Insight into the degradation of p-nitrophenol by visible-light-induced activation of peroxymonosulfate over Ag/ZnO heterojunction.
In this report, the peroxymonosulfate activation over Ag/ZnO heterojunction under visible light (Ag/ZnO/PMS/Vis) for p-nitrophenol (p-NP) contaminant degradation was conducted in detail. Herein, the catalyst dosage was decreased, and the results showed that a dosage of 0.5 g L-1 Ag/ZnO and 4 mM PMS almost completely degraded 30 mg L-1 p-NP after 90 min of irradiation. In addition, the PMS activation mechanism of Ag/ZnO/PMS/Vis system was proposed by investigations of the influence of PMS concentration, the FTIR spectra, UV-Vis spectroscopy, and electrochemical analyses. Additionally, the role of SO4•- in the photocatalytic reaction is determined by a combination of a trapping test using isopropanol and tert-butanol as probe compounds and electron spin resonance (ESR) spectroscopy. This report provides a potential alternative to remove persistent organic contaminants in sewage using PMS incorporated with Ag/ZnO under visible light irradiation.


Protective effects of melatonin and S-methylisothiourea on mechlorethamine induced nephrotoxicity.
In this study, we aimed to investigate the protective effects of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced nephrotoxicity. A total of 36 male Sprague-Dawley rats were divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Three groups received single dose of MEC (3.5 mg/kg) via transdermal route. Control animals were given saline only via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC. The tissue TNF-α, IL-1β, and NOx levels were found significantly different for all groups (P < 0.001). MEC application resulted in severe histopathological changes. Melatonin showed meaningful protection against kidney damage. But protection by SMT was weaker. TNF-α and IL-1β levels increased significantly with MEC application, and MEL and SMT ameliorated these increases in kidney tissue. MEC also elevated NOx levels in kidney tissue. Both inflammation and oxidative stress may have an important role in the MEC induced nephrotoxicity. MEL and SMT may also have anti-inflammatory properties, as well as anti-oxidant properties.


Deoxyribonucleic acid (DNA) biosensors for environmental risk assessment and drug studies.
In the present work, electrochemical DNA biosensors are proposed as a screening device for the rapid bio-analysis of environmental pollution and DNA-drug interaction studies. The binding of small molecules to DNA immobilised on disposable screen-printed electrodes has been measured through the variation of the electrochemical signal of guanine by square wave voltammetric scans. These kinds of biosensors were used to evaluate the soil contamination level in an Italian polluted area and the results were compared with several methods for the DNA damage detection, as Comet genotoxicity effects, aberrant anatelophases and micronucleated cells frequency on plant roots, and with fixed wavelength fluorescence (FF) by using 2-aminoanthracene as standard compound. The results showed the ability of the biosensors to distinguish in 11 min low, medium and high contaminated soils with good correlation with well established techniques as well as FF, Comet and genotoxicity tests. The same kind of biosensors was also used to evaluate the interaction of DNA with some anti-proliferative metallo drugs, and the electrochemical responses reflected the kind of interaction. The reproducibility of the electrochemical measurements of DNA guanine peak was estimated as less than 10% of relative standard deviation (R.S.D.%).


Is out-of-pocket cost a barrier to receiving repeat tests for chlamydia and gonorrhoea?
We aimed to examine whether out-of-pocket (OOP) costs associated with chlamydia (CT) and gonorrhoea (GC) screening tests is a barrier to receiving CT/GC re-screening and follow-up annual screening. A major health insurance claims database 2006-2010 was used for analysis. The date of first CT/GC diagnosis was used as the index date, and OOP costs at index date for screening tests were retrieved. A re-screening test and an annual screening were defined as tests that occurred within 90-180 days and 181-395 days of the index date, respectively. Re-screening rates were 11.7% and 10.9% and annual screening rates were 24.7% and 23.7% for CT and GC cases, respectively. Compared with the CT patients without OOP expenses, those with OOP expenses of $30 or higher had significantly reduced likelihood of receiving re-screening and annual screening. Similar results were found for GC patients. We concluded that OOP costs serve as a significant barrier to re-screening and annual screening.


A cis-regulatory element promoting increased transcription at low temperature in cultured ectothermic Drosophila cells.
Temperature change affects the myriad of concurrent cellular processes in a non-uniform, disruptive manner. While endothermic organisms minimize the challenge of ambient temperature variation by keeping the core body temperature constant, cells of many ectothermic species maintain homeostatic function within a considerable temperature range. The cellular mechanisms enabling temperature acclimation in ectotherms are still poorly understood. At the transcriptional level, the heat shock response has been analyzed extensively. The opposite, the response to sub-optimal temperature, has received lesser attention in particular in animal species. The tissue specificity of transcriptional responses to cool temperature has not been addressed and it is not clear whether a prominent general response occurs. Cis-regulatory elements (CREs), which mediate increased transcription at cool temperature, and responsible transcription factors are largely unknown. The ectotherm Drosophila melanogaster with a presumed temperature optimum around 25 °C was used for transcriptomic analyses of effects of temperatures at the lower end of the readily tolerated range (14-29 °C). Comparative analyses with adult flies and cell culture lines indicated a striking degree of cell-type specificity in the transcriptional response to cool. To identify potential cis-regulatory elements (CREs) for transcriptional upregulation at cool temperature, we analyzed temperature effects on DNA accessibility in chromatin of S2R+ cells. Candidate cis-regulatory elements (CREs) were evaluated with a novel reporter assay for accurate assessment of their temperature-dependency. Robust transcriptional upregulation at low temperature could be demonstrated for a fragment from the pastrel gene, which expresses more transcript and protein at reduced temperatures. This CRE is controlled by the JAK/STAT signaling pathway and antagonizing activities of the transcription factors Pointed and Ets97D. Beyond a rich data resource for future analyses of transcriptional control within the readily tolerated range of an ectothermic animal, a novel reporter assay permitting quantitative characterization of CRE temperature dependence was developed. Our identification and functional dissection of the pst_E1 enhancer demonstrate the utility of resources and assay. The functional characterization of this CoolUp enhancer provides initial mechanistic insights into transcriptional upregulation induced by a shift to temperatures at the lower end of the readily tolerated range.


Incidence of obstetric anal sphincter injuries after implementing the Triepi-45 tool to improve episiotomy angle in instrumental deliveries.
To assess the impact of Triepi-45-a tool that enables an episiotomy angle of 45° to be marked on the perineum at rest-on the incidence of obstetric anal sphincter injuries (OASIS) during operative vaginal delivery (OVD). A retrospective-prospective cohort study was performed among successive women who underwent OVD at Complejo Asistencial Universitario de de León, Spain, between 2011 and 2013 (preintervention cohort, n=986) and between 2014 and 2016 (intervention cohort, n=986) after implementation of an interventional programme in 2013 to improve the episiotomy angle, including use of Triepi-45, in OVD. The intervention cohort had a lower incidence of OASIS than the preintervention cohort (70/986 [7.1%] vs 93/986 [9.4%]), but the difference was not significant, owing to the low use of Triepi-45 in the intervention cohort (n=375). However, the OASIS incidence was significantly lower in the Triepi-45 cohort than in the preintervention cohort (18/375 [4.8%] vs 93/986 [9.4%]; odds ratio, 0.47; 95% confidence interval, 0.26-0.86). Use of Triepi-45 had a positive impact on reducing OASIS in OVD. It remains essential to raise obstetricians' awareness of the importance of the episiotomy angle and to implement the systematic use of tools to reduce the incidence of OASIS.


Fetal globoid cell leukodystrophy in one of twins.
Twins with high-risk globoid cell leukodystrophy (GLD) at the 6th gestational month were studied morphologically and enzymatically. One of them was affected and the other was probably the carrier of this disease. Central nervous system and other viscera developed normally for the gestational age in both fetuses. The lesions of GLD were found in the fetus with marked deficiency of galactocerebrosidase, but not in the probable carrier. The lesions were located only in the considerably myelinated areas viz., the brain stem and the spinal cord. Ultrastructurally, the globoid cells in the fetal GLD seemed to originate from glial cells, probably oligodendroglia.


Thrombotic burden, D-dimer levels and complete compression ultrasound for diagnosis of acute symptomatic deep vein thrombosis of the lower limbs.
Diagnostic algorithms for deep vein thrombosis (DVT) include D-dimer for its high negative predictive value, thus reducing the need for imaging. Small thrombi may be associated with low D-dimer levels, increasing false negatives. To assess the sensitivity and thus the false negative rates of standard and age-adjusted D-dimer cut offs for isolated distal DVT (IDDVT) in outpatients. We enrolled consecutive outpatients with suspected DVT of the lower limbs referring to our vascular emergency department from 2009 to 2018. Patients underwent D-dimer testing (STA, Stago, cut-off: 500 μg/L), pretest clinical probability (PTP) evaluation and complete compression ultrasonography. Follow-up was 3 months. Among 3948 patients (M:1554-39%, median age 69), 486 proximal DVTs (12.3%) and 348 IDDVTs (8.8%) were diagnosed. Median D-dimer was higher in proximal than IDDVT (3960 vs 1400 μgr/L; p = 0.001). The false negative rate of the standard D-dimer cut-off was 2% (95%CI: 0.8-3.2%) for proximal DVT and 14.7% (95% CI: 11-81%) for IDDVT. The false negative rate of the age-adjusted cut-off was 4.9% (3-7%) for proximal DVT and 19.5% (95% CI: 15.4-24.7%) for IDDVT. Small calf thrombi are associated with low D-dimer levels, and age-adjusted D-dimer may be below the cut-off more frequently in subjects with IDDVT than standard cut-off D-dimer, although such D-dimer levels might exclude IDDVT that require treatment.


Economics of planning electricity transmission considering environmental and health externalities.
Long-distance electricity transmission can achieve environmental benefits through the transfer of air pollutants. However, current electricity transmission investment decisions do not take enough environmental factors into account. This study combines Greenhouse Gas-Air Pollution Interactions and Synergies model with power system planning to reveal how regional differences in environmental and health losses affect the allocation of electricity at the spatial level. Based on the analysis of inter-provincial electricity interconnection in China, we find that the regional differences in environmental and health external costs of power generation are significant. Considering external costs in investment decisions will largely improve the economy of long-distance inter-regional electricity transfer dominated by ultra-high voltage lines, thus replacing a portion of intra-regional electricity transfer dominated by high voltage lines. Meanwhile, the increases in local health losses in major electricity exporting provinces are not significant, which can alleviate the regional equity issues caused by pollutant transfer.


Antiplatelet Medications and Biomarkers of Hemostasis May Explain the Association of Hematoma Appearance and Subsequent Hematoma Expansion After Intracerebral Hemorrhage.
To test the hypothesis that appearances of intracranial hematomas on diagnostic computed tomography (CT) are not idiosyncratic and reflect a biologically plausible mechanism, we evaluated the association between hematoma appearance on CT, biomarkers of platelet activity, and antiplatelet or anticoagulant medication use prior to admission. We studied 330 consecutively identified patients from 2006 to 2019. Biomarkers of platelet activity (platelet aspirin assay) and medication history (aspirin, clopidogrel) were prospectively recorded on admission. A blinded interpreter recorded the presence of hematoma appearances from the diagnostic scan. Associations were tested with parametric or nonparametric statistics, as appropriate. The black hole sign (101, 30%) was most prevalent, followed by the island sign (57, 17%) and blend sign (32, 10%). There was reduced platelet activity in patients with a black hole sign (511 [430-610] vs. 562 [472-628] aspirin reaction units, P = 0.01) or island sign (505 [434-574] vs. 559 [462-629] aspirin reaction units, P = 0.004). Clopidogrel use prior to admission was associated with the black hole sign (odds ratio 2.25, 95% confidence interval 1.02-4.98, P = 0.04). In patients with acute intracerebral hemorrhage, hematoma appearances on CT are associated with biomarkers of platelet activity and clopidogrel use prior to admission. Appearances of intracranial hematomas on CT may reflect reduced hemostasis from antiplatelet medication use.


l-Amino acid oxidase as a fish host-defense molecule.
An l-amino acid oxidase (LAO) is an amino acid metabolism enzyme that also performs a variety of biological activities. Recently, LAOs have been discovered to be deeply involved in innate immunity in fish because of their antibacterial and antiparasitic activity. The determinant of potent antibacterial/antiparasitic activity is the H2O2 byproduct of LAO enzymatic activity that utilizes the l-amino acid as a substrate. In addition, fish LAOs are upregulated by pathogenic bacteria or parasite infection. Furthermore, some fish LAOs show that the target specificity depends on the virulence of the bacteria. All results reflect that LAOs are new innate immune molecules. This review also describes the potential of the immunomodulatory functions of fish LAOs, not only the innate immune function by a direct oxidation attack of H2O2.


Amniotic band syndrome following septostomy in management of twin-twin transfusion syndrome: a case report.
Septostomy, a rupture of the diamniotic membrane separating monozygotic twins essentially creating a monoamniotic gestation, is a potential therapeutic modality for twin-twin transfusion syndrome (TTTS). This may be associated with complications including cord entanglement or complete rupture of the membranes. We report a case of severe amniotic band syndrome with cord amputation after septostomy. A 33-year-old woman with a Mo-Di twin pregnancy was diagnosed with TTTS at 18 weeks of gestation. Septostomy as well as amnioreduction were performed at 24 weeks of gestation. A repeat cesarean delivery was performed at 31 weeks resulting in a live recipient baby of 1340 g and a dead donor with amniotic band syndrome. The donor showed pieces of membrane tightening both legs. The right thigh became entangled in the bands connecting to the umbilical cord of the live fetus. The umbilical cord of the dead twin was completely amputated, whereas the umbilical cord of the live infant was also entrapped within the amniotic band resulting in small diameter and some degree of stricture. This is the first report of a rare but serious complication following septostomy.


Pupil Size and Reactivity in Pediatric Patients With Sickle Cell Disease.
Pupil size and reactivity have been studied to objectively measure pain utilizing pupillometry measurements. Given the challenges associated with treating vaso-occlusive pain in pediatric patients with sickle cell disease, better assessment tools are needed. The objective of this study is to establish normative values for pupil size and reactivity in pediatric patients with sickle cell disease with the hope that pupillometry can be used as a tool to objectively measure pain and response to treatment with analgesic medications. Readings were performed using a NeurOptics PLR-2000 pupillometer. Forty-four males and 38 females, all black, were studied. Their median age was 11 years (range: 2 to 21). When comparing our participants with white participants in a previously published pediatric study, there was a significant difference in maximum constriction velocity ( t =3.45, P =0.009), maximum pupil size ( t =-5.57 mm, P <0.0001), and minimum pupil size ( t =-3.24, P =0.002). There was no significant difference in pupil size and reactivity between patients with sickle cell disease and black patients without the disease when compared with the previously published study. Therefore, further investigation of pupillometry within the black population during vaso-occlusive crisis and in the "well state" is warranted in pediatric patients with sickle cell disease.


The effects of nitrogen and energy intake on the metabolism of normal, depleted and injured man: considerations for practical nutritional support.
This article illustrates how the nutritional and metabolic effects of a range of protein and energy intakes depend on the clinical state of the patient and how these considerations may be used to provide guidelines for nutritional support. First, it is necessary to define states and mechanisms of malnutrition and then discuss the biochemical processes which underlie nutritional rehabilitation.


Draft Genome Sequence of Streptococcus thermophilus Strain CBC-S77, Isolated from Homemade Dairy Foods in Bulgaria.
Here, we report the draft genome sequence of Streptococcus thermophilus strain CBC-S77. The strain was originally isolated from naturally processed, homemade dairy foods in West Rhode Mountain, Bulgaria. The genome was assembled in 148 contigs with a total length of 1,707,130 bp, with 1,563 coding genes and a GC content of 39.11%.


Interactive optimization of biosurfactant production by Paenibacillus alvei ARN63 isolated from an Iranian oil well.
The potential of an indigenous bacterial strain isolated from an Iranian oil field for the production of biosurfactant was investigated in this study. After isolation, the bacterium was characterized to be Paenibacillus alvei by biochemical tests and 16S ribotyping. The biosurfactant, which was produced by this bacterium, was able to lower the surface tension of media to 35 mN/m. Accordingly, thin layer chromatography (TLC) and FT-IR has been carried out to determine compositional analysis of the produced biosurfactant. After all the tests related to characterization of the biosurfactant produced by the isolated bacterium, it was characterized as lipopeptide derivative. The combination of central composite rotatable design (CCRD) and response surface methodology (RSM) was exploited to optimize biosurfactant production. Therefore, variations of four impressive parameters, pH, temperature, glucose and salinity concentrations were selected for optimization of growth conditions. The empirical model developed through RSM in terms of effective operational factors mentioned above was found to be adequate to describe the biosurfactant production. A maximum reduction in surface tension was obtained under the optimal conditions of 13.03 g/l glucose concentration, 34.76 °C, 51.39 g/l total salt concentration and medium pH 6.89.


Lower limb events in individuals with type 2 diabetes: evidence for an increased risk associated with diuretic use.
Recently, safety data signalled an increased risk of amputations in people taking canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor. If this side effect is due to drug-induced hypovolaemia, diuretics should also increase that risk. The aim of this study was to analyse the association between diuretic use and the risk of lower limb events (LLEs) in people with type 2 diabetes. SURDIAGENE (SUivi Rénal, DIAbète de type 2 et GENEtique) is a prospective observational cohort that includes people with type 2 diabetes enrolled from 2002 to 2012 and followed-up until onset of LLE, death or 31 December 2015, whichever came first. Primary outcome was the first occurrence of LLE, a composite of lower limb amputation (LLA) and lower limb revascularisation (LLR). The rates of primary outcome were compared between participants taking and not taking diuretics at baseline in a Cox-adjusted model. At baseline, of the 1459 participants included, 670 were taking diuretics. In participants with and without diuretics, the mean ages were 67.1 and 62.9 years and 55.8% and 59.8% were men, respectively. During a median follow-up of 7.1 years, the incidence of LLE was 1.80 per 100 patient-years in diuretic users vs 1.00 in non-users (p < 0.001). The HR for LLE in users vs non-users was 2.08 (95% CI 1.49, 2.93), p < 0.001. This association remained significant in a multivariable-adjusted model (1.49 [1.01, 2.19]; p = 0.04) and similar after considering death as a competing risk (subhazard ratio 1.89 [1.35, 2.64]; p < 0.001). When separated, LLA but not LLR, was associated with the use of diuretics: 2.01 (1.14, 3.54), p = 0.02 and 1.05 (0.67, 1.64), p = 0.84, respectively, in the multivariable-adjusted model. Among people with type 2 diabetes treated with diuretics, there was a significant increase in the risk of LLE, predominantly in the risk of LLA.


A fluorescent spectroscopy and modelling analysis of anti-heparanase aptamers-serum protein interactions.
Aptamers are short, single stranded oligonucleotide or peptide molecules that bind a specific target molecule and can be used for the delivery of therapeutic agents and/or for imaging and clinical diagnosis. Several works have been developed aiming at the production of aptamers and the study of their applications, but few results have been reported on plasmatic dynamics of such products. Aptamers against the heparanase enzyme have been previously described. In this work, the interactions of two constructs of the most promising anti-heparanase aptamer (molecular weights about 9200Da and 22000Da) to human and bovine serum albumins were studied by fluorescence quenching technique. Stern-Volmer graphs were plotted and quenching constants were estimated. Stern-Volmer plots obtained from experiments carried out at 25°C and 37°C showed that the quenching of fluorescence of HSA and BSA by the low molecular weight aptamer was a collisional phenomenon (estimated Stern-Volmer constant: 3.22 (±0.01)×10(5)M(-1) for HSA at 37°C and 2.47 (±0.01)×10(5)M(-1) for HSA at 25°C), while the high molecular weight aptamer quenched albumins by static process (estimated Stern-Volmer constant: 4.05 (±0.01)×10(5)M(-1) for HSA at 37°C and 6.20 (±0.01)×10(5)M(-1) for HSA at 25°C), interacting with those proteins constituting complexes. Linear Stern-Volmer plot from HSA titrated with the low MW aptamer suggested the existence of a single binding site for the quencher in this albumin. Differently, for aptamer 2, the slightly downward curvature of the Stern-Volmer plot of the titration for that albumin suggested a possible conformational change that led to the exposition of lower affinity binding sites in HSA at 25°C. Similarly, although short aptamerdoes not appear to form a stable complex (collisional interaction), the longer aptamer is found to form a stable complex with HSA. In addition, the behaviour of quenching curves for HSA and BSA and values estimated for ratio R1/R2 from model developed by Silva et al. suggest that the primary binding site in both aptamers is located closer to the tryptophan residue in sub domain IIA. It is likely that both aptamers are competing for the same primary site in albumin.


Guide to ethical decision-making for the critically ill: the three R's and Q.C.
Ethical decision-making for the care of the critically ill and injured has never been more difficult than it is today. Major technologic advances prolong life but often provide questionable benefit in human terms. Both the ethical commitment to the individual patient and the competition for access to expensive and scarce health resources prompt the search for clinically useful and operationally appropriate criteria for decision-making. The mnemonic 3 R's and Q.C. was evolved as a practical tool by which the ethical basis for interventions may be tested. The first tier, the 3 R's, is likely to resolve the vast majority of ethical issues. These are appropriately addressed at the bedside by clinicians who determine whether a proposed intervention is Rational, Redeeming, and Respectful. When the ethical issues cannot be resolved at the bedside on the basis of the 3 R's, a second tier of testing of Quality of Life and Cost (Q.C.) is triggered. This addresses decision-making which is not exclusively or even primarily in the skill domain or authority of most physicians. It calls for assistance by those who represent a broader base of societal involvement including multidisciplinary experts in ethics and law who serve as consultants or who are organized into medical center-wide ethics committees.


Influence of AS-7 on the storage lesion in young and old circulating erythrocytes.
Blood and its components are stored to meet the demands of blood transfusion. Erythrocytes undergo progressive modifications during storage known as storage lesions. Storage solutions were developed to improve shelf life and extend red cell viability. Therefore, the objective of this study is to analyze the effects of AS-7 on young and old erythrocytes during storage. Blood was collected from the blood bank at Kempegowda Institute of Medical Sciences (KIMS) hospital, Bengaluru. Erythrocytes were isolated from whole blood and separated based on its age using Percoll density gradient. The young and old erythrocytes were stored in AS-7 for 35 days and every 5th day, oxidative stress markers - Hemoglobin (Hb), Oxidative Hemolysis, Mechanical Fragility, Sialic Acid, Superoxides, Glucose, Lactate Dehydrogenase (LDH), Glutathione, antioxidant capacity (TACCUPRAC), Plasma Membrane Redox System (PMRS), antioxidant enzymes, lipid peroxidation, and protein oxidation products were assessed. Hb, glucose, TACCUPRAC, and superoxide dismutase reduced, while oxidative hemolysis, mechanical fragility, protein oxidation, and lipid peroxidation products increased in young and old cells over storage. LDH, PMRS, catalase, advanced oxidation protein products, and conjugate dienes were significant in old cells from day 5 itself, whereas in young cells towards the end of storage (from day 25). Oxidative insult was higher in old cells compared to young cells. AS-7 was beneficial to young erythrocytes during storage and thus laying the foundation for the possibilities of utilizing young cells as models for storage studies.


Salvage surgery with second free flap reconstruction for recurrent oral squamous cell carcinoma.
The purpose of this study was to evaluate the results of the reconstruction using the second free flap following resection of recurrent oral squamous cell carcinoma(OSCC). A total of 25 patients from 2005 to 2018 who had undergone salvage surgery and reconstruction using the second free flap for recurrent OSCC were included in this study. Medical records were reviewed to obtain demographic data, stages of the primary cancer, region of recurrent OSCC, the period until recurrence, type of the second reconstruction flaps, recipient vessels, survival rate of the flaps and 2- and 5-year survival rates. The patients were 13 males and 12 females. The average age was 64.1 years. Of the stages of primary cancer, stage IV patients accounted for the largest number with 13 patients (52.0%). The region of recurrent OSCC was the largest in the mandible with 13 patients, followed by 5 patients in the tongue and 4 patients in the buccal mucosa and maxilla. The mean time interval between the first and second reconstruction was about 34.1 months. Latissimus dorsi free flap and radial forearm free flap used in the second reconstruction were most frequently used in 11 patients (35.5%), followed by fibular composite free flap with 6 patients (19.4%). Facial artery in the recipient arteries of the second reconstruction was most frequently used with 13 cases (43.3%), followed by superior thyroid artery with 8 cases (26.7%) and lingual artery with 7 cases (23.3%). In the second free flap reconstruction, survival rate of the flaps was 96.8%. The 2- and 5-year survival rates in the patients were 70.0% and 62.5%, respectively. The study showed that the second free flap reconstruction with salvage surgery in resectable recurrent OSCC is a safe and reliable method with a high success rate of the flap and improvement of the 5-year survival rate.


Trophic transfer of polychlorinated biphenyls (PCB) in a boreal lake ecosystem: testing of bioaccumulation models.
Understanding the fate of persistent organic chemicals in the environment is fundamental information for the successful protection of ecosystems and humans. A common dilemma in risk assessment is that monitoring data reveals contaminant concentrations in wildlife, while the source concentrations, route of uptake and acceptable source concentrations remain unsolved. To overcome this problem, different models have been developed in order to obtain more precise risk estimates for the food webs. However, there is still an urgent need for studies combining modelled and measured data in order to verify the functionality of the models. Studies utilising field-collected data covering entire food webs are particularly scarce. This study aims to contribute to tackling this problem by determining the validity of two bioaccumulation models, BIOv1.22 and AQUAWEBv1.2, for application to a multispecies aquatic food web. A small boreal lake, Lake Kernaalanjärvi, in Finland was investigated for its food web structure and concentrations of PCBs in all trophic levels. Trophic magnification factors (TMFs) were used to measure the bioaccumulation potential of PCBs, and the site-specific environmental parameters were used to compare predicted and observed concentrations. Site-specific concentrations in sediment pore water did not affect the modelling endpoints, but accurate site-specific measurements of freely dissolved concentrations in water turned out to be crucial for obtaining realistic model-predicted concentrations in biota. Numerous parameters and snapshot values affected the model performances, bringing uncertainty into the process and results, but overall, the models worked well for a small boreal lake ecosystem. We suggest that these models can be optimised for different ecosystems and can be useful tools for estimating the bioaccumulation and environmental fate of PCBs.


Impaired catecholamine secretion as a cause of diabetic autonomic neuropathy.
Human and animal studies were performed to investigate the causes of diabetic autonomic neuropathy. Human diabetics, with and without autonomic neuropathy, were measured for plasma catecholamine response to insulin hypoglycemia and for urinary catecholamine excretion. In streptozotocin-diabetic rats, plasma catecholamine response and tissue catecholamine concentrations were measured at various stages of the disease. As the duration of the diabetic state lengthens in rats, there is a time-proportional stepwise decrease in plasma catecholamine response. This is similar to the clinical course observed in human diabetics, which also includes a reduction of catecholamine excretion after the appearance of autonomic neuropathy. After 6 weeks of diabetes, rat tissue is found to have an increased concentration of catecholamines; this may represent a compensatory reaction to the difficulties of secretion. At 13 weeks of diabetes, tissue catecholamine concentrations return to almost normal, when plasma responses have disappeared. These results suggest that the impaired secretion of catecholamines in diabetics may be a cause of diabetic autonomic neuropathy.


Fetal pulmonary venous flow pattern is determined by left atrial pressure: report of two cases of left heart hypoplasia, one with patent and the other with closed interatrial communication.
We report two cases of fetal left heart hypoplasia with extremes of size of interatrial communication, i.e. a closed foramen ovale and an atrial septal defect. Doppler examinations of the pulmonary veins showed almost to and fro flow in the fetus with the closed foramen ovale and, in contrast, a normal flow velocity waveform in the fetus with the atrial septal defect, despite mitral atresia. Our observations support the importance of left atrial pressure in the creation of a pulmonary venous flow pattern in the fetus.


The conundrum of hyperuricemia, metabolic syndrome, and renal disease.
The level of serum uric acid in human has been increasing over the last decades, and correlates with an increase prevalence of renal disease and metabolic syndrome. Understanding the role of uric acid in these conditions may provide clues for preventing the current epidemic of renal disease. Controversy still remains if hyperuricemia is simply a consequence or a cause of renal disease although epidemiological studies have attempted to resolve this issue. In this review, we discuss the clinical and experimental evidence for a causal role of hyperuricemia in renal diseases and potential relationships of hyperuricemia with metabolic syndrome.


Pharmacokinetics of tetrachloroethylene.
A physiological pharmacokinetic model is developed to describe the pharmacokinetics of tetrachloroethylene (PCE) in mice, rats, and humans. The body is divided into four tissue compartments (vessel-rich, muscle, slowly perfused fat, and liver) connected by the arterial and venous blood flow pathways. The physiological parameters of the model are blood flow rates, cardiac output, tissue volumes, ventilation rate, and tissue/air and blood/air partition coefficients. Metabolism is assumed to occur only in the liver compartment and is described by a combination of a linear metabolic component and a Michaelis-Menten component. The metabolic parameters for PCE were determined by fitting model predictions to species-specific empirical data. Comparison of model results with independent empirical data on inhalation and gavage exposures in mice, rats, and humans demonstrates that the physiological pharmacokinetic model can be used to determine the time course of PCE in these species. We show that human metabolic parameters can be predicted by scaling rat metabolic parameters as a function of body weight, whereas scaling of the metabolic parameters of mice overestimates human metabolism.


Clinical effectiveness and cost-effectiveness of neonatal screening for inborn errors of metabolism using tandem mass spectrometry: a systematic review.
To evaluate the clinical and cost-effectiveness of tandem mass spectrometry (MS)-based neonatal screening for inborn errors of metabolism (IEM). Fourteen electronic bibliographic databases covering biomedical, science, economic and grey literature, the reference lists of relevant articles and abstracts of conference proceedings and 18 health services research-related resources. This review is an update of two previous HTA reports of neonatal screening for IEM. These reports have been updated by a systematic review of published research (between 1995 and January 2002) on neonatal screening of inherited metabolic disorders using tandem MS. This was supplemented by a search for economic literature and the application of a modelling exercise to investigate the economics of using tandem MS within a neonatal screening programme in the UK. Evidence from the reviews of IEM found that the UK screening programme for phenylketonuria (PKU) was well established and there was universal agreement that neonatal screening for PKU was justified. Of the many other disorders that can be detected by tandem MS, the best candidate condition for a new screening programme was medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. For many other IEM that can be detected by tandem MS, robust clinical evidence was limited. Cost-effectiveness analysis using economic modelling indicated that substituting the use of tandem MS for existing technologies for the screening of PKU alone could not be justified. However, results from the economic modelling indicate that the addition of screening for MCAD deficiency as part of a neonatal screening programme for PKU using tandem MS would be economically attractive. Using an operational range of 50,000-60,000 specimens per system per year, the mean incremental cost for PKU and MCAD deficiency screening combined using tandem MS from the model was -23,312 British pounds for each cohort of 100,000 neonates screened. This cost saving is associated with a mean incremental gain of 59 life-years. Additional economic modelling using the available evidence does not support including other inherited metabolic diseases within a neonatal screening programme at present. The evidence appears to support the introduction of tandem MS into a UK neonatal screening programme for PKU and MCAD deficiency combined. Tandem MS has the potential for simultaneous multi-disease screening using a single analytical technique. Although the marginal cost of extending the programme to include other conditions may be relatively small, the application of this new technology to PKU and MCAD deficiency screening does not imply the wholesale inclusion of all disorders detectable by tandem MS. It is suggested that the primary focus of further research should be on the long-term effectiveness of treatment strategies on adverse outcomes (disabilities and impairments) under conventional management and the potential impact of early diagnosis using tandem MS.


Functional assessment of beta adrenoceptor subtypes in human colonic circular and longitudinal (taenia coli) smooth muscle.
The subtype and species related heterogeneity of beta adrenoceptors prompted a functional reappraisal of these molecular targets of motility inhibition in the human colon. Relaxation of muscle strips was measured in vitro. The following agonists had decreasing relaxing potency (effective concentration range 10(-8)-10(-4) mol/l): (-)isoprenaline (non-selective), terbutaline (beta(2) selective), CGP 12177 (beta(3) selective, also beta(1), beta(2) antagonist), and SR 58611A (beta(3) selective). Isoprenaline and terbutaline were more potent on circular than taenia strips; CGP 12177 and SR 58611A weakly and partially relaxed taenia but had little effect on circular strips. The potency of isoprenaline on circular strips was greatly reduced by the beta(1) selective antagonist CGP 20712 (10(-7) mol/l), and less so by ICI 118551 (10(-7) mol/l, beta(2) selective). CGP 20712 and ICI 118551 together (both 3 x 10(-6) mol/l) had no effect on taenia relaxation by SR 58611A and rendered isoprenaline and terbutaline virtually inactive on circular strips, although not on taenia, which was relaxed at higher than control concentrations and maximally by isoprenaline. Propranolol, a beta(1), beta(2) non-selective antagonist, at high concentrations (10(-5) mol/l) prevented taenia relaxation by CGP 12177 and SR 58611A; its quantitative antagonism of isoprenaline (in common with that of CGP 12177 used as an antagonist) was competitive in circular strips but not on taenia. beta(1), beta(2), and beta(3) adrenoceptors are functionally detectable in the human colon; agonist stimulation of any one type relaxed taenia but only isoprenaline was fully effective at the beta(3) subtype.


Shear wave elastography findings of de Quervain tenosynovitis.
Our aim was to evaluate the feasibility of using shear wave elastography (SWE) to assess first extensor compartment tendons rigidity and its alterations with tenosynovitis. We performed B-mode ultrasound and SWE to total number of 80 participants. All participants were evaluated clinically to call the diagnosis of de Quervain tenosynovitis or to rule out the diagnosis. We composed 2 groups. Group 1 included 40 healthy volunteers (33 females and 7 male participants with ages ranging from 24 to 60 years, median age was 37.5 years) and group 2 had 40 de Quervain patients (32 females and 8 male patients with ages ranging from 25 to 51 years, median age was 34 years). SWE measurements were repeated 3 times and arithmetic average was used for the final SWE value. The median SWE value of healthy group (group 1) was 72kPa and the de Quervain patient group (group 2) was 29kPa. Two groups demonstrated statistically significant difference (p<0.001). The ROC curve analysis was performed and the SWE value of 40.5kPA was calculated as a cut-off value for the diagnosis of de Quervain tenosynovitis with 95% specificity and 85% sensitivity. SWE modality can provide useful data regarding de Quervain tenosynovitis.


Enantioselective synthesis of β-pyrazole-substituted alcohols through an asymmetric ring-opening reaction of meso-epoxides.
An efficient and practical synthesis of optically pure β-pyrazole-substituted alcohols was achieved by an asymmetric ring-opening reaction of meso-epoxides with pyrazole derivatives as the nucleophile. In the presence of 1 mol % of an N,N'-dioxide-Sc(OTf)(3) complex, excellent enantioselectivity and yields were obtained from meso-epoxides. The process could also be used for a mixture of cis- and trans-stilbene oxides. A proposed transition-state model is provided.


Oxytocin-immunoreactive terminals synapse on oxytocin neurones in the supraoptic nucleus.
The neuropeptide oxytocin, synthesized by magnocellular neurones in the hypothalamus, is well known for its peripheral action during lactation and parturition after its release into the bloodstream from axons in the neurohypophysis. However, it may also be released centrally to control the activity of oxytocinergic neurones themselves. Oxytocin release has been measured from isolated magnocellular nuclei in vitro and in the cerebrospinal fluid. When injected into the third ventricle, the peptide increases the basal firing rate of oxytocinergic neurones as well as the frequency and amplitude of the bursts of action potentials they normally show before each reflex milk ejection. Oxytocin also excites magnocellular neurones when applied microiontophoretically. I now report that immunocytochemical staining reveals synapses in the supraoptic nucleus of the hypothalamus where both the pre- and postsynaptic elements contain oxytocin. These oxytocinergic synapses, impinging on their own neurones, may represent the anatomical basis for the hypothalamic release of this peptide and for the facilitatory action on its own secretion.


Feasibility of a smoking cessation intervention for teens in the emergency department: reach, implementation fidelity, and acceptability.
Traditional efficacy research alone is insufficient to move interventions from research to practice. Motivational interviewing has been adapted for brief encounters in a variety of health care settings for numerous problem behaviors among adolescents and adults. Some experts suggest that motivational interviewing can support a population health approach to reach large numbers of teen smokers without the resource demands of multi-session interventions. To determine the reach, implementation fidelity, and acceptability of a brief motivational tobacco intervention for teens who had treatment in a hospital emergency department. Among 74 teens 14 to 19 years old, 40 received a brief motivational tobacco intervention and 34 received brief advice/care as usual at baseline. Follow-up data were collected from the interventional group at 1, 3, and 6 months and from the control group at 6 months. For the interventional group, data also were collected from the teens' parents, the health care personnel who provided the intervention, and emergency department personnel. Findings indicated low levels of reach, high levels of implementation fidelity, and high levels of acceptability for teen patients, their parents, and emergency department personnel. Data suggest that practitioners can operationalize motivational interventions as planned in a clinical setting and that patients and others with an interest in the outcomes may find the interventions acceptable. However, issues of reach may hinder use of the intervention among teens in clinical settings. Further investigation is needed on mechanisms to reduce barriers to participation, especially barriers related to patient acuity.


Lithium/nutrition interaction in the brain: a single lithium administration impairs spreading depression in malnourished, but not in well-nourished rats.
Lithium salts exert electrophysiological and behavioral effects in animals and humans and have been used clinically in the treatment of bipolar disorders. Little is known about the lithium/nutrition interaction in the developing brain. This work aimed to determine, in adult rats, whether treatment with a single dose of lithium chloride (LiCl) would influence the propagation of the brain excitability-related phenomenon known as cortical spreading depression (CSD). Male well-nourished (W; fed a lab chow diet with 22% protein; n=22) and previously protein-malnourished rats (M; fed a low-quality 8% protein diet; proteins mostly from vegetable source; n=20) were treated at 75-80 days of age with a single intraperitoneal injection of either 50 mg/kg LiCl (n=9 W and 10 M rats) or saline (n=13 W and 10 M rats). When the pups were 90-110 days, CSD was elicited at the frontal cortex and recorded during 4 hours at two cortical parietal points. In malnourished, but not in well-nourished rats, lithium treatment lowered CSD velocities (P < 0.05), in comparison with saline-injected animals. In a third group (n=23), in which the low-protein diet was quantitatively corrected to 22%, the lithium effect disappeared (n=12), compared to saline (n=11). Our results demonstrate a facilitating effect of malnutrition on the CSD-impairing action of a single lithium administration, suggesting a lithium/nutrition interaction.


beta-Actin is confined to structures having high capacity of remodelling in developing and adult rat cerebellum.
Neurons undergo complex morphological changes during differentiation and in cases of plasticity. A major determinant of cell morphology is the actin cytoskeleton, which in neurons is comprised of two actin isoforms, non-muscle gamma- and beta-actin. To better understand their respective roles during differentiation and plasticity, their cellular and subcellular localization was examined in developing and adult cerebellar cortex. It was observed that gamma-actin is expressed at a constant level throughout development, while the level of beta-actin expression rapidly decreases with age. At the light microscopic level, gamma-actin staining is ubiquitous and the only developmental change observed is a relative reduction of its concentration in cell bodies and white matter. In contrast, beta-actin staining almost completely disappears from the cytoplasm of cell bodies, primary dendrites and axons. In young cerebellar cultures, gamma-actin is found in the cell body, neurites and growth cones, while beta-actin is mainly found in growth cones, as previously reported in other primary neuronal culture systems [Kaech et al. (1997), J. Neuroscience, 17, 9565-9572; Bassell et al., (1998), J. Neuroscience, 18, 251-265]. Electron microscopy of post-embedding immunogold-labelled tissue confirms the widespread distribution of gamma-actin, and also reveals an increased concentration of gamma-actin in dendritic spines in the adult. During development, beta-actin accumulation is observed in actively growing structures, e.g., growth cones, filopodia, cell bodies and axonal tracts. In the adult cerebellar cortex, beta-actin is preferentially found in dendritic spines, structures which are known to retain their capacity for morphological modifications in the adult brain. This differential subcellular localization and developmental regulation of the two actin isoforms point to their different roles in neurons.


Investigating inequities in hospital care among lesbian, gay, bisexual, and transgender (LGBT) individuals using social media.
Persons who identify as lesbian, gay, bisexual, and transgender (LGBT) face health inequities due to unwarranted discrimination against their sexual orientation or identity. An important contributor to LGBT health disparities is the inequitable or substandard care that LGBT individuals receive from hospitals. To investigate inequities in hospital care among LGBT patients using the popular social media platform Twitter. This study examined a dataset of Twitter communications (tweets) collected from February 2015 to May 2017. The tweets mentioned Twitter handles for hospitals (i.e., usernames for hospitals) and LGBT related terms. The topics discussed were explored to develop an LGBT position index referring to whether the hospital appears supportive or not supportive of LGBT rights. Results for each hospital were then compared to the Healthcare Equality Index (HEI), an established index to evaluate equity of hospital care towards LGBT patients. In total, 1856 tweets mentioned LGBT terms representing 653 unique hospitals. Of these hospitals, 189 (28.9%) were identified as HEI leaders. Hospitals in the Northeast showed significantly greater support towards LGBT issues compared to hospitals in the Midwest. Hospitals deemed as HEI leaders had higher LGBT position scores compared to non-HEI leaders (p = 0.042), when controlling for hospital size and location. This exploratory study describes a novel approach to monitoring LGBT hospital care. While these initial findings should be interpreted cautiously, they can potentially inform practices to improve equity of care and efforts to address health disparities among gender minority groups.


Preservation of feline anti-Toxoplasma gondii antibody activity using blood absorbed on filter paper stored under different conditions.
The present study deals with the successful long-term preservation of feline anti-Toxoplasma gondii antibody activity on filter paper strips stored with silica gel. When filter paper strips were kept at 25 degrees C with silica gel, antibody activity in blood samples was preserved for at least six months.


Effect of the Great East Japan Earthquake on cardiovascular diseases--report from the 10 hospitals in the disaster area.
We reported an increased occurrence of cardiovascular diseases (CVDs) after the Great East Japan Earthquake by examining ambulance records, but it had to be confirmed by cardiologists. We enrolled patients admitted to the cardiology department of the 10 hospitals in the disaster area from 4 weeks prior to 15 weeks after March 11 in the years 2008-2011 (n=14,078). The weekly occurrence of several CVDs, including heart failure (HF), pulmonary thromboembolism (PTE) and infectious endocarditis (IE), was sharply and significantly increased after the Earthquake. The Disaster caused significantly increases in the occurrence of HF, PTE and IE.


Insights from transgenic mouse models of PyMT-induced breast cancer: recapitulating human breast cancer progression in vivo.
Breast cancer is associated with the second highest cancer-associated deaths worldwide. Therefore, understanding the key events that determine breast cancer progression, modulation of the tumor-microenvironment and metastasis, which is the main cause of cancer-associated death, are of great importance. The mammary specific polyomavirus middle T antigen overexpression mouse model (MMTV-PyMT), first published in 1992, is the most commonly used genetically engineered mouse model (GEMM) for cancer research. Mammary lesions arising in MMTV-PyMT mice follow similar molecular and histological progression as human breast tumors, making it an invaluable tool for cancer researchers and instrumental in understanding tumor biology. In this review, we will highlight key studies that demonstrate the utility of PyMT derived GEMMs in understanding the molecular basis of breast cancer progression, metastasis and highlight its use as a pre-clinical tool for therapeutic discovery.


Morphine antinociception in the non-hibernating and hibernating states of the ground squirrel (Citellus lateralis).
Previous work in our laboratory demonstrated a significant reduction in the development of morphine physical dependence during hibernation, suggesting a major change in the ability of morphine to act on the central nervous system (CNS) during this naturally altered state. To further investigate the pharmacological actions of morphine during the hibernating (H) state, the present study recorded skin-twitch response (STR) latency as a measure of morphine antinociception in the golden-mantled ground squirrel (Citellus lateralis) during the non-hibernating (NH) and H states. Our results revealed that morphine antinociception continued to develop in hibernation. Moreover, the magnitude of antinociception displayed was greater during the H state than in the NH state. Tolerance to morphine's antinociceptive effects developed in both states as well. The results of the present study indicate that the hibernation-related reduction in the development of morphine dependence represents a selective, rather than a general, suppression of the CNS pharmacological actions of morphine during the H state.


Determinants of leaf temperature in California Mimulus species at different altitudes.
Leaf energy balance and gas-exchange characteristics were studied in Mimulus cardinalis at 400 m and Mimulus lewisii at 2,700 m in the Sierra Nevada of central California. In contrast to previous observations, leaf temperatures were not near 30° C at air temperatures from 20 to 40° C but were coupled quite closely to air temperature. Stomatal conductance in both species decreased in response to increases in the water vapor concentration gradient, a response opposite that required to establish 30°C leaf temperatures over a wide range of air temperatures. The temperature optima for photosynthesis were broad in both species but 5° C higher for M. cardinalis than for M. lewisii. The direct or indirect effects of altitude did not contribute significantly to the maintenance of constant leaf temperatures. For both species, maintaining constant leaf temperatures appears to be less important than avoiding inhibitory water stress or diffusion limitation of photosynthesis.


Joint recommendations for a total services account as a factor in simplifying contracts.
The objective of clinical trials is to transfer findings gained from basic research to patients and to result in innovative treatment approaches. Along with basic research, results from clinical trials thus represent a core area of medical advances. As a location for clinical trials, Germany is currently well-positioned and internationally competitive. This is evident in its position as No. 2 in Europe and No. 3 worldwide - behind the US and UK - in clinical trials of pharmaceuticals [1]. Maintaining and further improving this favorable positioning as a location for clinical trials is in the mutual interest of all parties involved in the field of clinical research, patients, trial sites and sponsors of clinical trials. For patients, clinical trials offer opportunities to gain early access to innovative therapy options. In addition to the scientific interest from medical faculties, clinical research is thereby an important aspect for university clinics in Germany as they fulfill their medical care mandate. Their involvement in clinical trials gives physicians the ability to gather experience with new treatment approaches at an early stage and to pass this know-how on to their patients. A location's clinical research is thus an important competitive factor in terms of international comparison as well. Industry likewise benefits from the favorable research infrastructure in Germany, which provides rapid patient recruitment and outstanding quality of results obtained and can thus contribute to the early approval of new drugs. From the perspective of the authors, it is therefore essential that Germany continues to remain competitive as a location for conducting clinical trials, precisely because the number of clinical trials is decreasing overall. Companies themselves are in international competition internally and externally, which often creates a certain pressure on trial preparation and thus on the start of a clinical trial. To ensure that a clinical trial can begin early, it is essential that contracts related to the trial are concluded quickly and simply, including remuneration for participants and full, transparent and comprehensible coverage of content for the business relationship. The swift agreement of key contractual and budgetary aspects is therefore in the interest of everyone involved. Against this backdrop, the German Association of Medical Faculties (MFT), the German Association of Academic Medical Centers (VUD), the Coordination Center for Clinical Studies (KKS-Netzwerk) and the German Association of Research-Based Pharmaceutical Companies (vfa) have held joint discussions regarding an important aspect of the contract negotiations - the cost consideration of clinical trials. As a result of these talks, these organizations have developed and published joint "Recommendations for the preparation of a total services calculation for remuneration related to the conduct of a clinical trial in a trial center" [2], [3]. The parties concerned share the conviction that, against the backdrops described, it would be helpful if the potential contract partners had access to recommendations that offer examples of constantly recurring cost positions in order to more precisely determine remuneration related to the conduct of a clinical trial. This article explains how the "Recommendations for the preparation of a total services calculation for remuneration related to the conduct of a clinical trial in a trial center" [2], [3] were developed and provides an overview of their content.


A prospective study of 'circumferential purse-string approximation' vs. primary linear skin closure in stoma reversal.
surgical site infection (SSI) is one of the most common complications that can occur after stoma closure. To date, there is no consensus on the ideal closure technique of the stoma wound to minimize postoperative SSI and multiple techniques have been proposed. We performed this study to assess the clinical outcome of wound healing after 'Primary Linear Closure' (PC) and 'Circumferential Purse-String Approximation' (CPA) techniques. this prospective observational study included all patients admitted to our tertiary care center, fulfilling the inclusion criteria for elective stoma closure from 1st March 2018 to 1 March 2020 and prospective study was conducted on wound healing after stoma closure to compare difference in SSI rate between the PC group and the CPA group and to discuss the differences in patient satisfaction with wound healing. The following study was carried out with 36 patients in purse-string group and 66 patients in linear closure group. surgical site infection (SSI) was observed only in primary linear closure group in 24% patients as opposed to 0% in purse string closure group. (p=0.039). Although the mean healing time of wound in linear closure group was significantly less than the purse string group (10.76 ± 5.68 days and 14.17 ± 2.04 days respectively), the overall total satisfaction score was higher in the purse string group. The purse string closure group showed significantly higher satisfaction score for expectations regarding appearance of scar/cosmesis, level of postoperative pain and difficulty of wound care (p>0.05). in our study, 'Circumferential Purse-String Approximation' is a superior technique than Primary Linear Closure for Stoma reversal in terms of rate of SSI and better overall patient satisfaction. CPA is a good alternative option, but further prospective randomized trials involving more patients are necessary before a definitive conclusion can be drawn.


Electricity systems in the limit of free solar photovoltaics and continent-scale transmission.
Solar photovoltaics, with sufficient power generation potential, low-carbon footprint, and rapidly declining costs, could supplant fossil fuels and help produce lower-cost net-zero emissions energy systems. Here we used an idealized linear optimization model, including free lossless transmission, to study the response of electricity systems to increasing prescribed amounts of solar power. Our results show that there are initially great benefits when providing solar power to the system, especially under deep decarbonization scenarios. The marginal value of additional solar power decreases substantially with increasing cumulative solar capacities. At costs near today's levels, the modeled zero-emission electricity system with free solar generation equaling twice the annual mean demand is more costly than a carbon-emitting natural-gas-based system supplying the same electricity demand with no solar. Taking full advantage of low-cost solar will depend on developing and deploying low-cost approaches to temporally shift either energy supply (e.g., storage) or electricity loads (e.g., load-shifting).


Transverse technique: complementary approach to measurement of first-trimester uterine artery Doppler.
To define a protocol for the first-trimester assessment of uterine artery pulsatility index (UtA-PI) using the new transverse technique, to evaluate UtA-PI measured using the transverse approach vs that obtained using the conventional sagittal approach and to determine if accelerated onsite training (in both methods) of inexperienced sonographers can achieve reproducible UtA-PI measurements comparable with those obtained by an experienced sonographer. This was a prospective observational study of women with a singleton pregnancy attending for routine combined first-trimester screening at 11 to 13 + 6 weeks' gestation. The study consisted of two parts, each conducted at a different center (Part 1 in Calgary, Canada and Part 2 in Hong Kong). In Part 1, UtA-PI measurements were performed using the transverse and sagittal techniques by four sonographers trained in both methods, in 10 cases each, and measurement indices (PI), time required and subjective difficulty in obtaining satisfactory measurements were compared. The one sample t-test and Wilcoxon signed rank test were used when appropriate. Bland-Altman plots were used to assess measurement agreement, and intraclass correlation coefficient (ICC) was used to evaluate measurement reliability. A target plot was used to assess measures of central tendency and dispersion. In Part 2, one experienced and three inexperienced sonographers prospectively measured UtA-PI using both approaches in 42 and 35 women, respectively. Inexperienced sonographers underwent accelerated onsite training by the experienced sonographer. Measurement approach and sonographer order were on a random basis. ICC, Bland-Altman and Passing-Bablok analyses were performed to assess measurement agreement and reliability and effect of accelerated training. In Part 1, no difference was observed between the two techniques in mean time to acquire the measurements (118 s for sagittal vs 106 s for transverse; P = 0.38). The four sonographers reported that the transverse technique was subjectively easier to perform (P = 0.04). Bias and ICC for mean UtA-PI between sagittal and transverse measurements were -0.05 (95% limits of agreement, -0.48 to 0.37) and 0.94, respectively. Measurements obtained using the transverse technique after correcting for gestational age were significantly closer to the expected distribution than those obtained using the sagittal technique. In Part 2, there were no significant differences in median UtA-PI measured using the different approaches for both experienced and inexperienced sonographers (P > 0.05 for all sonographers). Mean UtA-PI measurement reliability between approaches was high for the experienced (ICC = 0.92) and inexperienced (ICC > 0.80) sonographers. UtA-PI measurement approaches did not deviate from linearity, while bias ranged from -0.10 to 0.07. The median time required was similar between the techniques (56.1 s for sagittal vs 49.3 s for transverse; P = 0.054). This novel transverse approach for the measurement of UtA-PI in the first trimester appears to be comparable with the sagittal approach in terms of reliability, reproducibility and time required, and may be easier to perform. Providing accelerated onsite training can be helpful for improving the reliability of UtA-PI measurements and could potentially facilitate the broad implementation of first-trimester pre-eclampsia screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Combination of rituximab with therapeutic plasma exchange in a refractory case of thrombotic thrombocytopenic purpura (TTP).
Therapeutic plasma exchange is established treatment for patients with thrombotic thrombocytopenic purpura (TTP) and for refractory cases immunosuppressive therapy can also be considered. We present a refractory case of TTP which was managed with therapeutic plasma exchange and rituximab.


A shrimp gene encoding a single WAP domain (SWD)-containing protein regulated by JAK-STAT and NF-κB pathways.
Regulation of immune responses in animals is largely governed by the JAK-STAT and NF-κB pathways, which are conserved across vertebrates and invertebrates. At present, the relationship between these two pathways in invertebrates remains unclear. In the current study, a novel antimicrobial peptide termed LvSWD5 belonging to the Crustin family was identified from Pacific white shrimp Litopenaeus vannamei. The mature LvSWD5 peptide containing a single WAP domain (SWD) could directly bind bacteria and fungi and inhibit the growth of both Gram-positive and -negative bacteria in vitro. The LvSWD5 promoter was predicted to contain binding sites for STAT and NF-κB and could be regulted by the JAK-STAT and Relish pathways. The expression of LvSWD5 was up-regulated during bacterial, viral and fungal infections and silencing of LvSWD5 in vivo affected the expression of a series of immune related genes and decreased the phagocytic activity of hemocytes against V. Parahaemolyticus. Moreover, the susceptibility of shrimp to V. parahaemolyticus and white spot syndrome virus (WSSV) was significantly increased after silencing of LvSWD5, indicating that LvSWD5 could be involved in antibacterial and antiviral responses. These suggested that the JAK-STAT and NF-κB pathways could converge at the promoter level of a common target gene to regulate the immunity in shrimp.


Endoscopic biopsy and EUS for the detection of pathologic complete response after neoadjuvant chemoradiotherapy in esophageal cancer: a systematic review and meta-analysis.
Accurate determination of residual cancer status after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer could assist in selecting the optimal treatment strategy. The aim of this study was to review the evidence on the diagnostic accuracy of endoscopic biopsy and EUS after nCRT for detecting residual cancer at the primary tumor site (ypT+) and regional lymph nodes (ypN+) as opposed to a pathologic complete response (ypT0 and ypN0). PubMed/Medline, Embase, and the Cochrane library were systematically searched. The analysis included diagnostic studies reporting on the accuracy of endoscopic biopsy or EUS in detecting residual cancer versus complete response after nCRT for esophageal cancer with histopathology as the reference standard. Bivariate random-effects models were used to estimate pooled sensitivities and specificities and examine sources of heterogeneity. Twenty-three studies comprising 12 endoscopic biopsy studies (1281 patients), 11 EUS studies reporting on ypT status (593 patients), and 10 EUS studies reporting on ypN status (602 patients), were included. Pooled estimates for sensitivity of endoscopic biopsy after nCRT for predicting ypT+ were 34.5% (95% confidence interval [CI], 26.0%-44.1%) and for specificity 91.0% (95% CI, 85.6%-94.5%). Pooled estimates for sensitivity of EUS after nCRT were 96.4% (95% CI, 91.7%-98.5%) and for specificity were 10.9% (95% CI, 3.5%-29.0%) for detecting ypT+, and 62.0% (95% CI, 46.0%-75.7%) and 56.7% (95% CI, 41.8%-70.5%) for detecting ypN+, respectively. Endoscopic biopsy after nCRT is a specific but not sensitive method for detecting residual esophageal cancer. Although EUS after nCRT yields a high sensitivity, only a limited number of patients will have negative findings at EUS with still a substantial false-negative rate. Furthermore, EUS provides only moderate accuracy for detecting residual lymph node involvement. Based on these findings, these endoscopic modalities cannot be used to withhold surgical treatment in test-negative patients after nCRT. ( CRD42015016527.).


Studies on adsorption of dyes on beta-cyclodextrin polymer.
Beta-cyclodextrin (beta-CD) polymers are used for the removal of various dyes from aqueous solutions. Three insoluble polymers with different degrees of beta-CD were used. Results of adsorption experiments showed that these polymers exhibited high sorption capacities toward dyes. The mechanism of adsorption was both physical adsorption and hydrogen bonding due to the polymer and the formation of an inclusion complex due to the beta-CD molecules through host-guest interactions.


Glucose uptake in PC12 cells: GLUT3 vesicle trafficking and fusion as revealed with a novel GLUT3-GFP fusion protein.
The distribution of glucose transporters at the cell surface has a major impact on cellular glucose uptake. In muscle cells and adipocytes, this distribution is under the control of insulin; however, neuronal glucose uptake is not acutely regulated by insulin. Factors that affect the translocation of the neuronal glucose transporter isoform GLUT3 vesicles to and their fusion with the plasma membrane are not well understood. We report that GLUT3 in PC12 cells colocalizes with SNARE complex proteins SNAP-25 and syntaxin 1, suggesting that fusion of GLUT3-containing vesicles with the plasma membrane is mediated by these proteins. In addition, it seems that GLUT3 vesicle fusion is regulated, as depolarization increases GLUT3 insertion into the plasma membrane. To study the dynamics of GLUT3 vesicle trafficking, we have created a GLUT3-GFP fusion protein that is easily expressed in PC12 cells. Trafficking of GLUT3-GFP seems normal, as 1). its distribution is similar to endogenous GLUT3, 2). GLUT3-GFP containing vesicles fuse with the plasma membrane evidenced by labeling of the fusion protein with an antibody directed against the exofacial epitope of GLUT3, and 3). glucose uptake is similar to PC12 cells not transfected with GLUT3 fusion protein. These studies are the first to examine GLUT3 trafficking and fusion in PC12 cells, and establish a model system to study regulation of the neuronal glucose transporter.


The association of autophagy with polyethylenimine-induced cytotoxicity in nephritic and hepatic cell lines.
Polyethylenimine (PEI) is one of the most effective and widely used cationic macromolecules in experimental gene transfer/therapy protocols. However, the further clinical application of PEI is largely impeded by its cytotoxicity. Here we performed a fundamental investigation on the mechanism of PEI-induced cytotoxicity in both hepatic and nephritic cell lines. It was demonstrated that besides necrosis and apoptosis, autophagy was apparently associated with PEI-induced cytotoxicity and contributed to aggravated cell damage. Specifically, at the early stage (3 h) of PEI-induced cytotoxicity, autophagy was mainly correlated with lysosome damage, but in the later phase (after a 24-h recovery), autophagy was mainly related with mitochondrial injury. Modulation of Rab5, Rab7 expression and inhibition of clathrin-mediated endocytosis pathway significantly affected the formation of autophagosome, which suggested that the endolysosome transport pathway especially the clathrin-mediated endocytosis at least partly facilitated PEI-induced autophagy. As PEI-induced autophagy played a causative role in its cytotoxicity, it's highly recommended to design PEI-based gene-carriers that could avoid the endolysosome transport pathway.


Evaluation of somnolence in Parkinson's disease: comparison with age- and sex-matched controls.
The authors found a significantly higher prevalence of daytime somnolence in 201 patients with PD compared with 214 age- and sex-matched healthy control subjects (Epworth Sleepiness Scale score 5.6 vs 4.6). The prevalence of "sleep attacks" (SA) was about seven times higher in patients with PD than in control subjects (13.9% vs 1.9%; p < 0.0005). Multivariate analysis demonstrated that a higher dose of levodopa and longer duration of disease significantly predicted for SA in patients with PD. Epworth Sleepiness Scale scores of > or =10 had 71.4% sensitivity and 88.4% specificity for SA.


Dexamethasone therapy in neonates treated with extracorporeal membrane oxygenation.
To test the hypothesis that infants who received dexamethasone would have a shorter length of time on extracorporeal membrane oxygenation (ECMO). Study design Infants placed on ECMO for respiratory failure were randomly assigned to receive either dexamethasone for 3 days or placebo. Chest radiographs were scored through the use of a validated standard scoring system to assess lung injury. Thirty infants received dexamethasone and 29 received placebo. The median (25th%, 75th%) duration of time on ECMO was 143.5 (100, 313) hours in the dexamethasone group and 160 (111, 303) hours in the placebo group (not significant). Survival was 80% in the dexamethasone group and 83% in the placebo group. Radiographic lung injury scores (mean+/-SEM) were significantly improved in the dexamethasone group (10.5+/-0.6) versus placebo (12.3+/-0.5) on day 3 of ECMO (P=.013). Hypertension developed in 27 of the 30 infants receiving dexamethasone and 13 of the 29 infants in the placebo group during ECMO (P<.01). Dexamethasone given during the first 3 days of ECMO results in significant improvement in lung injury scores by day 3 of ECMO but does not significantly decrease the duration of ECMO or improve survival. The preponderance of evidence would not support the use of dexamethasone in this setting.


Self-reported sleep disturbances associated with procedural learning impairment in adolescents at ultra-high risk for psychosis.
Sleep disturbance contributes to impaired procedural learning in schizophrenia, yet little is known about this relationship prior to psychosis onset. Adolescents at ultra high-risk (UHR; N=62) for psychosis completed the Pittsburgh Sleep Quality Index (PSQI) and a procedural learning task (Pursuit Rotor). Increased self-reported problems with sleep latency, efficiency, and quality were associated with impaired procedural learning rate. Further, within-sample comparisons revealed that UHR youth reporting better sleep displayed a steeper learning curve than those with poorer sleep. Sleep disturbances appear to contribute to cognitive/motor deficits in the UHR period and may play a role in psychosis etiology.


Factors influenced on prognosis of reconstructive surgery for peripheral arterial occlusion: comparative study between arteriosclerosis obliterans and thromboangiitis obliterans.
Reconstructive surgery was carried out in 93 patients of ASO and TAO. Factors influenced on prognosis were studied being compared with ASO and TAO. Cumulative 5-year patency was 60% in ASO and 25% in TAO. Distal patency was shown by total score given in each site of arteriogram. Patency rate was well correlated with combinated factors such as total score of arteriogram and back flow at site of surgery. Period from onset of symptom to surgery and site of operation also correlated with patency statistically, though total serum cholesterol, ischemic time at reconstructive surgery, and amount of bleeding at operation did not relate to prognosis. Causes of early failure and special problems of late failure in TAO were studied.


Toughness in synthetic and biological multilayered systems.
Toughness in hard biological tissues is associated with fibrous or lamellar structures that deflect or stop growing cracks. In some cases, such as nacreous shell, protein interlayers absorb much of the crack energy. In other tissues, such as tooth enamel, the toughness derives from the mineral microstructure, and the small amount of residual protein apparently has little effect. There have been a number of efforts to make tough synthetic materials using layered structures. In this work, freeform fabrication has been used to make layered structures with a view to introducing similar toughness into brittle materials. Results are presented for epoxy-glass composites with glass fabric interlayers, porous alumina back-filled with aluminium metal, and layered glass-ceramic/silver materials.


Impact of hydroxyurea dose and adherence on hematologic outcomes for children with sickle cell anemia.
Hydroxyurea is the primary treatment for sickle cell anemia (SCA), yet real-world implementation in high-income settings is suboptimal. Variation in prescribed hydroxyurea dose and patient adherence in these settings can both affect actual exposure to hydroxyurea. Quantifying the contributions of hydroxyurea dose and medication adherence to the relationship between hydroxyurea exposure and hematologic parameters could inform strategies to optimize exposure and improve outcomes. We evaluated the relationship between hydroxyurea exposure, defined by average prescribed dose and adherence, and hematologic parameters using data from children with SCA who were enrolled in two prospective hydroxyurea adherence studies. Hydroxyurea adherence was assessed by video directly observed therapy or electronic pill bottle and medication administration record. Average prescribed dose was abstracted from prescriptions in patients' electronic medical record. Participants with a hydroxyurea exposure >20 mg/kg/day and ≤20 mg/kg/day were included in the higher and lower exposure groups, respectively. Forty-five participants were included in the analysis (56% male; median age 12 years [range 2-19]; 98% Black). Higher exposed participants (n = 23) were prescribed a higher dose (27.2 vs. 24.4 mg/kg/day, p = .002) and had better adherence (0.92 vs. 0.71, p ≤ .001) compared to lower exposed participants (n = 22). Higher exposure was associated with higher fetal hemoglobin (p = .04) and mean corpuscular volume (p = .02). Higher hydroxyurea exposure is associated with improved hematologic parameters in the high-income setting and is affected by both prescribed dose and adherence. Future studies are needed to optimize both adherence and hydroxyurea prescribing and confirm that increasing exposure improves clinical outcomes in this setting.


Decoding (patho-)physiology of the lung by advanced in vitro models for developing novel anti-infectives therapies.
Advanced lung cell culture models provide physiologically-relevant and complex data for mathematical models to exploit host-pathogen responses during anti-infective drug testing.


Changes in use of crack cocaine after drug misuse treatment: 4-5 year follow-up results from the National Treatment Outcome Research Study (NTORS).
Crack cocaine outcomes at 4-5 years are reported for 496 drug users recruited from UK treatment programmes. About one-third used crack at intake and at 4-5 years. The results show different outcome profiles. For crack users at intake, use was more than halved at follow-up. Among non-crack-users at intake, about a quarter used crack during follow-up, of whom about two-thirds had never used crack before. Polydrug use and use of other stimulants were associated with using crack. Crack users reported worse acquisitive crime and psychological health outcomes. About 10% reported injecting crack. The reductions in crack use are encouraging, but the onset of crack use among many non-users at intake suggests the need to develop more effective treatment interventions.


Form and Function: Learning Anatomy Using Ultrasound.
Ultrasound (US) is increasingly used across medical specialities as a diagnostic tool and medical faculties are therefore further incorporating imaging into their programmes. Using US within undergraduate instruction has several benefits. US, as a learning instrument, may strengthen existing anatomical knowledge and improve visual understanding of anatomy. The cost-effectiveness, as well as portability of the US, makes it a valuable means to add to traditional anatomy teaching modalities. Furthermore, students have an opportunity to develop skills in interpreting US images and this may add a different element to the learning of anatomy. This study aimed to explore undergraduate clinical anatomy students' perceptions of the use of US as an add-on to cadaveric dissection. Students were invited to participate in virtual focus group discussions. Three virtual focus group discussions were conducted, and 11 participants volunteered to take part. Thematic analysis of the data generated six themes. These are described as the study of living anatomy, learning cross-sectional anatomy, enhanced relevance of anatomy learning, increased interest in anatomy, instructional design, and the affective and technical experience of using US. The results suggest that it is feasible and advantageous to implement US sessions as an add-on to the teaching of anatomy during practical dissection sessions of clinical anatomy students. The use of innovative technologies such as US enhances the interest of students and allows them to develop dexterity and competencies in their learning process. The online version contains supplementary material available at 10.1007/s40670-023-01806-y.


[The diagnosis and treatment of Lyme disease: a report of six cases].
We retrospectively analyzed the clinical features, diagnosis, treatment, and prognosis of 6 cases of Lyme disease from November, 1994 to December, 1998. According to our report, doxycycline, penicillin, and ceftriaxone are effective drugs for Lyme disease. The shorter the disease course is, the better the treatment effect will be. Patients in phase III usually need repeated treatment.


Evaluation of functional nerve recovery with Visual-SSI--a novel computerized approach for the assessment of the static sciatic index (SSI).
Complete nerve transection (neurotmesis) of the rat sciatic nerve is a well-established animal model. The most frequently used behavioural for evaluation of neurotmesis-induced deficits is the walking track analysis with calculation of the sciatic functional index (SFI). More recently, the static sciatic index (SSI) has been developed, which shows a good correlation with the SFI. However, despite all advantages (high accessibility, easy handling, high accuracy, cost-effectiveness), the SSI is still not widely used. We, therefore, developed a novel programme ("Visual-SSI"), which will be made freely available for the assessment of the SSI. As gold-standard for the treatment of neurotmesis-induced nerve gaps, autologous nerve transplantation studies in the rat sciatic nerve model (n=16 [6 weeks], n=8 [12 weeks]) were carried out to test the effectiveness and feasibility of the Visual-SSI software. We observed a significant recovery starting from the pre-operative condition over the 3rd, 6th, 9th weeks until the 12th week after surgery (p<0.05). Theoretically, the SSI can be calculated from both rearing and normal standing position of the rats and we investigated whether the SSI is affected differentially by these positions. We observed no significant differences between animals in a rearing and normal standing stance (p>0.05). The present method combines efficiency (simplicity of use, rapid and economical setup) with accurate and precise quantification of the functional regeneration in the sciatic nerve lesion model of the rat.


High-efficiency production of bioactive oleosin-basic fibroblast growth factor in A. thaliana and evaluation of wound healing.
Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factors family. It is a highly specific mitogenic factor for many cell types, as though it be involved in wound repair, angiogenesis, nerve nutrition and embryonic development etc. Oil bodies have been applied for medicine, foodstuff and industry field. The heterogonous proteins expressed in oil bodies have distinct advantages, such as less purification steps and low costs. In this study, bFGF was expressed in A. thaliana seeds using oleosin fusion technology. The pOTB-bFGF vector contained an oleosin-bFGF fusion gene and a glufosinate resistance gene for selection. Transgenic A. thaliana lines were obtained by the floral dip method and protein expression was identified by SDS-PAGE and western blotting in transgenic A. thaliana lines. Moreover, MTT assays showed that the oil bodies expressed oleosin-bFGF fusion protein had a remarkable proliferation effect on NIH/3T3 cells and animal experiments showed that it could effectively decrease wound size and accelerate granulation tissue maturation. In conclusion, this may be a better method of producing oleosin-bFGF fusion protein to meet the increasing demand in its pharmacological application.


Photoperiod and gravistimulation-associated Tiller Angle Control 1 modulates dynamic changes in rice plant architecture.
TAC1 is involved in photoperiodic and gravitropic responses to modulate rice dynamic plant architecture likely by affecting endogenous auxin distribution, which could explain TAC1 widespread distribution in indica rice. Plants experience a changing environment throughout their growth, which requires dynamic adjustments of plant architecture in response to these environmental cues. Our previous study demonstrated that Tiller Angle Control 1 (TAC1) modulates dynamic changes in plant architecture in rice; however, the underlying regulatory mechanisms remain largely unknown. In this study, we show that TAC1 regulates plant architecture in an expression dose-dependent manner, is highly expressed in stems, and exhibits dynamic expression in tiller bases during the growth period. Photoperiodic treatments revealed that TAC1 expression shows circadian rhythm and is more abundant during the dark period than during the light period and under short-day conditions than under long-day conditions. Therefore, it contributes to dynamic plant architecture under long-day conditions and loose plant architecture under short-day conditions. Gravity treatments showed that TAC1 is induced by gravistimulation and negatively regulates shoot gravitropism, likely by affecting auxin distribution. Notably, the tested indica rice containing TAC1 displayed dynamic plant architecture under natural long-day conditions, likely explaining the widespread distribution of TAC1 in indica rice. Our results provide new insights into TAC1-mediated regulatory mechanisms for dynamic changes in rice plant architecture.


The micro-architecture of the cerebral cortex: functional neuroimaging models and metabolism.
In order to interpret/integrate data obtained with different functional neuroimaging modalities (e.g. fMRI, EEG/MEG, PET/SPECT, fNIRS), forward-generative models of a diversity of brain mechanisms at the mesoscopic level are considered necessary. For the cerebral cortex, the brain structure with possibly the most relevance for functional neuroimaging, a variety of such biophysical models has been proposed over the last decade. The development of technological tools to investigate in vitro the physiological, anatomical and biochemical principles at the microscopic scale in comparative studies formed the basis for such theoretical progresses. However, with the most recent introduction of systems to record electrical (e.g. miniaturized probes chronically/acutely implantable in the brain), optical (e.g. two-photon laser scanning microscopy) and atomic nuclear spectral (e.g. nuclear magnetic resonance spectroscopy) signals using living laboratory animals, the field is receiving even greater attention. Major advances have been achieved by combining such sophisticated recording systems with new experimental strategies (e.g. transgenic/knock-out animals, high resolution stereotaxic manipulation systems for probe-guidance and cellular-scale chemical-delivery). Theoreticians may now be encouraged to re-consider previously formulated mesoscopic level models in order to incorporate important findings recently made at the microscopic scale. In this series of reviews, we summarize the background at the microscopic scale, which we suggest will constitute the foundations for upcoming representations at the mesoscopic level. In this first part, we focus our attention on the nerve ending particles in order to summarize basic principles and mechanisms underlying cellular metabolism in the cerebral cortex. It will be followed by two parts highlighting major features in its organization/working-principles to regulate both cerebral blood circulation and neuronal activity, respectively. Contemporary theoretical models for functional neuroimaging will be revised in the fourth part, with particular emphasis in their applications, advantages/limitations and future prospects.


Measurement of urinary steroid production rates using stable-isotopes and GC-MS.
The urinary production rate of pregnenolone has been determined for a male subject using 7,7-d2-pregnenolone as an isotopic tracer.


Risk stratification in patients with Brugada syndrome: analysis of daily fluctuations in 12-lead electrocardiogram (ECG) and signal-averaged electrocardiogram (SAECG).
Risk stratification between symptomatic and asymptomatic patients with Brugada syndrome is not yet established. We compared daily fluctuations in 12-lead electrocardiogram (ECG) and signal-averaged ECG (SAECG) characteristics between symptomatic and asymptomatic patients with Brugada syndrome to identify new markers for distinguishing between high- and low-risk patients. Thirty-five patients with Brugada syndrome underwent ECG and SAECG simultaneously at least 4 times every 3 months. We evaluated daily fluctuations (differences between maximum and minimum values) in ECG and SAECG characteristics and compared them between symptomatic (N = 11), and asymptomatic (N = 24) patients. On ECG, the daily fluctuations in r-J interval (interval from QRS onset to J point) in leads V1, V2, and V6 were significantly larger in symptomatic than in asymptomatic patients (V1; 20 +/- 6 vs 10 +/- 8 msec, P < 0.01, V2; 22 +/- 8 vs 11 +/- 4 msec, P < 0.01, and V6; 24 +/- 7 vs 14 +/- 7 msec, P < 0.01). On SAECG, daily fluctuations in filtered QRS (f-QRS) duration and LAS40 were significantly larger in symptomatic than in asymptomatic patients (f-QRS; 15 +/- 7 vs 9 +/- 4 msec, P < 0.05, and LAS40; 21 +/- 7 vs 10 +/- 6 msec, P < 0.05). Instability of depolarization appears to be related to the risk of fatal ventricular arrhythmias in patients with Brugada syndrome. Daily fluctuations in ECG and SAECG characteristics could be useful for distinguishing between high- and low-risk patients with Brugada syndrome.


Repeated administration of antidepressants decreases field potentials in rat frontal cortex.
The effects of repeated administration of a tricyclic antidepressant, imipramine, and a selective serotonin reuptake blocker, citalopram, for 14 days (10 mg/kg p.o., twice daily), were studied ex vivo in rat frontal cortex slices prepared 48 h after last dose of the drug. Treatment with both antidepressants resulted in a decrease in the amplitude of field potentials evoked in layer II/III by stimulation of underlying sites in layer V. The amplitude ratio of pharmacologically isolated N-methyl-D-aspartic acid (NMDA) to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components of the field potential was reduced. These results indicate that chronic treatment with imipramine or citalopram results in an attenuation of glutamatergic synaptic transmission in the cerebral cortex.


A case of intravascular lymphoma diagnosed with a primary vitreoretinal lymphoma-like fundus lesion.
We report a case of intravascular lymphoma with primary vitreoretinal lymphoma-like fundus findings. A 61-year-old man with a one-week history of temporal visual field defect in the left eye was referred by a local ophthalmologist to our department. A yellowish-white raised patchy lesion was found in the nasal fundus of the left eye. Vitreoretinal lymphoma was suspected, and vitrectomy was performed in the left eye for diagnostic purpose. However, vitreous interleukin-10 concentration was low and no significant result was obtained. He had fever of around 38 °C, and respiratory failure that started 2 weeks before ophthalmological examination, worsened. Intravascular lymphoma was diagnosed from the results of histopathological examinations of transbronchial lung biopsy, bone marrow biopsy and random skin biopsy. With the start of systemic chemotherapy, the subretinal lesions shrank gradually and systemic condition was stable. However, 5 months after the start of chemotherapy, spread to the central nervous system was observed, and chimeric antigen receptor T cell (CAR-T) therapy was started in another hospital. After the start of CAR-T therapy, the subretinal lesions shrank further. Intravascular lymphoma may be accompanied by primary vitreoretinal lymphoma-like intraocular lesions. If intraocular lesions are accompanied by systemic symptoms such as fever of unknown origin, the possibility of intravascular lymphoma should be suspected and systemic work-up should be performed.


Peptidomics Methods Applied to the Study of Flower Development.
Understanding the global and dynamic nature of plant developmental processes requires not only the study of the transcriptome, but also of the proteome, including its largely uncharacterized peptidome fraction. Recent advances in proteomics and high-throughput analyses of translating RNAs (ribosome profiling) have begun to address this issue, evidencing the existence of novel, uncharacterized, and possibly functional peptides. To validate the accumulation in tissues of sORF-encoded polypeptides (SEPs), the basic setup of proteomic analyses (i.e., LC-MS/MS) can be followed. However, the detection of peptides that are small (up to ~100 aa, 6-7 kDa) and novel (i.e., not annotated in reference databases) presents specific challenges that need to be addressed both experimentally and with computational biology resources. Several methods have been developed in recent years to isolate and identify peptides from plant tissues. In this chapter, we outline two different peptide extraction protocols and the subsequent peptide identification by mass spectrometry using the database search or the de novo identification methods.


A framework and model for evaluating clinical decision support architectures.
In this paper, we develop a four-phase model for evaluating architectures for clinical decision support that focuses on: defining a set of desirable features for a decision support architecture; building a proof-of-concept prototype; demonstrating that the architecture is useful by showing that it can be integrated with existing decision support systems and comparing its coverage to that of other architectures. We apply this framework to several well-known decision support architectures, including Arden Syntax, GLIF, SEBASTIAN, and SAGE.


Robust trend tests for genetic association using matched case-control design.
Trend tests for genetic association using a matched case-control design are studied, which allows for a variable number of controls per case. However, the tests depend on the scores based on the underlying genetic model, thus it may result in substantial loss of power when the model is misspecified. Since the mode of inheritance may be unknown for complex diseases, robust trend tests in matched case-control studies are developed. Simulation is conducted to compare the trend tests and the robust trend tests under various genetic models. The results are applied to detect candidate-gene association using an example from a case-control aetiologic study of sarcoidosis.


Yellow nail syndrome with chylothorax after coronary artery bypass grafting.
Yellow nail syndrome is a rare condition considered secondary to functional anomalies of lymphatic drainage. Yellow nail syndrome is diagnosed through the triad of intrathoracic findings (30% being pleural effusions), nail discoloration, and lymphedema, with any two features sufficient for diagnosis. We report the second case of post-operative yellow nail syndrome. After coronary artery bypass grafting, our patient presented with chylothorax on post-operative day 13 and yellow toenail discoloration on post-operative day 28, diagnosing yellow nail syndrome. Initial conservative management with pigtail catheter drainage and low-fat diet with medium-chain triglycerides reduced chylous drainage from 350 mL/day on post-operative day 14 to < 100 mL/day on post-operative day 17. However, by post-operative day 18, drainage returned to 350 mL/day that persisted despite attempts to readjust the catheter position, replacement of catheter with chest tube, and transition to total parenteral nutrition and octreotide while nil per os. Lymphangiogram on post-operative day 32 did not identify the thoracic duct or cisterna chyli, precluding embolization. Talc and doxycycline pleurodeses performed on post-operative days 33 and 38, respectively, resolved his chylothorax and nail discoloration. Both yellow nail syndrome and chylothorax as a complication of coronary artery bypass grafting are rare entities. The proposed mechanism of post-operative chylothorax is iatrogenic injury to thoracic duct or collateral lymphatic vessels. Diagnosing yellow nail syndrome in patients with post-operative chylothorax (through co-existing yellow nail discoloration and/or lymphedema) may suggest predisposition to impaired lymphatic drainage, portending a difficult recovery and potentially indicating need for surgical management.