Intravascular monitoring and management of erythroblastosis fetalis.
Over a 27-month period 17 pregnancies in 16 patients with severe red blood cell isoimmunization were managed with intravascular transfusions performed in utero. Fourteen of these women were Rh negative and sensitized to D or to both D and C, and the remaining two patients were sensitized to the Kell antigen (K). In 12 of the 17 cases (71%) the first intravascular transfusion was performed at 26.5 weeks' gestation or earlier. Thirty-nine of 45 attempted transfusions (87%) were successfully performed. All were done percutaneously under ultrasonic guidance. Two procedures were partial exchanges, while the remainder were straight transfusions. Thirteen of the 17 fetuses (76%) were alive at birth and survived the neonatal period. Four fetuses died in utero at 25 to 26 weeks' gestation, all within 12 hours of an intravascular transfusion. When the 27 procedures attempted during the most recent 9 months of this series were compared with the 18 procedures attempted during the preceding 18 months, no appreciable differences in technical success or fetal outcome were evident. An analysis of this experience is presented, along with modifications in technique that have been implemented. Unresolved issues are discussed.


A generic miniature multi-feature programmable wireless powering headstage ASIC for implantable biomedical systems.
Wireless powering holds immense promise to enable a variety of implantable biomedical measurement systems with different power supply and current budget requirements. Effective power management demands more functionality in the headstage design like power level detection for range estimation and power save modes for sleep-wake operation. This paper proposes a single chip ASIC solution that addresses these problems by incorporating digitally programmable features and thus has the potential to enable wireless powering for many implantable systems. The ASIC includes an RF rectifier which has a peak efficiency of 17.9% at 900 MHz and 11.0% at 2.4 GHz, a robust 1 V bandgap reference and LDO voltage regulator whose output can be programmed in the range of 1 V-1.5 V, and can drive upto 4 mA of load current. The input RF power level detector has a threshold of 1.6 V and the power management block can be programmed to give a 6%, 12.5% or 25% duty cycle power line to the transmitter resulting in upto 60% reduction in average power. The ASIC was fabricated using the TSMC 65 nm process, occupies 1mm(2) die area and the headstage consumes ~300 μA at 1.2V regulated supply.


Predicting Likelihood for Coronary Artery Bypass Grafting After Non-ST-Elevation Myocardial Infarction: Finding the Best Prediction Model.
Up to half of patients with non-ST-elevation myocardial infarction (NSTEMI) do not receive dual antiplatelet therapy before angiography "pretreatment" because of the risk of increased bleeding if coronary artery bypass grafting (CABG) operation is needed. Several models have been published that predict the likelihood of CABG after NSTEMI, but they have not been independently validated. The purpose of this study was to validate these models and improve the best one. We studied patients with NSTEMI who were enrolled in the 24-center Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) registry between 2005 and 2008. Previous CABG prediction models were assessed using c-statistics and calibration assessments to determine the best model. Variables from TRIUMPH likely to be associated with CABG were tested to see whether they could improve the best model's performance. Among 2,473 patients with NSTEMI, 11.8% underwent in-hospital CABG. C-statistics for the Modified Thrombolysis in Myocardial Infarction, Treat Angina With Aggrastat and Determine the Cost of Therapy With an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction 18, Poppe, and Global Risk of Acute Coronary Events (GRACE) models were 0.54, 0.61, 0.61, and 0.62, respectively. The GRACE model showed the best discrimination and calibration. From the TRIUMPH registry, preselected variables were added to the GRACE model but did not significantly improve model discrimination. A GRACE model risk score of less than 9 had high sensitivity (96%), thus making it useful for predicting patients with NSTEMI who were at low risk for requiring CABG, which included approximately 21% of patients with NSTEMI. This study could not improve on the GRACE model, which had the best predictive value for identifying a need for CABG after NSTEMI with a broader range of predicted risk levels and high sensitivity, especially in patients with scores lower than 9.


Home-based self-delivered mirror therapy for phantom pain: a pilot study.
To test the feasibility and preliminary efficacy of self-delivered home-based mirror therapy for phantom pain. Uncontrolled prospective treatment outcome pilot study. Forty community-dwelling adults with unilateral amputation and phantom pain > 3 on a 0-10 numeric rating scale enrolled either during a one-time study visit (n = 30) or remotely (n = 10). Participants received an explanation of mirror therapy and were asked to self-treat for 25 min daily. Participants completed and posted back sets of outcomes questionnaires at months 1 and 2 post-treatment. Main outcome was average phantom pain intensity at post-treatment. A significant reduction in average phantom pain intensity was found at month 1 (n = 31, p = 0.0002) and at month 2 (n = 26, p = 0.002). The overall median percentage reduction at month 2 was 15.4%. Subjects with high education (> 16 years) compared with low education (< 16 years) (37.5% vs 4.1%) had greater reduction in pain intensity (p = 0.01). These findings support the feasibility and efficacy of home-based self-delivered mirror therapy; this low-cost treatment may defray medical costs, therapy visits, and the patient travel burden for people with motivation and a high level of education. More research is needed to determine methods of cost-effective support for people with lower levels of education.


Celecoxib induces apoptosis but up-regulates VEGF via endoplasmic reticulum stress in human colorectal cancer in vitro and in vivo.
In our previous study, we found that celecoxib, a kind of COX-2 inhibitor, led to cell apoptosis while up-regulating the expression of vascular endothelial growth factor (VEGF) in colorectal cancer HCT116 cells (COX-2 deficient), and endoplasmic reticulum (ER) stress was involved in the mechanism. Thus, we would like to explore whether these results are universal for other colorectal cancer cells, especially for COX-2-expressing ones, and whether the results in vitro and in vivo are matched. HT29 cells (COX-2 expressing) were treated with celecoxib under different conditions to evaluate cell apoptosis, VEGF expression and the activation of ER stress. HT29 and HCT116 xenograft tumor models were established to evaluate anti-tumor effects and verify the experiment results we obtained in vitro. Celecoxib (≥60 µM) up-regulated the expression of ER stress markers (GRP78 and CHOP) and induced cell apoptosis accompanying with a correlated increased expression of VEGF in HT29 cells. Celecoxib-induced gene expression and cell apoptosis were inhibited by an ER stress inhibitor, PBA. In xenograft models, celecoxib treatment inhibited tumor growth with increased GRP78 and VEGF, which was consistent with the results in vitro. Celecoxib, both in vitro and in vivo, induced apoptosis of colorectal cancer cells but increased the VEGF levels at the same time in a COX-2-independent manner, namely by activating ER stress. The increased VEGF would impair the effect of celecoxib and bring drug resistant; hence, the optimal schedule of the combination of celecoxib with anti-VEGF drugs needs to be explored.


Hemostatic and thrombotic disorders in the pediatric patient.
This review focuses on significant advances in the field of pediatric hemostasis and thrombosis, with a focus on published studies within the past decade. The evaluation and management of patients with excessive bleeding remain cornerstones of consultative hematology. We will describe the development of validated bleeding assessment tools relevant to pediatric practice, laboratory advances in the evaluation of von Willebrand disease, and a shift in clinical practice regarding the interpretation of normal coagulation studies in patients with significant bleeding phenotypes. There have also been critical advances in the management of hemostatic disorders. This review highlights new treatment paradigms in hemophilia and the rise of multidisciplinary medical homes for women living with bleeding disorders. Given the continued increase in the incidence of thrombosis, particularly in the hospital setting, a full call to arms against pediatric venous thromboembolism is now essential. We will describe recently completed clinical trials of direct oral anticoagulants in children and adolescents and ongoing work to elucidate the appropriate duration of therapy for children with provoked thrombosis. Recent work regarding the prevention of pediatric venous thromboembolism is highlighted, including studies of thromboprophylaxis and the development of risk prediction models for hospital-acquired thrombosis. Finally, we review advances in our understanding of thrombotic sequelae and the need for continued refinement of our evaluation tools. Despite the significant advances in pediatric hemostasis and thrombosis over the past decade, many unanswered questions remain for the next generation of investigators.


400nm ultra-broadband gratings for near-single-cycle 100 Petawatt lasers.
Compressing high-energy laser pulses to a single-cycle and realizing the "λ3 laser concept", where λ is the wavelength of the laser, will break the current limitation of super-scale projects and contribute to the future 100-petawatt and even Exawatt lasers. Here, we have realized ultra-broadband gold gratings, core optics in the chirped pulse amplification, in the 750-1150 nm spectral range with a > 90% -1 order diffraction efficiency for near single-cycle pulse stretching and compression. The grating is also compatible with azimuthal angles from -15° to 15°, making it possible to design a three-dimensional compressor. In developing and manufacturing processes, a crucial grating profile with large base width and sharp ridge is carefully optimized and controlled to dramatically broaden the high diffraction efficiency bandwidth from the current 100-200 nm to over 400 nm. This work has removed a key obstacle to achieving the near single-cycle 100-PW lasers in the future.


Self-Efficacy in Children with Functional Constipation Is Associated with Treatment Success.
To assess the relationship between self-efficacy, the belief that an individual can succeed at a goal, and short-term treatment outcome in children with functional constipation. Patients with functional constipation age 8-16 years completed the Self-Efficacy for Functional Constipation Questionnaire (SEFCQ), consisting of 14 statements about performing tasks needed for defecation. Patients completed SEFCQ before, immediately after, and 3 weeks after their clinic visit. Treatment success was defined as ≥3 bowel movements into the toilet and no fecal incontinence in the third week. 75% of patients had a successful outcome. Scores were higher in the group that was successful than in those that failed before, immediately after the visit, and 3 weeks later (P < .001). Self-efficacy improved at all time points in the group that was successful (P < .001). In the group that failed, scores improved immediately after clinic visit (P < .01) but were unchanged at follow-up (P > .05). Improved self-efficacy is associated with successful outcomes in children with functional constipation, thus, it may be beneficial to enhance self-efficacy for defecation during treatment.


Formation of biphenyl and dibenzofuran phytoalexins in the transition zones of fire blight-infected stems of Malus domestica cv. 'Holsteiner Cox' and Pyrus communis cv. 'Conference'.
In the rosaceous subtribe Pyrinae (formerly subfamily Maloideae), pathogen attack leads to formation of biphenyls and dibenzofurans. Accumulation of these phytoalexins was studied in greenhouse-grown grafted shoots of Malus domestica cv. 'Holsteiner Cox' and Pyrus communis cv. 'Conference' after inoculation with the fire blight bacterium, Erwinia amylovora. No phytoalexins were found in leaves. However, both classes of defence compounds were detected in the transition zone of stems. The flanking stem segments above and below this zone, which were necrotic and healthy, respectively, were devoid of detectable phytoalexins. The transition zone of apple stems contained the biphenyls 3-hydroxy-5-methoxyaucuparin, aucuparin, noraucuparin and 2'-hydroxyaucuparin and the dibenzofurans eriobofuran and noreriobofuran. In pear, aucuparin, 2'-hydroxyaucuparin, noreriobofuran and in addition 3,4,5-trimethoxybiphenyl were detected. The total phytoalexin content in the transition zone of pear was 25 times lower than that in apple. Leaves and stems of mock-inoculated apple and pear shoots lacked phytoalexins. A number of biphenyls and dibenzofurans were tested for their in vitro antibacterial activity against some Erwinia amylovora strains. The most efficient compound was 3,5-dihydroxybiphenyl (MIC=115 μg/ml), the immediate product of biphenyl synthase which initiates phytoalexin biosynthesis.


Sensitive assay of creatine kinase isoenzymes in human serum using M subunit inhibiting antibody and firefly luciferase.
A sensitive method for the assay of B subunit and total creatine kinase activity is described. The ATP formation in the creatine kinase reaction is continuously monitored by measuring the bioluminescence obtained with a purified firefly luciferase reagent. The B subunit activity is determined using an M subunit inhibiting antibody resulting in greater than 99.5% and approximately 50% inhibition of MM and MB isoenzymes, respectively. The bioluminescent method correlated well with a similar spectrophotometric method in the assay of B subunit as well as total creatine kinase activity (r greater than or equal to 0.98). However, the bioluminescent assay is considerably more sensitive, allowing the assay of B subunit activity in serum from healthy individuals. This is due to the inherent sensitivity of the bioluminescent assay of ATP, a reduced analytical interference from adenylate kinase and a reduced reagent blank. The within-series precision at 1 U/liter and greater than 52 U/liter corresponded to a C.V. of 14% and 3%, respectively. The method is as rapid and suitable for routine work as spectrophotometric methods. From a clinical point of view the new method is of particular interest in the early diagnosis of small acute myocardial infarctions.


Type-specific antigen of Streptococcus rattus strains (KAY1 and FA1). I. Characterization.
A serotype-specific antigen was extracted from Streptococcus rattus KAY1 strain isolated first in Japan from human dental plaque and purified on an ion exchange column to compare it chemically and immunologically with that of FA1 strain which had been examined extensively by previous workers. Antigens of both strains reacted in a double diffusion test specifically with anti-FA1 serum which had previously been demonstrated specific for the strains in the same test, agglutination reactions and/or radioimmunoassay using whole cells. After separation on a DEAE-Sephadex A-25 ion exchange column the antigen was found to be resistant to various enzymatic treatments with pronases, lipase and nucleases and produce a single precipitin band against absorbed anti-FA1 serum in immunoelectrophoresis. Chemical analysis of this antigen revealed that it composed of carbohydrate, protein and a few percentages of glycerol and phosphorus. Hapten inhibition tests between antigen and antibody showed that galactose as well as glucose were the most potent inhibitors, suggesting their involvement in the antigenic determinant. Involvement of the sugars was also supported by gas chromatographic analysis and abolishment of reactivity with antiserum after the treatment of antigens with NaIO4. Moreover, protein does not seem to be involved since after SDS-PAGE analysis an enzyme immunoassay gave a negative reaction with immunoblotted antigens.


Is platelet transfusion efficient to restore platelet reactivity in patients who are responders to aspirin and/or clopidogrel before emergency surgery?
The aim of this study was to confirm that emergency platelet transfusion effectively restores platelet function to patients receiving antiplatelet therapy (APT) with aspirin and/or clopidogrel. This was a prospective observational case report series conducted between January 1, 2009, and January 1, 2012. All responder patients according to the Verify Now device requiring emergency platelet transfusion because of a potentially life-threatening hemorrhage or before emergency neurosurgery were included. Aspirin or P2Y12-specific tests were used as appropriate for patients under aspirin or clopidogrel. Patients who were responders to aspirin had an aspirin reaction unit of less than 550, and patients who were responders to clopidogrel had an inhibition percentage of more than 20%. The Verify Now test was performed again after platelet transfusion. Pretransfusion and posttransfusion test results were compared. During the 36-month period, 25 patients met the inclusion criteria. Of these patients, 4 were receiving dual APT, 8 were receiving clopidogrel only, and 13 were receiving aspirin only. The average platelet transfusion dose was 0.12 UI/kg (range, 0.10-0.14 UI/kg). For patients under clopidogrel, the inhibition percentage lowered significantly after transfusion (median 54 [range, 31-69] before and 25 [range, 18-50] after transfusion; p < 0.005) but remained above the 20% threshold. Our patients were still responsive to clopidogrel after platelet transfusion. This result is conflicting with the existing literature. The median aspirin reaction unit of aspirin users before and after transfusion were 420 (range, 400-470) and 630 (range, 610-640), respectively (p = 0.001). The efficacy of platelet transfusion to restore aspirin-mediated disaggregation is confirmed by our case series. Platelet transfusion does not restore platelet function in patients under clopidogrel, but it is efficient for patients under aspirin. This sheds new light on previous large-scale studies that have been unable to show any effectiveness of emergency platelet transfusion in patients under APT. Emergency platelet transfusion may only be indicated in aspirin users who are responders and not in all patients under APT as is actually recommended.


Exercise addiction.
This article examines the nature of exercise addiction. It presents a broad, congruent and discerning narrative literature review with the aim of providing a deeper understanding of the condition 'exercise addiction', including symptoms and options for treatment. In addition, guidelines are provided with respect to 'healthy' levels of exercise. Criteria used for determining the eligibility of studies evaluated in the review included the provision of relevant information in studies identified using pertinent search terms. The review highlights some of the key distinctions between healthy levels of exercise and exercise addiction. The findings suggest that an individual who is addicted to exercise will continue exercising regardless of physical injury, personal inconvenience or disruption to other areas of life including marital strain, interference with work and lack of time for other activities. 'Addicted' exercisers are more likely to exercise for intrinsic rewards and experience disturbing deprivation sensations when unable to exercise. In contrast, 'committed' exercisers engage in physical activity for extrinsic rewards and do not suffer severe withdrawal symptoms when they cannot exercise. Exercisers must acquire a sense of life-balance while embracing an attitude conducive to sustainable long-term physical, psychological and social health outcomes. Implementation of recommendations by the Canadian Society for Exercise Physiology, which states that all apparently healthy adults between 18 and 64 years of age should accumulate at least 150 minutes of moderate (5 or 6 on a scale of 0-10) to vigorous (7 or 8 on a scale of 0-10) intensity aerobic physical activity per week in bouts of 10 minutes or more, also expressed as 30 minutes per day distributed over 5 days per week, would be a good start.


A 1H-MRS investigation of the medial temporal lobe in antipsychotic-naïve and early-treated first episode psychosis.
Schizophrenia is associated with significant brain abnormalities, including changes in brain metabolites as measured by proton magnetic resonance spectroscopy (MRS). What remains unclear is the extent to which these changes are a consequence of the emergence of psychotic disorders or the result of treatment with antipsychotic medication. We assessed 34 patients with first episode psychosis (15 antipsychotic naïve) and 19 age- and gender-matched controls using short-echo MRS in the medial temporal lobe bilaterally. Overall, there were no differences in any metabolite, regardless of treatment status. However, when the analysis was limited to patients with a diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, significant elevations of creatine/phosphocreatine (Cr/PCr) and myo-inositol (mI) were found in the treated group. These data indicate a relative absence of temporal lobe metabolic abnormalities in first episode psychosis, but suggest that some treatment-related changes in mI might be apparent in patients with schizophrenia-spectrum diagnoses. Seemingly illness-related Cr/PCr elevations were also specific to the diagnosis of schizophrenia-spectrum disorder and seem worthy of future study.


Ibopamine as a substitute for digitalis in patients with congestive heart failure on chronic digoxin therapy. Smith Kline and French Ibopamine Group.
The substitution of digoxin with ibopamine, a new inotropic and vasodilating agent, was evaluated in a multicenter study in 58 patients with mild-to-moderate congestive heart failure, stabilized on diuretics, and digoxin therapy. The study was a parallel, double-blind, randomized trial of four weeks duration in which half of the group continued the pre-study medication (diuretics and digoxin) and half of the group was treated with diuretics and ibopamine (100 mg, three times a day). At baseline evaluation, the two groups were similar for age, sex, underlying cardiac disease, duration of congestive heart failure, symptom score, cardiothoracic ratio, echocardiographic parameters of left ventricular function and exercise tolerance as measured by bicycle ergometry. After four weeks, no clinical deterioration was found in the patients treated with ibopamine in any measured parameter. There were two deaths during the study: a sudden death and one following an acute myocardial infarction. Both patients were on digoxin. This study suggests that in patients with mild-to-moderate congestive heart failure, ibopamine therapy may effectively and safely substitute digoxin therapy for up to four weeks, representing an option for patients requiring inotropic support but are at risk for potential digoxin toxicity.


A nomogram was developed using clinicopathological features to predict postoperative liver metastasis in patients with colorectal cancer.
The objective of this study is to examine the risk factors that contribute to the development of liver metastasis (LM) in patients who have suffered radical resection for colorectal cancer (CRC), and to establish a nomogram model that can be used to predict the occurrence of the LM. The present study enrolled 1377 patients diagnosed with CRC between January 2010 and July 2021. The datasets were allocated to training (n = 965) and validation (n = 412) sets in a randomly stratified manner. The study utilized univariate and multivariate logistic regression analyses to establish a nomogram for predicting LM in patients with CRC. Multivariate analysis revealed that T stage, N stage, number of harvested lymph nodes (LNH), mismatch repair (MMR) status, neutrophil count, monocyte count, postoperative carcinoembryonic antigen (CEA) levels, postoperative cancer antigen 125 (CA125) levels, and postoperative carbohydrate antigen 19-9 (CA19-9) levels were independent predictive factors for LM after radical resection. These factors were then utilized to construct a comprehensive nomogram for predicting LM. The nomogram demonstrated great discrimination, with an area under the curve (AUC) of 0.782 for the training set and 0.768 for the validation set. Additionally, the nomogram exhibited excellent calibration and significant clinical benefit as confirmed by the calibration curves and the decision curve analysis, respectively. This nomogram has the potential to support clinicians in identifying high-risk patients who may develop LM post-surgery. Clinicians can devise personalized treatment and follow-up plans, ultimately leading to an improved prognosis for patients.


[YAG laser vitreolysis for treatment of symptomatic vitreous opacities].
YAG laser vitreolysis is an innovative procedure to treat symptomatic vitreous floaters. The treatment decision is based on taking a comprehensive patient history, thorough clinical examination, realistic expectations, and detailed patient information including risk of the procedure. Manifestation of vitreous opacities and possible subjective impairments are considerably variable. Dynamic changes over time are possible. Therefore, not all vitreous opacities are suitable for laser treatment. A classification according to histoanatomical origin can aid the treatment decision. In comparison to other ophthalmic YAG laser applications, YAG laser vitreolysis differs predominantly by its specific technical equipment requirements. In addition, treatment is more complex and time consuming, requires appropriate experience and knowledge of the surgeon, and should be carried out with utmost care and accuracy.


Trafficking of receptor tyrosine kinases to the nucleus.
It has been known for at least 20 years that growth factors induce the internalization of cognate receptor tyrosine kinases (RTKs). The internalized receptors are then sorted to lysosomes or recycled to the cell surface. More recently, data have been published to indicate other intracellular destinations for the internalized RTKs. These include the nucleus, mitochondria, and cytoplasm. Also, it is recognized that trafficking to these novel destinations involves new biochemical mechanisms, such as proteolytic processing or interaction with translocons, and that these trafficking events have a function in signal transduction, implicating the receptor itself as a signaling element between the cell surface and the nucleus.


Interference coatings based on synthesized silicon nitride.
Silicon nitrides are synthesized by ion-assisted deposition with only one coating material and a nitrogen-ion-beam source. All the SiN(x) films are amorphous and mechanically strong. A wide range of refractive indices from 3.43 to 1.72 at a wavelength of 1550 nm is obtained. Near-IR antireflection coating and a bandpass filter based on the multilayers of SiN(x) and Si are demonstrated.


A size dependent folding contour for cytochrome C.
The paper describes an experimental construct of the folding route of the heme protein cytochrome-C. The construct highlights a slowing down near the nose of the folding funnel caused by the multiplicity of the energy traps near the native conformation created as a result of complex heme-peptide interaction. Interestingly the hydrodynamic size, the size heterogeneity and peroxidase activity serve as a triple measure of the distance of this near equilibrium departure from native conformation. Accordingly, the folding process is marked with a gradual and reversible reduction of mean hydrodynamic size, size heterogeneity and peroxidase activity (higher in unfolded state). The Dynamic Light Scattering based straightforward illustration of hydrodynamic size variation may serve as a model to slow folding observed in case of heme proteins, the heme itself serving as a natural facilitator for the native peptide conformation.


Longitudinal measurements of fetal breathing, body movements, heart rate, and heart rate accelerations and decelerations at 24 to 32 weeks of gestation.
Fetal breathing, fetal body movements, fetal heart rate, and fetal heart rate accelerations and decelerations were studied longitudinally in healthy fetuses between 24 and 32 weeks' gestation in the second and third hour following an 800 kcal maternal meal. The expected increase in fetal breathing following a maternal meal was not seen until fetuses were at 30 to 32 weeks' gestation. The number of body movements decreased and the interaction between body movements and fetal heart rate accelerations became more evident as fetuses became older. Fetal heart rate decelerations increased with gestational age, and the relative proportion of total decelerations that were either associated with body movements or were part of a deceleration/acceleration/deceleration complex increased from 24 to 32 weeks' gestation. The data support the hypothesis that gestational age is an important variable to consider when interpreting biophysical measurements in the human fetus at 24 to 32 weeks' gestation. Fetal body movements may be the single most important measurement of fetal health at these gestational ages.


Data regarding the effect of cannabis consumption on liver function in the prospective PAFIP cohort of first episode psychosis.
The presented article describes data from secondary analyses, related to the research article entitled "Cannabis consumption and Non-Alcoholic Fatty Liver Disease. A three years longitudinal study in first episode non-affective psychosis patients" [1]. We present detailed data regarding the socio-demographic and baseline clinical characteristics of a sample of 390 drug-naïve patients with a first episode of non-affective psychosis, and the differences between cannabis users and non-users in those characteristics. Tables also show the results from cross-sectional and longitudinal statistical analyses exploring the relation between cannabis consumption and liver function, after excluding those patients with hazardous alcohol drinking.


Children's reasoning about physics within and across ontological kinds.
Reasoning about seven physics principles within and across ontological kinds was examined among 188 5- and 7-year-olds and 59 adults. Individuals in all age groups tended to appropriately generalize what they learned across ontological kinds. However, children also showed sensitivity to ontological kind in their projections: when learning principles with reference to people they were more likely to assume that the principles apply to another person than to an inanimate object, and when learning with reference to an inanimate object they were more likely to assume that the principles apply to another inanimate object than to a person. Five-year-olds, but not 7-year-olds, projected concepts learned about people to a greater extent than principles learned about inanimate objects, closely paralleling the findings of Carey for the biological domain (Carey, S. (1985). Conceptual change in childhood. Cambridge, MA: MIT Press). Results from a separate sample of 22 5-year-olds suggest that the primary findings cannot be explained by response perseveration. The present findings indicate that children understand physics principles that apply to both animate and inanimate objects, but distinguish between these ontological kinds.


Understanding the limits of parametrial resection in radical hysterectomy: a randomized controlled trial.
The aim was to evaluate whether adding specific educational medical illustrations may help gynecologists to better understand the limits of parametrial resection in radical hysterectomy from type A to type C2. Study Design: randomized controlled trial. Institute of Obstetric and Gynecologic Pathology, University of Catania, Italy. Materials and methods: 30 senior Obstetrics and Gynecology (Ob/Gyn) residents and 30 general Ob/Gyn consultants were enrolled in the study, and randomized to two groups of 15 people (group A and group B). Both groups had a copy of the article on the Querleu-Morrow Classification of Radical Hysterectomy (2017) for reading comprehension. Group B also had 10 unpublished medical illustrations, prepared for this paper. After one month the level of self-perceived understanding related to parametrectomy limits in radical hysterectomy was evaluated in both groups using a numeric visual analog scale, where each participant evaluated his degree of comprehension. The data were statistically analyzed using the U Mann-Whitney test. Group A participants (only article) had a lower level of comprehension of parametrectomy limits compared to group B participants (article plus drawings). The difference between the mean scale score, reported by group A, equal to 5.9 ±1.4, and that reported by group B, equal to 7.2 ±1.5, was statistically significant (p < 0.01). The results of this study suggest that educational materials, such as the proposed drawings, may help both Ob/Gyn consultants and residents to better understand the relationship between the extent of parametrial resection and cervical disease severity, and the related postoperative complications.


Significant up-regulation of a novel gene, CLCP1, in a highly metastatic lung cancer subline as well as in lung cancers in vivo.
Most lung cancer patients are unfortunately uncurable and die because of widespread metastases, thus indicating the importance of identification of molecules with a crucial role in this process. Our previous expression profiling analysis of a highly metastatic lung cancer cell line, NCI-H460-LNM35, and its parental low metastatic line, NCI-H460-N15, revealed significant up-regulation of both known and unknown genes in LNM35. In this study, we describe the isolation and detailed characterizations of a novel gene, named CLCP1, which corresponds to one of such expression sequence tags with up-regulated expression in LNM35. The CLCP1 gene was found to encode a protein with 775 amino acids with structural similarities to, but distinct from neuropilins, cell surface receptors for VEGF165 and semaphorins. Notably, CLCP1 was shown to be up-regulated not only in LNM35 in association with its acquisition of metastatic phenotype during in vivo selection, but also in a significant fraction of lung cancers in vivo with high frequency in metastatic lesions, warranting future studies for a better understanding of the molecular mechanisms of lung cancer metastasis.


Minute time scale prolyl isomerization governs antibody recognition of an intrinsically disordered immunodominant epitope.
Conformational rearrangements in antibody·antigen recognition are essential events where kinetic discrimination of isomers expands the universe of combinations. We investigated the interaction mechanism of a monoclonal antibody, M1, raised against E7 from human papillomavirus, a prototypic viral oncoprotein and a model intrinsically disordered protein. The mapped 12-amino acid immunodominant epitope lies within a "hinge" region between the N-terminal intrinsically disordered and the C-terminal globular domains. Kinetic experiments show that despite being within an intrinsically disordered region, the hinge E7 epitope has at least two populations separated by a high energy barrier. Nuclear magnetic resonance traced the origin of this barrier to a very slow (t(1/2)∼4 min) trans-cis prolyl isomerization event involving changes in secondary structure. The less populated (10%) cis isomer is the binding-competent species, thus requiring the 90% of molecules in the trans configuration to isomerize before binding. The association rate for the cis isomer approaches 6 × 10(7) M(-1) s(-1), a ceiling for antigen-antibody interactions. Mutagenesis experiments showed that Pro-41 in E7Ep was required for both binding and isomerization. After a slow postbinding unimolecular rearrangement, a consolidated complex with K(D) = 1.2 × 10(-7) M is reached. Our results suggest that presentation of this viral epitope by the antigen-presenting cells would have to be "locked" in the cis conformation, in opposition to the most populated trans isomer, in order to select the specific antibody clone that goes through affinity and kinetic maturation.


Associations between long-term aircraft noise exposure, cardiovascular disease, and mortality in US cohorts of female nurses.
There is limited research examining aircraft noise and cardiovascular disease (CVD) risk. The objective of this study was to investigate associations of aircraft noise with CVD among two US cohorts, the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). Between 1994 and 2014, we followed 57,306 NHS and 60,058 NHSII participants surrounding 90 airports. Aircraft noise was modeled above 44 A-weighted decibels (dB(A)) and linked to geocoded addresses. Based on exposure distributions, we dichotomized exposures at 50 dB(A) and tested sensitivity of this cut-point by analyzing aircraft noise as categories (<45, 45-49, 50-54, ≥55) and continuously. We fit cohort-specific Cox proportional hazards models to estimate relationships between time-varying day-night average sound level (DNL) and CVD incidence and CVD and all-cause mortality, adjusting for fixed and time-varying individual- and area-level covariates. Results were pooled using random effects meta-analysis. Over 20 years of follow-up, there were 4529 CVD cases and 14,930 deaths. Approximately 7% (n = 317) of CVD cases were exposed to DNL ≥50 dB(A). In pooled analyses comparing ≥50 with <50 dB(A), the adjusted hazard ratio for CVD incidence was 1.00 (95% confidence interval: 0.89, 1.12). The corresponding adjusted hazard ratio for all-cause mortality was 1.02 (95% confidence interval: 0.96, 1.09). Patterns were similar for CVD mortality in NHS yet underpowered. Among participants in the NHS and NHSII prospective cohorts who generally experience low exposure to aircraft noise, we did not find adverse associations of aircraft noise with CVD incidence, CVD mortality, or all-cause mortality.


Biomechanical and clinical outcomes with shock-absorbing insoles in patients with knee osteoarthritis: immediate effects and changes after 1 month of wear.
To examine the effectiveness of shock-absorbing insoles in the immediate reduction of knee joint load, as well as reductions in knee joint load, pain, and dysfunction after 1 month of wear, in individuals with knee osteoarthritis (OA). Pre-post design with participants exposed to 2 conditions (normal footwear, shock-absorbing insoles) with a 1-month follow-up. University laboratory for testing and general community for intervention. Community-dwelling individuals (N=16; 6 men, 10 women) with medial compartment knee OA. Participants were provided with sulcus length shock-absorbing insoles to be inserted into their everyday shoes. Primary outcome measures included the peak, early stance peak, and late stance peak external knee adduction moment (KAM); the KAM impulse (positive area under the KAM curve); and peak tibial vertical acceleration. Secondary outcomes included walking pain, the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale and total score, and a timed stair climb task. There was a significant reduction in the late stance peak KAM with shock-absorbing insoles (P=.03) during follow-up compared with the baseline test session. No other immediate or longitudinal significant changes (P>.05) in the other KAM parameters or peak tibial acceleration after use of a shock-absorbing insole were observed. However, significant improvements in all measures of pain and function (P<.05) were observed. Shock-absorbing insoles produced significant reductions in self-reported knee joint pain and physical dysfunction with 1 month of wear in patients with knee OA despite no consistent changes in knee joint load. Further research using randomized controlled trials, with larger sample sizes and explorations into long-term use of shock-absorbing insoles and their effect on disease progression, is warranted.


Measurement of the surface-enhanced coherent anti-Stokes Raman scattering (SECARS) due to the 1574 cm(-1) surface-enhanced Raman scattering (SERS) mode of benzenethiol using low-power (<20 mW) CW diode lasers.
The surface-enhanced coherent anti-Stokes Raman scattering (SECARS) from a self-assembled monolayer (SAM) of benzenethiol on a silver-coated surface-enhanced Raman scattering (SERS) substrate has been measured for the 1574 cm(-1) SERS mode. A value of 9.6 ± 1.7×10(-14) W was determined for the resonant component of the SECARS signal using 17.8 mW of 784.9 nm pump laser power and 7.1 mW of 895.5 nm Stokes laser power; the pump and Stokes lasers were polarized parallel to each other but perpendicular to the grooves of the diffraction grating in the spectrometer. The measured value of resonant component of the SECARS signal is in agreement with the calculated value of 9.3×10(-14) W using the measured value of 8.7 ± 0.5 cm(-1) for the SERS linewidth Γ (full width at half-maximum) and the value of 5.7 ± 1.4×10(-7) for the product of the Raman cross section σSERS and the surface concentration Ns of the benzenethiol SAM. The xxxx component of the resonant part of the third-order nonlinear optical susceptibility |3 χxxxx((3)R)| for the 1574 cm(-1) SERS mode has been determined to be 4.3 ± 1.1×10(-5) cm·g(-1)·s(2). The SERS enhancement factor for the 1574 cm(-1) mode was determined to be 3.6 ± 0.9×10(7) using the value of 1.8×10(15) molecules/cm(2) for Ns.


Shear bond strength of veneering composite resin to titanium nitride coating alloy deposited by radiofrequency sputtering.
The success of dental restorations utilizing composite resin over cast alloy has been variable and affected by micro-leakage. The purpose of this study was to investigate the shear bond strength between a composite resin and cast dental alloy coated with a layer of titanium nitride (TiN). Cast disk specimens made of Au-Pd-Ag alloy were randomly divided into four groups. The first group was left uncoated as a control while one group was coated with a metal conditioner, and the other two were coated with TiN at either 200 or 500 W with a radiofrequency magnetron sputtering system. Each group was then bonded to one of two types of light-activated composite resin material. Shear bond strengths were tested and compared for each specimen. The bond strength of each group was analyzed by 2-way ANOVA and by post hoc multiple comparison tests (Fisher's PLSD). As the interaction among groups was not significant (p=0.27) by 2-way ANOVA, TiN coated groups were found to have improved shear bond strength compared with non-coated groups without metal conditioner for both resin composite materials by multiple comparison tests. Furthermore, TiN coating is significantly stronger than non-coated groups with metal conditioner for one of the two resin composite materials examined (p<0.01). The results suggested that metal surface modification by coated TiN represents a technique that may significantly improve the bond between the Au-Pd-Ag alloy and veneering resin composite.


Cellulose hydrolysis under extremely low sulfuric acid and high-temperature conditions.
The kinetics of cellulose hydrolysis under extremely low acid (ELA) conditions (0.07 wt%) and at temperatures >200 degrees C was investigated using batch reactors and bed-shrinking flow-through (BSFT) reactors. The maximum yield of glucose obtained from batch reactor experiments was about 60% for alpha-cellulose, which occurred at 205 and 220 degrees C. The maximum glucose yields from yellow poplar feedstocks were substantially lower, falling in the range of 26-50%. With yellow poplar feedstocks, a large amount of glucose was unaccounted for at the latter phase of the batch reactions. It appears that a substantial amount of released glucose condenses with nonglucosidic substances in liquid. The rate of glucan hydrolysis under ELA was relatively insensitive to temperature in batch experiments for all three substrates. This contradicts the traditional concept of cellulose hydrolysis and implies that additional factors influence the hydrolysis of glucan under ELA. In experiments using BSFT reactors, the glucose yields of 87.5, 90.3, and 90.8% were obtained for yellow poplar feedstocks at 205, 220, and 235 degrees C, respectively. The hydrolysis rate for glucan was about three times higher with the BSFT than with the batch reactors. The difference of observed kinetics and performance data between the BSFT and the batch reactors was far above that predicted by the reactor theory.


A minimax approach to the single-point method of drug dosing.
The single-point dose prediction method is based on the observation that for drugs obeying single compartment elimination kinetics there is a nearly constant reciprocal relation between the plasma level at a fixed time following a single loading dose and the dose that is required to maintain the desired steady state plasma level of the drug. This paper describes an improved method for choosing a plasma sampling time and a proportionality constant. It applies to either drugs administered intravenously or to drugs whose rates of absorption from the site of administration are very rapid compared to their rates of elimination from the body. The sampling time and proportionality constant chosen are those that minimize the maximum relative deviation of the maintenance dose estimated by the single-point method from the dose that would be estimated if the individual's true elimination rate constant were known. The paper also supplies a method to determine the maximum error that may be introduced into the estimation of the maintenance dose by using the single-point method.


DNA binding potential and cytotoxicity of newly designed pyrrolobenzodiazepine dimers linked through a piperazine side-armed-alkane spacer.
New pyrrolobenzodiazepine (PBD) dimers have been developed that are composed of two DC-81 subunits tethered to their C8 positions through piperazine moiety side-armed with alkaneoxy linkers (composed of 2-5 carbons). DNA thermal denaturation studies show that after 18h of incubation with calf thymus DNA at a 1:5 ligand/DNA ratio, one of them, 6a, increases the DeltaT(m) value by 24.0 degrees C. Thus, incorporation of a piperazine moiety instead of an inert alkanedioxy linker alone significantly enhances the DNA binding ability, and the analogous dimer 4 that lacks a piperazine moiety in the linker spacer elevates melting by only 15.1 degrees C under identical experimental conditions. This illustrates the effect of introducing a piperazine ring in the middle of such an alkanedioxy linker which produces several hydrophobic interactions and could also achieve a superior isohelical fit within the DNA minor groove. Interestingly, these dimers 6a-d are significantly more cytotoxic than 4 in a number of human cancer cell lines, in particular, compound 6c is highly potent for almost all the nine human cancer cell lines.


Incidence of chorioamnionitis in patients with meconium-stained amniotic fluid.
The goal of this study was to determine if meconium staining of the amniotic fluid (MSAF) is a marker for chorioamnionitis. In a retrospective, case-control investigation, we studied 100 patients with MSAF. Each patient was matched with a control who delivered during the same period but did not have MSAF. Subjects and controls were matched for age, parity, gestational age, mode of delivery, duration of rupture of membranes (ROM), length of internal monitoring, and number of examinations before and after ROM. The incidence of chorioamnionitis in controls and study patients was compared. The diagnosis of chorioamnionitis was based on clinical examination. Thirteen of the 200 patients [6.5%, 95% confidence interval (CI), 2.5-10.5%] developed chorioamnionitis. Of the 100 women with MSAF, 10 (10%, 95% CI, 4-16) were infected compared with only 3 controls (3%, 95% CI, 0-6, P = 0.04). The odds ratio (OR) for this comparison was 3.3, and the 95% CI was 1.02-10.63. MSAF is associated with an increased frequency of chorioamnionitis. Several factors could explain this association. Infection may cause fetal stress, leading to the release of meconium. MSAF may enhance the growth of bacteria by providing a rich medium of essential nutrients or growth stimulants. MSAF also may impair the host immune system so that chemotaxis or phagocytosis is diminished, thus allowing accelerated growth of microorganisms.


Demonstration of a "renogastric reflex" after rapid distension of renal pelvis and ureter in nonanesthetized patients.
Renal or ureteral diseases are often associated with nausea, vomiting, and abdominal pain. The aim of the current study was to investigate the cause of gastric manifestations that accompany renoureteral disorders. A 3F balloon-tipped catheter was introduced by means of a flexible cystoscope into the renal pelvis of 14 healthy volunteers (mean age 38.6 years; 10 men, 4 women), and the effect of rapid and slow renal pelvic and ureteral distension on the pyloric sphincter, gastric corpus, lower esophageal sphincter, and esophagus was recorded. The renal pelvis and ureter were then anesthetized and the tests repeated. Rapid renal pelvic distension effected a significant rise in pressure in the renal pelvis at the 6-mL distension and above and in the pyloric sphincter at 10 and 1 2 mL. Loin and epigastric pain as well as nausea in all subjects and vomiting in 5 occurred at the 10 and 1 2-mL distensions. Slow renal pelvic distension caused a renal pelvic pressure rise at the 8-mL distension and above but no pressure changes in the pyloric sphincter or gastric corpus; loin pain, but not nausea or vomiting, occurred. Rapid ureteral distension at 1 mL was associated with loin and epigastric pain in all subjects and vomiting in 3. No epigastric pain, nausea, or vomiting occurred with slow ureteral distension. Renal pelvic or ureteral distension, slow or rapid, caused no pressure changes in the lower esophageal sphincter or esophagus. Distension of the anesthetized renal pelvis or ureter effected no gastric or esophageal pressure changes and no nausea or vomiting. The study demonstrated the possible existence of a reflex relationship between the distension of the renal pelvis and ureter and the pressure of the pyloric sphincter. This reflex effect was reproducible and did not occur when the anesthetized renal pelvis or ureter was distended. We call this reflex relationship the "renogastric reflex" and suggest that it explains the cause of gastric manifestations that might occur with renoureteral disorders.


Perimenopausal hormone therapy is associated with regional sparing of the CA1 subfield: a HUNT MRI study.
Observational studies support a neuroprotective role of hormone therapy (HT) in the perimenopause, with hippocampal size being a widely used biomarker. We investigated the effect of HT started before the onset of menopause and lasting for at least 3 years on hippocampal volume and shape in 80 postmenopausal women and 80 controls matched on age and intracranial volume taken from a large community-based sample (Nord-Trøndelag Health Study-magnetic resonance imaging). The main effect of hormone group showed a statistically significant difference in hippocampal volumes (p = 0.028). Both the right (3.2%) and left (2.8%) hippocampal volumes were larger in the HT group but only significant for the right hippocampus (p = 0.023). Shape analysis revealed significant regional sparing of the medial aspect of the right hippocampal head and lateral aspect of the body extending to the tail, corresponding to the cornu ammonis, including part of the subiculum, in the HT group. A similar nonsignificant pattern was observed in the left hippocampus. The present study provides support for the critical window theory demonstrating that HT initiated in the perimenopause has neuroprotective properties.


Gastroparesis secondary to pulmonary vein cryoablation: a factor to consider.
We present a patient who underwent cryoballoon ablation for symptomatic atrial fibrillation, with gastroparesis five days later. The case was resolved with conservative measures such as prokinetics. The case was a 72-year-old female with a history of symptomatic paroxysmal atrial fibrillation treated with edoxaban. Pulmonary vein isolation using a cryoballoon catheter was performed. Five days later, she presented with upper abdominal pain, bloating and vomiting.


Stoichiometric Control of Guest Recognition of Self-Assembled Palladium(II)-Based Supramolecular Architectures.
We report flexible [Pd(L)2 ]2+ complexes where there is self-recognition, driven by π-π interactions between electron-rich aromatic arms and the cationic regions they are tethered to. This self-recognition hampers the association of these molecules with aromatic molecular targets in solution. In one case, this complex can be reversibly converted to an 'open' [Pd2 (L)2 ]4+ macrocycle through introduction of more metal ion. This is accomplished by the ligand having two bidentate binding sites: a 2-pyridyl-1,2,3-triazole site, and a bis-1,2,3-triazole site. Due to favourable hydrogen bonding, the 2-pyridyl-1,2,3-triazole units reliably coordinate in the [Pd(L)2 ]2+ complex to control speciation: a second equivalent of Pd(II) is required to enforce coordination to bis-triazole sites and form the macrocycle. The macrocycle interacts with a molecular substrate with higher affinity. In this fashion we are able to use stoichiometry to reversibly switch between two different species and regulate guest binding.


Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors.
Somatostatin analogues (SSAs) are widely used to treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Somatostatin receptor 2 (SSTR2) immunoreactivity serves as a predictive marker of the therapeutic efficacy of SSAs in pancreatic NETs. However, SSTR2 expression profiles in tumor cells and their association with the therapeutic efficacy of SSAs remains virtually unknown in gastrointestinal NETs (GI-NETs). Therefore, we evaluated the association between SSTR2 immunoreactivity and embryological origin and proliferative activity in 132 resected surgical tissues of GI-NETs. The correlation between SSAs' therapeutic efficacy and SSTR2 immunoreactivity was evaluated in 14 GI-NETs treated with SSAs. SSTR2 immunoreactivity was evaluated using Volante scores, immunoreactive scores, and digital image analysis (DIA). SSTR2 immunoreactivity was significantly negatively and positively correlated with the Ki-67 labeling index in foregut and hindgut NETs, respectively. In the normal mucosa, neuroendocrine cells in the rectum had significantly lower positive rates of SSTR2 than those in the stomach and duodenum. SSTR2 expression profiles in GI-NETs could differ by primary sites, while the difference of those between foregut and hindgut NETs might be derived from the SSTR2 status of normal neuroendocrine cell counterparts. In addition, DIA could provide a good alternative for predicting response to SSAs in evaluating SSTR2 immunoreactivity of GI-NETs.


Methylglyoxal induces hyperpermeability of the blood-retinal barrier via the loss of tight junction proteins and the activation of matrix metalloproteinases.
One of the early signs of diabetic retinopathy is the alteration of the blood-retinal barrier (BRB), which may involve the breakdown of endothelial cell tight junctions. Methylglyoxal (MGO) is a cytotoxic metabolite that is produced from glycolysis in vivo. Elevated levels of MGO are observed in a number of pathological conditions, including neurodegenerative disorders and diabetic complications. Herein, we hypothesize that increased levels of MGO disrupt the tight junction protein known as occludin protein by matrix metalloproteinases (MMPs), leading to breakage of the BRB. MGO was intravitreally injected into eyes of rats. BRB leakage, MMPs activity, and occludin were investigated in intravitreally MGO-injected eyes. When normoglycemic rats were intravitreally injected with 400 μM MGO, there was widespread leakage of fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) from the retinal vasculature when compared to control retinas. In addition, MGO-injected retinas demonstrated increases of both activity and expression of MMP-2 and MMP-9, and the degradation of occludin was found in the MGO-injected retinas. The results suggest that the activation of MMPs by elevated levels of MGO in the retina may facilitate an increase in vascular permeability by a mechanism involving proteolytic degradation of occludin. These findings may have implications for the role of MGO in the pathogenesis of diabetic retinopathy.


Manduca sexta caterpillars parasitized by the wasp Cotesia congregata stop chewing despite an intact motor system.
The parasitic wasp Cotesia congregata suppresses feeding in its host, the caterpillar Manduca sexta, during specific periods of wasp development. We examined both feeding behaviour and the neurophysiology of the mandibular closer muscle in parasitized and unparasitized control M. sexta to determine how the wasp may accomplish this. To test whether the wasps activated a pre-existing host mechanism for feeding cessation, we examined the microstructure of feeding behaviour in caterpillars that stopped feeding due to illness-induced anorexia or an impending moult. These microstructures were compared with that shown by parasitized caterpillars. While there were overall differences between parasitized and unparasitized caterpillars, the groups showed similar progression in feeding microstructure as feeding ended, suggesting a common pattern for terminating a meal. Parasitized caterpillars also consumed less leaf area in 100 bites than control caterpillars at around the same time their feeding microstructure changed. The decline in food consumption was accompanied by fewer spikes per burst and shorter burst durations in chewing muscle electromyograms. Similar extracellular results were obtained from the motorneuron of the mandibular closer muscle. However, chewing was dramatically re-activated in non-feeding parasitized caterpillars if the connectives posterior to the suboesophageal ganglion were severed. The same result was observed in unparasitized caterpillars given the same treatment. Our results suggest that the reduced feeding in parasitized caterpillars is not due to damage to the central pattern generator (CPG) for chewing, motor nerves or chewing muscles, but is more likely to be due to a suppression of chewing CPG activity by ascending or descending inputs.


[A lymphotropic method of therapy for patients with fresh forms of syphilis (clinical and experimental research)].
Experimental study of benzylpenicillin procain salt kinetics in lymphotropic and intramuscular administration of 600,000 U has revealed a more intensive saturation of the lymph system and a longer persistence of high concentrations of the drug in the blood serum, organs and tissues of the body after lymphotropic administration, as against intramuscular one. Comparison of the efficacies of 16-day courses of therapy of patients with fresh syphilis with benzylpenicillin procain salt administered lymphotropically (once daily, 600,000 U) or intramuscularly (twice daily, the same dose) has shown the advantages of the former method as regards the therapeutic, pharmacokinetic, and economic aspects.


Effect of nerve stimulation, denervation, and duct ligation, on kallikrein content and duct cell granules of the cat's submandibular gland.
Various procedures which reduce or deplete the kallikrein content of the cat's submandibular gland correspondingly reduce the number of apical granules in the striated duct cells. The kallikrein content is greatly reduced after chronic parasympathetic but not after sympathetic nerve section which suggests that the parasympathetic innervation is required for synthesis or storage of this enzyme.


Effect of cytoplasmic acidification on the membrane potential of T-lymphocytes: role of trace metals.
The effect of lowering intracellular pH on the membrane potential (Em) of rat thymic lymphocytes was studied using the potential-sensitive dye bis-oxonol. Cells were acid loaded by addition of the electroneutral K+/H+ exchanging ionophore nigericin. Acidification to pH 6.3 in Na(+)-free solution resulted in a biphasic change in Em: an early transient hyperpolarization followed by a sustained depolarization. These changes were associated with a rise in cytosolic free Ca2+ ([Ca2+]i). The hyperpolarization was eliminated when the change in [Ca2+]i was prevented using BAPTA, an intracellular Ca2+ chelator. Moreover, a similar hyperpolarization was elicited by elevation of [Ca2+]i at physiological pHi using ionomycin, suggesting involvement of Ca2(+)-activated K+ channels. In contrast, the depolarization phase could not be mimicked by raising [Ca2+]i with ionomycin. However, intracellular BAPTA effectively inhibited the acidification-induced depolarization. Inhibition was also obtained by extracellular addition of EGTA or dithiothreitol, even when the external free Ca2+ concentration remained unaltered. These observations suggested a possible role of contaminating trace metals. Cytosolic acidification is envisaged to induce intracellular accumulation of one or more trace metals, which induces the observed changes in Em. Accordingly, similar changes in Em can be induced without acidification by the addition of small amounts of Cu2+ to the medium. The ionic basis of the Em changes induced by acidification and the significance of these observations are discussed.


Trauma during pregnancy: outcomes and clinical management.
Trauma affects up to 6% to 7% of all pregnancies, and accounts for up to 46% of maternal death. Adverse consequences such as preterm labor and delivery, abruptio, fetomaternal hemorrhage, and fetal demise may be seen with even apparently minor degrees of injury. Maternal physiologic considerations are reviewed and a protocol for evaluation and management of the injured gravida is presented.


Diagnosis of ICD lead failure using continuous event marker recording.
Stored electrograms enhance the ability to evaluate therapy episodes in the third-generation implantable cardioverter defibrillator. These electrograms are recorded from either the shocking or rate sensing leads, but not both. As a result, differentiation of certain types of sensing abnormalities may be difficult prior to surgical exploration. We present a case of rate sensing lead failure due to an insulation break. Several minutes of recording of the event marker in the laboratory failed to document any abnormal sensing; the diagnosis was made by recording the event marker on a 24-hour continuous (Holter) monitor. The Holter monitor/event marker combination was of substantial diagnostic value and allowed for a more focused surgical evaluation and treatment.


Observations of nonadherence to recombinant human growth hormone therapy in clinical practice.
The effectiveness of all prescribed treatments is contingent on patient adherence. The reported levels of adherence to recombinant human growth hormone (r-hGH) therapy are highly variable, but it has been suggested that nonadherence might be as high as 36% to 49%. This commentary discusses the factors that affect long-term adherence to injection treatment, of which r-hGH therapy is a particular challenge. It also explores potential strategies to improve adherence to injection treatments in clinical practice. The opinion of the authors was validated and supported by published literature. A PubMed literature search was conducted in November 2006, identifying English-language articles containing key terms growth hormone, adherence, and compliance. This study found that factors associated with poor adherence to injection treatments include patients' lack of understanding of their disease, patient age, chronicity of the disease, complex treatment regimens, and insufficient information on the implications of nonadherence. Strengthening the patient-physician relationship by providing the patient with a clear understanding of his/her disease and the benefits of adherence, making improvements in injection devices, and eliminating subjective illness concepts, might increase adherence to SC injection treatments, thereby reducing increasing health care costs associated with nonadherence. Poor adherence to r-hGH therapy has a dual effect, in that it leads to reduced efficacy out-comes and increased health care costs. Implementing strategies to improve adherence with injection treatment might be of particular clinical benefit to patients undergoing r-hGH therapy.


Characterization of a partial duplication of the aflatoxin gene cluster in Aspergillus parasiticus ATCC 56775.
A partial duplication of the complete aflatoxin gene cluster containing homologues of aflR-aflJ-adhA-estA-norA-ver1and omtB was identified from Aspergillus parasiticus ATCC 56775. The genes, verA-avnA-verB-avfA, between ver1 and omtB in the complete gene cluster, however, were not found. One-hybrid assays showed that the duplicated aflRgene ( aflR2) encoded a protein that could activate transcription just as that encoded by aflR1,the aflR gene in the complete gene cluster. Two-hybrid assays showed that AFLR2 also interacted with a putative coactivator, AFLJ1, at comparable levels to AFLR1. Deletion of aflR1 resulted in the loss of production of aflatoxin precursors, which suggested that aflR2could not completely replace the function of aflR1. Point mutations found in adhA2, pre-termination in ver1B and norA2,and a large deletion in omtB2 probably render these duplicated genes to become nonfunctional. A close examination of the history of isolates reported to have a partial duplication suggested that duplication of the aflatoxin cluster is not a prevalent event.


Bacterial cellulose-based biomaterials: From fabrication to application.
Driven by its excellent physical and chemical properties, BC (bacterial cellulose) has achieved significant progress in the last decade, rendering with many novel applications. Due to its resemblance to the structure of extracellular matrix, BC-based biomaterials have been widely explored for biomedical applications such as tissue engineering and drug delivery. The recent advances in nanotechnology endow further modifications on BC and generate BC-based composites for different applications. This article presents a review on the research advancement on BC-based biomaterials from fabrication methods to biomedical applications, including wound dressing, artificial skin, vascular tissue engineering, bone tissue regeneration, drug delivery, and other applications. The preparation of these materials and their potential applications are reviewed and summarized. Important factors for the applications of BC in biomedical applications including degradation and pore structure characteristic are discussed in detail. Finally, the challenges in future development and potential advances of these materials are also discussed.


Optimizing culture conditions for heterotrophic-assisted photoautotrophic biofilm growth of Chlorella vulgaris to simultaneously improve microalgae biomass and lipid productivity.
In order to solve the technical bottleneck that the biomass yield and lipid accumulation cannot be increased simultaneously during microalgae growth, a heterotrophic-assisted photoautotrophic biofilm (HAPB) growth mode of Chlorella vulgaris was constructed. The light penetration capability of the microalgae biofilm formed through heterotrophic-assisted photoautotrophic growth was 64% stronger than that formed by photoautotrophic growth. Due to the different demands of autotrophic and heterotrophic growth of microalgae, the nutrient environment and growth conditions were optimized to fully utilize the advantages and potentials of the HAPB culture model. An optimized molar ratio of total inorganic carbon (CO2) to total organic carbon (glucose) (20:1) and a molar ratio of total carbon to total nitrogen (72:1) were obtained. The maximum specific growth rate of Chlorella vulgaris increased by 78% compared to that before optimization. Meanwhile, the lipid content and yield increased by 120% and 147%, respectively, up to 47.53% and 41.95 g m-2.


Expression and processing of gastrin in pancreatic adenocarcinoma.
Gastrin is a trophic hormone and promotes growth of gastrointestinal and non-gastrointestinal cancers. Studies both in vitro and in vivo have suggested that pancreatic cancer cells not only have the ability to respond to circulating forms of gastrin but also to respond to the autocrine production of gastrin and its precursors. The aim of this study was to identify the expression of CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin in both normal pancreas and pancreatic adenocarcinoma. Tissue sections from patients with normal pancreas (n = 10) and pancreatic cancer (n = 22) were assessed using immunohistochemical methods for CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin expression. Normal pancreas showed no expression of receptor or gastrin isoforms except for occasional cells in the islets. Definite expression of CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin was observed in 95, 91, 55 and 23 per cent of sections from patients with pancreatic cancer respectively. Pancreatic cancer cells express CCK-B/gastrin receptor and gastrin precursor forms in most patients. Expression of the gastrin precursor forms is probably related to autocrine production. New therapeutic strategies need to be developed for the management of pancreatic cancer. Targeting gastrin and its receptor may provide a novel treatment option.


N-acetylmuramic acid inhibits spore germination and germination enzymes.
This report describes the inhibition of spore germination by N-acetylmuramic acid. At concentrations of 20 mM and higher, the rate of germination of the treated spores was ten-fold lower than that of the control spores. The inhibitor also depressed the activity of two germination-related enzymes; a coat-associated hexosaminidase and a core enzyme. These findings suggests that N-acetylmuramic acid affects spore germination by inhibition of the corticolytic enzymes. The results are discussed with respect to the possible role of these enzymes in germination.


Relationship between weight loss and regular dental management of older adults residing in long-term care facilities: a 1-year multicenter longitudinal study.
This study aimed to determine the association between home visits by a dentist and regular oral hygiene management by a dental hygienist (regular dental management: RDM) and weight loss among older adults in long-term care facilities. A total of 468 older residents from 26 Japanese long-term care facilities participated in two surveys in 2018 and 2019. Participants were divided into two groups based on their diet during the baseline survey (regular diet, n = 256; dysphagia diet, n = 212). Participants with a regular diet were further divided into those who exhibited a weight loss ≥ 5% over 1 year (weight loss group: n = 77) and those with a weight loss < 5% (consistent weight group: n = 179). The explanatory variables were age, sex, baseline weight, Barthel index, and clinical dementia rating, as well as the patients' medical history of pneumonia, stroke, diabetes, and depression (which is reportedly associated with weight). Additionally, a Poisson regression with robust standard error, was carried out to analyze the explanatory variables, namely the prevalence of RDM noted during the study and functional teeth (which seemed to affect weight loss). A multivariate analysis revealed that older residents' lack of RDM, clinical dementia assessment, and their history of pneumonia (prevalence rate ratio: 0.35, 95% confidence interval 0.24-0.95) were all significantly associated with weight loss when on a regular diet. Thus, weight loss and RDM were related to each other. Weight loss may be suppressed by incorporating RDMs during the early nursing care for older residents on regular diets.


The GTPase superfamily: a conserved switch for diverse cell functions.
Proteins that bind and hydrolyse GTP are being discovered at a rapidly increasing rate. Each of these many GTPases acts as a molecular switch whose 'on' and 'off' states are triggered by binding and hydrolysis of GTP. Conserved structure and mechanism in myriad versions of the switch--in bacteria, yeast, flies and vertebrates--suggest that all derive from a single primordial protein, repeatedly modified in the course of evolution to perform a dazzling variety of functions.


Emotional empowerment through information research and communication to reduce fear of COVID-19 among nursing students: a randomised controlled trial.
Despite an existing body of literature on anxiety reduction using multi-component methods, little is known about the effect of active student participation in research and communication of scientific information on anxiety and fear reduction. The aim of this study is to evaluate the impact of quality scientific information research and the production of informative videos on the preventive aspects of COVID-19 on fear and anxiety reduction. A randomised controlled trial was conducted with 220 undergraduate nursing students in the first year of the nursing degree. The participating students were randomised into two groups. The experimental group carried out an intervention based on a database search for information on preventing COVID-19 and production of a video giving scientific reasons why prevention measures should be followed. In the control group, students created posters and videos about theoretical aspects of one module of the nursing degree. Both groups were surveyed before and after the intervention, measuring their state of resilience, preventive behaviours, level of anxiety, and fear of COVID-19. The intervention group showed a greater decrease in fear levels after the intervention than those in the control group. There were no differences between the groups in terms of resilience, preventive behaviours, or anxiety. In the experimental group, there was a significant decrease in anxiety levels and fear levels after the intervention compared to the baseline levels. An intervention based on active participation in searches for high-quality scientific information and production of information videos on COVID-19 prevention reduced fear and anxiety caused by COVID-19 among nursing students. We have retrospectively registered the trial in Open Science Framework and the identification number is https://doi.org/10.17605/OSF.IO/6QU5S .


Effects of Hypericum perforatum extract and its main bioactive compounds on the cytotoxicity and expression of CYP1A2 and CYP2D6 in hepatic cells.
Hypericum perforatum (H. perforatum) is one of the most used medicinal plants. However, it has been associated with relevant interactions with several drugs. This situation is probably mediated by cytochrome P450 enzymes (CYP450), namely the 1A2 (CYP1A2) and 2D6 (CYP2D6) isoforms This study aims to assess the cytotoxic and CYP1A2 and CYP2D6 inductive and/or inhibitory effects of a H. perforatum extract and its main bioactive components in hepatic cell lines. A MTT proliferation assay was performed in WRL-68, HepG2 and HepaRG cells after exposition to different concentrations of H. perforatum extract, hypericin and hyperforin for 24 and 72 h. Then, a real-time PCR analysis was accomplished after incubating the cells with these products evaluating the relative CYP1A2 and CYP2D6 expression. These products have relevant cytotoxicity at a 10 μM concentration and it was also demonstrated for the first time that H. perforatum can lead to a significant CYP1A2 and CYP2D6 induction in all cell lines. Moreover, hypericin seems to induce CYP1A2 in HepG2 cells and to inhibit its expression in HepaRG cells while hyperforin induced CYP1A2 in HepG2 and in WRL-68 cells. Additionally, hypericin and hyperforin induce CYP2D6 in HepG2 cells but inhibits its expression in HepaRG and in WRL-68 cells. This study not only evidenced that H. perforatum extract and two of its bioactive components can have toxic effects in hepatic cell lines but also emphasized the potential risk of the consumption of H. perforatum with CYP1A2- and CYP2D6-metabolized drugs.


MiR-133a-3p/Sirt1 epigenetic programming mediates hypercholesterolemia susceptibility in female offspring induced by prenatal dexamethasone exposure.
Mounting evidence indicates that adverse intrauterine conditions increase offspring's hypercholesterolemia susceptibility in adulthood. This study aimed to confirm prenatal dexamethasone exposure (PDE)-induced hypercholesterolemia susceptibility in female adult offspring rats, and elucidate its intrauterine programming mechanism. Pregnant Wistar rats were injected with dexamethasone subcutaneously (0, 0.1 and 0.2 mg/kg·d) from gestational day (GD) 9 to 20. Serum and liver of the female offspring were collected at GD21 and postnatal week (PW) 12 and 28. PDE offspring showed elevated serum total cholesterol (TCH) levels and a cholesterol phenotype of high cardiovascular disease risk at PW12 and PW28. The histone acetylation levels of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) and its expression were consistently increased in the PDE offspring both in utero and after birth. Moreover, PDE promoted glucocorticoid receptor (GR) nuclear translocation and miR-133a-3p expression and inhibited sirtuin-1 (Sirt1) expression in the fetal liver. In vitro, dexamethasone increased intracellular and supernatant TCH levels and miR-133a-3p expression, decreased SIRT1 expression, and promoted HMGCR histone acetylation and expression in bone marrow mesenchymal stem cells (BMSCs) hepatoid differentiated cells and HepG2 cell line. GR siRNA, miR-133a-3p inhibitor or SIRT1 overexpression reversed dexamethasone-induced downstream molecular and phenotypic changes. Furthermore, elevated TCH levels in umbilical cord blood and increased HMGCR expression in peripheral blood mononuclear cells (PBMCs) were observed in human female neonates who had received dexamethasone treatment during pregnancy. In conclusion, PDE can cause persistent enhancement of hepatic cholesterol synthesis function before and after birth through GR/miR-133a-3p/Sirt1 pathway, eventually leading to increased hypercholesterolemia susceptibility in female offspring rats.


Multi-residue method for fast determination of pesticide residues in plants used in traditional chinese medicine by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry.
An ultra-high-performance liquid chromatographic-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous quantification and identification of 116 pesticide residues which were most widely used in plants used in Traditional Chinese Medicine (TCM) in 15 min has been developed and validated. Samples were extracted and cleaned up with modified QuEChERS method and detected by UHPLC-MS/MS under multiple reactions monitoring mode, and quantified by matrix-match calibration. The validation study was carried out on five different matrixes following DG SANCO/2007/3131 of the European Quality Control Guidelines. The linearity of the calibration was good between 5 and 100 ng ml⁻¹ concentration ranges, and the limits of quantification (LOQs) less than 0.01 mg/kg for most pesticides. The mean recoveries of almost all pesticides were in the range from 70% to 120% at three concentration levels ranging from 0.01 mg/kg to 0.1mg/kg with relative standard deviations (RSD) better than 15%. The method was applied on 138 real samples from 102 different kinds of Chinese herbal medicine. 95 positive samples were detected. This method is fast, robust, accurate, selective, sensitive and easy to operate.


The dioxygen cycle. Spectral, kinetic, and thermodynamic characteristics of ferryl and peroxy intermediates observed by reversal of the cytochrome oxidase reaction.
The catalytic mechanism of O2 reduction by cytochrome oxidase was studied in isolated mitochondria and mitoplasts by partial reversal of the reaction. At a high redox potential (Eh) of cytochrome c, high pH, and a high electrochemical proton gradient (delta mu H+) across the inner mitochondrial membrane, the initial ferriccupric state (O) of the oxidized enzyme's bimetallic oxygen reaction center is converted to ferryl (F) and peroxy (P) intermediates, the optical spectroscopic properties of which are reported in detail. This is associated with reversed electron transfer from the bimetallic center to ferricytochrome c. The kinetics of reduction of ferricytochrome c by the reversed electron transfer process are compared with the kinetics of formation of F and P. The results are consistent with transfer of one electron from the ferric-cupric bimetallic center (O) to cytochrome c, yielding the F intermediate, followed by transfer of one electron from the latter to cytochrome c, yielding the P state. In the absence of an effective redox buffer, poising cytochrome c highly oxidized, these primary events are immediately followed by reoxidation of cytochrome c, which is ascribed to forward electron transfer to enzyme molecules still in the O state. This forward reaction also results in accumulation of the P intermediate. Kinetic stimulations of the data predict equilibrium constants for the reversed electron transfer steps, and Em,7 values of approximately 1.1 and 1.2 V may be calculated for the F/O and P/F redox couples, respectively, at delta mu H+ and delta psi equal to zero. Taken together with previously measured Em,7 values, these data indicate that it is the two-electron reduction of bound dioxygen to bound peroxide that is responsible for the irreversibility of the catalytic dioxygen cycle of cell respiration.


Endogenous release of hepoxilin A3 from isolated perifused pancreatic islets of Langerhans.
Pancreatic islets of Langerhans were perifused with Krebs-bicarbonate solution containing glucose (5 and 10 mM). The perifusate was spiked with tetradeuterated hepoxilin A3 and was extracted and analysed by gas chromatography-mass spectrometry using NICI detection. Evidence is presented showing the presence of hepoxilin A3 as the hydrolysis product trioxilin A3. These results demonstrate for the first time that this pathway is active in intact cells; this finding, taken together with our previous evidence that hepoxilins possess insulin secretagogue properties further supports our hypothesis that these products could play a role as endogenous mediators of insulin release.


Diagnosis and management of testicular torsion: pitfalls and perils.
When a patient presents with acute scrotal pain and physical findings do not permit confident exclusion of testicular torsion, the initial step in management is immediate consultation with a urologist, pediatric surgeon, or general surgeon. Scrotal imaging is fallible and takes time that may be critical to salvage of the testis. Manual detorsion may be indicated when specialty support is not immediately available, but even if this technique is apparently successful, the patient should be transferred to specialty care without delay.


Isolation and Comparative Genomic Analysis of T1-Like Shigella Bacteriophage pSf-2.
The increasing prevalence of antibiotic-resistant Shigella sp. emphasizes that alternatives to conventional antibiotics are needed. Siphoviridae bacteriophage (phage), pSf-2, infecting S. flexneri ATCC(®) 12022 was isolated from Geolpocheon stream in Korea. Morphological analysis by transmission electron microscopy revealed that pSf-2 has a head of about 57 ± 4 nm in diameter with a long tail of 136 ± 3 nm in length and 15 ± 2 nm in width. One-step growth analysis revealed that pSf-2 has latent period of 30 min and burst size of 16 PFU/infected cell. The DNA genome of pSf-2 is composed of 50,109 bp with a G+C content of 45.44 %. The genome encodes 83 putative ORFs, 19 putative promoters, and 23 transcriptional terminator regions. Genome sequence analysis of pSf-2 and comparative analysis with the homologous T1-like Shigella phages, Shfl1 and pSf-1, revealed that pSf-2 is a novel T1-like Shigella phage. These results showed that pSf-2 might have a high potential as a biocontrol agent to control shigellosis. Also, the genomic information may lead to further understanding of phage biodiversity, especially T1-like phages.


Pooled Analysis of Rivaroxaban therapy for acute venous thromboembolism in FIRST registry, SWIVTER and DRESDEN NOAC registry.
The direct factor Xa inhibitor rivaroxaban is approved for the treatment of venous thromboembolism (VTE), based on the results of large phase III trials. To confirm rivaroxaban's effectiveness and safety in routine clinical care of patients with VTE. Data were obtained from prospective, noninterventional registries: the FIRST registry (United Kingdom), DRESDEN NOAC registry (Germany), and SWIVTER (Switzerland). Baseline characteristics of these registries and effectiveness and safety outcome rates for the FIRST and DRESDEN NOAC registries were compared. A total of 1841 rivaroxaban-treated patients with acute VTE (57.9% male, 76.6% deep vein thrombosis [DVT]; 23.4% pulmonary embolism ± DVT; median age, 61 years) were included: 1217 from the FIRST registry, 418 from the DRESDEN NOAC registry, and 206 from SWIVTER. Median time between VTE diagnosis and initiation of rivaroxaban was 1.4 ± 1.81 days (25th-75th percentile 1-1; range, 0-15 days). On-treatment outcome rates for the FIRST and DRESDEN NOAC registries were 0.74 per 100 patient-years (95% confidence interval [CI], 0.35-1.54) versus 0.96 per 100 patient-years (95% CI, 0.46-2.01) for VTE recurrence; 1.16 per 100 patient years (95% CI, 0.64-2.09) versus 2.51 per 100 patient-years (95% CI, 1.58-3.98) for ISTH major bleeding and 1.69 per 100 patient-years (95% CI, 1.21-2.35) versus 1.73 per 100 patient-years (95% CI, 1.27-2.36) for all-cause mortality (intention-to-treat analysis), respectively. Overall treatment outcomes were consistent with the results of the phase III rivaroxaban trials in VTE treatment, indicating that the use of rivaroxaban offers acceptable treatment results also in routine care. However, we observed significant differences in patient characteristics and management patterns across Switzerland, the United Kingdom, and Germany, limiting direct comparisons of unadjusted outcome event rates between registries.


Investigation of a new core-shell particle column for ion-pair reversed-phase liquid chromatography analysis of oligonucleotides.
A new core-shell particle column showed excellent performance and durability for separation of short (∼21-mer) ribonucleic acid (RNA) oligonucleotides by ion-pair reversed-phase liquid chromatography (IP-RPLC). Previously investigated core-shell C18 columns showed excellent peak shapes and separations of closely eluting impurities by IP-RPLC. However, these columns showed only modest long-term stability at the neutral pH and elevated column temperatures of ≥60°C, typically used for IP-RPLC analysis of oligonucleotides. The newly introduced SunShell C18 column provided separations comparable to the previously evaluated core-shell columns, but with significantly improved long-term column stability when operated at neutral pH and elevated column temperature.


Effects of soil conservation measures in a partially vegetated area after forest fires.
After forest fires on the east coast of Korea in 2000, some burnt areas were left untreated. Although 80% of the area was reasonably revegetated within 3 months, about 20% of the area was partially vegetated, mainly due to a low density of sprouters and poor growing conditions (eroded soil and steep slopes). Three years after the fires, the effect of soil conservation measures, such as mulching with wood chips, seeding with native plant species and log erosion barriers (LEBs), on runoff and soil erosion were examined using runoff plots. Wood chip mulching greatly reduced runoff and sediment yields and these effects were consistent regardless of the volume of rainfall. Neither seeding nor LEBs reduced runoff and sediment yields. No positive or negative effects of mulching, seeding or LEBs on ground vegetation cover were observed. The ineffectiveness of seeding and LEBs may have been due to the steep slope, the failure of germination and establishment of seeded plants, and the small diameter of logs. Treating hill slopes with mulch should be considered where post-fire regeneration is slow and there is an absence of organic material such as litter.


A tutorial on aphasia test development in any language: Key substantive and psychometric considerations.
There are a limited number of aphasia language tests in the majority of the world's commonly spoken languages. Furthermore, few aphasia tests in languages other than English have been standardized and normed, and few have supportive psychometric data pertaining to reliability and validity. The lack of standardized assessment tools across many of the world's languages poses serious challenges to clinical practice and research in aphasia. The current review addresses this lack of assessment tools by providing conceptual and statistical guidance for the development of aphasia assessment tools and establishment of their psychometric properties. A list of aphasia tests in the 20 most widely spoken languages is included. The pitfalls of translating an existing test into a new language versus creating a new test are outlined. Factors to consider in determining test content are discussed. Further, a description of test items corresponding to different language functions is provided, with special emphasis on implementing important controls in test design. Next, a broad review of principal psychometric properties relevant to aphasia tests is presented, with specific statistical guidance for establishing psychometric properties of standardized assessment tools. This article may be used to help guide future work on developing, standardizing and validating aphasia language tests. The considerations discussed are also applicable to the development of standardized tests of other cognitive functions.


An exploratory cross-sectional study of immune checkpoint inhibitors and immuno-related adverse events: Knowledge and influencing factors among Japanese oncology nurses.
Adequate knowledge of immune checkpoint inhibitors (ICIs) and associated immune-related adverse events (irAEs) is essential for managing such events. However, the level of knowledge among Japanese nurses remains unclear. This study aimed to investigate the current status of ICIs and irAE knowledge and the factors influencing them, among outpatient nurses caring for patients undergoing ICI treatment. An exploratory cross-sectional study was conducted at 450 facilities nationwide. Participants completed a self-administered online questionnaire consisting of three parts, measuring personal and environmental attributes and awareness and knowledge of irAEs. Questions were based on multiple literature sources and were evaluated and validated by medical oncologists and certified oncology nurses. A total of 196 (response rate: 36%) nurses responded to the survey at 109 facilities (valid responses: 192; rate: 35%). The correct response rate was 27.6% for questions on general ICI knowledge and 15.6% for general irAE knowledge. Questions on pulmonary dysfunction had the highest correct response rate (41.7%), while those on neuromuscular/joint dysfunction had the lowest (1%). The mean correct response rates were 76% for general knowledge and 48.1% for ICI-specific knowledge. Multiple regression analysis showed that the most influential factor was the participants' study schedule (P < 0.05). There is room for nurses to acquire additional knowledge about ICIs and irAEs. The use of patient education tools and a study schedule significantly increased knowledge scores. Further research is needed to identify when and how to provide nurses with opportunities to acquire additional ICI and irAE-related knowledge.


Ethnobotanical literature survey of medicinal plants in the Dominican Republic used for women's health conditions.
This ethnobotanical literature survey is part of an on-going study in New York City investigating Dominican and Chinese healing systems and the herbal treatments used for the following women's conditions: uterine fibroids (benign tumors of uterine smooth muscle); menorrhagia (excessive uterine bleeding); endometriosis (growth of endometrial tissue outside of the uterus); and hot flashes (sudden brief sensations of heat commonly experienced during menopause). The objectives of this survey were: (1) to search literature on medicinal plants used in the Dominican Republic and identify those used for the above listed conditions and their symptoms; (2) to compare the use between herbal treatments reported in the literature with those prescribed by Dominican healers in New York City; and (3) to evaluate the extent to which healers may have changed their use of plants in order to adapt to availability in the New York City environment. A total of 87 plant species were reported in the Dominican literature for these conditions and symptoms. Nineteen species overlapped from the literature survey and the fieldwork with Dominican healers in New York City, representing 29% (n=65) of the plants prescribed by healers in New York City. This study offers a model to investigate changes in plant use as people migrate to urban centers where they are surrounded by diverse cultures, healing systems, and new environments.


Micropulsed diode laser therapy: evolution and clinical applications.
Many clinical trials have demonstrated the clinical efficacy of laser photocoagulation in the treatment of retinal vascular diseases, including diabetic retinopathy. There is, however, collateral iatrogenic retinal damage and functional loss after conventional laser treatment. Such side effects may occur even when the treatment is appropriately performed because of morphological damage caused by the visible endpoint, typically a whitening burn. The development of the diode laser with micropulsed emission has allowed subthreshold therapy without a visible burn endpoint. This greatly reduces the risk of structural and functional retinal damage, while retaining the therapeutic efficacy of conventional laser treatment. Studies using subthreshold micropulse laser protocols have reported successful outcomes for diabetic macular edema, central serous chorioretinopathy, macular edema secondary to retinal vein occlusion, and primary open angle glaucoma. The report includes the rationale and basic principles underlying micropulse diode laser therapy, together with a review of its current clinical applications.


Obsession-compulsion, locus of control, depression, and hopelessness: a construct validity of the Arabic Obsessive-Compulsive Scale in American and Kuwaiti students.
In samples of 144 American and 209 Kuwaiti college students, the correlations among scores on the Arabic Obsessive-Compulsive Scale and external locus of control (.26, .25), depression (.31, .55) and hopelessness (.27, .43) were significant and positive in both samples, denoting the construct validity of the Obsessive-Compulsive Scale. Thus, it can be recommended for use in both countries.


The challenge of long-term tetrahydrobiopterin (BH4) therapy in phenylketonuria: Effects on metabolic control, nutritional habits and nutrient supply.
BH4-sensitive phenylketonuria (PKU) patients relax their phenylalanine (Phe) restricted diet due to increased Phe tolerance, while keeping dried blood Phe concentrations with in the therapeutic range. We aimed to investigate metabolic control, eating habits and nutrient supply under long-term BH4-therapy. Retrospective analysis of mean dried blood Phe concentrations and their variability, food and nutrient intake in BH4-sensitive patients (n = 8, 3f, age 6.0-16.6 y) under classical dietary treatment for one year and during the three years after initiation of BH4. Phe concentrations of BH4-sensitve PKU patients remained within therapeutic range throughout the observation period, independent of therapeutic regime. Under BH4, Phe tolerance increased significantly (493.2 ± 161.8 mg/d under classical diet vs 2021.93 ± 897.4 mg/d two years under BH4; P = 0.004). Variability of Phe concentrations remained unchanged (mean SD; P = 1.000). Patients adjust their food choice and significantly increased their intake of cereals, potatoes, dairy products and meat (P = 0.019, P = 0.016, P = 0.016 and P = 0.016, respectively). Under diet changes after implementation of BH4 a drop in micronutrient intake (vitamin D, folic acid, iron, calcium, iodine) could be revealed (P = 0.005, P < 0.001, P = 0.004, P = 0.001, P = 0.003, respectively). BH4-sensitive PKU patients can achieve good metabolic control under an adjuvant BH4- or a BH4 monotherapy. The liberalized diet under BH4 seems to jeopardize the quality of patients' nutrition, and these patients require close follow-up and special nutrition education to minimize the risk for imbalanced diet and nutrient deficiencies.


Molecular mechanisms of changes in TNF-alpha production by blood mononuclears in chronic viral hepatitis C.
Chronic viral hepatitis C is associated with decreased production of TNF-alpha by the peripheral blood mononuclear leukocytes irrespective of virus genotype and degree of the morphological activity of the process in the liver. This process positively correlates with the increase in the content of TNF-alpha soluble receptor (molecular weight 55 kDa), which can play a role in the mechanisms of immunopathogenesis of long persistence of hepatitis C virus in the body.