Duloxetine for major depressive disorder and daytime and nighttime hot flashes associated with the menopausal transition.
We sought to obtain preliminary data regarding the efficacy of duloxetine for major depressive disorder (MDD) during the menopausal transition. The secondary outcomes were vasomotor symptoms (VMS, or hot flashes), specifically assessed as daytime or nighttime, and anxiety. After a single-blind placebo lead-in, peri- and postmenopausal women with MDD (n=19) received eight weeks of open-label treatment with duloxetine (60 mg/day). The Hamilton Rating Scale for Depression (17-item) (HAM-D) was the primary outcome measure. Hot flashes were monitored prospectively using daily diaries, the Greene Climacteric Scale (GCS), and the Hot Flash-Related Daily Interference Scale (HFRDIS). Anxiety was measured with the Generalized Anxiety Disorder scale (GAD-7). Of 19 participants treated with duloxetine, 16 (84.2%) were evaluable (returned for ≥ 1 follow up), and 13 (68.4%) completed the study. Three discontinued due to side effects. The pre-treatment and final median HAM-D scores were 15 (interquartile range [IQR] 14-18), and 6.5 (IQR 4-11.5), respectively, reflecting a significant decrease (p=.0006). The response and remission rates were 56.3% (all responders were also remitters, having ≥ 50% decrease in HAM-D scores and final scores ≤ 7). Anxiety improved with treatment (p=.012). GCS and HFRDIS scores decreased significantly. Among those who reported hot flashes at baseline, number and severity of hot flashes improved significantly overall (p=.009 and p=.008, respectively). Daytime but not nighttime hot flashes improved significantly. These data support further study of duloxetine for the treatment of a spectrum of symptoms associated with the menopausal transition.


Caveolinopathy: Clinical, histological, and muscle imaging features and follow-up in a multicenter retrospective cohort.
CAV3 gene mutations, mostly inherited as an autosomal dominant trait, cause various skeletal muscle diseases. Clinical presentations encompass proximal myopathy, distal myopathy, or isolated persistent high creatine kinase (CK) with a major overlapping phenotype. Twenty-three patients with CAV3 symptomatic mutations, from 16 different families, were included in a retrospective cohort. Mean follow-up duration was 24.2 ± 15.0 years. Clinical and functional data were collected during the follow-up. The results of muscle imaging, electroneuromyography, muscle histopathology, immunohistochemistry, and caveolin-3 Western blot analysis were also compiled. Exercise intolerance was the most common phenotype (52%). Eighty percent of patients had calf hypertrophy, and only 65% of patients presented rippling. One patient presented initially with camptocormia. A walking aid was required in only two patients. Electroneuromyography was mostly normal. CK level was elevated in all patients. No patient had cardiac or respiratory impairment. Muscle imaging showed fatty involvement of semimembranosus, semitendinosus, rectus femoris, biceps brachialis, and spinal muscles. Almost all (87%) of the biopsies were abnormal but without any specific pattern. Whereas a quarter of patients had normal caveolin-3 immunohistochemistry results, Western blots disclosed a reduced amount of the protein. We report nine mutations, including four not previously described. No phenotype-genotype correlation was evidenced. Caveolinopathy has diverse clinical, muscle imaging, and histological presentations but often has limited functional impact. Mild forms of the disease, an atypical phenotype, and normal caveolin-3 immunostaining are pitfalls leading to misdiagnosis.


Reactivity of ACTH and synthetic ACTH peptides with antisera to human calcitonin.
We studied reactivity of highly purified pituitary hormones in our human calcitonin (hCT) radioimmunoassay (RIA) which can detect 1 pg of hCT. ACTH at doses of greater than 1 microgram of peptide per RIA tube reacted in the hCT assay, as did beta-endorphin (beta EPH) at a dose of 10 micrograms per tube. No reactivity was observed with comparable concentrations of all other known pituitary hormones. ACTH also reacted at doses greater than 1 microgram per tube with 7 other hCT antisera which recognized differing antigenic determinants in the calcitonin molecule but it was not reactive with 2 antisera against porcine calcitonin or 2 antisera against salmon calcitonin. This slight degree of cross-reactivity of hACTH and beta EPH in the hCT RIA cannot account for the presence of immunoreactive CT in pituitary glands. Nevertheless, antisera used for the localization of peptides must be rigorously tested for the existence of cross-reactivities with other possible substances, especially if such antisera detect the peptide in unexpected tissues.


Protective effects of paraoxonase-1, vitamin E and selenium, and oxidative stress index on the susceptibility of low density lipoprotein to oxidation in diabetic patients with/without coronary artery disease.
The oxidative modification of low density lipoprotein (LDL) is closely associated with an increased risk for coronary artery disease (CAD) in diabetic patients. The purpose of this study is to investigate the relation between serum vitamin E and selenium, paraoxonase-1 (PON1) activity, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and oxidative stress index (OSI) values with the susceptibility of LDL to oxidative modification and the possibility of CAD in diabetic patients. This study was designed as a case control survey of 82 diabetes patients divided into two groups including T2DM alone (as group I) and both T2DM and CAD (as group II). Fasting blood samples were taken to the assay of fasting blood glucose (FBG), HbA1c, total cholesterol (TC), TAC, TOS, MDA, OSI, vitamin E, selenium, oxidized low density lipoprotein (Ox-LDL), and activity of PON1. Ox-LDL, MDA, TOS, and OSI values in groups II were significantly higher compared with group I (all with P value = 0.000). TAC, vitamin E, selenium, and PON1 activity values were significantly lower in group II compared with groups I (P value = 0.000; P value = 0.000; P value = 0.007; P value = 0.003, respectively). There were significant relationships between the amounts of TAC, TOS, OSI, and vitamin E with the amounts of PON1 activity and Ox-LDL (p < 0.05). But Ox-LDL and PON1 activity correlated weakly with together (p = 0.094). Results of this study support the belief that oxidative stress might be an important etiologic factor which makes some diabetics more susceptible to CAD. Increased oxidative stress may be a potential therapeutic target in the prevention and management of CAD in diabetic patients.


Growth, biomass, carbon storage and nutrient distribution in Gmelina arborea Roxb. stands on red lateritic soils in central India.
Growth, biomass, carbon storage and nutrient (N, P and K) variations in 1 to 6-year-old chronosequence plantations of Gmelina arborea were studied in three degraded red lateritic sites in central India. Growth parameters (dbh, total height and number of branches) varied significantly due to difference in age and site quality, but tree density showed non-significant variation. Stand biomass ranged from 3.94 (1-year-old) to 53.67 Mgha(-1) (6-year-old) and stand carbon in 6-year-old plantations ranged from 24.12 to 31.12 Mgha(-1) at different sites. Among the tree components, the stem wood accounted for maximum C (56.25% at site 1) followed by branches (19.8% at site 3), roots (18.51% at site 2) and foliage (7.01% at site 3). Mean annual C accretion at 6 years age of plantation was highest in site 3 and it was 0.35, 2.66, 0.965 and 0.87 Mgha(-1) for leaf, stem, branches and roots, respectively. Quantity of nutrients increased with age. Total nitrogen accumulation in 6-year-old stands at the three sites ranged from 212.9 to 279.5 kgha(-1) with a mean annual storage of 238.43 kgha(-1) and total K ranged from 170.8 to 220.5 kgha(-1) with a mean annual storage of 189.93 kgha(-1). Phosphorous accumulation was lowest with a mean storage of 16.75 kgha(-1). The organic carbon and nutrients in the soils improved significantly after 6 years of G. arborea planting. Soil organic carbon increased from 8.46 to 14.02 Mgha(-1) within 6 years. At soil depths 0-20 cm, 21-40 cm and 41-60 cm, available N enhanced by 14.85%, 11.98% and 11.25%, K by 10%, 9.13% and 10.63%, whereas phosphorous declined by 26%, 23% and 20%, respectively. At 6 years, G. arborea stands sequestered 31.37 Mgha(-1) carbon. The nutrient management strategies in relation to carbon accretion in G. arborea stands on degraded lateritic sites are discussed.


Very slow oscillatory activities in lateral geniculate neurons of freely moving and anesthetized rats.
In urethane anesthetized rats many lateral geniculate neurons display a strong very slow oscillatory behavior in the range of 0.025-0.01 Hz. One of the aims of the present study was to determine whether very slow oscillatory activity in this range can also be obtained in barbiturate anesthetized and in awake animals, respectively. Although very slow oscillations were found in geniculate neurons both during awakeness and during anesthesia, significant differences in peak frequencies of oscillations under the three experimental conditions (barbiturate, urethane, awake) were demonstrated. In addition, we have tested the influence of glutamate antagonists and GABA agonists as well as antagonists on the very slow oscillatory activity in urethane anesthetized rats. Very slow oscillatory activity which could be blocked by the continuous illumination of the eyes was re-induced by iontophoresis of NMDA and non-NMDA glutamate antagonists. GABA(A) as well as GABA(B) agonists also caused a significant re-induction of very slow oscillatory activity under light conditions. In the dark, muscimol, a GABA(A) agonist, significantly enhanced the very slow oscillatory activity, i.e. muscimol either induced it or reduced the frequency of very slow oscillations. For the whole sample, GABA antagonists did not have a significant influence on the very slow oscillatory activity. Autocorrelation analysis based on the spike interval histograms and determination of the spectrum of autocorrelograms revealed the significance of periodicity.


Testing the Generalizability of an Automated Method for Explaining Machine Learning Predictions on Asthma Patients' Asthma Hospital Visits to an Academic Healthcare System.
Asthma puts a tremendous overhead on healthcare. To enable effective preventive care to improve outcomes in managing asthma, we recently created two machine learning models, one using University of Washington Medicine data and the other using Intermountain Healthcare data, to predict asthma hospital visits in the next 12 months in asthma patients. As is common in machine learning, neither model supplies explanations for its predictions. To tackle this interpretability issue of black-box models, we developed an automated method to produce rule-style explanations for any machine learning model's predictions made on imbalanced tabular data and to recommend customized interventions without lowering the prediction accuracy. Our method exhibited good performance in explaining our Intermountain Healthcare model's predictions. Yet, it stays unknown how well our method generalizes to academic healthcare systems, whose patient composition differs from that of Intermountain Healthcare. This study evaluates our automated explaining method's generalizability to the academic healthcare system University of Washington Medicine on predicting asthma hospital visits. We did a secondary analysis on 82,888 University of Washington Medicine data instances of asthmatic adults between 2011 and 2018, using our method to explain our University of Washington Medicine model's predictions and to recommend customized interventions. Our results showed that for predicting asthma hospital visits, our automated explaining method had satisfactory generalizability to University of Washington Medicine. In particular, our method explained the predictions for 87.6% of the asthma patients whom our University of Washington Medicine model accurately predicted to experience asthma hospital visits in the next 12 months.


Rate of misdiagnosis and clinical usefulness of the correct diagnosis in exudative neovascular maculopathy secondary to AMD versus pachychoroid disease.
The aim of this study was to explore the relative prevalence and clinical differences between age-related macular degeneration (AMD) and pachychoroid disease in patients older than 50 years with newly diagnosed exudative neovascular maculopathy, and also assess the rate of misdiagnosis between these two disorders. In this retrospective observational study, we reviewed data from patients 50 years of age and older with newly diagnosed treatment-naïve exudative macular neovascularization (MNV) secondary to AMD or pachychoroid disease. Of the 139 patients (139 eyes) who fulfilled the inclusion criteria, 35 patients were graded as being affected by pachychoroid disease complicated by exudative MNV and 104 subjects had neovascular AMD. Therefore, prevalence of pachychoroid disease complicated by exudative MNV was 25.2% (confidence interval-CI 18.2-33.2%). Mean ± SD age was 67.0 ± 8.8 years in the pachychoroid disease group and 80.6 ± 6.6 years in the neovascular AMD group (P < 0.0001). At baseline, BCVA was better in patients with pachychoroid disease complicated by exudative MNV (0.4 ± 0.3 LogMAR vs. 0.7 ± 0.5 LogMAR, P = 0.003). At the 1-year follow-up visit, BCVA was still better in patients with pachychoroid-associated MNV (0.34 ± 0.32 LogMAR vs. 0.59 ± 0.52 LogMAR; P = 0.005). In our study cohort, 19 patients were graded to be affected by pachychoroid disease complicated by exudative MNV even though a diagnosis of neovascular AMD was erroneously reported in their medical records at baseline. In conclusion, pachychoroid disease is a frequent cause of exudative MNV in aged patients with a high rate of misdiagnosis. A correct diagnosis may be important as these two disorders differ in terms of clinical characteristics and prognosis.


Percutaneous ultrasound-guided needle tenotomy for treatment of chronic tendinopathy and fasciopathy: a meta-analysis.
To systematically assess the efficacy of percutaneous ultrasound-guided needle tenotomy (PUNT) in the treatment of chronic tendinopathy and fasciopathy. A comprehensive literature search was performed with the following search terms: tendinopathy, tenotomy, needling, Tenex, fasciotomy, ultrasound-guided, and percutaneous. Inclusion criteria consisted of original studies evaluating pain or function improvement after PUNT. Meta-analyses investigating standard mean differences were performed to assess the pain and function improvement. Thirty-five studies with 1674 participants (1876 tendons) were enrolled in this article. Of which 29 articles were included in meta-analysis and the remaining 9 articles without enough numeric data were included in descriptive analysis. PUNT significantly alleviated pain with the standard mean difference of 2.5 (95% CI: 2.0-3.0; p < 0.05), 2.2 (95% confidence interval (CI): 1.8-2.7; p < 0.05), and 3.6 (95% CI: 2.8-4.5; p < 0.05) points in short-term, intermediate-term, and long-term follow-up intervals, respectively. It was also associated with marked improvement in function with 1.4 (95% CI: 1.1-1.8; p < 0.05), 1.8 (95% CI: 1.3-2.2; p < 0.05), and 2.1 (95% CI: 1.6-2.6; p < 0.05) points, respectively in short-term, intermediate-term, and long-term follow-ups. PUNT improved pain and function at short-term intervals with persistent results on intermediate- and long-term follow-ups. PUNT can be considered an appropriate minimally invasive treatment for chronic tendinopathy with a low rate of complications and failures. Tendinopathy and fasciopathy are two common musculoskeletal complaints that can cause prolonged pain and disability. PUNT as a treatment option could improve pain intensity and function. • The best improvement in pain and function was achieved after the first 3 months following PUNT and was continued to the intermediate- and long-term follow-ups. • No significant difference was found between different tenotomy methods in terms of pain and function improvement. • PUNT is a minimally invasive procedure with promising results and low complication rates for treatments of chronic tendinopathy.


Aberrant expression of neutrophil and macrophage-related genes in a murine model for human neutrophil-specific granule deficiency.
Neutrophil-specific granule deficiency involves inheritance of germline mutations in the CCAAT/enhancer-binding protein epsilon (C/EBPE) gene. Humans and mice lacking active C/EBPepsilon suffer frequent bacterial infections as a result of functionally defective neutrophils and macrophages. We hypothesized that these defects reflected dysregulation of important immune response genes. To test this, gene expression differences of peritoneally derived neutrophils and macrophages from C/EBPepsilon-/- and wild-type mice were determined with DNA microarrays. Of 283 genes, 146 known genes and 21 expressed sequence tags (ESTs) were down-regulated, and 85 known genes and 31 ESTs were up-regulated in the C/EBP-/- mice. These included genes involved in cell adhesion/chemotaxis, cytoskeletal organization, signal transduction, and immune/inflammatory responses. The cytokines CC chemokine ligand 4, CXC chemokine ligand 2, and interleukin (IL)-6, as well as cytokine receptors IL-8RB and granulocyte-colony stimulating factor, were down-regulated. Chromatin immunoprecipitation analysis identified binding of C/EBPepsilon to their promoter regions. Increased expression for lipid metabolism genes apolipoprotein E (APOE), scavenger receptor class B-1, sorting protein-related receptor containing low-density lipoprotein receptor class A repeat 1, and APOC2 in the C/EBPepsilon-/- mice correlated with reduced total cholesterol levels in these mice before and after maintenance on a high-fat diet. Also, C/EBPepsilon-deficient macrophages showed a reduced capacity to accumulate lipids. In summary, dysregulation of numerous, novel C/EBPepsilon target genes impairs innate immune response and possibly other important biological processes mediated by neutrophils and macrophages.


Paid Organ Donation: An Italian Perspective.
The only countries that have allowed financial incentives for organ donation are Iran since 1988, and later on, Singapore and Saudi Arabia. In Europe, and of course in Italy, financial incentives for donors are prohibited. The author has completed extensive research via the Internet (PubMed) of worldwide scientific literature on paid organ donation, also researching studies concerning public opinion on organ commercialism and "regulated markets". Italian transplant laws also have been reported and analyzed.


Pyrolysis temperature and biochar redox activity on arsenic availability and speciation in a sediment.
Biochar is widely used for water and soil remediation in part because of its local availability and low production cost. However, its effectiveness depends on physicochemical properties related to its feedstock and pyrolysis temperature, as well as the environmental conditions of its use site. Furthermore, biochar is susceptible to natural aging caused by changes in soil or sediment moisture, which can alter its redox properties and interactions with contaminants such as arsenic (As). In this study, we investigated the effect of pyrolysis temperature and biochar application on the release and transformations of As in contaminated sediments subjected to redox fluctuations. Biochar application and pyrolysis temperature played an important role in As species availability, As methylation, and dissolved organic carbon concentration. Furthermore, successive flooding cycles that induced reductive conditions in sediments increased the As content in the solution by up to seven times. In the solid phase, the application of biochar and the flooding cycle altered the spatial distribution and speciation of carbon, iron (Fe) and As. In general, the application of biochar decreased the reduction of Fe(III) and As(V) after the first cycle of flooding. Our results demonstrate that the flooding cycle plays an important role in the reoxidation of biochar to the point of enhancing the immobilization of As.


An observational study of the quality of care for chronic kidney disease: a Buffalo and Albany, New York metropolitan area study.
The database of a major regional health insurer was employed to identify the number and frequency of covered patients with chronic kidney disease (CKD). We then examined the characteristics of their care as defined, in part, by the frequency of physician visits and specialty referral, the characteristics of laboratory testing and total costs as indices of the quality of care of the subject population. This retrospective, cross-sectional study analyzed insurance claims, laboratory results and medication prescription data. Patients with two estimated glomerular filtration rate readings below 60 ml/min/1.73 m(2) (n = 20,388) were identified and classified by CKD stage. The prevalence of CKD stages 3a and above was 12 %. Vascular comorbidities were common with prevalence increasing steadily from stage 3a through stage 5. Only 55.6 % of stage 4 CKD patients had claims for nephrology visits within one year of their index date. Fifty-nine percent of patients had claims for renin-angiotensin system (RAS) blockers. Twenty-five percent of patients in stage 3a CKD filled a prescription for non-steroidal anti-inflammatory drugs. Fifty-two percent of patients who developed end-stage renal disease received their first dialysis treatment as inpatients. The pattern of medical practice observed highlights apparent deficiencies in the care of CKD patients including inappropriate medication use, delayed nephrology referral, and a lack of preparation for dialysis. This study shows the potential value of using large patient databases available through insurers to assess and likely improve regional CKD care.


Conjugation of DNA fragments to protein carriers by glutaraldehyde: immunogenicity of oligonucleotide-hemocyanin conjugates.
The practical realization of the concept of specific immunotherapy for systemic lupus erythematosus (SLE) has been hampered, thus far, by an inability to link DNA fragments to carrier protein. In this paper, a novel technique is described, in which glutaraldehyde is the linking agent. A 2-stage method was used to link oligonucleotides to a soluble protein carrier, such as keyhole limpet hemocyanin (KLH) or human gamma globulin (HGG), whereas a 1-stage technique was sufficient to link oligonucleotides to sheep red cells. Both the ultraviolet absorbance spectrum and diphenylamine assay demonstrated that oligonucleotides were coupled to soluble protein. The conjugate of oligonucleotide to protein carrier appears to be recognized by anti-DNA antibody since oligonucleotide linked to either KLH or HGG inhibited the binding of anti-DNA antibody in vitro, and oligonucleotide-coupled sheep cells are agglutinating by seropositve sera from lupus patients. In addition, oligonucleotide-KLH raised hemagglutinating antibody to denatured DNA in C57BL/6, DBA/2 or NZB mice, as well as IgG antibody as detected by SPRIA in C57BL/6 and DBA/2 mice. The significance of this new method for the development of an antigen specific therapy of SLE is discussed.


Comparison of fat suppression strategies in 3D spiral coronary magnetic resonance angiography.
In the present study, the impact of the two different fat suppression techniques was investigated for free breathing 3D spiral coronary magnetic resonance angiography (MRA). As the coronary arteries are embedded in epicardial fat and are adjacent to myocardial tissue, magnetization preparation such as T(2)-preparation and fat suppression is essential for coronary discrimination. Fat-signal suppression in three-dimensional (3D) thin- slab coronary MRA based on a spiral k-space data acquisition can either be achieved by signal pre-saturation using a spectrally selective inversion recovery pre-pulse or by spectral-spatial excitation. In the present study, the performance of the two different approaches was studied in healthy subjects. No significant objective or subjective difference was found between the two fat suppression approaches. Spectral pre-saturation seems preferred for coronary MRA applications due to the ease of implementation and the shorter cardiac acquisition window.


The Medicinal Potential of Mesenchymal Stem/Stromal Cells in Immuno- and Cancer Therapy.
Cancer is a highly lethal disease that causes millions of deaths worldwide, thus representing a major public health challenge [...].


Effect of sprayed techniques on the surface microstructure and in vitro behavior of nano-HAp coatings.
Supersonic atmospheric plasma spray (SAPS) technique is a classical method which is employed to coat the carbon/carbon (C/C) composites by nano-hydroxyapatite (HAp) powders to decrease the biologically inert, hydrophobic drawbacks of substrate surfaces. In recent years, profiting from the promoting of energy conservation and environmental protection, more emphasis was placed on industrial manufacturing to simplify the experimental steps. This paper aims to study the preparation of nano-HAp coatings by suspension plasma spray (SPS) instead of the original SAPS technique. A denser, more uniform and less defective coating is successfully fabricated on C/C substrate using SPS technique. More important, fewer surface flaws in SPS coating could be observed by scanning electron microscopy (SEM) which shows that the large drawbacks of the coating have disappeared during spraying process. Meanwhile, except for HAp, phase compositions of the SPS coating appear with slight calcium oxide (CaO, 0.8%) and tricalcium phosphate (TCP, 30.7%), and then all CaO as well as TCP phases transform into dicalcium phosphate anhydrous (DCPA, 60.6%) after microwave-hydrothermal (MH) treatment. Thermal analysis (TG/DSC) reveals that SPS coating (97.51%) has a higher thermal stability than that of the SAPS coating (82.37%). Also, in comparison, the SPS coating after MH treatment (SPS-MH coating) exhibits better thermal properties (92.76%). In addition, compared to the SAPS and SPS coatings, due to the more flaw reduction and phase transformation, SPS-MH coating shows a better biological properties according to the surface microstructure in simulation body fluid (SBF) solution and cell spreading area on coating. The highest corrosion resistance with the current density of 3.9798 × 10-7 A/cm2 and a potential of 0.0419 V is achieved for SPS-MH coating.


Effects of exogenous glycine betaine and cycloleucine on photosynthetic capacity, amino acid composition, and hormone metabolism in Solanum melongena L.
Although exogenous glycine betaine (GB) and cycloleucine (Cyc) have been reported to affect animal cell metabolism, their effects on plant growth and development have not been studied extensively. Different concentrations of exogenous glycine betaine (20, 40, and 60 mmol L-1) and cycloleucine (10, 20, and 40 mmol L-1), with 0 mmol L-1 as control, were used to investigate the effects of foliar spraying of betaine and cycloleucine on growth, photosynthesis, chlorophyll fluorescence, Calvin cycle pathway, abaxial leaf burr morphology, endogenous hormones, and amino acid content in eggplant. We found that 40 mmol L-1 glycine betaine had the best effect on plant growth and development; it increased the fresh and dry weight of plants, increased the density of abaxial leaf hairs, increased the net photosynthetic rate and Calvin cycle key enzyme activity of leaves, had an elevating effect on chlorophyll fluorescence parameters, increased endogenous indoleacetic acid (IAA) content and decreased abscisic acid (ABA) content, and increased glutamate, serine, aspartate, and phenylalanine contents. However, cycloleucine significantly inhibited plant growth; plant apical dominance disappeared, plant height and dry and fresh weights decreased significantly, the development of abaxial leaf hairs was hindered, the net photosynthetic rate and Calvin cycle key enzyme activities were inhibited, the endogenous hormones IAA and ABA content decreased, and the conversion and utilization of glutamate, arginine, threonine, and glycine were affected. Combined with the experimental results and plant growth phenotypes, 20 mmol L-1 cycloleucine significantly inhibited plant growth. In conclusion, 40 mmol L-1 glycine betaine and 20 mmol L-1 cycloleucine had different regulatory effects on plant growth and development.


Hydrocarbon uptake in hydrocarbon fermentations.
Candida lipolytica (strain ATCC 8662) was grown on a simple defined medium with n-hexadecane as the main carbon source under batch fementation conditions. The relative importance of the cells growing in the aqueous phase on the overall kinetics was studied. The effect of interfacial tension, unoccupied interfacial area, and pseudosolubility on the specific growth was also studied. Results are presented and discussed here.


[Female genital mutilations, forced marriages, and early pregnancies].
Female genital mutilations, as well as forcible childhood marriage and their correlate adolescent pregnancies are traditional practices which, not only violate the dignity, but also jeopardize the health, and even the life, of women and their children. The complications of genital mutilations are frequent for a number of reasons: the fact that the clitoris is highly vascularized, the nature of the mutilations, excision or infibulation, and the poor conditions of hygiene. The short term complications are pain, hemorrhage, shock, and urinary retention. Medium term complications include gangrene, septicemia, tetanus, pelvic inflammatory disease, HIV/AIDS, and hepatitis B or C infections. Serious sequelae may occur, including infertility and gynecologic disorders, and sexual life is invariably altered. The main obstetrical complications of genital mutilations are genital lacerations involving the labia minor and the perineum, which can lead to hemorrhage and sequelae such as urinary or anal incontinence, recto-vaginal and vesico-vaginal fistulas. The role of doctors, which is delicate because these customs are entrenched, is to detect genital mutilations, repair them and prevent them, by participating in health education programs. The consequences of forcible childhood marriage are serious, besides the fact that this is a disguised form of rape. The obstetrical risks favored by the underdevelopment of the uterus and the pelvis, include uterine rupture, preeclampsia and eclampsia, and obstetrical hemorrhage. The fetus/neonate are jeopardized by these complications, which can result in perinatal asphyxia and death, as well as the high rates of intrauterine growth retardation and preterm delivery. The impact of genital mutilations on delivery are compounded in childhood pregnancies for anatomical reasons, but also because these adolescents or children are extremely vulnerable and have poor access to perinatal care. In France, as well as in Africa, non-governmental and women's rights organizations are active in preventing these practices. We strongly recommend that these groups should receive aid and encouragement.


Calcaneus bone mineral density in Japanese women with rheumatoid arthritis.
The aim of this study was to investigate the relationships among bone mineral densities (BMD) in the calcaneus and leg activity of daily living (L-ADL) in rheumatoid arthritis (RA) patients. We measured and compared calcaneus BMD using single X-ray absorptiometry and lumbar spine and femoral neck BMD using dual X-ray absorptiometry in 158 Japanese female outpatients with RA and 358 normal controls (NC). Regardless of whether the women were premenopausal or postmenopausal, calcaneus and femoral neck BMDs in the RA group were significantly lower than in the NC group. Calcaneus BMD correlated with the modified health assessment questionnaire, L-ADL score, and 10-m walking time, regardless of whether the patients were premenopausal or postmenopausal (P<0.01). We conclude that calcaneus BMD reflects the L-ADL of RA patients very well and allows us to perform the same level of BMD evaluation as that with current BMD measurement methods.


Progress on the pathological tissue microenvironment barrier-modulated nanomedicine.
Imbalance in the tissue microenvironment is the main obstacle to drug delivery and distribution in the human body. Before penetrating the pathological tissue microenvironment to the target site, therapeutic agents are usually accompanied by three consumption steps: the first step is tissue physical barriers for prevention of their penetration, the second step is inactivation of them by biological molecules, and the third step is a cytoprotective mechanism for preventing them from functioning on specific subcellular organelles. However, recent studies in drug-hindering mainly focus on normal physiological rather than pathological microenvironment, and the repair of damaged physiological barriers is also rarely discussed. Actually, both the modulation of pathological barriers and the repair of damaged physiological barriers are essential in the disease treatment and the homeostasis maintenance. In this review, we present an overview describing the latest advances in the generality of these pathological barriers and barrier-modulated nanomedicine. Overall, this review holds considerable significance for guiding the design of nanomedicine to increase drug efficacy in the future.


Structure-dependent degradation of nitroimidazoles by cobalt-manganese layered double hydroxide catalyzed peroxymonosulfate process.
The increasing concentration of nitroimidazoles antibiotics (NIs) in the water environment has great threat to human and ecosystem security. Herein, the degradation rates of four NIs were found to vary with their molecular structures using Co3Mn-layered double hydroxide (LDH) catalyzed peroxymonosulfate oxidation process. Specifically, the degradation efficiency of secnidazole (SNZ) was determined to be the highest with a reaction rate of 0.24 min-1, which was 3.6, 2.3 and 1.8 times to that of menidazole (MZ), metronidazole (MTZ) and ornidazole (ONZ), respectively. During the reaction, 8.3% of Co2+ and 8.4% of Mn3+ transformed to Co3+ and Mn4+ after reaction, respectively. The conversion of bimetallic valence in Co3Mn-LDH donated electrons (e-) for PMS activation, resulting in the production of 1O2, OH, SO4- and O2-. Density functional theory (DFT) calculation showed that the presence of electron-donating groups (-CH3 and -OH) and the absence of electron-withdrawing atom (Cl) leaded to the richest active sites in the molecular structure of SNZ, which thus contributed to the highest degradation efficiency of SNZ. By deducing the structure-dependent degradation pathways of four NIs, the carbon chain of SNZ was found to be more easily attacked to form MTZ and MZ because of its unique active sites, resulting in the faster degradation rate of SNZ than MTZ and MZ. This study may provide a valuable insight into the effects of molecular structures on the degradation rates and transformation pathways of NIs.


Antioxidant capacity and cytotoxicity of sulfated polysaccharide TLH-3 from Tricholoma lobayense.
Polysaccharide TLH-3 from the fruit body of Tricholoma lobayense Heim has shown outstanding antioxidant activity. In order to further explore it, TLH-3 was successfully modified to obtain a sulfated derivative (STLH-3). The chemical characteristics of STLH-3 and TLH-3 were determined by high performance liquid chromatography and infrared spectroscopy. Antioxidant activity and cytotoxicity of the samples were investigated in vitro. The antioxidant activities of STLH-3 were significantly improved. In the four indicators of antioxidant activity, the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion scavenging activities of STLH-3 have exceeded that of Vitamin C (Vc). The cytotoxicity against tumor cells including human cervical carcinoma cell line (HeLa) and human breast cancer cell line (MCF-7) of STLH-3 was obviously stronger than that of TLH-3. STLH-3 had no toxic on human embryonic lung fibroblasts (HELF) cells. These results suggested that STLH-3 would be a promising bioactive macromolecule for potential applications in the field of health care and pharmaceutical.


Mortality and industrial employment. III. Industries with high standard mortality ratios for persons with social security coverage in 1960 and 1965.
Data are available on a 1% sample of social security covered employees by industry, age, sex and race for years 1960 and 1965 and their mortality through 1972. Previous papers have reported on overall rates by age, sex and race and on industries in which mortality appears to be increased among younger workers. In this paper mortality ratios, compared to the expected overall race-sex-age specific rates for this population, are shown for the Standard Industrial Classification two-digit-industry classes for the 1960 and the 1965 cohorts. Among women employed in four industries involving chemical exposures, an abrupt increase in mortality occurred around 1965. Possible reasons for this are discussed. The epidemiologic usefulness of social security mortality data for occupational and preventive purposes and for surveillance is emphasized.


How can Electrospinning Further Service Well for Pharmaceutical Researches?
The past two decades have witnessed the enormous success and progress of electrospinning, as well as its broad and useful applications in pharmaceutics as a laboratory pharmaceutical nanotechnology. Everything in the past is a preface, in which the large screen opens for electrospinning and electrospun nanofibers (particularly those multiple-fluid electrospinning processes and the related multiple-chamber nanostructures) to stride into a new stage and the real commercial applications. In this commentary, four hot regions are identified for the further progress of the applications of electrospinning in pharmaceutics, in which electrospinning and its products can provide more and better services to the development of pharmaceutics.


Evaluating the effect of prebiotics on the gut microbiome profile and β cell function in youth with newly diagnosed type 1 diabetes: protocol of a pilot randomized controlled trial.
Data show that disturbances in the gut microbiota play a role in glucose homeostasis, type 1 diabetes (T1D) risk and progression. The prebiotic high amylose maize starch (HAMS) alters the gut microbiome profile and metabolites favorably with an increase in bacteria producing short chain fatty acids (SCFAs) that have significant anti-inflammatory effects. HAMS also improves glycemia, insulin sensitivity, and secretion in healthy non-diabetic adults. Additionally, a recent study testing an acetylated and butyrylated form of HAMS (HAMS-AB) that further increases SCFA production prevented T1D in a rodent model without adverse safety effects. The overall objective of this human study will be to assess how daily HAMS-AB consumption impacts the gut microbiome profile, SCFA production, β cell heath, function, and glycemia as well as immune responses in newly diagnosed T1D youth. We hypothesize that HAMS-AB intake will improve the gut microbiome profile, increase SCFA production, improve β cell health, function and glycemia as well as modulate the immune system. We describe here a pilot, randomized crossover trial of HAMS-AB in 12 newly diagnosed T1D youth, ages 11-17 years old, with residual β cell function. In Aim 1, we will determine the effect of HAMS-AB on the gut microbiome profile and SCFA production; in Aim 2, we will determine the effect of HAMS-AB on β cell health, function and glycemia; and in Aim 3, we will determine the peripheral blood effect of HAMS-AB on frequency, phenotype and function of specific T cell markers. Results will be used to determine the effect-size estimate of using HAMS-AB. We anticipate beneficial effects from a simple, inexpensive, and safe dietary approach. The Institutional Review Board at Indiana University approved the study protocol. The findings of this trial will be submitted to a peer-reviewed pediatric journal. Abstracts will be submitted to relevant national and international conferences. NCT04114357; Pre-results.


Endothelial cell density after photorefractive keratectomy for moderate myopia using a 213 nm solid-state laser system.
To evaluate whether photorefractive keratectomy (PRK) for moderate myopia using a solid-state laser with a wavelength of 213 nm alters the corneal endothelial cell density. University refractive surgery center. The corneal endothelium was analyzed preoperatively and 1, 6, and 12 months postoperatively using corneal confocal microscopy (modified HRT II with a Rostock Cornea Module, Heidelberg Engineering) in 60 eyes (30 patients). Patients were randomized to have myopic PRK using a 213 nm wavelength solid-state laser (study group) or a conventional 193 nm wavelength excimer laser (control group). Three endothelial images were acquired in each of 30 preoperative normal eyes to evaluate the repeatability of endothelial cell density measurements. Repeated-measures analysis of variance was used to compare the variations in endothelial cell density between the 2 lasers and the changes in endothelial cell density over time. There were no statistically significant differences in sex, age, corneal pachymetry, attempted correction, preoperative endothelial cell density, or postoperative refractive outcomes (uncorrected visual acuity, best spectacle-corrected visual acuity, and spherical equivalent refraction) between the 2 groups (P>.05). The coefficient of repeatability of endothelial cell density was 131 cells/mm(2). The measured endothelial cell count per 1.0 mm(2) did not significantly change up to 1 year postoperatively in either group (both P>.05). No statistically significant difference was found between the 2 groups in any postoperative interval (P>.05). Photorefractive keratectomy for moderate myopia using a 213 nm wavelength solid-state laser or a conventional 193 nm wavelength excimer laser did not significantly affect corneal endothelial density during the 1-year postoperative period.


Predicting malignancy in patients with adrenal tumors using 18 F-FDG-PET/CT SUVmax.
18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) parameters may help distinguish malignant from benign adrenal tumors, but few have been externally validated or determined based on definitive pathological confirmation. We determined and validated a threshold for 18 F-FDG-PET/CT maximum standard uptake value (SUVmax) in patients who underwent adrenalectomy for a nonfunctional tumor. Database review identified patients with 18 F-FDG-PET/CT images available (training cohort), or only SUVmax values (validation cohort). Discriminative accuracy was assessed by area under the curve (AUC), and the optimal cutoff value estimated by maximally selected Wilcoxon rank statistics. Of identified patients (n = 171), 86 had adrenal metastases, 20 adrenal cortical carcinoma, and 27 adrenal cortical adenoma. In the training cohort (n = 96), SUVmax was significantly higher in malignant versus benign tumors (median 8.3 vs. 3.0, p < .001), with an AUC of 0.857. Tumor size did not differ. The optimal cutoff SUVmax was 4.6 (p < .01). In the validation cohort (n = 75), this cutoff had a sensitivity of 75% and specificity 55%. 18 F-FDG-PET/CT SUVmax was associated with malignancy. Validation indicated that SUVmax ≥ 4.6 was suggestive of malignancy, while lower values did not reliably predict benign tumor.


Lessons learned: use of WGS in real-time investigation of suspected intrahospital SARS-CoV-2 outbreaks.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been a continuing source of hospital-acquired infection and outbreaks. At Akershus University Hospital in Norway, traditional contact tracing has been combined with whole-genome sequencing (WGS) surveillance in real-time to investigate potential hospital outbreaks. To describe the advantages and challenges encountered when using WGS as a real-time tool in hospital outbreak investigation and surveillance during the SARS-CoV-2 pandemic. Routine contact tracing in the hospital was performed for all healthcare workers (HCWs) who tested positive for SARS-CoV-2. Viral RNA from all positive patient and HCW samples was sequenced in real-time using nanopore sequencing and the ARTIC Network protocol. Suspected outbreaks involving five or more individuals with viral sequences were described. Nine outbreaks were suspected based on contact tracing, and one outbreak was suspected based on WGS results. Five outbreaks were confirmed; of these, two outbreaks were supported but could not be confirmed by WGS with high confidence, one outbreak was found to consist of two different lineages, and two outbreaks were refuted. WGS is a valuable tool in hospital outbreak investigations when combined with traditional contact tracing. Inclusion of WGS data improved outbreak demarcation, identified unknown transmission chains, and highlighted weaknesses in existing infection control measures.


Natural killer cell cytotoxicity: role of calmodulin.
The phenothiazine derivatives, fluphenazine and trifluoperazine which are known to bind to calmodulin and to inhibit its activity, abrogate the development of both spontaneous and interferon-enhanced cytotoxicity of mouse splenic lymphocytes enriched for NK cell activity. Phenothiazines also inhibit the rapid increase in cyclic GMP levels in interferon-treated splenic lymphocytes. Furthermore, treatment of mouse splenic lymphocytes with electrophoretically pure interferon, alpha/beta caused a marked decrease in the level of calmodulin within 1 to 4 hours. These results provide evidence that calmodulin may play a role in the development of NK cell cytotoxicity and that the effect of interferon on calmodulin may constitute part of the molecular mechanism of interferon action.


3D puzzle-inspired construction of large and complex organ structures for tissue engineering.
3D printing as a powerful technology enables the fabrication of organ structures with a programmed geometry, but it is usually difficult to produce large-size tissues due to the limited working space of the 3D printer and the instability of bath or ink materials during long printing sessions. Moreover, most printing only allows preparation with a single ink, while a real organ generally consists of multiple materials. Inspired by the 3D puzzle toy, we developed a "building block-based printing" strategy, through which the preparation of 3D tissues can be realized by assembling 3D-printed "small and simple" bio-blocks into "large and complex" bioproducts. The structures that are difficult to print by conventional 3D printing such as a picture puzzle consisting of different materials and colors, a collagen "soccer" with a hollow yet closed structure, and even a full-size human heart model are successfully prepared. The 3D puzzle-inspired preparation strategy also allows for a reasonable combination of various cells in a specified order, facilitating investigation into the interaction between different kinds of cells. This strategy opens an alternative path for preparing organ structures with multiple materials, large size and complex geometry for tissue engineering applications.


Gestational diabetes mellitus. Is further improvement necessary?
The maternal antepartum, intrapartum, and neonatal characteristics of 158 patients with gestational diabetes mellitus (GDM) attending a large teaching hospital between 1979 and 1983 were described and compared with a matched nondiabetic control group. The primary cesarean section rate in patients with GDM (18%) was significantly greater than in the control group (11%, P less than 0.04). Neonatal macrosomia, as reflected in mean birthweight (P less than 0.04), the number of neonates weighing greater than 4 kg (P less than 0.05) and large-for-gestational-age infants (P less than 0.05), and the birthweight adjusted for gestational age (K-score, P less than 0.01) was significantly increased in the diabetic group. The characteristics of patients with GDM treated with diet alone and diet and insulin together were examined. The insulin-therapy group was characterized by more patients older than 25 yr (P less than 0.01) and a higher mean birthweight (3743 +/- 677 g) (P less than 0.02) than the diet-alone group. This may reflect an increased magnitude of glucose intolerance in the insulin-treated group. Obese patients with GDM delivered heavier neonates than the nonobese patients with GDM (P less than 0.01). Although there was no difference between the groups, perinatal mortality was present in this study. These data indicate that the major perinatal morbidity in GDM included increased cesarean section for fetal macrosomia. Early diagnosis with strict diagnostic criteria and rigid antenatal surveillance may result in further improvements in outcome.


Measuring rates of intraflagellar transport along Caenorhabditis elegans sensory cilia using fluorescence microscopy.
Intraflagellar transport (IFT), the kinesin-2 and IFT-dynein-dependent bidirectional movement of multisubunit protein complexes called IFT-particles and associated cargo molecules along ciliary axonemes, is thought to be essential for the assembly and maintenance of virtually all eukaryotic cilia and flagella. Transport assays that allow measurements of the rates of movement of specific, fluorescently tagged, functional components of the IFT machinery, including motors, IFT particle subunits, and putative cargo, were first developed in Caenorhabditis elegans sensory cilia, and they have proved to be an important and valuable tool for dissecting the molecular mechanisms of IFT. We describe how these transport assays are performed in our laboratory and summarize the information that has been obtained by using them concerning the mechanisms of action and regulation of the motors that drive IFT, the composition and organization of the IFT-particles, and the identification of IFT-dynein subunits and ciliary tubulin isotypes as likely cargo proteins of kinesin-2-driven anterograde IFT.


Extramammary Paget's Disease: A Review of the Literature Part II: Treatment and Prognosis.
Extramammary Paget's disease (EMPD) is a rare malignancy with unclear pathophysiology that occurs predominantly on apocrine-rich skin. Surgery is the treatment of choice; however, procedures tend to be extensive and associated with a high rate of recurrence. To review the current literature on EMPD regarding treatment and prognosis. Literature review using PubMed search for articles related to EMPD. Extramammary Paget's disease classically presents as a slowly growing red plaque, which often mimics an inflammatory condition leading to significant delay in diagnosis. Diagnosis requires histopathologic examination and is often supported by immunohistochemical analysis. Once a diagnosis of EMPD is made, the patient must be risk-stratified and evaluated for an underlying malignancy. Standard of treatment is surgery, with data suggesting that Mohs micrographic surgery may have superior clinical outcomes and lower recurrence rates. Alternatives such as photodynamic therapy and topicals have been explored and may be appropriate in certain situations. Patients with EMPD generally have a good prognosis with a 5-year overall survival rate of 75% to 95%.


Hydrogen bonding interactions of polyamines with the 2' OH of RNA.
Polyamines and other charged amines bind to RNA by hydrogen bonding to the 3' phosphate and to the 2' OH. This mode of binding suggests a mechanism by which DNA and RNA might be distinguished by enzymes.


Approach-avoidance biases to self-harm cues in young people with self-harm.
The urge to self-harm can be likened to craving in addictive behaviours. However, it remains unclear whether cognitive mechanisms involved in craving, such as attentional biases to cues, also underpin the urge to self-harm. A Dot Probe Task was used to investigate attentional biases to self-harm cues in young people aged 16-25 with self-harm. Cues were shown for either 0.2 s or 2 s. Dot Probe Task performance in the Self-harm group (N = 50) was compared with age-matched Healthy Controls (N = 50) and age- and negative-affect (Depression Anxiety Stress Scale-21) matched controls with no self-harm (N = 50). The Self-harm group showed significantly greater avoidance of self-harm cues than Healthy Controls at 2 s. The Negative Affect group showed significantly less difficulty disengaging from self-harm cues than the Self-harm group and Healthy Controls at 2 s. There were no between-group differences in attentional bias at 0.2 s. Study limitations that may affect attentional biases in the Self-harm group include not measuring indicators of recovery and recruiting only from the community potentially missing more severe self-harm presentations in clinical settings. Avoidance of self-harm cues in young people with self-harm may reflect conflict around self-harm behaviour, consistent with ambivalence models of craving. An ability to disengage from self-harm cues may be a protective factor in young people with higher levels of negative affect who do not self-harm. Whether these attentional biases represent a quantifiable marker of treatment response or susceptibility to relapse in individuals with self-harm remains an area for future investigation.


Detection of potential enteric pathogens in children with severe acute gastroenteritis using the filmarray: Results from a three - years hospital-based survey in Northern Italy.
Acute gastroenteritis (AGE) are leading causes of morbidity and mortality in children. Therefore, rapid pathogens identification is needed. The AGE aetiology was investigated from 2018 to 2020 in 2,066 children in Parma (Italy) by FilmArray Gastrointestinal Panel and Enterovirus-targeting RT-PCR. Pathogens were detected in 1,162 (56.2%) stool samples from as many children; 798 (68.7%) were single and 364 (31.3%) mixed infections (68.7% vs 31.3%, P < 0.0001). Children aged 0-5 years showed the highest infection incidence (66.1%). The most frequent pathogens were Enteropathogenic Escherichia coli (EPEC; 19.14%), Clostridioides difficile (10.42%), Norovirus (10.36%), Enterovirus (9.44%), and Campylobacter (9.21%). EPEC, Campylobacter, enteroaggregative E. coli, Norovirus, and Rotavirus showed seasonality. The incidence of pathogens detected decreased between 2018 and 2020 (42.7% vs 20.8%, P < 0.0001), seemingly for the preventive measures imposed by the severe acute respiratory syndrome coronavirus-2 pandemic. A putative aetiology in half the children examined and an estimate of enteric pathogens epidemiology were assessed.


Methods for the estimation of high density cholesterol, comparison between two laboratories.
The determination of HDL by quantification of HDL-cholesterol was investigated using different methods and employing the Abell method as reference. The routinely applied direct method of Huang (calibrated on Abell standardized sera) and the enzymatic method of Röschlau were tested. Results show that with the Huang method, as compared to Abell values, a total laboratory error of less than 4.5 mg/100 can be achieved in 95% of the cases. The enzymatic method gave rise to erroneous results. Comparisons between two laboratories in experiments using random and pool sera are presented.


Intact growth factors are conserved in the extracellular matrix of ancient human bone and teeth: a storehouse for the study of human evolution in health and disease.
For the first time we have extracted, solubilized and identified growth factors, such as insulin growth factor II (IGF-II), bone morphogenetic protein-2 (BMP-2), and transforming growth factor-beta (TGF-beta), from archaeological compact human bone and tooth dentin dating from the late pre-ceramic pottery Neolithic (late PPNB) and the early Middle Ages. These factors are typical of special physiological or pathological situations in the metabolism of bone. The extracellular matrix proteins from bone and teeth of individuals from the late PPNB and early Middle Ages were separated by 2-D electrophoresis and more than 300 different protein spots were detected by silver staining. The matrix protein patterns of compact bone and tooth from the same individual (early Middle Ages) are very different and only 16% of the protein spots were detected in both compact bone and tooth dentin.


Changes in endometrial receptivity in women with Asherman's syndrome undergoing hysteroscopic adhesiolysis.
To determine whether there is any improvement in the endometrial receptivity in infertile women with Asherman's syndrome undergoing hysteroscopic adhesiolysis. This was a prospective observational clinical analysis of 40 infertile patients who underwent hysteroscopic adhesiolysis for Asherman's syndrome in a tertiary level hospital. Endometrial thickness and blood flow impedance of the uterine spiral artery by transvaginal color pulsed Doppler ultrasound was measured post-menstrual on day 2/3 and post-menstrual on day 21 pre- and post-hysteroscopic adhesiolysis or at a randomly chosen time in patients with amenorrhea. The age of the patients was 18-36 years (mean 29.2 years). The mean duration of infertility was 6.9 years. There were 27 (67.5 %) women with primary infertility and 13 (32.5 %) had secondary infertility. 22 (55 %) women had had genital tuberculosis in the past. A significant improvement in the endometrial thickness was observed on day 2 (p < 0.0001) and day 21 (p < 0.0001) 3 months post-adhesiolysis. The spiral artery RI was statistically significant (p < 0.04) on day 2 pre-adhesiolysis compared to post-adhesiolysis. A significant improvement in the endometrial thickness was observed post-adhesiolysis. A high blood flow impedance of spiral artery perhaps impairs growth of the endometrium making it unsuitable for successful implantation.


Partial characterization of the lipidome of the cold-water scallop, Chlamys islandica.
Fingerprinting of the main lipid components of the digestive gland of the Icelandic scallop-Chlamys islandica-has been performed by ultra-high-performance liquid chromatography coupled with time of flight high-resolution mass spectrometry, UHPLC-HRMS/ToF. This method allowed the identification of 224 lipids, including phosphatidylcholines (PC), plasmanyl (PC-O)/plasmenyl (PC-P) phosphatidylcholines, lyso-phosphatidylcholines (LPC), and their plasmanyl/plasmenyl forms (LPC-O/LPC-P). Diacylglycerols (DG), triacylglycerols (TG), and cholesteryl esters (CE) were the neutral lipids (NL) analyzed. While all of the lipids showed a strong seasonal dependence in terms of quantity, only NLs presented significant qualitative changes. Principal component analysis (PCA) of TG and DG profiles evidenced a prevalence of low unsaturated TGs and DGs in spring, which were replaced by species with a higher degree of unsaturations in summer. In autumn, long and highly unsaturated TGs constitute the lipid fraction of the digestive gland of the scallop, while DG species offer a mixed profile. This study contributes to the characterization and the elucidation of the lipidome of Chlamys islandica and provides baseline data for further study of the effects of pollutants on the lipidome of the Icelandic scallop, often used as a sentinel species in biomonitoring programs.


The nature of pulsar radiation.
Pulsar radiation may be due to particles which gyrate while moving in bunches along curved orbits. If emitted by electrons, the pulses should come from near the speed of light circle; if emitted by protons, they should arise within a few stellar radii of the underlying star.


Time-to-arrival estimations to simulated pedestrians.
Driving a vehicle requires individuals' awareness of their surroundings to prevent collisions with other vehicles, objects, and pedestrians. While previous research has investigated time-to-arrival (TTA) in real-world and simulated driving situations, there is little information on how pedestrian reflectance and time of day impact TTA. The present study investigated how vehicle velocity, viewing time, pedestrian reflectance, and time of day affected individuals' estimates of TTA. We used recorded driver-perspective footage of a vehicle approaching simulated pedestrians at different velocities during daytime and nighttime. We found that TTA was consistently underestimated, with the most accurate TTA estimates occurring at the lowest vehicle velocity. We also found TTA accuracy was better during daytime conditions. Pedestrian reflectance did not produce a significant main effect, but it did interact significantly with both velocity and time of day. These results suggest that multiple variables are responsible for TTA estimation. A better understanding of what factors may affect TTA estimates helps both researchers who investigate the phenomenon and laypersons who strive for safe driving practices.


Clinical study in Chinese patients with late-infantile form neuronal ceroid lipofuscinoses.
Clinical findings, pathological features and tripeptidyl peptidase 1 (TPP1) activity and genetic mutation analysis data of nine patients affected with the late-infantile form of neuronal ceroid lipofuscinoses (LINCL) in China are systematically reviewed with long-term follow-up. The patients were enrolled if curvilinear bodies were found on lymphocyte, skin or muscle specimens' examination, and/or reduction of tripeptidyl peptidase 1 (TPP1) activity were detected. CLN2 gene mutation were tested in five patients. The patients have onset age of 2-3.5 years, and most of them initially present partial seizure, and then progressed to deteriorated mental function, refractory myoclonic seizures, impaired vision, and ataxia with cerebellar atrophy. Discrete small vacuolated lymphocytes are found in 5-10% lymphocytes in 5 patients examined. Curvilinear bodies were found in vacuolated lymphocytes, in skin and muscle tissues. Tripeptidyl peptidase 1 (TPP1) activities are reduced in 5 patients with different CLN2 gene mutation. Detection of vacuolated lymphocytes may be a screen method for LINCL, ultrastructural examination of lymphocytes, combined with TPP1 activity assay, allowing for a definite and faster diagnosis and classification with minimal invasion.


OrderedList--a bioconductor package for detecting similarity in ordered gene lists.
OrderedList is a Bioconductor compliant package for meta-analysis based on ordered gene lists like those resulting from differential gene expression analysis. Our package quantifies the similarity between gene lists. The significance of the similarity score is estimated from random scores computed on perturbed data. OrderedList illustrates list similarity in intuitive plots and determines the score-driving genes for further analysis. http://www.bioconductor.org email@example.com Please visit our webpage on http://compdiag.molgen.mpg.de/software.


Repressors vs. low- and high-anxious coping styles: EEG differences during a modified version of the emotional Stroop task.
In this study of 49 undergraduate university women, those exhibiting a repressive coping style - characterized by defensiveness against negative emotions - were compared to women with low-anxious and high-anxious coping styles during neutral and negative versions of a computerized emotional Stroop task (EST). Using Weinberger, Schwartz, and Davidson's (1979) approach, the present study implemented the Marlowe-Crowne Social Desirability and the Spielberger Trait Anxiety scales for selection. Participants viewed neutral or negative words during the EST but responded to the color of the word. Analysis of continuous EEG recordings for the negative vs. neutral words revealed that the repressor group differed significantly from the other two groups in many aspects but that low- vs. high-anxious groups differed in fewer aspects. Based upon Eysenck and Derakshan's (1997) model, repressor women appear to differ from low- and high-anxious women by utilizing an inhibitory process to avoid perceiving low-intensity threatening stimuli.


Synthesis and antioxidative activity of metalloporphyrins bearing 2,6-di-tert-butylphenol pendants.
The novel metalloporphyrins (M=HH, Fe, Mn, Co, Cu, Zn) bearing 2,6-di-tert-butylphenol pendants as antioxidant substituents, and a long chain hydrocarbon palmitoyl group have been synthesized. The oxidation of compounds by PbO2 leads to the formation of the corresponding 2,6-di-tert-butylphenoxyl radicals studied by EPR. The activity of porphyrins in lipid peroxidation has been examined using (1) in vitro lipid peroxidation induced by tert-butylhydroperoxide in respiring rat liver mitochondria, (2) in vitro lipid peroxidation in liver homogenates of Wistar strain rats, and (3) a model process of peroxidation of (Z)-octadec-9-enic (oleic) acid as a structural fragment of lipids. The activity of these compounds depends dramatically on the nature of metal and might be changed from antioxidative (M=HH, Mn, Cu, Zn) to indifferent (M=Co), and to pro-oxidative one (M=Fe). The anti- or pro-oxidative action of these compounds may be derived from the concurrence between the involvement of 2,6-di-tert-butylphenol pendants acting as radical scavengers and redox active metal center promoting oxidation processes. The results of this study suggest that the polytopic compounds combining in one molecule 2,6-di-tert-butylphenol pendants, metalloporphyrin moiety, and a palmitoyl group, are membrane active compounds and might be studied in an effort to find novel pharmaceutical agents.


Substance P-like immunoreactive trigeminal ganglion cells supplying the cornea.
Trigeminal ganglion cells supplying the cornea were traced with intra-axonally transported horseradish peroxidase and, subsequently studied for the presence of substance P-like immunoreactivity. Approximately 0%-30% of trigeminal ganglion cells contained immunoreactive substance P. These cells were of a small size (15-50 micrometers in diameter) and were distributed throughout the ganglion. The ganglion cells supplying the cornea were of a relatively small size as well but were confined to the anteromedial part of the ganglion. Some of these cells were found to contain immunoreactive substance P.


The computer-aided facial reconstruction system.
A computer imaging system was introduced into the facial reconstruction process. The system, which consists of the image processing unit for skull morphometry and the image editing unit for compositing facial components on the skull images, was an original construction. The image processor generates the framework for building a face onto the digitized skull image. For reconstructing a facial image on the framework, several possible data sets of facial components suitable for the skull morphology are selected from the database by operating our original application software. The most suitable cutout samples of facial components are pasted up over the framework in accordance with the anatomical criteria. The database of facial components consists of 24 contours, 18 eyes, 9 eyebrows, 27 noses, 9 lips and 16 hairstyles. After provisional reconstruction, the facial image is retouched by correcting skin colors and shades with an 'electronic painting device'. The resulting image is a great improvement on images made by the conventional clay and drawing method, both in the operational aspect and in the flexibility of creating multiple versions. The present system facilitates a rather objective and rapid approach and allows us easily to generate a range of possible faces. The computer-aided facial reconstruction will lead to an increase in chances of positive identification in practical cases.


Generation of New Hairless Alleles by Genomic Engineering at the Hairless Locus in Drosophila melanogaster.
Hairless (H) is the major antagonist within the Notch signalling pathway of Drosophila melanogaster. By binding to Suppressor of Hairless [Su(H)] and two co-repressors, H induces silencing of Notch target genes in the absence of Notch signals. We have applied genomic engineering to create several new H alleles. To this end the endogenous H locus was replaced with an attP site by homologous recombination, serving as a landing platform for subsequent site directed integration of different H constructs. This way we generated a complete H knock out allele HattP, reintroduced a wild type H genomic and a cDNA-construct (Hgwt, Hcwt) as well as two constructs encoding H proteins defective of Su(H) binding (HLD, HiD). Phenotypes regarding viability, bristle and wing development were recorded, and the expression of Notch target genes wingless and cut was analysed in mutant wing discs or in mutant cell clones. Moreover, genetic interactions with Notch (N5419) and Delta (DlB2) mutants were addressed. Overall, phenotypes were largely as expected: both HLD and HiD were similar to the HattP null allele, indicating that most of H activity requires the binding of Su(H). Both rescue constructs Hgwt and Hcwt were homozygous viable without phenotype. Unexpectedly, the hemizygous condition uncovered that they were not identical to the wild type allele: notably Hcwt showed a markedly reduced activity, suggesting the presence of as yet unidentified regulatory or stabilizing elements in untranslated regions of the H gene. Interestingly, Hgwt homozygous cells expressed higher levels of H protein, perhaps unravelling gene-by-environment interactions.


Serum Maresin 1 levels in idiopathic acute anterior uveitis patients.
The purpose of the present study is to assess the levels of Maresin 1 (MaR1) in patients with idiopathic acute anterior uveitis (IAAU) and to compare the MaR1 results with healthy controls. This study includes 24 patients with idiopathic AAU and 24 healty controls (C). The serum MaR1 levels were analyzed using enzyme-linked immunosorbent assays (ELISA). The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured at the time of diagnosis. MaR1 levels were statistically significant when the IAAU group was compared with group C (P<0.001). When idiopathic AAU patients were compared with group C, no statistically significant difference was found between ESR and CRP levels (P=0.086, P=0.549 respectively). Serum MaR1 levels are an important biomarker of disease in patients with idiopathic AAU.


Left ventricular mass as a predictor of cardiovascular events in the era of hypertension management using home blood pressure measurement: the J-HOP study.
Target organ damage (TOD) is associated with a risk of cardiovascular disease (CVD) independent of blood pressure (BP); however, this association has been observed based on the assessment of office BP. We studied 1641 patients (mean age 64.8 ± 11.7 years) with CVD risk factors who underwent home BP measurement over a 14-day period and evaluated TOD at baseline and then performed follow-up examination of the J-HOP (Japan Morning Surge-Home Blood Pressure) study results. During the median follow-up of 6.6 ± 3.5 years, 115 participants experienced a CVD event. After adjustment for CVD risk factors, including office systolic BP, the adjusted hazard ratios expressing the risk of CVD events were 1.30 (95% confidence interval, 1.15-1.52), 1.27 (1.04-1.56), and 1.25 (1.11-1.40) per one-SD increase in log-transformed urinary albumin creatinine ratio (UACR, 0.57 mg/gCre), brachial-ankle pulse wave velocity (baPWV, 342 cm/s) and left ventricular mass index (LVMI, 26.6 g/m2) assessed by echocardiography, respectively. Even after adding home systolic BP as a covariate, these associations remained except for the association with baPWV (all P < 0.05). The C-statistic for the base model including office and home systolic BP for the risk of CVD events was 0.783 (95% CI: 0.743, 0.824), which significantly increased to 0.795 (95% CI: 0.757, 0.834) after adding LVMI, and changed slightly but not significantly with the addition of UACR or baPWV. Adding UACR, baPWV, or both to the model including LVMI did not improve CVD event prediction. In the modern era of hypertension management using home BP measurement, TOD indicators, especially LVMI, provide superior CVD event prediction independent of and beyond home BP.


Innovativeness and the effects of urbanization on risk-taking behaviors in wild Barbados birds.
The effects of urbanization on avian cognition remain poorly understood. Risk-taking behaviors like boldness, neophobia and flight distance are thought to affect opportunism and innovativeness, and should also vary with urbanization. Here, we investigate variation in risk-taking behaviors in the field in an avian assemblage of nine species that forage together in Barbados and for which innovation rate is known from previous work. We predicted that birds from highly urbanized areas would show more risk-taking behavior than conspecifics from less urbanized parts of the island and that the differences would be strongest in the most innovative of the species. Overall, we found that urban birds are bolder, less neophobic and have shorter flight distances than their less urbanized conspecifics. Additionally, we detected between-species differences in the effect of urbanization on flight distance, more innovative species showing smaller differences in flight distance between areas. Our results suggest that, within successful urban colonizers, species differences in innovativeness may affect the way species change their risk-taking behaviors in response to the urban environment.


Occupational hazards and illnesses of Filipino women workers in export processing zones.
This was a baseline study on occupational exposure and health problems among women workers in export processing zones. Physical, chemical, and ergonomic hazards were evaluated and measured through workplace ambient monitoring, survey questionnaires, and interviews with 500 respondents in 24 companies (most were female at 88.8%). The top 5 hazards were ergonomic hazards (72.2%), heat (66.6%), overwork (66.6%), poor ventilation (54.8%), and chemical exposure (50.8%). The most common illnesses were gastrointestinal problems (57.4%), backache (56%), headache (53.2%), and fatigue/weakness (53.2%). Logistic regression showed an association between certain work-related factors and occupational illnesses, and psychosocial problems. Highly significant associations were hearing loss with years spent in the company (p=.005) and gender (p=.006), headache and dizziness with poor ventilation (p=.000), backache with prolonged work (p=.003). These results will have implications for policy and program formulation for women workers' concerns and issues in export zones.


Development of mechanics and pulmonary reflexes.
The mechanical properties of the respiratory system are paramount in converting neural output into ventilation. The highly compliant chest wall of the newborn results in chest distortion and volume loss during inspiration and, as the chest is also unable to resist the inward recoil of the lung, there is a reduction in lung volume at end expiration (functional residual capacity) and a tendency for alveoli to collapse. Vagal innervation of the lungs and airways is responsible for eliciting various reflexes that result in the dynamic modification of respiratory mechanics and an improvement in ventilation. From the first breath, the newborn increases the frequency of augmented breaths to improve lung compliance and prolongs the expiratory time constant in order to increase the amount of air remaining in the lung at end expiration and help prevent lung collapse. This review examines the respiratory mechanics of the mammalian neonate at birth and during early development together with the vagal reflexes that are responsible for the dynamic modification of respiratory mechanics in order to ensure that effective gas exchange occurs from birth.


Iodine-125--labeled estradiol: a gamma-emitting analog of estradiol that binds to the estrogen receptor.
17 beta-[16 alpha-125I]Iodoestradiol has been synthesized by exchange of 16 beta-bromoestradiol with Na125I. The iodinated product is readily separated from the bromo reactant by column chromatography. It concentrates in the rat uterus in vivo and binds avidly and specifically to the uterine estrogen receptor in vitro.


The use of molecular genetics in the improvement of agricultural populations.
Substantial advances have been made in the genetic improvement of agriculturally important animal and plant populations through artificial selection on quantitative traits. Most of this selection has been on the basis of observable phenotype, without knowledge of the genetic architecture of the selected characteristics. However, continuing molecular genetic analysis of traits in animal and plant populations is leading to a better understanding of quantitative trait genetics. The genes and genetic markers that are being discovered can be used to enhance the genetic improvement of breeding stock through marker-assisted selection.


Laboratory diagnosis of bacteremia by headspace gas-liquid chromatography.
The growth of Staphylococcus aureus, Streptococcus pneumoniae, S. fecalis, S. sanguis, S. bovis, S. mitior, S. agalactiae, Escherichia coli, A-D group, Klebsiella aerogenes, K. oxytoca, Enterobacter cloacae, Proteus mirabilis, Serratia marcescens, Pasteurella multocida or Listeria monocytogenes in 83 blood cultures was detected in a 1.5-min analysis using head-space gas-liquid chromatography. Two hundred and twenty-four blood cultures in which there was no growth of micro-organisms were negative in the analysis. The analysis detected the growth of S. epidermidis in only 6 of 26 blood cultures and failed to detect the growth of Pseudomonas aeruginosa, Candida albicans and species of Micrococcus, Corynebacterium or Bacillus in 18 blood cultures.


Guanylate cyclase from the rat renal medulla. Physical properties and comparison with adenylate cyclase.
Guanylate cyclase from the rat renal medulla is found in both the soluble and particulate fractions of the cell. Sucrose density gradient centrifugation and gel filtration in H2O and D2O indicate that the enzyme from the soluble cell fraction has the following properties: S20w, 6.3 S; Stokes radius, 54 A; partial specific volume, 0.75 ml/g; mass, 154,000 daltons; f/fo, 1.4; axial ratio (prolate ellipsoid), 7. The addition of 0.1% Lubrol PX to this fraction activates the enzyme and changes thartial specific volume, 0.74 ml/g; mass, 148,000 daltons; f/fo, 1.6; axial ratio (prolate ellipsoid), 11. These findings show that detergent activates the enzyme by changing its conformation and not simply by dispersing nonsedimentable membrane fragments. The dimensions of this guanylate cyclase in detergent are very similar to those of detergent-solubilized adenylate cyclase from the same tissue (Neer, E.J. (1974) J. Biol. Chem. 249, 6527-6531). Guanylate cyclase can be solubilized from the particulate cell fraction with 1% Lubrol PX but has properties quite different from those of the guanylate cyclase in the soluble cell fraction. It is a large aggregate with a value of S20,w of about 10 S, Stokes radius of 65 A, and a mass of approximately 300,000 daltons. However, the peaks of guanylate cyclase activity in column effluents and sucrose density gradients are very broad indicating a mixture of different size proteins. The conditions used to solubilize guanylate cyclase from the particulate fraction also solubilize adenylate cyclase, and the two activities can be separated on the same sucrose gradient. Studies of this sort require a rapid, accurate guanylate cyclase assay. We have developed an assay for guanylate cyclase activity which meets these criteria by adapting the competitive protein binding assay for guanosine cyclic 3':5' monophosphate originally described by Murad et al. (Murad, F., Manganiello, V., and Vaughn, M. (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 736-739).


Neurotransmitter modulation of neuronal calcium channels.
There are many different calcium channels expressed in the mammalian nervous system, but N-type and P/Q-type calcium channels appear to dominate the presynaptic terminals of central and peripheral neurons. The neurotransmitter-induced modulation of these channels can result in alteration of synaptic transmission. This review highlights the mechanisms by which neurotransmitters affect the activity of N-type and P/Q-type calcium channels. The inhibition of these channels by voltage-dependent and voltage-independent mechanisms is emphasized because of the wealth of information available on the intracellular mediators and on the effect of these pathways on the single-channel gating.


Thioredoxin reductase as a novel biomarker for the diagnosis and efficacy prediction of gastrointestinal malignancy: a large-scale, retrospective study.
Our aim was to investigate the rationality and accuracy of plasma TrxR activity as an efficient tool in the early diagnosis of gastrointestinal malignancy, and whether TrxR can be used to evaluate the therapeutic efficacy of gastrointestinal malignancy. We enrolled a total of 5091 cases, including 3736 cases in gastrointestinal malignancy, 964 in benign diseases, and 391 cases in healthy controls. We also performed receiver operating characteristic (ROC) analysis to evaluate diagnostic efficiency of TrxR. Finally, we detected pre- and post-treatment level of TrxR and common tumor markers. The plasma TrxR level in patients with gastrointestinal malignancy [8.4 (6.9, 9.7) U/mL] was higher than that in patients with benign disease [5.8 (4.6, 6.9) U/mL] and healthy control [3.5 (1.4, 5.4) U/mL]. Plasma TrxR showed a significant diagnostic advantage with an AUC of 0.897, compared with conventional tumor markers. In addition, the combination of TrxR and conventional tumor markers can further improve the diagnostic efficiency. We derived the optimal cut-off value of plasma TrxR as a diagnostic marker of gastrointestinal malignancy according to Youden index of 6.15 U/mL. After measuring the change trend of TrxR activity and conventional tumor markers before and after anti-tumor treatments, we found that their change trend was generally consistent, and the plasma TrxR activity was significantly decreased in patients treated with chemotherapy, targeted therapy and immunotherapy. Our findings recommend that plasma TrxR activity could be monitored as an efficient tool for the early diagnosis of gastrointestinal malignancy and as a feasible tool to evaluate the therapeutic effect.


Acute liver failure associated with lamotrigine in children with epilepsy: A report of two cases and thoughts on pharmacogenomics.
Pediatric acute liver failure (PALF) is a rare and life-threatening clinical syndrome for which drug-induced liver injury is a cause. Lamotrigine (LTG) is generally a safe and effective antiseizure medication, and PALF related to LTG has rarely been reported. Here, we describe two cases of PALF associated with LTG in children with epilepsy. In both patients, LTG was used in combination with valproic acid at an initial dose exceeding the recommended dose, which increased the risk of adverse reactions. In addition, single nucleotide polymorphisms of genes associated with the pharmacokinetics and pharmacodynamics of LTG were selected for pharmacogenomic testing. However, the results revealed that genotypes of the patients had variable effects on the serum concentration and therapeutic responsiveness of LTG and therefore did not explain the clinical manifestations well. The findings of this case report caution clinicians to be aware of the risk of liver failure when using antiseizure medication in polytherapy, especially LTG in combination with valproic acid. When administered to children, the recommended dosage of LTG should be strictly followed. Further pharmacogenomic studies are needed to help improve the efficacy and safety of epilepsy treatment in the future.


Stochastic modeling of bacterial adhesion: a two-step mechanism with linear adhesion rate.
Stochastic analysis of bacterial adhesion onto the surface of solid substrate is presented. Bacterial adhesion is assumed to occur in two steps: (i) a reversible adhesion between bacteria and solid surface; bacteria on the surface are weakly bound during this period, followed by (ii) an irreversible surface reaction which results in a strong binding force between bacteria and the surface; bacteria are considered to be in adhered form at this stage. The stochastic representation provides both the macroscopic and fluctuating information about the transient behavior of the phenomenon under consideration.


Atopic dermatitis apparently caused by type 2 CD8+ T cells in an AIDS patient.
A patient with atopic dermatitis and acquired immune deficiency syndrome (AIDS) had demonstrated blood eosinophilia, high levels of serum IgE and intracytoplasmic IL-4 in the CD8+ but not in the CD4+ cells, decreased numbers of CD4+ cells, and low levels of IL-2 in both CD4+ and CD8+ cells. These results, reflecting a predominant influence of type 2 CD8+ cells, suggest they were involved in the genesis exacerbation of the patient's atopic dermatitis.


Exploring the relationship of rush hour period and fatal and non-fatal crash injuries in the U.S.: A systematic review and meta-analysis.
Road crashes are preventable causes of morbidity and mortality. In the U.S., substantial crashes occur during the rush hour period. The rush hour represents the period of the day during which the density of humans and vehicles in the road environment is highest. In the U.S., the rush hour period is bi-modal, occurring in the morning and the afternoon, at times that vary by state and urban-rural status. This systematic review and meta-analysis aimed to evaluate the association between the rush hour period and fatal and non-fatal crash injuries. Selected articles were limited to peer-reviewed full-text articles that measured crash injury as an outcome and rush hour as either a predictor, covariate, stratification, or a control variable. A total of 17 articles were identified for systematic review and nine articles were included in the meta-analysis. Across the selected studies, the rush-hour period signified the period of "peak traffic flow." During the rush hour period, aggressive driving behavior, truck driving, bicycle riding, and precipitation were associated with increased crash events or crash injuries. Across the nine studies included in the meta-analysis, the effective sample size was 236,433. The rush-hour period was associated with a 28% increased risk of fatal crash injury (Pooled RR: 1.28; 95% CI: 1.11-1.45) and the morning rush hour period was associated with 36% increased crash injury risk (Pooled RR: 1.36; 95% CI: 1.13-1.59). The rush hour period, though less commonly studied as a predictor of fatal and non-fatal crash injuries, represents an important domain in need of crash injury prevention attention. The knowledge of the pattern of crash injuries, as it varies across countries, states, regions, and county can inform policy and intervention, in the presence of competing public health needs.


A comparison of treatment planning techniques for low-dose-rate (LDR) prostate brachytherapy.
The purpose of this study was to compare low-dose-rate prostate brachytherapy treatment plans created using three retrospectively applied planning techniques with plans delivered to patients. Treatment plans were created retrospectively on transrectal ultrasound (TRUS) scans for 26 patients. The technique dubbed 4D Brachytherapy was applied, using TRUS and MRI to obtain prostatic measurements required for the associated webBXT online nomogram. Using a patient's MRI scan to create a treatment plan involving loose seeds was also explored. Plans delivered to patients were made using an intraoperative loose seed TRUS-based planning technique. Prostate V100 (%), prostate V150 (%), prostate D90 (Gy), rectum D0.1cc (Gy), rectum D2cc (Gy), urethra D10 (%), urethra D30 (%), and prostate volumes were measured for each patient. Statistical analysis was used to assess and compare plans. Prostate volumes measured by TRUS and MRI were significantly different. Prostate volumes calculated by the webBXT online nomogram using TRUS- and MRI-based measurements were not significantly different. Compared with delivered plans, TRUS-based 4D Brachytherapy plans showed significantly lower rectum D0.1cc (Gy) values, MRI-based 4D Brachytherapy plans showed significantly higher prostate V100 (%) values and significantly lower rectum D0.1cc (Gy), urethra D10 (%), and urethra D30 (%) values, and loose seed MRI-based plans showed significantly lower prostate V100 (%), prostate D90 (Gy), rectum D0.1cc (Gy), rectum D2cc (Gy), urethra D10 (%), and urethra D30 (%) values. TRUS-based 4D Brachytherapy plans showed similar dosimetry to delivered plans; rectal dosimetry was superior. MRI can be integrated into the 4D Brachytherapy workflow. The webBXT online nomogram overestimates the required number of seeds.


Bleeding risk in randomized controlled trials comparing warfarin and aspirin: a systematic review and meta-analysis.
Warfarin and aspirin (acetylsalicylic acid [ASA]) are the most commonly used anticoagulant and antiplatelet drugs in the treatment of cardiovascular disease. To provide a pooled estimate of the bleeding risk from randomized controlled trials (RCTs) comparing warfarin and ASA at the dose ranges recommended in evidence-based guidelines. Ovid MEDLINE, Embase and the Cochrane Library, up to September 2011, were searched for RCTs comparing bleeding rates in adult patients randomized to warfarin, target International Normalized Ratio (INR) 2.0-3.5, and ASA, 50-650 mg daily, with at least 3 months of follow-up. Pooled odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated with the inverse variance method and the random effects model. Four thousand four hundred and forty-two abstracts were screened, resulting in eight included studies for final analysis. A pooled estimate derived from the 2904 patients enrolled indicated a trend towards an increase in major bleeding risk in those randomized to warfarin (OR 1.27; 95% CI 0.83-1.94). The pooled OR for intracranial hemorrhage in patients treated with warfarin vs. ASA was 1.64 (95% CI 0.71-3.78), and that for extracranial major bleeding was 1.03 (95% CI 0.61-1.75). Minor bleeding, from a 1748-patient sample, was more common in warfarin patients (OR 1.50; 95% CI 1.13-2.00). This meta-analysis failed to find a statistically significant difference in major bleeding between warfarin, target INR 2.0-3.5, and ASA, 50-650 mg daily. The trend towards increased bleeding with warfarin appears to be explained by an excess of intracranial bleeding in warfarin patients.


Endotoxin in storage medium of human corneal grafts and clinical course after penetrating normal-risk keratoplasty.
It is well known that endotoxins in storage medium may stimulate cytokine production and expression of adhesion molecules as well as endothelial damage in human corneal grafts. It has been supposed that endotoxin exposure of corneal grafts may, therefore, cause immune reactions and lead to reduced endothelial cell count after penetrating keratoplasty. It was the purpose of this prospective study to evaluate if this hypothesis is true. A consecutive series of 274 samples of sterile organ culture storage medium from 274 human corneal grafts was collected between August 1998 and February 1999 and tested for endotoxin using Limulus amebocyte-lysate assay (LAL) after 7 days of organ culture. Threshold endotoxin level was set at 1.0 U/ml. A total of 161 grafts were transplanted and 113 were discarded. Within the 161 corneas transplanted, 62 were grafted to normal-risk patients and 99 to high-risk patients. Only normal-risk keratoplasty patients were included in the study and followed for at least 10 months. Immune reactions, graft failures, and postoperative endothelial cell counts were recorded. The mean endotoxin level in organ culture medium of all transplanted grafts was 1.07+/-2.96. Mean endotoxin level in organ culture medium of discarded grafts was 1.68+/-5.76, with 71 samples being below and 42 above the threshold of 1.0 U/ml called endotoxin-negative and endotoxin-positive, respectively. In all 36 culture medium samples from the 62 grafts transplanted to the group of normal-risk keratoplasty patients were endotoxin-negative and 26 endotoxin-positive. An influence of endotoxin levels on incidence of immune reactions, graft failure, and postoperative endothelial cell counts could not be revealed in patients with normal-risk keratoplasty. Low endotoxin levels in storage medium neither seem to promote immune reactions nor to contribute to postoperative chronic endothelial cell loss in normal-risk keratoplasty patients.


Ectopic expression of Irx3 and Irx5 in the paraventricular nucleus of the hypothalamus contributes to defects in Sim1 haploinsufficiency.
The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of Sim1-expressing neurons critical for feeding regulation. Sim1 haploinsufficiency results in hyperphagic obesity with disruption of PVH neurons, yet the molecular profiles of PVH neurons and the mechanism underlying the defects of Sim1 haploinsufficiency are not well understood. By single-cell RNA sequencing, we identified two major populations of Sim1+ PVH neurons, which are differentially affected by Sim1 haploinsufficiency. The Iroquois homeobox genes Irx3 and Irx5 have been implicated in the hypothalamic control of energy homeostasis. We found that Irx3 and Irx5 are ectopically expressed in the Sim1+ PVH cells of Sim1+/− mice. By reducing their dosage and PVH-specific deletion of Irx3, we demonstrate that misexpression of Irx3 and Irx5 contributes to the defects of Sim1+/− mice. Our results illustrate abnormal hypothalamic activities of Irx3 and Irx5 as a central mechanism disrupting PVH development and feeding regulation in Sim1 haploinsufficiency.


Physicochemical properties and adsorption state of aluminum adjuvants with different processes in vaccines.
Aluminum salts are by far the most widely used adjuvants for human vaccines, showing acceptable safety and efficacy. Previous studies have shown that each aluminum adjuvant have different charges and morphologies, but whether the manufacturing and production processes affects the physicochemical properties of aluminum adjuvant has not yet been reported. In this study, we explored the physical and chemical properties of different aluminum adjuvants and Hib, sIPV antigens through particle size, zeta potential and morphological characteristics. The adsorption rate and efficacy were also investigated. The results showed that the preparation process had an impact on the physical and chemical properties of aluminum adjuvants, including differences in the particle size,zeta potential and morphological structure. Hib vaccine had larger particle size than sIPV vaccine with different aluminum adjuvants in the process of vaccine preparation. In addition, by measuring the adsorption rate, increasing the concentration of phosphate or Aluminum phosphate (AP) can improve the adsorption rate of Hib, but Aluminium hydroxide (AH) and amorphous aluminum hydroxyphosphate sulfate (AAHS) adjuvants are not affected. In vivo result showed that increasing the adsorption rate of Hib could enhance the Hib-IgG antibody titers. In conclusion, this study provides a reference for the application of adjuvants in vaccines by studying the physicochemical properties and adsorption conditions of different aluminum adjuvants and antigens.


Acoustic surveillance of cough for detecting respiratory disease using artificial intelligence.
Can smartphones be used to detect individual and population-level changes in cough frequency that correlate with the incidence of coronavirus disease 2019 (COVID-19) and other respiratory infections? This was a prospective cohort study carried out in Pamplona (Spain) between 2020 and 2021 using artificial intelligence cough detection software. Changes in cough frequency around the time of medical consultation were evaluated using a randomisation routine; significance was tested by comparing the distribution of cough frequencies to that obtained from a model of no difference. The correlation between changes of cough frequency and COVID-19 incidence was studied using an autoregressive moving average analysis, and its strength determined by calculating its autocorrelation function (ACF). Predictors for the regular use of the system were studied using a linear regression. Overall user experience was evaluated using a satisfaction questionnaire and through focused group discussions. We followed-up 616 participants and collected >62 000 coughs. Coughs per hour surged around the time cohort subjects sought medical care (difference +0.77 coughs·h-1; p=0.00001). There was a weak temporal correlation between aggregated coughs and the incidence of COVID-19 in the local population (ACF 0.43). Technical issues affected uptake and regular use of the system. Artificial intelligence systems can detect changes in cough frequency that temporarily correlate with the onset of clinical disease at the individual level. A clearer correlation with population-level COVID-19 incidence, or other respiratory conditions, could be achieved with better penetration and compliance with cough monitoring.