Transvaginal cholecystectomy without laparoscopic support using prototype flexible endoscopic instruments in a porcine model.
Transvaginal cholecystectomy with laparoscopic assistance has been performed safely in humans. The next goal was to develop a natural orifice transluminal endoscopic surgery (NOTES) technique to perform cholecystectomy without laparoscopic instruments using one flexible endoscope and flexible accessories. The aim of the study was to test the feasibility of the procedure in a survival porcine model. Cholecystectomies were attempted in five 88-130-lb. pigs with a planned 2-week survival. Prototype flexible instruments (NOTES Toolbox, Ethicon Endo-Surgery, Inc.) were used to aid in access, dissection, and removal of the gallbladder via the transvaginal route. Cholecystectomy could be completed without abdominal incision using prototype instruments in four out of five pigs. The cystic duct could be exposed with a flexible hook knife and clips applied. The steerable trocar improved stability and the precision of the dissection. The critical view was established in all five pigs. Dissection of the gallbladder off the liver bed was imprecise resulting in gallbladder perforation in all pigs and liver hemorrhage in two. At necropsy, all clips on the cystic duct were secure and no bile leak, bowel injury, or adhesions were present. NOTES cholecystectomy without laparoscopic support is feasible but challenging using prototype flexible endoscopic devices. A prototype clip applier was effective in controlling the cystic duct. Further improvements in instrument design to ensure precision and safety are needed before flexible devices should be used for pure NOTES procedures in humans.


Microgeographical study of insecticide resistance in Triatoma infestans from Argentina.
Chagas disease is a chronic parasitic infection restricted to America where it is currently estimated that 90 million people are at risk of acquiring the infection. Chemical control with pyrethroid insecticides has been effective to reduce disease transmission in several areas of the Southern Cone, although insecticide resistance has evolved and diminished the campaigns' results. Considering previous reports on the different levels of resistance between Triatoma infestans from different geographical areas, the objective of this work was to determine if T. infestans populations are toxicologically structured within localities. Response to the insecticide was measured and compared between houses of two Argentine localities. Different toxicity of deltamethrin was detected between dwellings of Chaco province, accounting for both susceptible and resistant houses within the same locality. However no difference was found among houses of Salta province. The results obtained in this work suggest that geographical structure is present not only at the between localities level, but also at the microgeograhical level.


Late lactation in small mammals is a critically sensitive window of vulnerability to elevated ambient temperature.
Predicted increases in global average temperature are physiologically trivial for most endotherms. However, heat waves will also increase in both frequency and severity, and these will be physiologically more important. Lactating small mammals are hypothesized to be limited by heat dissipation capacity, suggesting high temperatures may adversely impact lactation performance. We measured reproductive performance of mice and striped hamsters (Cricetulus barabensis), including milk energy output (MEO), at temperatures between 21 and 36 °C. In both species, there was a decline in MEO between 21 and 33 °C. In mice, milk production at 33 °C was only 18% of that at 21 °C. This led to reductions in pup growth by 20% but limited pup mortality (0.8%), because of a threefold increase in growth efficiency. In contrast, in hamsters, MEO at 33 °C was reduced to 78.1% of that at 21 °C, yet this led to significant pup mortality (possibly infanticide) and reduced pup growth by 12.7%. Hamster females were more able to sustain milk production as ambient temperature increased, but they and their pups were less capable of adjusting to the lower supply. In both species, exposure to 36 °C resulted in rapid catastrophic lactation failure and maternal mortality. Upper lethal temperature was lowered by 3 to 6 °C in late lactation, making it a critically sensitive window to high ambient temperatures. Our data suggest future heat wave events will impact breeding success of small rodents, but this is based on animals with a long history in captivity. More work should be performed on wild rodents to confirm these impacts.


Lactoferrin in benign hypertrophy and carcinomas of the prostatic gland.
Using immunoperoxidase procedures, the presence of lactoferrin was investigated in benign hypertrophy (40 cases), differentiated adenocarcinomas (20 cases) and undifferentiated carcinomas (10 cases) of the prostate. In benign hypertrophy, the glandular epithelium and the secretory product were consistently negative. Strong staining for lactoferrin was always observed in neoplastic cells of differentiated adenocarcinomas and in their endoluminal material; in contrast, a very slight positivity was noted in undifferentiated carcinomas. These findings are discussed in relation to the different degree of neoplastic glandular differentiation and functional activity of prostatic carcinomas.


Expression of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) GluR2/3 receptors in the developing rat pineal gland.
The expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type glutamate (GluR2/3) receptors and N-methyl-D-aspartate receptor subtype 1 (NMDAR1) was carried out by immunohistochemistry, double immunofluorescence and real-time RT-PCR analysis in the pineal glands of 1-day to 6-wk-old rats in the present study. GluR2/3 immunopositive cells were distributed throughout the pineal gland and showed branching processes in all age groups. The NMDAR1 immunoreactivity, however, was observed in fewer branched cells. A constitutive mRNA expression of NMDAR1, GluR2 and GluR3 was detected in the pineal glands of various ages and showed no significant difference between the age groups studied. Immunohistochemical and double immunofluorescence results showed that the GluR2/3 were mainly expressed and co-localized with OX-42-positive microglia/macrophages and the glial fibrillary acidic protein (GFAP)-positive astrocytes. Co-localization of NMDAR1 with OX-42- and GFAP-positive cells was much less. The expression of these receptors on the glial cells suggests that they may be involved in the development and growth of the pineal gland in the early postnatal period (1 day to 3 wk) and subsequently in the regulation of melatonin synthesis.


Association between a Calcium-to-Magnesium Ratio and Osteoporosis among Puerto Rican Adults.
The ratio of calcium-to-magnesium intake (Ca:Mg) may be important for bone due to their competitive absorption. The Ca:Mg ratio has been related to health outcomes, but few studies have related it to bone. The purpose of this analysis was to examine associations between the Ca:Mg intake with bone mineral density (BMD) and osteoporosis among Puerto Rican adults. Adults, aged 47-79 y, from the Boston Puerto Rican Osteoporosis Study, with complete BMD and dietary data (n = 955) were included. BMD was assessed with dual-energy X-ray absorptiometry and diet by a food frequency questionnaire. Calcium and magnesium intakes from food were energy adjusted, and the Ca:Mg was calculated. Adjusted linear and logistic regression models were utilized for testing associations between Ca:Mg and bone outcomes. Calcium intake was greater in the highest compared with lowest tertile, whereas magnesium intake was similar across tertiles. Mean BMD at hip sites was higher in the middle, compared with the lowest, tertile. Higher odds of osteoporosis were observed for the highest and lowest tertiles, compared with the middle tertile, after adjustment (T3 compared with T2 OR: 2.79; 95% CI: 1.47, 5.3; T1 compared with T2 OR: 2.01; 95% CI: 1.03, 3.92). Repeated analyses without supplement users (n = 432) led to stronger differences and ORs, but lost significance for some comparisons. Dietary calcium and magnesium are important for bone, perhaps not independently. The Ca:Mg intake ratio appeared most protective within a range of 2.2-3.2, suggesting that a balance of these nutrients may be considered in recommendations for osteoporosis..


Examining patient comprehension of emergency department discharge instructions: Who says they understand when they do not?
Patient comprehension of emergency department (ED) discharge instructions is important for ensuring that patients understand their diagnosis, recommendations for treatment, appropriate follow-up, and reasons to return. However, many patients may not fully understand their instructions. Furthermore, some patients may state they understand their instructions even when they do not. We surveyed 75 patients on their perception of their understanding of their ED discharge instructions, and asked them specific questions about the instructions. We also performed a chart review, and examined patients' answers for correlation with the written instructions and medical chart. We then performed a statistical analysis evaluating which patients claimed understanding but who were found to have poor understanding on chart review. Overall, there was no significant correlation between patient self-reported understanding and physician evaluation of their understanding (ρ = 0.221, p = 0.08). However, among female patients and patients with less than 4 years of college, there was significant positive correlation between self-report and physician evaluation of comprehension (ρ = 0.326, p = 0.04 and ρ = 0.344, p = 0.04, respectively), whereas there was no correlation for male patients and those with more than 16 years of education (ρ = 0.008, p = 0.9, ρ = -0.041, p = 0.84, respectively). Patients' perception of their understanding may not be accurate, especially among men, and those with greater than college education. Identifying which patients say they understand their discharge instructions, but may actually have poor comprehension could help focus future interventions on improving comprehension.


Wheat grain proteomic and protein-metabolite interactions analyses provide insights into plant growth promoting bacteria-arbuscular mycorrhizal fungi-wheat interactions.
Proteomic, protein-protein and protein-metabolite interaction analyses in wheat inoculated with PGPB and AMF identified key proteins and metabolites that may have a role in enhancing yield and biofortification. Plant growth-promoting bacteria (PGPB) and arbuscular mycorrhizal fungi (AMF) have an impact on grain yield and nutrition. This dynamic yet complex interaction implies a broad reprogramming of the plant's metabolic and proteomic activities. However, little information is available regarding the role of native PGPB and AMF and how they affect the plant proteome, especially under field conditions. Here, proteomic, protein-protein and protein-metabolite interaction studies in wheat triggered by PGPB, Bacillus subtilis CP4 either alone or together with AMF under field conditions was carried out. The dual inoculation with native PGPB (CP4) and AMF promoted the differential abundance of many proteins, such as histones, glutenin, avenin and ATP synthase compared to the control and single inoculation. Interaction study of these differentially expressed proteins using STRING revealed that they interact with other proteins involved in seed development and abiotic stress tolerance. Furthermore, these interacting proteins are involved in carbon fixation, sugar metabolism and biosynthesis of amino acids. Molecular docking predicted that wheat seed storage proteins, avenin and glutenin interact with secondary metabolites, such as trehalose, and sugars, such as xylitol. Mapping of differentially expressed proteins to KEGG pathways showed their involvement in sugar metabolism, biosynthesis of secondary metabolites and modulation of histones. These proteins and metabolites can serve as markers for improving wheat-PGPB-AMF interactions leading to higher yield and biofortification.


[Case report of frontobasal reconstruction and volume augmentation using a free gracilis muscle flap and autologous fat grafting: utilising the free flap as a scaffold for fat transplantation].
This case report shows the interdisciplinary treatment of a 28-year-old woman suffering from a pronounced frontal volume defect after severe craniocerebral trauma. The combination of cranioplasty using a polymethylmethacrylate (PMMA) implant, free gracilis muscle flap transfer for soft tissue coverage and serial autologous fat grafting into the muscle flap for subsequent contouring enabled both an adequate and aesthetic reconstruction. This example demonstrates the feasibility of treating increasingly complex composite defects in a multidisciplinary setting, when plastic surgeons are involved.


DNA threading bis(9-aminoacridine-4-carboxamides): effects of piperidine sidechains on DNA binding, cytotoxicity and cell cycle arrest.
We describe the synthesis of a series of DNA-threading bis(9-aminoacridine-4-carboxamides) comprising ethylpiperidino and N-methylpiperidin-4-yl sidechains, joined via neutral flexible alkyl chains, charged flexible polyamine chains and a semi-rigid charged piperazine linker. Their cytotoxicity towards human leukaemic cells gives IC(50) values ranging from 99 to 1100 nM, with the ethylpiperidino series generally being more cytotoxic than the N-methylpiperidin-4-yl series. Measurements with supercoiled DNA indicate that they bisintercalate.


Development of a new serological assay for the diagnosis of Clostridium difficile infections with prognostic value.
The most common hospital-acquired enteral infection is caused by Clostridium difficile. Unfortunately, Clostridium difficile infections (CDI) are of high risk to recur and little is known about how to predict recurrences. Previous findings have shown that high risk for recurrence correlates with low levels of C. difficile toxin-A and -B specific antibodies suggesting the protective role of humoral immunity against bacterial virulence factors. Therefore, the aim of this study was to develop an immunoassay, which specifically measures C.difficile toxin-specific antibodies in the serum that might be correlated with the risk of recurrence. We developed a simple ELISA to measure the quantity of toxin-A and -B-specific antibodies in human serum. The assay was then used to test anti-toxin immune response in healthy controls, in patients with primary CDI and patients with CDI recurrence. The developed assay is simple, reproducible and fast. When using this test in a small clinical trial our results showed a trend toward a higher antibody level in those patients with only one episode of CDI, whereas patients with recurrent CDI had less anti-toxin A or B-specific antibodies in their serum indicating inadequate C. difficile anti-toxin immunity may facilitate recurrent infections. It has already been observed that low antibody levels are associated with recurrent CDI (Bauer et al., 2014). The findings of our clinical trial show a similar trend. Our developed ELISA test could help to conduct further research and it might be helpful in clinical use to detect patients of high risk for CDI recurrence.


The impact of a sepsis performance improvement program in the emergency department: a before-after intervention study.
The latest Surviving Sepsis Campaign guidelines advocate that all hospitals use sepsis performance improvement programs. However, there is a limited evidence about how to structure such programs and what their potential impact is on sepsis management and outcomes in the emergency department (ED). In this study, we evaluated the implementation of a sepsis performance improvement program in the ED including a dedicated sepsis response team and analyzed the management and outcomes of sepsis patients before and after. We conducted a before-after interventional study in the ED of the Amsterdam University Medical Centers, the Netherlands. The sepsis performance improvement program included regular educational meetings, daily audits and weekly feedback, a screening tool, and a dedicated multidisciplinary sepsis response team. We studied all adult patients who presented to the ED with a suspected infection and a Modified Early Warning Score (MEWS) ≥ 3 during their stay. In the postintervention phase, these patients were seen by the sepsis team. Process-related and patient-related outcomes were measured between November 2019 and February 2020 (preintervention) and December 2021-May 2022 (postintervention). A total of 265 patients were included in the primary study, 132 patients preintervention and 133 patients postintervention. The postintervention phase was associated with improvements in nearly all process-related outcomes, such as a shorter time to antibiotics (66 vs. 143 min; p < 0.001), increased number of lactate measurements (72.9 vs. 46.2%; p < 0.001), and improved completeness of documented MEWS scores (85.0 vs. 62.9%; p < 0.001). Except for an improvement in the number of immediate versus delayed ICU admissions (100% immediate vs. 64.3% immediate; p = 0.012), there was no improvement in the other patient-related outcomes such as 28 days mortality (14.3 vs. 9.1%; p = 0.261), during the postintervention phase. Our program stimulated physicians to make timely decisions regarding diagnostics and treatment of sepsis in the ED. Implementing the sepsis performance improvement program was associated with significant improvements in most process-related outcomes but with minimal improvements in patient-related outcomes in our cohort.


Dopamine and food reward: effects of acute tyrosine/phenylalanine depletion on appetite.
It has been suggested that obese individuals over-eat in order to compensate for deficits in the dopaminergic reward system. The current study used acute tyrosine/phenylalanine depletion (ATPD) to investigate the effect of reduced dopamine function on appetite and the reward value of food in healthy volunteers. The compensatory-eating hypothesis would predict an increase in the reward value and consumption of food following depletion by this method. In a double-blind, counterbalanced, crossover study, 17 male participants (mean age=29.2 (SEM=2.7) years; mean body mass index=24.4 (SEM=0.6) kg/m(2)) were administered with a tyrosine/phenylalanine-free mixture (TYR/PHE-free; depletion condition) and a balanced amino acid mixture (BAL; control). Plasma amino acid levels were measured at baseline and peak depletion (300 min). Appetite, willingness to pay for food, liking, desired portion size and ad libitum food intake were also assessed. The TYR/PHE-free mixture was associated with significant decreases in tyrosine, phenylalanine, and the ratio of tyrosine+phenylalanine to the other large neutral amino acids (all p<.001). There were no effects on our measures of willingness to pay for food or liking. However, in the TYR/PHE-free condition, participants reported significantly lower levels of hunger following a fixed-test meal relative to the BAL condition. In conclusion, we found no evidence for compensatory eating following ATPD. Our results also provide support for the role of dopamine in motivational components of eating.


Patterns and Outcomes of the Top of the Basilar Artery Syndrome: The Role of the Posterior Communicating Artery.
Clinical syndromes secondary to infarcts in the distal basilar artery (BA) area have been described as "top of the basilar" (TOB) syndrome. However, in the era of advanced imaging technology, it has been realized that the clinical and imaging features are quite diverse in patients with distal BA occlusion. The aim of the present study was to investigate the patterns and clinical outcomes of TOB assessed with modern images and categorize TOBs accordingly. Additionally, we examined the possible influence of the posterior communicating artery (PcoA) on the patterns of TOB. Patients with distal BA occlusion on magnetic resonance angiography were categorized as TOB-A, and those with multiple lesions in the distal BA territory on diffusion-weighted magnetic resonance imaging as TOB-L. Patients with angiographically and lesion distribution-defined TOB were classified as having TOB-A&L; those with angiographically defined TOB as having TOB-A without TOB-L; and those with lesion distribution-defined TOB as having TOB-L without TOB-A. The PcoA was categorized as "textbook-type" (good P1) and "fetal-type" (absent P1). Factors associated with unfavorable short-term outcomes (modified Rankin Scale 5-6 at discharge), and 1-year and long-term mortalities, were assessed. Of 1,466 patients with ischemic stroke in the posterior circulation who were admitted to Asan Medical Center within 24 h of symptom onset, 124 (8.5%) had TOB, including 45 with TOB-A&L, 44 with TOB-A, and 35 with TOB-L. NIHSS scores (21 [9.5-26] vs. 6 [3-11.5] vs. 6 [3-9]; p < 0.01) and rates of motor deficit (75.6 vs. 54.5 vs. 34.4%; p < 0.01), concomitant pontine lesions (17.8 vs. 25.0 vs. 2.9%; p < 0.01), PcoA presence (44.4 vs. 68.2 vs. 25.7%; p < 0.01), and unfavorable short-term outcomes (62.2 vs. 25.0 vs. 14.3%; p < 0.01) differed significantly in the 3 patient groups. Multivariate analysis showed that textbook-type PcoA was independently associated with a lower frequency of unfavorable short-term outcomes (OR 0.15, 95% CI 0.03-0.70). Reperfusion therapy (hazard ratio [HR] 0.25, 95% CI 0.07-0.89) and the presence of textbook-type PcoA (HR 0.20, 95% CI 0.05-0.90) were associated with a lower 1-year mortality rate after stroke. Patterns and clinical outcomes of TOB vary and are affected by the hemodynamic status of the arterial system, such as BA recanalization and the presence of textbook-type PcoA.


Intracellular free calcium concentrations in isolated pancreatic acini; effects of secretagogues.
Isolated pancreatic acini were loaded with the calcium selective fluorescent indicator, quin-2. Measurements of cellular K+ content and lactic dehydrogenase release indicated that cell viability was not affected by quin-2 loading. The concentration of intracellular free calcium of unstimulated acinar cells was calculated to be 180 +/- 4 nM. When cells suspended in media containing millimolar calcium were exposed to the secretagogues carbachol and cholecystokinin a rapid increase in [Ca2+]i occurred. Both the amplitude and rate of rise of the concentration increase were dose dependent with [Ca2+]i reaching a maximum of 860 +/- 41 nM. The dose-response relationship coincides with the known concentration dependence of the stimulation of amylase release by these agents. In the absence of extracellular calcium, carbachol was still able to elicit a rise in [Ca2+]i. These studies indicate that pancreatic secretagogues induce an increase in [Ca2+]i of acinar cells, both in the presence or absence of extracellular calcium.


Epidemiology of knee injuries in children.
We analyzed 91 consecutive metaphyseal fractures, physeal injuries, and ligament ruptures in children aged 0-14 years. In the younger children, metaphyseal fractures dominated, whereas teenager had ligament rupture associated with low-energy trauma and physeal injury with high-energy trauma.


A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases.
To determine the maximum tolerated dose (MTD) of stereotactic body radiation therapy (SBRT) for liver metastases. A multicenter Phase I clinical trial was conducted. Eligible patients had one to three liver metastases, tumor diameter <6 cm, and adequate liver function. The first cohort received 36 Gy to the planning target volume (PTV) in three fractions (F). Subsequent cohorts received higher doses up to a chosen maximum of 60 Gy/3F. At least 700 mL of normal liver had to receive a total dose <15 Gy. Dose-limiting toxicity (DLT) included acute Grade 3 liver or intestinal toxicity or any acute Grade 4 toxicity. The MTD was exceeded if 2/6 patients in a cohort experienced DLT. Eighteen patients were enrolled (10 male, 8 female): median age, 55 years (range, 26-83 years); most common primary site, colorectal (6 patients); median aggregate gross tumor volume, 18 ml (range, 3-98 ml). Four patients had multiple tumors. No patient experienced a DLT, and dose was escalated to 60 Gy/3F without reaching MTD. Biologically potent doses of SBRT are well tolerated in patients with limited liver metastases. Results of this study form the basis for an ongoing Phase II SBRT study of 60 Gy over three fractions for liver metastases.


Leveraging OpenStreetMap and Multimodal Remote Sensing Data with Joint Deep Learning for Wastewater Treatment Plants Detection.
Humans rely on clean water for their health, well-being, and various socio-economic activities. During the past few years, the COVID-19 pandemic has been a constant reminder of about the importance of hygiene and sanitation for public health. The most common approach to securing clean water supplies for this purpose is via wastewater treatment. To date, an effective method of detecting wastewater treatment plants (WWTP) accurately and automatically via remote sensing is unavailable. In this paper, we provide a solution to this task by proposing a novel joint deep learning (JDL) method that consists of a fine-tuned object detection network and a multi-task residual attention network (RAN). By leveraging OpenStreetMap (OSM) and multimodal remote sensing (RS) data, our JDL method is able to simultaneously tackle two different tasks: land use land cover (LULC) and WWTP classification. Moreover, JDL exploits the complementary effects between these tasks for a performance gain. We train JDL using 4,187 WWTP features and 4,200 LULC samples and validate the performance of the proposed method over a selected area around Stuttgart with 723 WWTP features and 1,200 LULC samples to generate an LULC classification map and a WWTP detection map. Extensive experiments conducted with different comparative methods demonstrate the effectiveness and efficiency of our JDL method in automatic WWTP detection in comparison with single-modality/single-task or traditional survey methods. Moreover, lessons learned pave the way for future works to simultaneously and effectively address multiple large-scale mapping tasks (e.g., both mapping LULC and detecting WWTP) from multimodal RS data via deep learning.


Sangiangols A and B, Two New Dolabellanes from an Indonesian Marine Soft Coral, Anthelia sp.
A new, rare trinor-dolabellane diterpenoid, sangiangol A (1), and one new dolabellane diterpenoid, sangiangol B (2), together with known cembranes and dolabellanes (3-8), were isolated from the ethyl acetate layer of an extract of an Indonesian marine soft coral, Anthelia sp. Compounds 1-8 exhibited moderate cytotoxicity against an NBT-T2 cell line (0.5-10 µg/mL). The structures of the new compounds were determined by analyzing their spectra and a molecular modelling study. A possible biosynthetic pathway for sangiangols A (1) and B (2) is presented. Cytotoxicity requires two epoxide rings or a chlorine atom, as in 4 (stolonidiol) and 5 (clavinflol B).


Barium alginate as a skeleton coating graphene oxide and bentonite-derived composites: Excellent adsorbent based on predictive design for the enhanced adsorption of methylene blue.
The phenomenon that calcium alginate does not exhibit high adsorption capacity as a carrier material has not been reasonably explained or solved. In this paper, a new viewpoint that the orbital energy level of metal ions and the binding degree of the α-l-guluronate and β-d-mannuronate units affect the adsorption performance of the composite was innovatively proposed. Taking barium alginate (BA) as an example, the possibility of replacing calcium alginate is discussed. Barium alginate/graphene oxide (BA/GO) membranes and three-dimensional (3D) barium alginate-bentonite-graphene oxide derived (3D-BA) hydrogels were prepared by vacuum freeze-drying to remove methylene blue. The structure and morphology of the prepared adsorbents were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, thermogravimetry and Fourier transform infrared spectroscopy. The effects of adsorbent dosage, doping ratio, temperature, contact time, pH value and initial dye concentration on the adsorption performance of BA composites were investigated. The adsorption capacities of the BA/GO and 3D-BA materials were 1011.3 and 710.3 mg/g, respectively. The BA/GO membrane exhibited stable filtration performance against high concentrations of dyes. Benefiting from the strong interaction between bentonite, sodium alginate and Ba2+, the 3D-BA hydrogel showed higher thermal stability and better adsorption efficiency than other materials. The Elovich kinetic model and Sips equation can appropriately describe the adsorption process. The results show that barium alginate is a better carrier material than calcium alginate.


Unsymbolized thinking.
Unsymbolized thinking--the experience of an explicit, differentiated thought that does not include the experience of words, images, or any other symbols--is a frequently occurring yet little known phenomenon. Unsymbolized thinking is a distinct phenomenon, not merely, for example, an incompletely formed inner speech or a vague image, and is one of the five most common features of inner experience (the other four: inner speech, inner seeing, feelings, and sensory awareness). Despite its high frequency, many people, including many professional students of consciousness, believe that such an experience is impossible. However, because the existence of unsymbolized thinking indicates that much experienced thinking takes place without any experience of words or other symbols, acknowledging the existence of unsymbolized thinking may have substantial theoretical import.


Characterization and optimization of fluorescein isothiocyanate labeling of humanized h2E2 anti-cocaine mAb.
Fluorescein isothiocyanate (FITC) is widely used to fluorescently label reactive lysine residues on proteins, including antibodies. The rate and extent of labeling varies with reaction conditions, concentration of label, and the concentration and nature of the protein. Fluorescently labeled proteins are very useful, and one use for FITC labeled mAbs is development of assays to measure anti-mAb antibodies produced in vivo during treatment with antibody therapeutics. Our laboratory has developed a humanized anti-cocaine mAb (h2E2) intended for the treatment of cocaine use disorders. Thus, a well characterized FITC labeled h2E2 mAb is needed to quantitate possible anti-mAb antibodies. The time course of labeling and the relative incorporation of FITC into the heavy and light chains, as well as into the Fab and Fc portions of the mAb, was assessed. A novel use of differential scanning fluorimetry in the absence of any extrinsic fluorophore was developed and demonstrated to be capable of measuring antigen (cocaine) binding. In addition, the effect of increasing degrees of labeling by FITC on the thermodynamic parameters driving the binding of cocaine to the mAb was assessed via isothermal titration calorimetry (ITC). This binding technique, unlike others developed recently to measure cocaine binding, is not dependent on, or subject to interference by, the absorbance or fluorescence of the incorporated FITC label. The methods and results reported herein guide the optimization of FITC labeling needed for anti-mAb assays and other assays important for the development of therapeutic mAbs, which are some of the most specific and clinically useful drugs available.


Structural and dynamic views of GM1 ganglioside.
The ganglioside GM1 mediates various physiological and pathological processes mainly through the formation of GM1 clusters on cell surfaces. Therefore, detailed characterization of conformational properties of the glycan moiety of GM1 and the structures and interactions of this glycosphingolipid in membrane environments is necessary for better understanding of the clustering-coupled functional promotion. Nuclear magnetic resonance (NMR) spectroscopy has provided conformational information of GM1 in solution as well as in membrane-like environments. Recently, sophisticated paramagnetism-assisted NMR approaches combined with molecular dynamics simulations have enabled the quantitative exploration of conformational spaces of a series of gangliosides, including GM1, taking into account their minor conformations. NMR techniques have also been successfully applied to investigations of the dynamic interactions of GM1 clusters with amyloidogenic proteins such as amyloid β and α-synuclein associated with neurodegenerative disorders. Further integration of experimental and computational approaches will open up new possibilities to provide structural views of the more complicated heterogeneous systems exemplified by microdomains involving GM1.


Perceptual association enhances intersensory temporal precision.
The brain is able to extract associative regularities between stimuli and readjust the perceived timing of correlated sensory signals. In order to elucidate whether these two mechanisms interact with each other or not, we exposed participants to two different visual stimuli (a circle and a triangle) that appeared continuously and unpredictably, for 5min. While the circle always preceded the tone for 700ms, the triangle did not. Yet, the triangle could appear, by chance, before and after the tone, and between the circle and the tone. In two different test blocks, conducted before and after the 5-min exposure phase, participants performed simultaneity judgments regarding one of the visual stimuli (the circle or the triangle) and the exposed tone presented at different stimulus onset asynchronies. The results revealed that the precision at judging the temporal relation between the 'associated figure' (the circle) and the tone increased significantly after the 5-min exposure. This effect was not observed for the non-associated figure (the triangle) and occurred even when participants reported to be unaware of any association between the stimuli presented. This pattern of results indicates that the perceptual association between sensory signals can influence their subjective temporal processing.


The protein tyrosine phosphatase CD45 is required for interleukin 6 signaling in U266 myeloma cells.
The objective of this study was to examine whether CD45 mediates interleukin 6 (IL-6) signaling in human multiple myeloma (MM) cells. We chose U266 MM cells as a study model and isolated cells into CD45+ and CD45- subpopulations. CD45+ and CD45- U266 cells were cocultured with bone marrow stromal cells (BMSCs). IL-6-induced proliferation in CD45+ U266 cells was inhibited by vanadate, a potent protein tyrosine phosphatase inhibitor. However, IL-6-independent CD45- U266 cell growth was not affected by vanadate. CD45+ U266 cells, but not CD45- U266 cells, have the capability of cell adhesion concomitant with actin filament polymerization at the adherent cells. Adhesion of CD45+ U266 cells to BMSCs was impaired by vanadate. We clarified the signaling differences between CD45+ and CD45- U266 cells in response to IL-6. In CD45+ U266 cells, IL-6 increased tyrosine phosphorylation of gp130 and STAT3 and stimulated the level of Mcl-1 protein expression. An association between CD45 and the Src-family protein tyrosine kinase, Lyn, was maintained in the presence of IL-6; the formation of the CD45/Lyn complex was impaired by vanadate. Additionally, IL-6-induced Lyn kinase activity in CD45+ U266 cells was increased by the cross-linking of CD45, and this increase was due to the dephosphorylation of Tyr507 at Lyn. In conclusion, IL-6-dependent MM cells require CD45 to initiate IL-6 signaling and to maintain Lyn kinase activity, both of which are essential for cell proliferation and cell adhesion.


Embryo apoptosis may be a significant contributing factor in addition to aneuploidy inhibiting live deliveries once a woman reaches age 45.
To determine the relative role of aneuploidy vs embryo apoptosis as the etiologic factor of poor pregnancy rates with advancing age. A retrospective review of chemical vs clinical vs live delivery pregnancy rates in women aged 40-42, 43-45, and > or = 45 years is reported. The data were further stratified according to oocyte reserve based on day 3 serum follicle-stimulating hormone (FSH) < or = 11 mIU/ml vs >12 mIU/ml. For women aged 40-42 years there were no differences in live delivery pregnancy rates in women with normal vs decreased egg reserve (DOR). There were no differences in live delivery pregnancy rates in women aged 40-42 years vs 43-44 years with normal oocyte reserve; however despite no differences in clinical pregnancy rates in women aged 43-44 years with normal vs DOR, the live delivery pregnancy rates were markedly lower in the group with DOR. In contrast, there were very low chemical pregnancy rates in women aged > or = 45 years. As seen in younger women, there does not appear to be any increased risk of meiosis errors in women aged 40-42 years with DOR compared to women of the same age with normal reserve. Low pregnancy rates in women aged 43-44 years with DOR is related to meiosis errors. In contrast the very low chemical pregnancy rates found in women aged > or = 45 years despite embryo transfer (ET) suggest embryo apoptosis is mostly responsible for poor pregnancy rates in this very advanced reproductive age group.


Impact of obstructive sleep apnea on aortic disease occurrence: A meta-analysis.
Aortic diseases, mainly including aortic dilatation, aortic aneurysm (AA) and aortic dissection (AD), have high morbidity and mortality. Many studies have suggested that obstructive sleep apnea (OSA) acts as a candidate risk factor for aortic diseases. Thus, we performed a meta-analysis to explore comprehensively the effect of OSA on the risk of aortic disease occurrence. We searched PubMed, Embase and Cochrane Library databases from inception to February 2022 to identify studies investigating the association between OSA and aortic diameter dilatation, the prevalence of OSA in individuals with or without AA/AD and the incidence of AA/AD in individuals with or without OSA. The Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) were respectively used to evaluate the quality of the included cohort and cross-sectional studies. A random or fixed effect model was used to generate pooled effects according to interstudy heterogeneity. Sensitivity analyses were performed to test the robustness of the results. We identified 10 observational publications with 214,127 participants in this meta-analysis. OSA was significantly associated with increased aortic diameter (WMD = 1.46, 95% CI, 1.10-1.83, p < 0.001). OSA prevalence was higher in patients with AA/AD compared to their counterparts without AA/AD (OR = 1.90, 95% CI, 1.30-2.76, p = 0.001). No significant difference in the incidence of AA/AD was observed in individuals with or without OSA (RR = 0.85, 95% CI, 0.62-1.16, p = 0.307). Sensitivity analyses did not modify these results. This meta-analysis suggests that OSA is associated with aortic diameter dilatation but does not affect AA/AD occurrence.


[Peritoneal lavage for the early diagnosis of intraabdominal injuries in blunt traumas. Personal results].
Peritoneal lavage has been found to be a simple, uncomplicated method of examination providing much information in cases of blunt abdominal trauma. It permits decision to start surgical procedures in adequate trauma at short notice and is performed routinely at our clinic in patients suffering from craniocerebral trauma, even in the absence of clinical symptoms of intraabdominal lesions. The advantage of the method is little need of time, personnel and surgery as well as the fact that it can be applied also by relatively unskilled doctors and does not really require a specialist. The precision of the method is high. An important factor for successful application is the use of sufficient quantities of a lavage solution.


Input organization and plasticity of hypocretin neurons: possible clues to obesity's association with insomnia.
The lateral hypothalamic hypocretin (also called orexin) neurons have emerged as instrumental in triggering arousal and regulating energy metabolism. The lack of hypocretin signaling is the cause of narcolepsy while elevated hypocretin levels induce arousal, elevated food intake, and adiposity. Here, we report an unorthodox synaptic organization on the hypocretin neurons in which excitatory synaptic currents and asymmetric synapses exert control on the cell bodies of these long-projective neurons with minimal inhibitory input. Overnight food deprivation promotes the formation of more excitatory synapses and synaptic currents onto hypocretin cells; this is reversed by re-feeding and blocked by leptin administration. This unique wiring and acute stress-induced plasticity of the hypocretin neurons correlates well with their being involved in the control of arousal and alertness that are so vital to survival, but this circuitry may also be an underlying cause of insomnia and associated metabolic disturbances, including obesity.


Some characteristics of the in vivo antitumor immunity exhibited by mice cured of a large MOPC-315 tumor by a low dose of melphalan.
BALB/c mice cured of a large MOPC-315 or MOPC-104E plasmacytoma following treatment with a low dose (2.5 mg/kg) of melphalan (L-PAM) were resistant to challenge with the other plasmacytoma but to a much lesser extent than to challenge with the autochthonous plasmacytoma. The resistance of the L-PAM-cured MOPC-315-tumor bearers to challenge with MOPC-104E tumor cells was increased when the MOPC-104E tumor cells were admixed with MOPC-315 tumor cells prior to their inoculation. This enhanced resistance to MOPC-104E cells was due to elimination of the MOPC-104E tumor cells through an innocent bystander killing effect since it did not render the mice more resistant to a subsequent challenge with MOPC-104E tumor cells alone. Administration of carrageenan to L-PAM-cured MOPC-315-tumor bearers 1 day after the challenge with the mixture of MOPC-104E and MOPC-315 tumor cells drastically reduced the ability of the mice to resist the tumor challenge. All of the tumors that developed in such mice were of MOPC-104E origin only (as judged by the binding specificity of the myeloma proteins secreted by the tumor cells as well as that present on their surface) even though (a) the tumor inoculum used consisted of up to 10-fold more MOPC-315 than MOPC-104E tumor cells and (b) the MOPC-315 tumor cells divide more rapidly. The same protocol of carrageenan treatment did not reduce the ability of normal BALB/c mice to develop in vivo a primary cell-mediated cytotoxic response nor a primary antibody response indicating that it has no effect on the initiation of an immune response. Therefore, it is conceivable that carrageenan treatment reduced the ability of L-PAM-cured MOPC-315-tumor bearers to reject a challenge with MOPC-315 and MOPC-104E tumor cells by interfering at the effector stage. The ability of the L-PAM-cured MOPC-315-tumor bearers to reject the MOPC-315 cells present in the challenge mixture was reduced when the mice were treated with anti-Thy 1.2 antibody but not with carrageenan, indicating that T-cells independent from carrageenan-sensitive effector cells are required for the rejection of the MOPC-315 tumor cells. Thus, at least two different effector mechanisms participate in the rejection of a challenge composed of MOPC-315 and MOPC-104E tumor cells by L-PAM-cured MOPC-315-tumor bearers.(ABSTRACT TRUNCATED AT 400 WORDS)


Clinical proteomics stretch goals: EuPA 2012 roundtable report.
The field of clinical proteomics is faced with multiple challenges which need to be overcome in order to improve our understanding of human diseases and provide management solutions. Researchers interested in clinical proteomics assembled for a roundtable discussion at the European Association for Proteomics (EuPA) conference held in Glasgow in July 2012, to discuss these challenges and highlight the key areas for successful clinical proteomic studies. This report shares topics of discussion and the resulting stretch goals of clinical proteomics for researchers to strive towards.


Catecholamines in critical care.
Catecholamines (norepinephrine, epinephrine, and dopamine) are released into circulation in response to stress and injury and as part of the body's attempt at vasoregulation in response to circulatory failure. Norepinephrine is released from sympathetic nerve terminal, and epinephrine and dopamine are released from the adrenal medulla. Plasma levels of these catecholamines have been reported to be elevated in various clinical settings: congestive heart failure, myocardial infarction, cardiopulmonary bypass, diabetic ketoacidosis, hypoxia, hemorrhage, and septic shock. These amines have both beneficial and detrimental effects on survival. Both norepinephrine and dopamine are often employed in the critically ill to selectively increase cardiocerebral and renal blood flow, respectively.


Conjunctivorhinostomy. A study of 21 cases.
The results from 21 cases (in 19 patients) of conjunctivorhinostomy were evaluated. Twelve cases were successful. The operative technique and especially the need for meticulous post-operative care is discussed. A close post-operative follow-up is mandatory, since most of the failures were caused by loss of the Jones' tube.


Reimplantation of oesophageal bronchus following a type III oesophageal atresia repair.
Oesophageal atresia can be associated with communicating bronchopulmonary foregut malformations, the most common being the oesophageal bronchus. Lung resection may be mandatory, but conservative treatment correcting the abnormal airway has been proposed, raising the difficult issue of perioperative ventilatory support. The authors report a case of successful reimplantation of oesophageal bronchus revealed after surgical cure of an oesophageal atresia with tracheo-oesophageal fistula.


Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
To define the prevalence of lower urinary tract symptoms (LUTS) and outcomes for sexual function after endorectal pull-through (EPT) for Hirschsprung disease (HD) compared to controls. To date, similar controlled studies are lacking. Patients aged ≥4years (n=123) operated on for HD at our center between 1987 and 2011 were invited to answer questionnaires on LUTS and sexual function (aged ≥16years). Patients with an intellectual disability and patients with a definitive endostomy were excluded. Patients were matched to three controls and also invited to a clinical follow-up for urological investigations including urine flow measurement, renal tract ultrasound, and urinalysis. Altogether, 59 responses concerning LUTS and 24 responses concerning sexual functions were analyzed. No significant differences were demonstrated in the overall prevalence of LUTS between patients (67%) and controls (80%), nor in the prevalence of frequent LUTS (14% vs. 16%; P=NS for both). One patient (2%) had a urethral stricture after laparotomy-assisted EPT. Male patients reported sexual satisfaction and erectile function similar to controls (P>0.10). Female patients were currently less in stable relationships compared to controls (25% vs. 83%, P=0.005). Our results support the safety of EPT in patients with HD with regard to preservation of the integrity and functioning of the genitourinary tract.


Sirolimus-eluting and paclitaxel-eluting stents for the treatment of coronary bifurcations.
The aim of the study was to compare the outcomes of sirolimus-eluting (SES) and paclitaxel-eluting (PES) stent implantation in coronary bifurcations treated with either a 1-stent or 2-stent strategy. The study used a retrospective cohort analysis of consecutive de novo bifurcations, excluding left main, treated with SES or PES between April 2003 and June 2005. We identified 170 bifurcations in 161 patients treated with SES and 119 bifurcations in 112 patients treated with PES. During a median follow-up of 1,061 days (interquartile range 814-1,314), 43 patients (26.7%) in the SES group and 28 (25.0%) in the PES group had a major adverse cardiac event (P = .78). The angiographic restenosis rate per bifurcation was 20.9% and 25.9%, respectively (P = .41). There was no difference overall in the occurrence of target lesion revascularization (TLR) per bifurcation, 22 with SES (12.9%) and 18 with PES (15.1%), P = .61. The TLR rate was similar for SES and PES in bifurcations treated with 1 stent (6.7% vs 11.4%, P = .40) and in bifurcations treated with both branch stenting (20.0% vs 20.4%, P =1.0). In this cohort, the long-term clinical outcomes appear similar overall between SES and PES in the treatment of coronary bifurcations irrespective of whether a 1-stent or 2-stent strategy was used.


Fas-mediated apoptosis of hepatic cells.
While the fas/fas ligand system has been extensively investigated in immuno-competent cells, the place of this system in the physiology and pathophysiology of liver cells remains to be clarified. Although we know that fas is present at the surface of hepatocytes--the main hepatic cells--the role of this membranous protein in physiological conditions is not yet elucidated. However it is the localization of fas on the plasma membrane of hepatocytes which explains why these cells are mainly destroyed by apoptosis--in a picture resembling human fulminant hepatitis--when mice are administered with anti-fas antibodies or fas ligand. It is also established that fas is surexpressed in some human chronic liver diseases, such as those induced by hepatitis B or C virus, a situation which could explain the pathogenesis of some liver lesions occurring during these diseases, such as the apoptosis of hepatocytes in piecemeal necrosis. Finally the fact that caspases, a group of cysteine proteases activated in fas-induced apoptosis, opens the way to inhibition of these enzymes by synthetic peptides and to prevent and treat hepatocyte apoptosis. Demonstration of this possibility has been recently reported in animals presenting fulminant hepatitis induced by anti-fas antibodies.


Relation of HVJ (Sendai virus) production to cell growth phase in persistently infected mouse 3T3 cells.
Using 3T3 mouse fibroblasts persistently infected with temperature-sensitive HVJ (3T3-HVJ pi), the relationship between production of HVJ and cell growth was investigated. In these cells the highest virus release into the culture media occurred from 24 to 48 hours after seeding. The release gradually decreased as the cultures approached confluency, at which time it was reduced below 1-2 per cent of that on day 2 in parallel with the decrease of both cellular DNA and RNA synthesis rates. Comparative examination in growing and resting HVJ carrier 3T3 cells showed that amounts of nucleocapsids and rate of viral structural protein synthesis in the latter phase was reduced to 4-5 per cent of those in the former phase. In addition, viral replication and transcription rates in the resting phase were found to be suppressed to 8-9 per cent of levels detected in the growing phase. These results suggest that the reduced virus production in the resting HVJ carrier cells may be mainly due to the suppression of viral RNA synthesis.


Measurement of plasma glycoside level following pengitoxin administration.
16-Acetyl-gitoxin, the cardioactive metabolite of pengitoxin, was estimated by the 86Rb uptake technique. In 70 consecutive patients taking an oral maintenance dose of pengitoxin 0.4 mg (Pentagit), the mean plasma concentration was 20.8 +/- 6.7 ng/ml. Toxic signs were not observed up to plasma levels of 40 ng per ml.


Using the Nursing Interventions Classification to identify nursing interventions in free-text nursing documentation in adult psychiatric outpatient care setting.
To identify and describe nursing interventions in patient documentation in adult psychiatric outpatient setting and to explore the potential for using the Nursing Interventions Classification in documentation in this setting. Documentation is an important part of nurses' work, and in the psychiatric outpatient care setting, it can be time-consuming. Only very few research reports are available on nursing documentation in this care setting. A qualitative analysis of secondary data consisting of nursing documentation for 79 patients in four outpatient units (years 2016-2017). The data consisted of 1,150 free-text entries describing a contact or an attempted contact with 79 patients, their family members or supporting networks and 17 nursing care summaries. Deductive and inductive content analysis was used. SRQR guideline was used for reporting. We identified 71 different nursing interventions, 64 of which are described in the Nursing Interventions Classification. Surveillance and Care Coordination were the most common interventions. The analysis revealed two perspectives which challenge the use of the classification: the problem of overlapping interventions and the difficulty of naming group-based interventions. There is an urgent need to improve patient documentation in the adult psychiatric outpatient care setting, and standardised nursing terminologies such as the Nursing Interventions Classification could be a solution to this. However, the problems of overlapping interventions and naming group-based interventions suggest that the classification needs to be further developed before it can fully support the systematic documentation of nursing interventions in the psychiatric outpatient care setting. This study describes possibilities of using a systematic nursing language to describe the interventions nurses use in the adult psychiatric outpatient setting. It also describes problems in the current free text-based documentation.


Computed tomographic evaluation of the solitary nonpulmonic nodule.
CT has demonstrated its usefulness in the evaluation of the known solitary pulmonic nodule, however its application to the solitary nonpulmonic nodule has not been emphasized. Three cases illustrate the applicability of CT in localization of a nodule. The importance of obtaining bone windows in these cases is stressed. When comparison plain films and routine techniques are unsatisfactory, CT is valuable in providing a noninvasive means of diagnosis and patient reassurance.


Hemispace and information control by the two cerebral hemispheres: which interaction?
Two experiments employing subjects with different experience in tactile discrimination (blind and seeing subjects) were carried out to investigate the effect of the space location of stimuli on the information processing activity of the two cerebral hemispheres. An angle discrimination task that yields a right hemisphere superiority was used. In Experiment 1, seeing subjects showed a general superiority of the left hand (right hemisphere) which was more pronounced in the left hemispace with respect to the central and the right hemispace performance. In Experiment 2, blind subjects showed a significant superiority of the left hand in the central and in the left hemispace and no difference between the two hands in the right hemispace. In both experiments hemispace differences were due only to the modification of the left hand (right hemisphere) performance. These results suggest that the hemispace control by the contralateral hemisphere interacts only with the activity of the hemisphere dominant in the information processing.


General practitioner deprivation payments in Northern Ireland: is the current system equitable?
The allocation of General practitioners deprivation payments has been a contentious issue since it was first proposed. This paper examines the method of allocation of such payments in Northern Ireland. A more equitable system would be based on enumeration districts, have a lower Jarman score and a closer relationship between Jarman score and remuneration. Unlike other parts of the UK these changes are now possible in Northern Ireland and should be implemented.


Optimum dietary sources and levels of selenium improve growth, antioxidant status, and disease resistance: re-evaluation in a farmed fish species, Nile tilapia (Oreochromis niloticus).
The objective of this study was to investigate the effects of sources and levels of selenium (Se) on juvenile Nile tilapia (Oreochromis niloticus). A completely randomized design involving a 2 × 3 factorial arrangement of treatments was used in this study. Organic Se (L-selenomethionine; SeMet) and inorganic Se (sodium selenite; Na2SeO3) were each added to the basal diet at 1, 3 and 5 mg Se/kg. The basal diet, without Se supplementation, was used as a control. There was a total of 7 experimental diets, and each was fed in triplicate to groups of fish with an initial average body weight of 13.5 g for 8 weeks. The results showed that growth performance was significantly affected by dietary sources and levels of Se (P < 0.05). Fish fed diets supplemented with SeMet of 1.0 mg Se/kg resulted in higher growth performance compared to basal diet (P < 0.05), but Na2SeO3 supplementation did not affect growth. The feed conversion ratio was significantly decreased as dietary sources of SeMet (P < 0.05). Interestingly, fish fed diets supplemented with both forms of Se had lower cholesterol levels than those fed the basal diet (P < 0.05). Moreover, dietary sources and levels of Se significantly increased (P < 0.05) the antioxidant enzyme activities such as lysozyme, catalase, myeloperoxidase, superoxide dismutase and glutathione peroxidase. Dietary sources and levels of Se significantly could enhance the Nile tilapia resistance against Streptococcusagalactiae infection (P < 0.05). Overall, it can be concluded that the inclusion level of 1.0 mg Se/kg of organic Se in the diet is suggested to be the optimal level for the growth performance and immune response of Nile tilapia. Therefore, dietary supplementation with Se is useful for improving growth, antioxidant status, immune response, and disease resistance.


Autogenous reversed vein bypass for lower extremity ischemia in patients with absent or inadequate greater saphenous vein.
This report has presented the results of 329 reversed vein bypasses performed for lower extremity ischemia over a 6 3/4 year period. One hundred eighty-nine bypasses were formed from intact ipsilateral greater saphenous veins of adequate size and length. One hundred forty bypasses were formed in patients in whom the ipsilateral greater saphenous vein was absent or of inadequate size or length to complete the bypass. The grafts in these patients were accomplished using a variety of techniques including distal graft origin, use of arm veins and lesser saphenous veins, and use of vein splicing. The patency rates of these grafts were equivalent to those achieved using adequate intact ipsilateral greater saphenous vein. In view of these results, we conclude that the absence of a greater saphenous vein does not preclude successful autogenous lower extremity vein bypass and that prosthetic bypass is rarely justified.


Kinetics of enzymes subject to very strong product inhibition: analysis using simplified integrated rate equations and average velocities.
Enzymes which catalyze energetically unfavorable reactions in the physiological direction are likely to be strongly inhibited by the reaction products. (Some energetically favorable reactions may also display strong "product inhibition" when assayed in the reverse direction.) In some cases, the inhibition caused by an accumulating product is so potent that true initial velocities cannot be directly determined using conventional assay methods. Continuous removal of the inhibitory product may be mitigated against by the nature of the assay or the unavailability of the appropriate coupling enzyme. It can be shown that if (a) only one inhibitory product is allowed to accumulate and (b) the substrate concentrations remain essentially constant over the assay period (i.e. Kproduct less than or equal to 10(-2)Ksubstrate, so that the decreasing reaction rate stems only from progressive product inhibition), then plots of reciprocal average (apparent) velocity (i.e. 1/v = t/[P]) versus [P] are linear and extrapolate to 1/v0, the reciprocal of the initial uninhibited velocity at the fixed substrate concentrations. Intercept replots give the usual initial velocity reciprocal plot patterns and permit Vmax and the substrate Km's to be determined. Slope replots are diagnostic of the type of inhibition exerted by the accumulating product and permit the inhibition constants to be determined. If all the appropriate coupling enzymes are available, some kinetic mechanisms can be diagnosed using data derived from the reaction progress curves in the presence of one accumulating product at a time.


Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity.
Mice homozygous for the fat mutation develop obesity and hyperglycaemia that can be suppressed by treatment with exogenous insulin. The fat mutation maps to mouse chromosome 8, very close to the gene for carboxypeptidase E (Cpe), which encodes an enzyme (CPE) that processes prohormone intermediates such as proinsulin. We now demonstrate a defect in proinsulin processing associated with the virtual absence of CPE activity in extracts of fat/fat pancreatic islets and pituitaries. A single Ser202Pro mutation distinguishes the mutant Cpe allele, and abolishes enzymatic activity in vitro. Thus, the fat mutation represents the first demonstration of an obesity-diabetes syndrome elicited by a genetic defect in a prohormone processing pathway.


A critical review of piezoelectric ultrasonic transducers for ultrasonic-assisted precision machining.
Piezoelectric ultrasonic-assisted precision machining (PUAPM) technology is considered to be an efficient and environmentally friendly machining strategy by virtue of cutting force reduction, ductile cutting promotion, tool wear and machining noise reduction. Piezoelectric ultrasonic transducer (PUT) provides ultrasonic energy for PUAPM system, which is the core component to ensure the normal operation of the system. PUTs for PUAPM devices have emerged endlessly in recent decades and have been successfully applied in many fields, such as MEMS, biomedicine, optoelectronics, aerospace, etc. However, there is no comprehensive classification and analysis of the basic configurations, excitation principles, typical structures, performance analyses and control strategies for PUT. This work gives a critical review of research on PUT in recent years, especially the structural optimization, application expansion and ultrasonic energy stabilization in PUAPM. The influence mechanism of excitation mode, modal type, modal combination, horn structure and ceramic arrangement on the optimization of PUT structure is summarized. The improvement effect and mechanism of PUT vibration dimension, amplitude, frequency and structural characteristics on surface roughness, surface texture and cutting force are discussed. In addition, the causes of PUT amplitude fluctuation, and the influence of sensing and control methods on PUT amplitude regulation and system integration are analyzed. This review will help in understanding the current development and diversified applications of PUT and will promote the application of ultrasonic technology in more fields.


The discovery of acylated beta-amino acids as potent and orally bioavailable VLA-4 antagonists.
Acylated beta-amino acids are described as potent, specific and orally bioavailable antagonists of VLA-4. The initial lead was identified from a combinatorial library. Subsequent optimization using a traditional medicinal chemistry approach led to significant improvement in potency (up to 8-fold) while maintaining good pharmacokinetic properties.


Interactive distance learning for orthodontic residents: utilization and acceptability.
Sharing resources through distance education has been proposed as 1 way to deal with a lack of full-time faculty in orthodontic residency programs. To keep distance education for orthodontic residents as cost-effective as possible while retaining interaction, we developed a "blended" interactive distance learning approach that combines observation of Web-based seminars with live postseminar discussions. For the 2009-2010 academic year, a grant from the American Association of Orthodontists opened access to the blended learning experience to all orthodontic programs in the United States and Canada. The specific aims of this project were to (1) measure programmatic interest in using blended distance learning, (2) determine resident and faculty interest, (3) determine the seminars' perceived usefulness, and (4) elicit feedback regarding future use. Participants in this project were expected to (1) read all assigned articles before viewing a recorded seminar, (2) watch a 1 to 1.5 hour recording of an actual interactive seminar on a Web site, and (3) participate in a 30-minute follow-up discussion immediately after watching the recorded seminar either with a faculty member at the participating institution or via a videoconference with the leader of the Web-based seminar. The residents and faculty then completed surveys about the experience. Half (52%) of the 63 orthodontic programs in the United States fully participated in this project. The blended approach to distance learning was judged to be effective and enjoyable; faculty members were somewhat more enthusiastic about the experience than were residents. Most residents were not adequately prepared for the seminars (only 14% read all preparatory articles in depth); this impacted their perception of the effectiveness and enjoyability of the experience (P = 0.0016). Prepared residents reported a greater ability to learn from the seminars (P = 0.0035) than those who did not read, and also indicated that they were more likely to use the seminars again (P = 0.0018). Despite feedback regarding the need for technologic improvements of the recorded seminars, such as better editing, more frequent slides, quicker pace, and improved sound quality, most residents and faculty agreed that they would like to use this approach to distance learning again. Blended distance learning is an acceptable method of instruction that allows residents to access various experts, supplement traditional instructor-led training, and ease the strain of current faculty shortages. The content of the recorded seminars needs to remain evidence-based, and some technologic aspects of the recordings should be improved.


Nebulized versus invasively delivered surfactant therapy for neonatal respiratory distress syndrome: A systematic review and meta-analysis.
Pulmonary surfactant (PS) is commonly used for the treatment of neonatal respiratory distress syndrome (NRDS), several randomized controlled trials (RCTs) have evaluated the role of nebulized versus invasively delivered PS, yet the results remained inconsistent. Therefore, we aimed to conduct this meta-analysis to evaluate the effects and safety of nebulized versus invasively delivered PS in the treatment of NRDS. We searched PubMed et al databases from inception date to May 15, 2020 for RCTs that compared nebulized vs invasively delivered PS. Two authors independently screened the studies and extracted data from the published articles. Summary odd ratios (OR) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated for each outcome by means of fixed- or random-effects model. Two RCTs with a total of 95 preterm neonates were identified, with 48 neonates received PS nebulization and 47 neonates undergone invasive PS administration. There was no significant difference in the SpO2 level (MD = -0.44, 95% CI -6.01 to 5.12) and the A/APaO2 level (MD = 0.01, 95% CI -0.02 to 0.05) 1 hour after treatment among 2 groups. But the duration of mechanical ventilation in the nebulization groups was significantly less than that of invasive group (MD = -30.70, 95% CI -41.45 to 19.95). Given the limited evidences, the effects and safety of nebulized versus invasively delivered PS still need further verification.


Differences in salivary secretion and epidermal growth factor concentrations in mild reflux esophagitis and non-erosive reflux disease.
Sex differences in salivary secretion have been reported among healthy subjects. In the present study, salivary secretion and salivary epidermal growth factor (EGF) concentrations were investigated in mild reflux esophagitis patients, non-erosive reflux disease (NERD) patients, and healthy controls by matching the sex ratio. Thirty-three (male:female = 11:22) patients with NERD, 33 (11:22) with mild reflux esophagitis, and 33 (11:22) healthy controls were recruited for this case-control study. Salivary secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount of saliva secretion, salivary pH, and salivary pH after acid loading as an index of the acid-buffering capacity were measured. Salivary EGF concentrations were measured by ELISA. No significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between the mild reflux esophagitis and NERD groups. However, the amount of saliva secretion and the acid-buffering capacity in the mild reflux esophagitis group and the amount of saliva secretion, salivary pH, and the acid-buffering capacity in the NERD group were significantly lower than those in the healthy control group. No significant differences were noted in salivary EGF concentrations between the mild reflux esophagitis and NERD groups. After matching the sex ratio, the saliva secretion was significantly lower in patients with mild reflux esophagitis and NERD than in healthy controls. However, no significant differences were observed in the amount of saliva secretion or salivary EGF concentrations between both groups.


Preliminary results of consolidation chemotherapy following concurrent chemoradiation after radical surgery in high-risk early-stage carcinoma of the uterine cervix.
To evaluate the efficacy and toxicity of consolidation chemotherapy after concurrent chemoradiation (CCRT) with 5-fluorouracil (5-FU) and cisplatin in the treatment of high-risk, early stage cervical carcinoma after radical surgery. Women with clinical stage IB and IIA cervical carcinoma, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes, positive margins, parametrial involvement, or all three, were divided into either a CCRT alone group or a consolidation chemotherapy after CCRT group. Three cycles of chemotherapy were given to the CCRT alone group, and six cycles to the consolidation chemotherapy group. Women in each group received 50.4 Gy external radiation in 28 fractions to a standard pelvic field. Chemotherapy consisted of cisplatin 60 mg/m2 (X 1) and 5-FU 1000 mg/m2/d (X 5) every 3 weeks, with the first and second cycles given concurrent with radiation. Survival and toxicity were compared between the two groups. Forty women were evaluable (25 in the CCRT alone group and 15 in the consolidation chemotherapy group). The estimated 2-year progression-free survival was 87.7% in the CCRT alone group and 67.0% in the consolidation chemotherapy group. The estimated 2-year overall survival was 95.8% in the CCRT alone group and 100% in the consolidation chemotherapy group. However, no significant differences were found in progression-free and overall survival in the two groups (P = 0.17 and P = 0.29, respectively). Grade 2 or higher leukopenia and neutropenia were significantly more frequent in the consolidation chemotherapy group than in the CCRT alone group (P = 0.02 and P < 0.01, respectively). Although the sample size was small, and this study was not randomised, these results suggest that consolidation chemotherapy may not improve survival. Rather, it may increase haematologic toxicities for women with high-risk, early stage cervical carcinoma who undergo radical surgery followed by CCRT.


Phosphorylation of Serine 402 Regulates RacGAP Protein Activity of FilGAP Protein.
FilGAP is a Rho GTPase-activating protein (GAP) that specifically regulates Rac. FilGAP is phosphorylated by ROCK, and this phosphorylation stimulates its RacGAP activity. However, it is unclear how phosphorylation regulates cellular functions and localization of FilGAP. We found that non-phosphorylatable FilGAP (ST/A) mutant is predominantly localized to the cytoskeleton along actin filaments and partially co-localized with vinculin around cell periphery, whereas phosphomimetic FilGAP (ST/D) mutant is diffusely cytoplasmic. Moreover, phosphorylated FilGAP detected by Phos-tag is also mainly localized in the cytoplasm. Of the six potential phosphorylation sites in FilGAP tested, only mutation of serine 402 to alanine (S402A) resulted in decreased cell spreading on fibronectin. FilGAP phosphorylated at Ser-402 is localized to the cytoplasm but not at the cytoskeleton. Although Ser-402 is highly phosphorylated in serum-starved quiescent cells, dephosphorylation of Ser-402 is accompanied with the cell spreading on fibronectin. Treatment of the cells expressing wild-type FilGAP with calyculin A, a Ser/Thr phosphatase inhibitor, suppressed cell spreading on fibronectin, whereas cells transfected with FilGAP S402A mutant were not affected by calyculin A. Expression of constitutively activate Arf6 Q67L mutant stimulated membrane blebbing activity of both non-phosphorylatable (ST/A) and phosphomimetic (ST/D) FilGAP mutants. Conversely, depletion of endogenous Arf6 suppressed membrane blebbing induced by FilGAP (ST/A) and (ST/D) mutants. Our study suggests that Arf6 and phosphorylation of FilGAP may regulate FilGAP, and phosphorylation of Ser-402 may play a role in the regulation of cell spreading on fibronectin.


Simultaneous use of laparoscopy and endoscopy for minimally invasive resection of gastric subepithelial masses - analysis of 93 interventions.
Subepithelial gastric tumors are common findings during upper gastrointestinal endoscopy. Tumor resection is mostly done laparoscopically, but there is still discussion concerning the size of lesion for which the treatment may be minimally invasive; additionally there is very little data available concerning patient outcome after minor access surgery. Clinicopathologic features and survival data of 93 consecutive patients undergoing a combined laparoscopic-endoscopic approach for gastric submucosal tumors were prospectively analyzed. Analysis included preoperative diagnostic work-up, perioperative data, and postoperative complications. Follow-up was carried out for patients with GIST to check for tumor recurrence. It was possible to resect 88 of 93 lesions by the laparoscopic-endoscopic approach, with tumor-free margins in all patients. Intraoperative endoscopy facilitated exact tumor localization in 92 patients. Most lesions were removed by endoscopic-laparoscopic wedge resection or, less frequently, by a combined transgastric approach. Mean operative time was 90.7 min; the postoperative hospitalization was 7.3 days. Adverse events appeared in 7.5%, and conversion to open surgery was required in 6.5%. For patients suffering from gastrointestinal stromal tumors, there was no tumor recurrence at a mean follow-up of 40 months. Combined laparoscopic-endoscopic "rendez-vous" procedures are easy to perform and offer a curative approach for almost all gastric submucosal lesions. The technique is associated with low morbidity and short hospitalization. Though even patients with large GISTs of intermediate and high risk were treated, no tumor recurrence has been observed to date.


The RNA-binding protein HuR opposes the repression of ERBB-2 gene expression by microRNA miR-331-3p in prostate cancer cells.
ERBB-2 overexpression is associated with the development and progression of cancer and mediates its resistance to therapy. It has been suggested that post-transcriptional mechanisms control the overexpression of ERBB-2 in prostate cancer (PCa). We recently demonstrated that the 3'-untranslated region (3'-UTR) of ERBB-2 mRNA contains two specific target sites for binding of the microRNA miR-331-3p and that miR-331-3p represses ERBB-2 expression and signaling in PCa cells. Here we investigate a U-rich element situated in close proximity to the distal miR-331-3p target site in the ERBB-2 3'-UTR. Specific binding of HuR to this U-rich element promotes ERBB-2 expression in PCa cells. We show that HuR antagonizes the repressive action of miR-331-3p on its distal ERBB-2 3'-UTR target site. These results support a model in which the interplay between RNA-binding proteins and microRNAs controls the post-transcriptional regulation of gene expression and suggest that both HuR and miR-331-3p participate in the overexpression of ERBB-2 observed in some PCas.


Free boundary dimers: random walk representation and scaling limit.
We study the dimer model on subgraphs of the square lattice in which vertices on a prescribed part of the boundary (the free boundary) are possibly unmatched. Each such unmatched vertex is called a monomer and contributes a fixed multiplicative weight z>0 to the total weight of the configuration. A bijection described by Giuliani et al. (J Stat Phys 163(2):211-238, 2016) relates this model to a standard dimer model but on a non-bipartite graph. The Kasteleyn matrix of this dimer model describes a walk with transition weights that are negative along the free boundary. Yet under certain assumptions, which are in particular satisfied in the infinite volume limit in the upper half-plane, we prove an effective, true random walk representation for the inverse Kasteleyn matrix. In this case we further show that, independently of the value of z>0, the scaling limit of the centered height function is the Gaussian free field with Neumann (or free) boundary conditions. It is the first example of a discrete model where such boundary conditions arise in the continuum scaling limit.


The enigmatic origin of olfactory schwannoma.
We present a case of so-called olfactory schwannoma in a 17-year-old male. The diagnostic procedures included computed tomography and digital subtraction angiography. Histological examination with tumor markers, S100, Leu-7 (CD57) and EM showed the tumor tissue to be a schwannoma. Arguments are raised that olfactory schwannomas are comparable to or even occur as intracerebral schwannomas with frontal localisation.


Direct measurement of retinal vessel diameter: comparison with microdensitometric methods based on fundus photographs.
A new method for the direct measurement of retinal vessel diameter was developed and the results were compared with those of two computer-assisted semiautomatic microdensitometric methods. The direct measurement method was based on automated detection of vessel edges by processing the one-dimensional retinal image obtained by a linear image sensor set in a fundus camera; results are obtained in real-time. Thirty-eight points on 36 vessels (15 points on arteries and 23 points on veins) of two normal volunteers (four eyes) were selected as the measurement points. Two observers measured the vessel diameters at these points and the interobserver variation of the direct method and the microdensitometric methods was compared. The coefficient of variation and the interobserver variation of the direct method for all measurements were 1.71 + 1.13% and 2.25 + 1.92%, respectively. There was no significant difference between the measured values for the two observers with the direct method (paired t-test, P > 0.05), and the interobserver variation of the direct method was smaller than those of the microdensitometric methods. This newly developed direct method for measurement of retinal vessel diameter not only avoids systematic errors that result from film development or the characteristics of the film, but also generates reproducible results in real-time and small interobserver variation.


Monoclonal antibody-resistant mutants selected with a respiratory syncytial virus-neutralizing human antibody fab fragment (Fab 19) define a unique epitope on the fusion (F) glycoprotein.
A recombinant human antibody fragment, designated RSV Fab 19, efficiently neutralizes respiratory syncytial virus (RSV). Here we report the results of our sequence analysis of antibody escape mutants that identified F glycoprotein amino acids critical for binding of human or murine RSV F-neutralizing antibodies.


Immunity after (re)vaccination of paediatric patients following haematopoietic stem cell transplantation.
Loss of specific immunity follows allogeneic haematopoietic stem cell transplantation (HSCT) in the majority of cases. Responses to (re)vaccinations can be used as indicators of a functional immunological recovery. Twenty-three paediatric recipients of HSCT were enrolled in a single centre setting and responses to scheduled immunizations analysed. Immunity to vaccine-preventable diseases was impaired post HSCT, but (re)vaccinations induced protective responses in 59-100%, depending on the vaccine, regardless of prior graft-versus-host disease (GVHD) history. Despite the marked impact of moderate to severe chronic prior GVHD on both the qualitative and quantitative T-cell recovery post allogenic HSCT, most paediatric recipients of allogeneic stem cell grafts appear to attain protective antibody levels after immunization.


Identifying the predictors of severe psychological distress by auto-machine learning methods.
Social stress in daily life and the COVID-19 pandemic have greatly impacted the mental health of the population. Early detection of a predisposition to severe psychological distress is essential for timely interventions. This paper analyzed 4036 samples participating in the 2019-2020 National Health Information Trends Survey (HINTS) and identified 57 candidate predictors of severe psychological distress based on univariate chi-square and t-test analyses. Five machine learning methods, namely logistic regression (LR), automatic generalized linear models (Auto-GLM), automatic random forests (Auto-Random Forests), automatic deep neural networks (Auto-Deep learning) and automatic gradient boosting machines (Auto-GBM), were employed to model synthetic minority oversampling technique-based (SMOTE) resampled data and identify predictors of severe psychological distress. Predictors were evaluated by odds ratios in logistic models and variable importance in the other models. Forty-seven variables were identified as significant predictors of severe psychological distress, including 13 sociodemographic variables and 34 variables related to individual lifestyle and behavioral habits. Among them, new potentially relevant variables related to an individual's level of concern and trust in cancer information, exposure to health care providers, and cancer screening and awareness are included. The performance of each model was evaluated using five-fold cross-validation. The optimal model performance-wise was Auto-GBM with an accuracy of 89.75%, a precision of 89.68%, a recall of 89.31%, an F1-score of 89.48% and an AUC of 95.57%. Significant predictors of severe psychological distress were identified in this study and the value of machine learning methods in predicting severe psychological distress is demonstrated, thereby enhancing pre-prediction and clinical decision-making of severe psychological distress problems.


Effects of a bacterial extract on local immunity of the lung in patients with chronic bronchitis.
Our findings demonstrate that Broncho-Vaxom (BV) displays possibly via the gut-associated immune system different effects on the lymphatic system of the lung: a positive influence on the helper/suppressor T-lymphocyte balance, an increase of gamma interferon, a stimulation of the reduced alveolar macrophage activity, and a regulation of BAL IgA to a distinct level whereby the serum IgE is reduced. By these effects BV is able to modulate impaired local and systemic immune function. The observed relationship between the inflammation score and the BAL fluid composition supports the view that the improvement of the mucosa lesion found in nearly all of our patients with chronic bronchitis occurs as the result of the pleiotropic immunomodulating effects of Broncho-Vaxom.


Measurement of sarcoplasmic reticulum Ca2+ ATPase activity using high-performance liquid chromatography.
The goal of this investigation was to develop an assay whereby we could measure changes in ATP, ADP, and phosphocreatine (PCr) during stimulation of the sarcoplasmic reticulum (SR) Ca2+ ATPase. After stopping the enzyme reaction, compounds were extracted by perchloric acid and separated by reversed-phase high-performance liquid chromatography (HPLC). Absorbance of ATP and ADP was monitored at 260 nm, and detection of PCr was done at 205 nm. Chromatograms show that peaks associated with each compound are clearly separated and easily detected. The SR Ca2+ ATPase assay was run for various time periods and using varying free [Ca2+]. The changes in ATP and ADP contents were linear with increasing time and varied as expected with increasing free [Ca2+]. The ATPase activities determined using changes in ATP and ADP were nearly identical to those determined using previously established assays. When PCr was added to the assay, we were able to confirm that the Ca2+ ATPase uses ATP that is synthesized locally from PCr via creatine kinase (CK). The results indicate that this is a valid and reliable method for examining SR Ca2+ ATPase activity and for investigating its interaction with CK.


Comparison of recombinant α-hemoglobin from Crocodylus siamensis expressed in different cloning vectors and their biological properties.
Hemoglobin (Hb) is an important component in red blood cells of the vertebrate. It is a major respiratory protein with oxygen or carbon dioxide transport function. Hb has been reported to contain bioactive peptides which have antibacterial and antioxidant activities. In this study, the alpha-chain hemoglobin(αHb) gene of Crocodylus siamensis was cloned into the three different expression vectors and expressed in Escherichia coli BL21 (DE3). The recombinant αHb proteins from all constructs could be expressed and purified. The result from UV-visible absorption spectra showed a similar pattern of all recombinant proteins to the oxy-hemoglobin form of intact Hb. The different recombinant αHb could exhibit antioxidant activities. All recombinant proteins could inhibit the growth of Bacillus spp. Especially, most of the recombinant proteins could inhibit the growth of Bacillus amyloliquefaciens TISTR 1045 better than intact one. The result obtained from this study can provide us further information about the possibility using of αHb as a supplementary food.


Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages.
Exosomes are extracellular vesicles characterized by their size, source, release mechanism and contents. MicroRNAs (miRNAs) are single stranded non-coding RNAs transcribed from DNA. Exosomes and miRNAs are widespread in eukaryotic cells, especially in mesenchymal stem cells (MSCs). MSCs are used for tissue regeneration, and also exert paracrine, anti-inflammatory and immunomodulatory effects. However, the use of MSCs is controversial, especially in the presence or after the remission of a tumor, due to their secretion of growth factors and their migration ability. Instead of intact MSCs, MSC-derived compartments or substances could be used as practical tools for diagnosis, follow up, management and monitoring of diseases. Herein, we discuss some aspects of exosomal miRNAs derived from MSCs in the progression, diagnosis and treatment of various diseases. Video Abstract.


S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress.
Increased oxidative stress has an important role in asthmatic airway inflammation and remodeling. A potent methyl donor, S-adenosylmethionine (SAMe), is known to protect against tissue injury and fibrosis through modulation of oxidative stress. The aim of this study was to evaluate the effect of SAMe on airway inflammation and remodeling in a murine model of chronic asthma. A mouse model was generated by repeated intranasal challenge with ovalbumin and Aspergillus fungal protease twice a week for 8 weeks. SAMe was orally administered every 24 h for 8 weeks. We performed bronchoalveolar lavage (BAL) fluid analysis and histopathological examination. The levels of various cytokines and 4-hydroxy-2-nonenal (HNE) were measured in the lung tissue. Cultured macrophages and fibroblasts were employed to evaluate the underlying anti-inflammatory and antifibrotic mechanisms of SAMe. The magnitude of airway inflammation and fibrosis, as well as the total BAL cell counts, were significantly suppressed in the SAMe-treated groups. A reduction in T helper type 2 pro-inflammatory cytokines and HNE levels was observed in mouse lung tissue after SAMe administration. Macrophages cultured with SAMe also showed reduced cellular oxidative stress and pro-inflammatory cytokine production. Moreover, SAMe treatment attenuated transforming growth factor-β (TGF-β)-induced fibronectin expression in cultured fibroblasts. SAMe had a suppressive effect on airway inflammation and fibrosis in a mouse model of chronic asthma, at least partially through the attenuation of oxidative stress and TGF-β-induced fibronectin expression. The results of this study suggest a potential role for SAMe as a novel therapeutic agent in chronic asthma.


Surgical intervention for congenital diaphragmatic hernia: open versus thoracoscopic surgery.
To compare open repair (OR) with thoracoscopic repair (TR) for congenital diaphragmatic hernia (CDH) in neonates. Twenty-four neonatal CDH cases diagnosed prenatally or within 6 h of birth at our institute from 2002 to 2012 with mild pulmonary hypertension managed without inhaled nitric oxide, were studied. OR was routine until 2006 (n = 14; L:R = 12:2) and TR became routine in 2007 (n = 10; L:R = 10:0). All subjects had identical management. Gestational age at birth: OR 37.4 ± 1.6 vs. TR: 38.3 ± 1.1 weeks (p = 0.10); birth weight 2,636 ± 490 vs. 2,887 ± 429 grams (p = 0.20); preoperative A-aDO(2): 308 ± 200 vs. 331 ± 195 mmHg (p = 0.79); and operating time (min): 161 ± 42 vs. 194 ± 76 (p = 0.27). In TR, intraoperative cardiopulmonary status was stable, intraoperative hemorrhage was significantly less (4.8 ± 6.0 vs. 1.1 ± 0.1 grams; p = 0.038), wound cosmesis was excellent without surgical site infections, while, maximum postoperative CRP (2.0 ± 1.5 vs. 1.5 ± 1.1 mg/dL; p = 0.30), commencement of enteral feeding (6.9 ± 2.8 vs. 5.6 ± 2.8 days; p = 0.27), and length of postoperative hospitalization (36 ± 22 vs. 34 ± 12 days; p = 0.66) were improved, but not significantly. One OR case required surgery for intestinal obstruction. Thoracoscopic repair appears to be as effective as OR for treating selected cases of CDH in neonates, with excellent wound cosmesis.


Biochemical analysis of a lithopedion.
Lithopedions are very rare; the medical literature mentions 330 cases. In the present case, a calcified lithopedion was found in the abdominal cavity of a 69-year-old woman who had died of unrelated causes. In general, the different organs of the lithopedion were easily distinguishable macroscopically. Microscopic examination detected reasonably well preserved structure only in skeletal muscle. Dry weight studies showed a definite dehydration (mummification) had taken place. Chemical analysis revealed a shell consisting mostly of inorganic constituents. Quantitative inorganic analysis of tissues was done and results compared to normal tissues. These results showed significant decrease of K and Cl, significant increase in Mg, P, Na and enormous increase in Ca. These data are compatible with the histologically observed calcification of the tissues. Under proper conditions, presumably dormant enzymes were reactivated in brain, liver, and muscle, although the total activity was low. Discernible LDH isoenzymes were found in liver and muscle. Discernible CK isoenzymes were found in brain and muscle.


Won't you be my neighbor? Using an ecological approach to examine the impact of community on revictimization.
An ecological model is used to explore the moderating effects of community-level variables on the relation between childhood sexual, physical, and emotional abuse and adult intimate partner violence (IPV) within a sample of 98 African American women from low incomes. Results from hierarchical, binary logistics regressions analyses show that community-level variables (perceived neighborhood disorder and community cohesion) moderated the relation between childhood emotional abuse and adult physical IPV. Findings support the use of an ecological approach in examining the phenomena of revictimization. Clinical implications from a community and ecological perspective are discussed.


Cryopreserved arterial allografts vs rifampin-soaked Dacron for the treatment of infected aortic and iliac grafts.
Aortic and iliac graft infections remain complex clinical problems with high mortality and morbidity. Cryopreserved arterial allografts (CAAs) and rifampin-soaked Dacron (RSD) are options for in situ reconstruction. This study aimed to compare the safety and effectiveness of CAA vs RSD in this setting. Data from patients with aortic and iliac graft infections undergoing in situ reconstruction with either CAA or RSD from January 2002 through August 2022 were retrospectively analyzed. Our primary outcomes were freedom from graft-related reintervention and freedom from reinfection. Secondary outcomes included comparing trends in the use of CAA and RSD at our institution, overall survival, perioperative mortality, and major morbidity. A total of 149 patients (80 RSD, 69 CAA) with a mean age of 68.9 and 69.1 years, respectively, were included. Endovascular stent grafts were infected in 60 patients (41 CAA group and 19 RSD group; P ≤ .01). Graft-enteric fistulas were more common in the RSD group (48.8% RSD vs 29.0% CAA; P ≤ .01). Management included complete resection of the infected graft (85.5% CAA vs 57.5% RSD; P ≤ .01) and aortic reconstructions were covered in omentum in 57 (87.7%) and 63 (84.0%) patients in the CAA and RSD group, respectively (P = .55). Thirty-day/in-hospital mortality was similar between the groups (7.5% RSD vs 7.2% CAA; P = 1.00). One early graft-related death occurred on postoperative day 4 due to CAA rupture and hemorrhagic shock. Median follow-up was 20.5 and 21.5 months in the CAA and RSD groups, respectively. Overall post-discharge survival at 5 years was similar, at 59.2% in the RSD group and 59.0% in the CAA group (P = .80). Freedom from graft-related reintervention at 1 and 5 years was 81.3% and 66.2% (CAA) vs 95.6% and 92.5% (RSD; P = .02). Indications for reintervention in the CAA group included stenosis (n = 5), pseudoaneurysm (n = 2), reinfection (n = 2), occlusion (n = 2), rupture (n = 1), and graft-limb kinking (n = 1). In the RSD group, indications included reinfection (n = 3), occlusion (n = 1), endoleak (n = 1), omental coverage (n = 1), and rupture (n = 1). Freedom from reinfection at 1 and 5 years was 98.3% and 94.9% (CAA) vs 92.5% and 87.2% (RSD; P = .11). Two (2.9%) and three patients (3.8%) in the CAA and RSD group, respectively, required graft explantation due to reinfection. Aorto-iliac graft infections can be managed safely with either CAA or RSD in selected patients for in situ reconstruction. However, reintervention was more common with CAA use. Freedom from reinfection rates in the RSD group was lower, but this was not statistically significant. Conduit choice is associated with long-term surveillance needs and reinterventions.


Validation of LittleEARS questionnaire in Hindi language.
Subjective measures of auditory development are equally important as objective measures to obtain a realistic image of the hearing status in infants and toddlers. The objectives of the current study were to translate and validate the LittleEARS questionnaire into the Hindi language, to calculate its psychometric properties and establish a regression curve of the scores obtained as a function of age, to calculate the inter-test and test retest reliability of the same. The secondary objectives were to compare the scores obtained by the normal hearing children and those with hearing impairment and to plot a regression curve of total scores obtained by the hearing-impaired children as a function of the duration of auditory training attended since their first fit of the device. The procedures involved conventional translation, reverse translation, and content validation before administering the questionnaire. The translated version was administered to parents of 59 children with normal hearing and 41 children with hearing impairment. The finalized version had good reliability and efficient internal consistency with a Cronbach alpha value of 0.96. The mean scores obtained by the normal hearing children showed a progressive pattern as a function of age. The LittleEARS questionnaire has been successfully translated and validated into the Hindi language with excellent validity and reliability and can be used for screening and early identification of hearing impairment and in evaluating the outcome of audiological treatment approaches.


UAV-based time-series phenotyping reveals the genetic basis of plant height in upland cotton.
Plant height (PH) is an important agronomic trait affecting crop architecture, biomass, resistance to lodging and mechanical harvesting. Elucidating the genetic governance of plant height is crucial because of the global demand for high crop yields. However, during the rapid growth period of plants the PH changes a lot on a daily basis, which makes it difficult to accurately phenotype the trait by hand on a large scale. In this study, an unmanned aerial vehicle (UAV)-based remote-sensing phenotyping platform was applied to obtain time-series PHs of 320 upland cotton accessions in three different field trials. The results showed that the PHs obtained from UAV images were significantly correlated with ground-based manual measurements, for three trials (R2 = 0.96, 0.95 and 0.96). Two genetic loci on chromosomes A01 and A11 associated with PH were identified by genome-wide association studies (GWAS). GhUBP15 and GhCUL1 were identified to influence PH in further analysis. We obtained a time series of PH values for three field conditions based on remote sensing with UAV. The key genes identified in this study are of great value for the breeding of ideal plant architecture in cotton.