrichment of PHA producers, and acidification products mainly composed of propionic and acetic acid are preferred considering the regulation of polymer composition in PHA accumulation stage.


Racial/ethnic and gender disparities in renal cell carcinoma incidence and survival.
We used a population based cancer registry to examine trends in renal cell carcinoma incidence and survival among 4 racial/ethnic groups (white, black, Hispanic and Asian/Pacific Islander) and both genders. Race/ethnicity, gender, age, staging, length of survival and cause of death data were analyzed using 39,434 cases of renal cell carcinoma from 1988 to 2004 from the California Cancer Registry. Annual age adjusted incidence rates and relative survival rates were calculated for the racial/ethnic and gender groups. These rates and the percent of localized cancer were plotted by year, and Microsoft Excel was used to calculate linear regression equations. Median age was also calculated. Z-tests and chi-square tests were performed to determine p values. An increase in renal cell carcinoma incidence was found with localized cancer accounting for most of the increase. Black patients had a significantly higher incidence rate (p <0.0001) and lower survival rate (p <0.0001) than all other races/ethnicities despite having more localized cancer (p <0.005). Black patients were also diagnosed at a younger age (p <0.0001) than their counterparts. On the other hand Asian/Pacific Islanders had a lower incidence rate (p <0.0001) and higher survival rate (p <0.05) than all other races/ethnicities. Males had approximately twice the incidence rate of females and a lower survival rate (p <0.005). Higher incidence rates and lower survival rates were identified among black and male patients compared to their counterparts, while Asian/Pacific Islanders showed the opposite trends. Such racial/ethnic and gender disparities in renal cell carcinoma incidence and survival may help elucidate biological, behavioral and environmental factors that can potentially be addressed.


Evaluation of a single-use gastroscope in patients presenting with suspected upper gastrointestinal hemorrhage: a pilot feasibility study (One-Scope I).
BACKGROUND : Outbreaks of multidrug-resistant bacteria due to contaminated duodenoscopes and infection risks during the COVID-19 pandemic have driven the development of single-use endoscopes. The first single-use gastroscope is now available in Europe. Besides waste disposal and cost issues, the infection risk and performance remain unclear. We aimed to evaluate a single-use gastroscope in patients with signs of upper gastrointestinal bleeding. METHODS : 20 consecutive patients presenting with clinical signs of upper gastrointestinal bleeding between October and November 2022 were included in this case series. The primary aim was technical success, defined as access to the descending duodenum and adequate assessment of the upper gastrointestinal tract for the presence of a bleeding site. RESULTS : The primary aim was achieved in 19/20 patients (95 %). The bleeding site was identified in 18 patients. A therapeutic intervention was performed in six patients (two cap-mounted clips, one standard hemostatic clip, two variceal band ligations, one hemostatic powder, two adrenaline injections); technical and clinical success were achieved in all six patients. Two crossovers to a standard gastroscope occurred. CONCLUSIONS : Use of single-use gastroscopes may be feasible for patients presenting for urgent endoscopic evaluation and treatment of upper gastrointestinal bleeding.


The role of Mendelian genetics in strategic models on animal behaviour.
The authors combine known models for the evolution of (a) strategies in animal conflicts, and (b) gene frequencies for differential fecundity in order to relate the sociobiological notion of evolutionarily stable strategy with the genetic mechanism of Mendelian populations.


Efficacy and safety of tranexamic acid in unicompartmental knee arthroplasty: A systematic review and meta-analysis.
This meta-analysis aimed to assess whether administration tranexamic acid (TXA) could reduce blood loss and vascular events in patients undergoing unicompartmental knee arthroplasty (UKA). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and case control trials (CCT) that compared outcomes of patients who did and did not receive TXA during UKA. We searched Cochrane Central Register of including PubMed, EMBASE, Web of Science, the Cochrane Library, Wan Fang data, CBM and CNKI for relevant studies. We assessed the risk of bias of the included studies and calculated pooled risk estimates. The primary outcome was operation time, intraoperative blood loss, postoperative HCT, postoperative HB, transfusion rate, dominant blood loss, postoperative drainage volume, hidden blood loss, total blood loss, postoperative ROM,postoperative VAS score, postoperative complications. Data were using fixed-effects or random-effects models with standard mean differences and risk ratios for continuous and dichotomous variables, respectively. Finally, 9 clinical studies with 744 patients were included in this meta-analysis. Compared with the control group, TXA group could reduced transfusion rate, dominant blood loss, postoperative drainage volume, hidden blood loss, and total blood loss, and increased postoperative HB with statistically significance. The main findings of this meta-analysis are that the transfusion rate, dominant blood loss, postoperative drainage volume, hidden blood loss, total blood loss and postoperative HB in the tranexamic acid group were superior to those in the routine group. Additional high-quality RCTs should be conducted in the future.


1,10-Phenanthroline and 1,10-phenanthroline-terminated ruthenium(II) complex as efficient capping agents to stabilize gold nanoparticles: application for reversible aqueous-organic phase transfer processes.
1,10-Phenanthroline (phen) and 1,10-phenanthroline-terminated ruthenium(II) complex [Ru-Lphen](2+) have been used to stabilize and functionalize gold nanoparticles (Au-NPs). The strong interaction between the nitrogen atoms of phen and the surface of Au-NPs allowed for the phase transfer of Au-NPs from toluene to aqueous phase containing [Ru-Lphen](2+). Reverse phase transfer of these Au-NPs from water to acetonitrile by substituting the Cl(-) counter anion by PF(-)(6) has also been demonstrated. Such facile post-functionalization, phase transfer and solvent transfer processes using metallic complexes bearing a terminal phenanthroline pendant group constitute a prerequisite for further studies of the electronic and optical properties of these NCs in various media.


Sexual victimization and anxiety and mood disorders: a case-control study based on the Danish registry system.
Aims This study aimed to examine the relationship between rape and the subsequent psychiatric diagnosis of any anxiety or mood disorder. Data from the Danish Civil Registration System and the Danish Psychiatric Central Register were used to identify a sample of female victims who had visited a centre for rape victims during an index year and their subsequent psychiatric records were compared with a matched control group. While controlling for demographic variables and previous psychiatric disorders, the effect of sexual victimization increased the likelihood of a subsequent diagnosis of an anxiety disorder but not a mood disorder. Sexual victimization significantly increases the likelihood of experiencing an anxiety disorder, and therefore victims require post-assault information and support.


The morphologic analysis of a not well-known anatomical structure's calcifications (Bochdalek's flower basket calcifications).
The aim of the study was to define the morphology of calcifications belonging to a not very well-known anatomical structure (calcification of foramen of Luschka/Bochdalek's flower basket calcification [Boc FBC]). Two hundred sixty-four computed tomography (CT) scans obtained from healthy patients were included in the study (50.0038 ± 24.78309 [0-92 years old] [mean age ± standard deviation; range]). The morphology of the calcifications in the fourth ventricle (CFV) and Boc FBC was evaluated and compared with other common intracranial calcifications in each patient. Boc FBC was detected in 22.35% (59/264) of the patients. Out of 101 patients aged above 60 years, 59 presented Boc FBC (the rate increased to 55.45%), thus in our sample 94.91% of the detected Boc FBCs (56/59) were seen after 60 years of age. No Boc FBC was found under the age of 50. Statistically, there was a highly significant correlation between Boc FBC and pineal/habenular (p < 0.01) as well as choroid plexus calcifications (p < 0.01). The correlation between CFV and Boc FBC was significant (p < 0.05). It was found that 37.3% of Boc FBCs had a conical form. This form was not accompanied by any vascular calcifications, either basilar or vertebral. Therefore, seeing the conical form was valuable in the differential diagnosis. In our study, Boc FBCs were seen in advanced age and were not encountered under the age of 50. The conical form was seen in one-third of the cases, but it was a very beneficial finding for distinguishing Boc FBC from other calcifications if any. In the advanced age group, calcifications, especially choroid plexus calcifications and pineal/habenular calcifications, are highly associated with Boc FBC. In the presence of CFV, the probability of encountering Boc FBC is very high.


Response to self-care practice messages among patients with diabetes mellitus visiting Jimma University medical center facility based cross sectional design application of extended parallel process model.
To determine response to self-care practice message among patients with diabetes in Jimma University Medical center based on the Extended Parallel Process Model. A facility-based cross-sectional study was conducted. Jimma University Medical Center is found in Jimma town. A total of 343 patients with diabetes participated in the study; making a response rate of 93.9%. All patients with diabetes who were 18 years and above and who were on follow up and registered were included in the study and those with Gestational DM were excluded. Multivariable logistic regression analysis. Responsive respondents scored high in self-care practice score as compared to other respondents. educational status, information sources, knowledge, and preferred message appeals were independent predictors of controlling the danger of diabetes. There is a significant gap in controlling the danger of diabetes. Variables like the level of education, knowledge of diabetes mellitus, information sources, and message appeals were independent predictors of controlling the danger of diabetes. Designing message having higher efficacy while maintaining the level of threat is the best that fits the existing audience's message processing to bring about desired diabetic self-care Practice.


Development of a predictive radiomics model for lymph node metastases in pre-surgical CT-based stage IA non-small cell lung cancer.
To develop and validate predictive models using clinical parameters, radiomic features and a combination of both for lymph node metastasis (LNM) in pre-surgical CT-based stage IA non-small cell lung cancer (NSCLC) patients. This retrospective study included 649 pre-surgical CT-based stage IA NSCLC patients from our hospital. One hundred and thirty-eight (21 %) of the 649 patients had LNM after surgery. A total of 396 radiomic features were extracted from the venous phase contrast enhanced computed tomography (CECT). The training group included 455 patients (97 with and 358 without LNM) and the testing group included 194 patients (41 with and 153 without LNM). The least absolute shrinkage and selection operator (LASSO) algorithm was used for radiomic feature selection. The random forest (RF) was used for model development. Three models (a clinical model, a radiomics model, and a combined model) were developed to predict LNM in early stage NSCLC patients. The area under the receiver operating characteristic (ROC) curve (AUC) value and decision curve analysis were used to evaluate the performance in LNM status (with or without LNM) using the three models. The ROC analysis (also decision curve analysis) showed predictive performance for LNM of the radiomics model (AUC values for training and testing, respectively 0.898 and 0.851) and of the combined model (0.911 and 0.860, respectively). Both performed better than the clinical model (0.739 and 0.614, respectively; delong test p-values both<0.001). A radiomics model using the venous phase of CE-CT has potential for predicting LNM in pre-surgical CT-based stage IA NSCLC patients.