Modulation of memory and visuospatial processes by biperiden and rivastigmine in elderly healthy subjects.
The central cholinergic system is implicated in cognitive functioning. The dysfunction of this system is expressed in many diseases like Alzheimer's disease, dementia of Lewy body, Parkinson's disease and vascular dementia. In recent animal studies, it was found that selective cholinergic modulation affects visuospatial processes even more than memory function. In the current study, we tried to replicate those findings. In order to investigate the acute effects of cholinergic drugs on memory and visuospatial functions, a selective anticholinergic drug, biperiden, was compared to a selective acetylcholinesterase-inhibiting drug, rivastigmine, in healthy elderly subjects. A double-blind, placebo-controlled, randomised, cross-over study was performed in 16 healthy, elderly volunteers (eight men, eight women; mean age 66.1, SD 4.46 years). All subjects received biperiden (2 mg), rivastigmine (3 mg) and placebo with an interval of 7 days between them. Testing took place 1 h after drug intake (which was around Tmax for both drugs). Subjects were presented with tests for episodic memory (wordlist and picture memory), working memory tasks (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Visuospatial abilities were assessed by tests with high visual scanning components (tangled lines and Symbol Digit Substitution Test). Episodic memory was impaired by biperiden. Rivastigmine impaired recognition parts of the episodic memory performance. Working memory was non-significantly impaired by biperiden and not affected by rivastigmine. Motor learning as well as visuospatial processes were impaired by biperiden and improved by rivastigmine. These results implicate acetylcholine as a modulator not only of memory but also of visuospatial abilities.


Timing estimation for gait in water from inertial sensor measurements: Analysis of the performance of 17 algorithms.
Walking in water is used for rehabilitation in different pathological conditions. For the characterization of gait alterations related to pathology, gait timing assessment is of primary importance. With the widespread use of inertial sensors, several algorithms have been proposed for gait timing estimation (i.e. gait events and temporal parameters) out of the water, while an assessment of their performance for walking in water is still missing. The purpose of the present study was to assess the performance in the temporal segmentation for gait in water of 17 algorithms proposed in the literature. Ten healthy volunteers mounting 5 tri-axial inertial sensors (trunk, shanks and feet) walked on dry land and in water. Seventeen different algorithms were implemented and classified based on: 1) sensor position, 2) target variable, and 3) computational approach. Gait events identified from synchronized video recordings were assumed as reference. Temporal parameters were calculated from gait events. Algorithm performance was analysed in terms of sensitivity, positive predictive value, accuracy, and repeatability. For walking in water, all Trunk-based algorithms provided a sensitivity lower than 81% and a positive predictive value lower than 94%, as well as acceleration-based algorithms, independently from sensor location, with the exception of two Shank-based ones. Drop in algorithm sensitivity and positive predictive value was associated to significant differences in the stride pattern of the specific analysed variables during walking in water as compared to walking on dry land, as shown by the intraclass correlation coefficient. When using Shank- or Foot-based algorithms, gait events resulted delayed, but the delay was compensated in the estimate of Stride and Step time; a general underestimation of Stance- and overestimation of Swing-time was observed, with minor exceptions. Sensor position, target variable and computational approach determined different error distributions for different gait events and temporal parameters for walking in water. This work supports an evidence-based selection of the most appropriate algorithm for gait timing estimation for walking in water as related to the specific application, and provides relevant information for the design of new algorithms for the specific motor task.


Identification of the putative binding pocket of valerenic acid on GABAA receptors using docking studies and site-directed mutagenesis.
β2/3-subunit-selective modulation of GABAA receptors by valerenic acid (VA) is determined by the presence of transmembrane residue β2/3N265. Currently, it is not known whether β2/3N265 is part of VA's binding pocket or is involved in the transduction pathway of VA's action. The aim of this study was to clarify the localization of VA's binding pocket on GABAA receptors. Docking and a structure-based three-dimensional pharmacophore were employed to identify candidate amino acid residues that are likely to interact with VA. Selected amino acid residues were mutated, and VA-induced modulation of the resulting GABAA receptors expressed in Xenopus oocytes was analysed. A binding pocket for VA at the β(+) /α(-) interface encompassing amino acid β3N265 was predicted. Mutational analysis of suggested amino acid residues revealed a complete loss of VA's activity on β3M286W channels as well as significantly decreased efficacy and potency of VA on β3N265S and β3F289S receptors. In addition, reduced efficacy of VA-induced IGABA enhancement was also observed for α1M235W, β3R269A and β3M286A constructs. Our data suggest that amino acid residues β3N265, β3F289, β3M286, β3R269 in the β3 subunit, at or near the etomidate/propofol binding site(s), form part of a VA binding pocket. The identification of the binding pocket for VA is essential for elucidating its pharmacological effects and might also help to develop new selective GABAA receptor ligands.


Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration.
Although hair testing is well established for the assessment of past drug exposure, uncertainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. Seven volunteers with a history of stimulant use received 4×10 mg (low) doses of sustained release S-(+)-MAMP HCl within 1 week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4×20 mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC-MS-MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng mg(-1)). MAMP T(max) occurred from 1 to 2 weeks after both doses, with C(max) ranging from 0.6 to 3.5 ng mg(-1) after the low and 1.2 to 5.3 ng mg(-1) after the high MAMP doses. AMP C(max) in hair was 0.1-0.3 ng mg(-1) and 0.2-0.5 ng mg(-1), respectively, for low and high doses. Highly dose-related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2 ng mg(-1) cut-off for at least 2 weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15 ± 0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r(2)=0.90, p=0.00) and AMP (r(2)=0.94, p=0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between C(max) and melanin. This study demonstrated that despite large inter-individual differences, the incorporation of MAMP and AMP into hair is dose-related with much of the observed scatter of MAMP and AMP concentrations explained by melanin concentration in hair.


The ban operon of bacteriophage P1. Localization of the promoter controlled by P1 repressor.
Repression of a strong promoter localized 5' to the P1 ban gene is a prerequisite for cloning the ban operon in the multicopy plasmid pBR325. Repression is brought about by the binding of P1 repressor to the operator of the ban operon (Heisig, A., Severin, I., Seefluth, A. K., and Schuster, H. (1987) Mol. Gen. Genet. 206, 368-376). Binding of RNA polymerase in vitro overlaps with the operator and is inhibited by P1 repressor as shown by electron microscopy. The mutant P1 bac, which renders ban expression constitutive, contains a single base pair exchange within the operator. As a consequence, more repressor is required (i) for the inhibition of binding of RNA polymerase, and (ii) for the electrophoretic retardation of a P1 bac DNA fragment when compared to the corresponding bac+ fragment. A P1 ban recombinant plasmid containing a 4-base pair deletion close to the operator still allows binding of repressor but not of RNA polymerase. By that means, a repressible promoter is located at the P1 map position 72 in a distance of about 2.5 kilobase pairs to the beginning of the ban gene.


Chylous ascites following retroperitoneal lymphadenectomy: report of 2 cases with guidelines for diagnosis and treatment.
Two cases of chylous ascites following retroperitoneal lymphadenectomy are presented. The first case, a 3-year-old girl, undersent a right radical nephrectomy and retroperitoneal lymph node dissection for Wilms' tumor. Chylous ascites developed postoperatively and resolved after 3 months of supportive therapy. The second case, a 45-year-old woman, underwent a right radical nephrectomy and retroperitoneal lymph node dissection for renal carcinoma. Chylous ascites occurred postoperatively and resolved after a single paracentesis. Diagnosis, evaluation, and therapeutic modalities are outlined and the literature is reviewed.


A liquid metal dressing for anti-inflammatory and anti-infection applications to treat diabetic wounds.
We report a dual-effect liquid metal dressing with antibiotic delivery and hydrogen generation capacity for antibacterial and anti-inflammatory applications. This material provides a gentle approach for H2 therapy and responsive drug delivery, and can treat chronic diabetic wounds.


The Efficacy of Self-Report Measures in Predicting Social Phobia in African American Adults.
Empirical literature pertaining to anxiety in African Americans has been relatively sparse. More recent studies indicate that the construct of social fear is different in African Americans than in non-Hispanic Whites. Although some of these studies have examined factor structure utilizing self-report measures of anxiety in African American samples, none to date have examined the clinical utility of these measures in predicting anxiety diagnoses, particularly social phobia. A total of sixty-five African American adults from the community completed the Fear Survey Schedule-Second Edition (FSS-II), Social Anxiety Interaction Scale (SIAS), Social Phobia Scale (SPS), and Albany Panic and Phobia Questionnaire (APPQ). The Anxiety Disorder Interview Schedule-Fourth Edition (ADIS-IV) was administered to all participants to specify differential diagnoses of anxiety and related disorders. Twenty-three African American adults were diagnosed with social phobia leaving 42 diagnostic controls. Results suggest that the social anxiety factors were highly predictive of a social phobia diagnosis (AUC=.84 to .90; CI .73-.98, p<.01) and sensitivity and specificity rates revealed optimal cutoff scores for each measure. The optimal cutoff scores reveal the clinical utility of the social fear factor from these measures in screening for social phobia in African Americans. Future direction and implications are discussed. Psychinfo, PubMed, Medline.


Scope of symptoms and self-management strategies for chemotherapy-induced peripheral neuropathy in breast cancer patients.
This study explored the self-management strategies utilized by female breast cancer patients to cope with the impact of chemotherapy-induced peripheral neuropathy (CIPN) symptoms. We also examined the variety of taxane-related side effects in women with and without CIPN in order to discriminate the CIPN symptom experience. A purposive sample of 25 patients treated with docetaxel or paclitaxel were recruited, half with and half without CIPN. Semistructured interviews and patient level data were utilized for this exploratory, descriptive study. Interview data were analyzed with the constant comparative method; patient level data were abstracted from the electronic medical record. Participants were aged 24-60 years, were currently receiving chemotherapy or within 6 months of having completed treatment, and 14 had CIPN. CIPN impacted routine activities, functions, and behaviors in the areas of domestic, work, and social/leisure life. Multiple self-management and coping strategies to minimize the impact of CIPN symptoms were reported; the focus was on movement to reduce symptoms, attitude awareness, logistics to simplify demands, and environmental change. Women with and without CIPN were similar in the quantity and type of other reported side effects. CIPN affects breast cancer patients' routine activities, functions, and behaviors, but they develop management strategies to reduce the impact. The management strategies reported in this study suggest breast cancer patients may adopt interventions that focus on exercise, mindfulness, occupational therapy, and environmental planning toward the goal of reducing the impact of CIPN symptoms on their lives.


Prevalence, characteristics, and prognosis role of type 1 ST elevation in the peripheral ECG leads in patients with Brugada syndrome.
Despite isolated reports of Brugada syndrome (BrS) in the inferior or lateral leads, the prevalence and prognostic value of ST elevation in the peripheral electrocardiographic (ECG) leads in patients with BrS remain poorly known. To study the prevalence, characteristics, and prognostic value of type 1 ST elevation and ST depression in the peripheral ECG leads in a large cohort of patients with BrS. ECGs from 323 patients with BrS (age 47 ± 13 years; 257 men) with spontaneous (n = 141) or drug-induced (n = 182) type 1 ECG were retrospectively reviewed. Two hundred twenty-five (70%) patients were asymptomatic, 72 (22%) patients presented with unexplained syncope, and 26 (8%) patients presented with sudden death (12 patients) or appropriated implantable cardioverter-defibrillator therapies (14 patients) at diagnosis or over a mean follow-up of 48 ± 34 months. Thirty (9%) patients presented with type 1 ST elevation in at least 1 peripheral lead (22 patients in the aVR leads, 2 in the inferior leads, 5 in both aVR and inferior leads, and 1 in the aVR and VL leads). Patients with type 1 ST elevation in the peripheral leads more often had mutations in the SCN5A gene, were more often inducible, had slower heart rate, and higher J-wave amplitude in the right precordial leads. Twenty-seven percent (8 of 30) of the patients with type 1 ST elevation in the peripheral leads experimented sudden death/appropriate implantable cardioverter-defibrillator therapy, whereas it occurred in only 6% (18 of 293) of other patients (P < .0001). In multivariate analysis, type 1 ECG in the peripheral leads was independently associated with malignant arrhythmic events (odds ratio 4.58; 95% confidence interval 1.7-12.32; P = .0025). Type 1 ST elevation in the peripheral ECG leads can be seen in 10% of the patients with BrS and is an independent predictor for a malignant arrhythmic event.


Infrastructural capital in the Israeli vaccination campaign against COVID-19.
This article examines the Israeli vaccination campaign against COVID-19, focusing on the state's acquisition of the vaccines from the pharmaceutical company Pfizer. In December 2020, Israel signed an agreement with Pfizer to purchase enough doses to vaccinate its entire population. In the months that followed, the country became a world leader in vaccination rates. But how was Israel able to purchase large quantities of then-scarce vaccines in the first place? To answer this question, I examine reports and publications by government and civil society bodies as well as news coverage about the campaign. Drawing on insights from the sociology of the state and from science and technology studies, I argue that Israel was able to secure vaccines by using its state-power as a form of currency. Theoretically, I suggest the term "infrastructural capital" - which I define as the resources a state can provide to an external capitalist actor by virtue of its power - to explain how Israel traded with Pfizer. In the conclusion, I discuss the potential implications of this case for other cases.


Cellular and molecular damage of Phanerochaete chrysosporium by the oxidation hair dyes.
The toxic effect of the oxidation hair dyes on Phanerochaete chrysosporium was investigated by exposure of this fungus in a nitrogen-limited culture medium to various concentrations of the oxidation hair dyes. The results showed that both the size and the dry weight of the mycelial pellets of P. chrysosporium could be reduced when the concentration of the oxidation hair dyes was higher than 300 mg/L. By using the AFLP analysis and the UPGMA dendrogram, the DNA damage of P. chrysosporium by the oxidation hair dyes was also detected. Comparing with that in the control, the percent polymorphism under different concentrations of the oxidation hair dyes increased. In the meantime, the DNA similarity was decreased, which meant that the DNA damage was aggravated with an increase in the concentrations of the oxidation hair dyes. Thus, as an environmental pollutant, the oxidation hair dyes have a toxic effect on P. chrysosporium at both cellular and molecular levels.


Laparoscopic pelvic surgery after reconstructive surgery with vertical rectus abdominis muscle flap: A case report.
Patients who have experienced vertical rectus abdominis muscle (VRAM) flap reconstruction are under risk of the abdominal incisional hernia (donor site hernia), and laparotomy increases the risk. We present the case of a 71-year-old nulliparous woman who experienced radical vulvectomy against extramammary Paget disease and reconstructive surgery with VRAM flap 7 years ago and developed right ovarian tumor. In this case, right ovarian tumor was removed with laparoscopic surgery, instead of laparotomy, and the risk of incisional hernia was successfully minimized. Incisional (donor site) hernia after reconstructive surgery using VRAM flap has been reported in between 2 and 10%. While VRAM flap can fill larger amount of skin and subcutaneous tissue to recipient site, the risk of postoperative incisional hernia of abdominal wall is substantial. Reconstructive surgery of with VRAM flap is required for extramammary vulvar Paget disease expanding wide range, and develops the risk of incisional hernia. Laparoscopic surgery should be applied in patients who have experienced VRAM flap reconstruction and developed pelvic tumor for avoiding the risk of incisional hernia as long as it can be allowed on oncologic aspects such as recurrence.


Hemolytic hyperbilirubinemia after percutaneous device closure of left ventricular pseudoaneurysm: a disregarded complication.
Surgical repair of a left ventricular pseudoaneurysm is challenging. Percutaneous closure with an AMPLATZER Septal Occluder (AGA Medical Corporation, Golden Valley, MN) has evolved to be an effective alternative to conventional surgery with less complication. We report a case of severe hemolytic hyperbilirubinemia and acute renal failure after percutaneous left ventricular pseudoaneurysm endoprothesis repair, which required conventional surgical repair through a left thoracotomy to treat this complication. The rationale and results of such an off-the-label usage of AMPLATZER Septal Occluder were reexamined. Residual leakages were not rare findings in the reviewed literature. The indications for this approach should be individualized.


Results of lung volume reduction surgery in patients meeting a national emphysema treatment trial high-risk criterion.
A report from the National Emphysema Treatment Trial indicated that lung volume reduction candidates with a forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of 20% or less of predicted value were at high risk for mortality and were unlikely to benefit from surgical intervention. This article examines the applicability of the National Emphysema Treatment Trial findings to our own patients. We reviewed 280 patients who underwent bilateral lung volume reduction surgery at our institution between January 1993 and December 2001. All patients met our selection criteria, including heterogeneous distribution of emphysema. Of these 280 patients, 20 patients had both a preoperative forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of less than or equal to 20% of the predicted normal values, thus meeting one National Emphysema Treatment Trial criterion for high risk. Outcomes of the 20 patients were assessed through 5 years after the operation. The survival of the 20 patient cohort was compared with that of the 260 patients not meeting the National Emphysema Treatment Trial high-risk criterion. Ninety-day operative mortality included 1 (5%) patient. In all patients the forced expiratory volume in 1 second increased from 0.46 L (17%) to 0.78 L (32%), a 73% change; the diffusing capacity of carbon monoxide increased from 16% to 27%, a 70% improvement; residual volume decreased from 6.33 L (305%) to 4.26 L (205%), a 33% improvement; and room air arterial partial pressure of oxygen increased from 55 mm Hg to 64 mm Hg. Kaplan-Meier 5-year survivals did not differ between the high-risk and non-high-risk groups. Patients with a forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of 20% or less of predicted value might experience improvements in lung function, exercise tolerance, and quality of life with acceptable morbidity and mortality after lung volume reduction surgery.


Prognostic significance of cytological differentiation grading in estrogen-treated prostatic carcinoma diagnosed by fine-needle aspiration biopsy. (Five-year follow-up of 496 patients).
The value of fine-needle aspiration biopsy of carcinoma of the prostate and its cytological grading is demonstrated. The grade of morphological differentiation in cytological smears has proved to be a reliable criterion for the prognosis in 496 estrogen-treated prostatic carcinoma patients. The life expectancy of low-differentiated and anaplastic cancer patients undergoing treatment is so poor that the justification for antiandrogen treatment in this group of carcinomas appears extremely doubtful. For this reason, the degree of differentiation of the tumor should be considered when undertaking therapeutic measures in view of its relevance for the prognosis.


Expression of B. subtilis Phytase gene driven by fruit specific E8 promoter for enhanced minerals, metabolites and phytonutrient in cucumber fruit.
The fruit nutrigenomics is an interesting and important research area towards nutrition enhancement. The phytic acid is one of the major antinutrient compound, present in seeded fruits and crops. It hinders the absorption of iron (Fe), zinc (Zn), magnesium (Mg), potassium (K) and calcium (Ca), causing mineral deficiencies. In the present study, the BsPhy gene was overexpressed in the cucumber fruits using the tomato fruit specific E8 and constitutive CaMV 35S promoter. The E8 promoter imparted heterologous expression of GUS gene in cucumber fruits, furthermore, the fruit specific expression of E8 promoter with BsPhy gene was confirmed in transgenics (E8::BsPhy) using anti rabbit-phytase antibody. The physio-biochemical analysis of transgenics revealed, maximum phytase activity in E8::BsPhy cucumber fruits at 10 days after anthesis (DAA) compared to 35S::BsPhy and wild-type (WT) fruits. Consequently, E8::BsPhy fruits also showed increased amount of inorganic phosphorus (Pi), total phosphorus (P), minerals (Zn, Fe, Mg, K, Ca), total carotenoid and other macronutrients at 10 DAA compared to 35S::BsPhy fruits. The metabolite profiling of fruits (10 DAA) showed increased sugars, amino acids, sugar acids and polyols, in both E8::BsPhy and 35S::BsPhy transgenics suggesting higher phytate metabolism, compared to WT fruits. Interestingly, both the transgenic fruits showed higher fruit biomass and yield along with improved nutritional quality, which can be attributed to increased P and Zn contents in transgenic fruits, compared to WT fruits. Our findings reveal that the BsPhy gene enhances minerals and macronutrients in transgenic cucumber fruits making it nutritious and healthy.


Guideline No. 440: Management of Monochorionic Twin Pregnancies.
This guideline reviews the evidence-based management of normal and complicated monochorionic twin pregnancies. Women with monochorionic twin or higher order multiple pregnancies. Implementation of these recommendations should improve the management of both complicated and uncomplicated monochorionic (and higher order multiple) twin pregnancies. They will help users monitor monochorionic twin pregnancies appropriately and identify and manage monochorionic twin complications optimally in a timely manner, thereby reducing perinatal morbidity and mortality. These recommendations entail more frequent ultrasound monitoring of monochorionic twins compared to dichorionic twins. Published literature was retrieved through searches of PubMed and the Cochrane Library using appropriate MeSH headings (Twins, Monozygotic; Ultrasonography, Prenatal; Placenta; Fetofetal Transfusion; Fetal Death; Fetal Growth Retardation). Results were restricted to systematic reviews, randomized controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. The content and recommendations were drafted and agreed upon by the principal authors. The Board of the SOGC approved the final draft for publication. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). Maternal-fetal medicine specialists, obstetricians, radiologists, sonographers, family physicians, nurses, midwives, residents, and other health care providers who care for women with monochorionic twin or higher order multiple pregnancies. Canadian (SOGC) guidelines for the diagnosis, ultrasound surveillance and management of monochorionic twin pregnancy complications, including TTTS, TAPS, sFGR (sIUGR), acardiac (TRAP), monoamniotic twins and intrauterine death of one MC twin. RECOMMENDATIONS.


The role of transparency in da Vinci stereopsis.
The majority of natural scenes contains zones that are visible to one eye only. Past studies have shown that these monocular regions can be seen at a precise depth even though there are no binocular disparities that uniquely constrain their locations in depth. In the so-called da Vinci stereopsis configuration, the monocular region is a vertical line placed next to a binocular rectangular occluder. The opacity of the occluder has been mentioned to be a necessary condition to obtain da Vinci stereopsis. However, this opacity constraint has never been empirically tested. In the present study, we tested whether da Vinci stereopsis and perceptual transparency can interact using a classical da Vinci configuration in which the opacity of the occluder varied. We used two different monocular objects: a line and a disk. We found no effect of the opacity of the occluder on the perceived depth of the monocular object. A careful analysis of the distribution of perceived depth revealed that the monocular object was perceived at a depth that increased with the distance between the object and the occluder. The analysis of the skewness of the distributions was not consistent with a double fusion explanation, favoring an implication of occlusion geometry in da Vinci stereopsis. A simple model that includes the geometry of the scene could account for the results. In summary, the mechanism responsible to locate monocular regions in depth is not sensitive to the material properties of objects, suggesting that da Vinci stereopsis is solved at relatively early stages of disparity processing.


Vegetation induced distinctions between radionuclide distribution in soils (Austria).
In 2019 and 2020, the layers - down to a maximum depth of 30 cm - of 43 soil samples from different regions in Austria were measured gamma-spectrometrically to determine their activity concentration (in Bq/kg and Bq/m³) of 234Th, 214Pb, 214Bi, 210Pb, 228Ac and 40K. 137Cs activity concentration (in Bq/m³) will be found in the supplementary data file only. A basic statistical analysis was carried out and explained variances for distinctions primarily between meadows and forests. Ternary diagrams were applied to represent equilibrium status of inventories and layer activities between 238U-equivalent, 226Ra-equivalent and 210Pb. A method using ternary diagrams for identifying of element-specific dampening effects in remote sensing is presented in the report (ternary "adjustment" diagrams). The tendencies between forest and meadows sites are heterogeneous, but distinctions between coniferous and deciduous forest are extremely likely. Geological settings dominate the distributions, slightly altered by anthropogenic influence, which includes the kind of vegetation. Focusing on top soil layers (first and/or second layer) facilitates discrimination according to vegetation. At some sites changes of activities in the grass root layer (at 15 cm) were observed.


The PDLIM5 gene and lithium prophylaxis: an association and gene expression analysis in Sardinian patients with bipolar disorder.
A number of studies support the notion that lithium interacts with the protein kinase C (PKC) pathway, an important mediator of several intracellular responses to neurotransmitter signaling. PDLIM5 (PDZ and LIM domain 5; LIM) is an adaptor protein that selectively binds the isozyme PKC(epsilon) to N-type Ca(2+) channels in neurons. We tested for an association between three single nucleotide polymorphisms (SNPs) at the PDLIM5 gene and lithium prophylaxis in a Sardinian sample comprised of 155 bipolar patients treated with lithium. In order to evaluate whether PDLIM5 expression interacts with lithium response, we carried out gene expression analysis in lymphoblastoid cells of 30 bipolar patients. No association was shown between PDLIM5 polymorphisms and lithium response. When PDLIM5 expression was evaluated, no significant differences were detected between Full Responders to lithium (total score>or=7) and other patients (total score<or=6). Our negative findings do not exclude involvement of PDLIM5 in lithium prophylaxis, and further investigation is warranted.


A robust optimization model for tactical capacity planning in an outpatient setting.
Tactical capacity planning is a key element of planning and control decisions in healthcare settings, focusing on the medium-term allocation of a clinic's resources to appointments of different types. One of the most scarce resources in healthcare is physician time. Due to uncertainty in demand for appointments, it is difficult to provide an exact match between the planned physician availability and appointment requests. Our study uses cardinality-constrained robust optimization to develop tactical capacity plans which are robust against uncertainty, providing a feasible allocation of capacity for all realizations of demand to the extent allowed by the budget of uncertainty. The outpatient setting we consider sees first-visit patients and re-visit patients, and both patient types have access time targets. We experimentally evaluate our robust model and its practical implications under different levels of conservatism. We show that we can guarantee 100% feasibility of the robust tactical capacity plan while not being fully conservative, which will lead to the clinic saving money while being able to meet demand despite uncertainty. We also show how the robust model helps us to identify the critical time periods leading to worst case physician peak load, which could be valuable to decision-makers. Throughout the experiments, we find that the step of translating available data into an uncertainty set can influence the true conservatism of a solution.


Microscale thermophoresis analysis of the molecular interaction between small nuclear ribonucleoprotein polypeptide G and the RING finger domain of RBBP6 towards anti-cancer drug discovery.
Regulatory core-splicing proteins are now becoming highly promising therapeutic targets for the development of anti-cancer drugs. SNRPG and RBBP6 are two good examples of regulatory core-splicing proteins involved in tumorigenesis and tumor development whose multi-functional role is primarily mediated by protein-protein interactions. Over the years, skepticism abutting from the two onco-proteins has been mounting. Suggestive evidence using yeast 2-hybrid technique observed possible involvement between SNRPG and the RING finger domain of RBBP6. However, the putative interaction remains elusive and yet to be characterized. In this study, we developed the first MST-based assay to confirm the interaction between SNRPG and the RING finger domain of RBBP6. The results demonstrated a strong binding affinity between SNRPG and the RING finger domain of RBBP6 with a KD in the low nanomolar concentration range of 3.1596 nM. The results are congruent with previous findings suggesting possible involvement between the two proteins in cancer-cell networks, thereby providing a new mechanistic insight into the interaction between SNRPG and the RING finger domain of RBBP6. The interaction is therapeutically relevant and represents a great milestone in the anti-cancer drug discovery space. Identification of small molecule inhibitors to modulate the binding affinity between the two proteins would therefore be a major breakthrough in the development of new PPI-focused anti-cancer drugs.


Lateralization of the human brain.
It is often suggested that cerebral asymmetry, when a consistent direction of asymmetry prevails, is unique to humans. We now know that many other species exhibit directionally consistent cerebral and behavioral asymmetries. Nevertheless, the predominance of left-cerebral dominance for language and manual functions may have played a special role in human evolution, even though precursors may be found in other animals-and especially in the great apes. I argue that the common cerebral asymmetry for these functions derives from the origins of language in manual gestures. These, in turn, may originate in specialized circuits for grasping that have been identified in primates, and lateralization may have been progressively introduced as praxic and linguistic functions became more complex.


Fungal control of pathogenic fungi isolated from wild plants in Taif Governorate, Saudia Arabia.
Twenty two plants were collected from Taif Governorate and identified as: Euphorbia glomerifera, Juniperus procera, Launaea mucronata, Capparis dcidua, Punica granatum, Opuntia ficus, Prunus persica, Eucalyptus globulus, Medicago sativa, Artemisia monosperma, Trichodesma calathiforme, Artemisia judaica, Foeniculum vulgare, Phagnalon sinaicum, Rumex dentatus, Asphodelus aestives, Pulicaria crispa, Launae sonchoides, Forsskaolea tenacissima, Arnebia hispidissima, Avena spp and Aerva lanata. Pathogenic fungi were isolated from some of these plants and identified as Alternaria alternate, Ulocladium botrytis, Cladosporium spp, Cephalosporium spp, Penicillium chrysogenum, Fusarium oxysporum and Humicola grisea. Four antagonistic isolates were tested, 2 from Gliocladium fungus and 2 from Trichoderma fungus. We found that all the four antagonistic isolates (G. deliquescens, G. virens, T. viride and T. hamatum) significantly inhibited the radial growth of the pathogenic fungi tested, with different ratios. The results indicated that the antibiotics produced by the antagonists were more effective than the fungus itself and differ with different fungi. Coating plant stems with antagonists or with antagonist extracts reduce the severity of the disease but not prevent it in all tested pathogens.


The excitatory thalamo-"cortical" projection within the song control system of zebra finches is formed by calbindin-expressing neurons.
The learning and production of vocalizations in songbirds are controlled by a system of interconnected brain nuclei organized into a direct vocal motor pathway and an anterior forebrain (pallium-basal ganglia-thalamo-pallial) loop. Here we show that the thalamo-pallial ("thalamo-cortical") projection (from the medial part of the dorsolateral thalamic nucleus to the lateral magnocellular nucleus of the anterior nidopallium--DLM to LMAN) within the anterior forebrain loop is composed of cells positive for the calcium-binding protein calbindin. We show that the vast majority of cells within DLM express calbindin, based both on immunocytochemistry (ICC) for calbindin protein and in situ hybridization for calb mRNA. Using a combination of tract-tracing and ICC we show that the neurons that participate in the DLM-to-LMAN projection are calbindin-positive. We also demonstrate that DLM is devoid of cells expressing mRNA for the GABAergic marker zGAD65. This observation confirms that the calbindin-expressing cells in DLM are not GABAergic, in accordance with previous electrophysiological data indicating that the DLM-to-LMAN projection is excitatory. Furthermore, we use ICC to determine the trajectory of the fibers within the DLM-to-LMAN projection, and to demonstrate a sex difference in calbindin expression levels in the fibers of the DLM-to-LMAN projection. Our findings provide a clear-cut neurochemical signature for a critical projection in the songbird vocal control pathways that enable song learning.


Impact of endurance exercise on levodopa-associated cortisol release and force increase in patients with Parkinson's disease.
Levodopa (LD) application improves motor symptoms and reduces cortisol levels in patients with Parkinson's disease (PD). Endurance exercise enhances cortisol release in proportion to the intensity of the effort and thus may counteract the LD associated cortisol decrease. We measured levels of cortisol and LD over an 1-h long interval following administration of soluble 200 mg LD/50 mg benserazide with concomitant maximal grip strength assessment in 16 PD patients under cued conditions during rest and endurance exercise. The motor response, the plasma levels of cortisol and LD did not significantly differ between both conditions. Cortisol concentrations significantly decreased even during exercise. Grip strength only significantly went up during rest. Endurance exercise did not counteract the LD associated decreased cortisol release. Since cortisol improves muscle function, the lack of increase in maximal grip strength following LD administration during exercise may contribute to reduced exercise capacity, which is reported by PD patients.


Radioimmunoassay of myelin basic protein. A methodological evaluation.
Three techniques for separating free antigen from antigen-antibody complexes have been applied to radioimmunoassay of myelin basic protein: cold ethanol precipitation of complexes, dextran-coated charcoal precipitation of free antigen, and second antibody precipitation of complexes. After optimization of the incubation and separation steps, the 3 methods were evaluated for precision and accuracy when applied to both spinal fluid and brain tissue homogenates. For determinations in brain tissue all 3 methods showed the same precision and gave largely the same values, though the ethanol method gave slightly lower levels. For spinal fluid the ethanol and dextran-charcoal methods gave the same values, but the double antibody method gave values only 1/3 as high. With spinal fluid, the precision of the dextran-charcoal method was poor compared with that of the other two. The double antibody method proved to be the method of choice for brain tissue samples, when the results of the incubation and separation steps, and the precision and accuracy of the determinations were taken into account. However, for an unknown reason values for spinal fluid were too low by this method. Therefore the ethanol precipitation method is recommended for spinal fluid samples and the double antibody method for brain tissue samples.


Research on the Intelligent Display of Cultural Relics in Smart Museums Based on Intelligently Optimized Digital Images.
The smart museum is a new platform for the appreciation and display of cultural relics across time and space. In the era of 3D scanning technology, computer technology, and network technology, it is necessary to deeply study the smarter and more perfect forms of smart museums. This article, through the analysis of the characteristics of the display level of the smart museum, tries to create a new humanized and intelligent display of cultural relics.


Screening for morbidly adherent placenta in early pregnancy.
To estimate the diagnostic accuracy of a two-stage strategy for early prediction of morbidly adherent placenta (MAP). In the first stage, at 11-13 weeks' gestation, women with low-lying placenta and history of uterine surgery are classified as being at high risk for MAP and, in the second stage, at 12-16 weeks, these high-risk pregnancies are assessed at a specialist MAP clinic. This was a prospective study in women having an ultrasound scan at 11-13 weeks' gestation as a part of routine pregnancy care. Women with low-lying placenta and a history of uterine surgery were followed up at a specialist MAP clinic at 12-16 weeks' gestation, 20-24 weeks and 28-34 weeks. At each visit to the MAP clinic, an ultrasound scan was carried out and the following features suggestive of MAP were recorded: non-visible Cesarean section scar; bladder wall interruption; thin retroplacental myometrium; presence of intraplacental lacunar spaces; presence of retroplacental arterial-trophoblastic blood flow; and irregular placental vascularization demonstrated by three-dimensional power Doppler. Screening at 11-13 weeks was carried out in 22 604 singleton pregnancies, 1298 (6%) of which were considered to be at high risk of MAP because they had previous uterine surgery and low-lying placenta. At the MAP clinic at 12-16 weeks, the diagnosis of MAP was suspected in 14 cases and this was confirmed at delivery in 13. In the rest of the population, there were no cases of MAP. Accurate prediction of MAP can be achieved by ultrasound examination at 12-16 weeks' gestation. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


A systematic review of neuropsychiatric and cognitive assessments used in clinical trials for amyotrophic lateral sclerosis.
Up to 50% of people with amyotrophic lateral sclerosis (ALS) experience cognitive dysfunction, whilst depression and anxiety are reported in up to 44% and 33%, respectively. These symptoms impact on quality of life, and are associated with a poorer prognosis. Historically, outcomes in clinical trials have focused on the effect of candidate drugs on physical functioning. We reviewed the past 25 years of clinical trials of investigative medicinal products in people with ALS, since the licensing of riluzole, and extracted data on frequency and type of assessment for neuropsychiatric symptoms and cognitive impairment. Trial registry databases, including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed, were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 31/10/2019. No language restrictions were applied. Outcome measures, exclusion criteria and assessment tool used were extracted. 216 trials, investigating 26,326 people with ALS, were reviewed. 35% assessed neuropsychiatric symptoms, and 22% assessed cognition, as Exclusion Criteria or Outcome Measures. 3% (n = 6) of trials assessed neuropsychiatric symptoms as a Secondary Outcome Measure, and 4% (n = 8) assessed cognition as Outcome Measures; only one trial included assessments for both cognition and neuropsychiatric symptoms as Outcome Measures. Three ALS-specific assessments were used in six trials. Trials for people with ALS have neglected the importance of neuropsychiatric symptoms and cognitive impairment. Evaluation of these extra-motor features is essential to understanding the impact of candidate drugs on all symptoms of ALS. CRD42020175612.


Development and Validation of a Principal Implementation Practices Measure: The Principal Implementation Questionnaire.
Measurement of principal implementation behaviors has proved difficult to researchers in educational leadership due to a lack of consensus on the operational definitions of leadership constructs. The Principal Implementation Questionnaire (PIQ) was developed and validated with the intention of providing clarity in the assessment of principal leadership behaviors in the implementation of effective reading programs. Constructs were operationally defined within the context of the population of interest, with subsequent item writing centered around the constructs. A resulting calibration sample of principals from Florida Reading First schools was used to test the hypothesized measurement model to determine how well the items were described by the proposed factors. Results from LISREL analyses revealed a well-fitted model, based on numerous fit indices.


Post-reproductive Health: Window of Opportunity for Preventing Comorbidities.
Post-reproductive health is a challenging issue as it is surrounded by many controversies. Menopausal hormone therapy (MHT) has witnessed a rise and fall over last several years. We do understand that comorbidities incidence rises beyond menopause and we need to prevent them. When MHT was used universally, the risk-benefit ratio became unfavorable. Hence, the use of MHT dropped drastically. But newer studies have introduced the concept of window of opportunity, wherein MHT does not have harmful effects, but in fact it will prevent comorbidities associated with menopause. This editorial focuses on the prevention of menopause- and MHT-related comorbidities.


Additivity of detector responses of a portable direct-reading 10.2 eV photoionization detector and a flame ionization gas chromatograph for atmospheres of multicomponent organics: use of PID/FID ratios.
The H-Nu PI-101 with a photoionization detector (PID) of 10.2 eV and the Century OVA-128 equipped with a flame ionization detector (FID) were evaluated for the additivity of their responses to a defined mixture of dissimilar organic vapors at a 0 and 90% relative humidity (RH). The responses of both instruments were additive as long as the effect of RH was accounted for with the PID. The PI-101 was not as precise as the Century OVA-128 for 90% RH atmospheres. PID/FID ratios did not change in the presence of 90% RH as long as the effect of RH also was accounted for in the PID reading.


ICV melatonin reduces acute stress responses in neonatal chicks.
Melatonin is involved in a variety of biological functions including sleep and stress. Our previous study indicated that neonatal layer chicks were more susceptible to stress than broilers. However, it is not clear whether differences exist in melatonin concentrations between both types of chickens, nor is it known whether melatonin is directly involved in stress in neonatal chickens. In the present study we first compared melatonin concentrations in brain tissues (pineal gland, brain stem, telencephalon, and optic lobe) between neonatal broiler and layer chicks raised under either 12 h light:12 h dark cycle (lights on at 07:00 h) or continuous illumination. Although melatonin concentrations were much higher in broilers than layers at night under the alternative light-dark cycle, these differences disappeared under the 24 h illumination. We thus chose neonatal layers for a test system. We then investigated if intracerebroventricular (ICV) injection of melatonin modulated plasma corticosterone concentrations under continuous illumination. Neonatal layer chicks housed in groups were ICV injected (1) with melatonin (0, 0.116 and 1.16 microg) or with nothing as an intact control followed by isolation in an open-field environment for 10 min; and (2) were given one of the followings treatments: nothing (intact control), control (0 microg), corticotropin-releasing factor (CRF) (0.01 microg), melatonin (1.16 microg), or CRF (0.01 microg) + melatonin (1.16 microg). Ten minutes thereafter blood was collected via heart puncture to determine plasma corticosterone content. Isolation resulted in a significant increase in corticosterone concentration, and both doses of ICV melatonin completely suppressed this increase (P<0.01). CRF injection resulted in a strong increase in plasma corticosterone concentrations (P<0.01). Co-injection with melatonin attenuated the CRF-induced corticosterone elevation in plasma (P<0.01). Our findings provide direct evidence that melatonin modulates the activity of the hypothalamo-pituitary-adrenal axis in chicks.


Molecular docking studies of the interaction between propargylic enol ethers and human DNA topoisomerase IIα.
Having identified a novel human DNA topoisomerase IIα (TOP2) catalytic inhibitor from a small and structure-focused library of propargylic enol ethers, we decided to analyze if the chirality of these compounds plays a determinant role in their antiproliferative activity. In this study, we describe for the first time the synthesis of the corresponding enantiomers and the biological evaluation against a panel of representative human solid tumor cell lines. Experimental results show that chirality does not influence the reported antiproliferative activity of these compounds. Docking studies of corresponding enantiomers against TOP2 reinforce the finding that the biological effect is not chiral-dependent and that these family of compounds seem to act as TOP2 catalytic inhibitors.


The relationships between oral status, physical and mental health, nutritional status and diet type in elderly Japanese women with dementia.
To suggest methods for maintaining an adequate nutritional status for elderly patients with dementia by evaluating the relationships between oral status, physical and mental health, and feeding conditions. Feeding difficulties in dementia patients are related to food intake, and failure to eat may be associated with weight loss in long-term care facilities. The relationship between compromised oral function and diet is still unclear. A cross-sectional study of 94 elderly women with dementia (mean age 89.6 +/- 5.6 years) from a nursing home was undertaken to investigate their oral, physical and mental and nutritional status. There were significant differences in serum albumin (p = 0.0284), N-ADL (p = 0.0005), NM scale (p = 0.0004) and HDS-R (p = 0.0004) between denture wearers and non-denture wearers. However, there were no significant differences in body mass index between denture wearers and non-denture wearers. A suitable type of diet and assistance with feeding could maintain the nutritional status of elderly patients with dementia if they are still feeding themselves. The nutritional support team will benefit from the participation of a dentist.


Evaluation of treatment modalities and prognostic factors in children with congenital nasolacrimal duct obstruction.
To evaluate the success rates of probing and silicone intubation and risk factors for failure of these procedures. This retrospective cohort study included patients who were diagnosed with congenital nasolacrimal duct obstruction (NLDO) and underwent probing or intubation as the primary procedure. Demographic data, clinical features, intraoperative, and postoperative data were evaluated. The patients were divided into four subgroups based on age: 12-24 months, 25-36 months, 37-48 months, and >48 months. The procedure was considered successful when all preoperative signs disappeared with normal dye disappearance test and a positive Jones primary dye test. Statistical analysis was performed to determine the risk factors for failure, and P < 0.05 was statistically significant. The cohort comprised 350 subjects (162 males [46%]) who underwent a total of 454 nasolacrimal duct surgeries. The mean chronological age at time of surgery was 32.6 ± 22.1 months (range, 12-132 months). The overall success rate was 84.8%. Probing was performed 188 times, with a success rate of 80.3%; intubation was performed 266 times, with a success rate of 88%. Intubation was more successful than probing in patients with bilateral congenital nasolacrimal duct obstruction, Down syndrome, history of acute dacryocystitis, lack of preoperative massage, or intraoperative observation of either a "tight" obstruction or obstruction at sites other than at the level of Hasner's valve. Primary nasolacrimal duct intubation should be considered in these higher risk patients.


Group B streptococcal vertebral osteomyelitis in an adult.
Group B beta-hemolytic streptococcus (Streptococcus agalactiae) vertebral osteomyelitis was diagnosed in a 65-year-old man. The patient received a 3-week course of in-hospital intravenous ampicillin followed by ceftriaxone and continued to receive ceftriaxone therapy on an ambulatory basis for 3 more weeks. Hospitalization and follow-up were uncomplicated with no neurological sequelae. Review of the medical literature documented only 15 cases of group B streptococcal osteomyelitis in adults and only three cases of vertebral osteomyelitis due to this pathogen. As in most adult patients with group B streptococcal infections, the patient had coexisting chronic conditions (chronic obstructive lung disease, diabetes mellitus) but bacteremia was not present. Although uncommon, group B streptococcus should be considered as an opportunistic pathogen in patients with debilitating conditions, but vertebral osteomyelitis is even rarer.


A new species of Zaglyptogastra Ashmead, 1900 (Hymenoptera: Braconidae: Braconinae) from Vietnam.
The moderately large genus Zaglyptogastra Ashmead, 1900 is newly recorded for Vietnam and one new species, Z. vietnamica Long sp. n., is described and illustrated. Differences between the new species and two described species, Z. aswada El-Heneidy & Quicke, 2007, from Indonesia (Sumatra) and Z. vitalisi (Turner, 1919), from Laos, are given.


Nox4 and nox2 NADPH oxidases mediate distinct cellular redox signaling responses to agonist stimulation.
The NADPH oxidase isoforms Nox2 and Nox4 are coexpressed in many cell types and are implicated in agonist-stimulated redox-sensitive signal transduction. We compared the involvement of Nox2 versus Nox4 in redox-sensitive protein kinase activation after agonist stimulation. We transfected HEK293 cells with Nox2 or Nox4 and compared ROS production and activation of mitogen activated protein kinases (MAPKs), Akt, and GSK3beta after acute agonist stimulation. Nox4 overexpression substantially increased basal ROS generation whereas ROS generation in response to angiotensin II and tumor necrosis factor (TNF)alpha was enhanced in Nox2-overexpressing cells. Nox4 overexpression induced basal activation of ERK1/2 and JNK whereas Nox2-transfected cells showed a modest increase in p38MAPK activation. After angiotensin II or TNFalpha treatment, JNK activation was augmented in Nox2 but not Nox4-transfected cells, whereas insulin augmented phosphorylation of p38MAPK, Akt, and GSK3beta specifically in Nox4-overexpressing cells and JNK specifically in Nox2-overexpressing cells. These data indicate that Nox2 and Nox4 exhibit distinctive patterns of acute activation by angiotensin II, TNFalpha, and insulin and regulate the activation of distinct protein kinases.


The role of "children's hearings" in child abuse and neglect.
The juvenile justice system established in Scotland in 1971, in which lay volunteers play a central part, provides a framework for making decisions about children in need of care and protection as well as those who have committed delinquent acts. Although cases of child abuse and neglect have come increasingly to the attention of children's hearings in recent years, they nevertheless constitute a small fraction of a workload dominated by cases of delinquency and truancy. A recent Scotland-wide study of the hearings system therefore gave only limited attention to the processing of abuse and neglect referrals. As a step towards rectifying this imbalance, a separate enquiry was carried out in 1981, when 43 such hearings were systematically observed and the participating panel members interviewed. Examination of these results indicates a heavy dependence on social workers' recommendations, a reluctance to open up sensitive areas for discussion, even though these may be of central importance, and an apparent lack of curiosity about the arrangements made for children removed from their homes, and the implications of these. In general, it is concluded that the anxiety generated by child abuse and neglect has prevented panel members from recognizing the distinctive features of their role in the decision-making process and has led them to fall back on an inappropriate model of practice derived from delinquency hearings. An alternative model is outlined.


The effect of participation in a Fitness Rewards Program on medical care expenditures in an employee population.
In 2008, the University of Minnesota began offering the Fitness Rewards Program (FRP) that provides a monthly credit toward fitness center dues for individuals who exercise at a participating facility at least 8 times per month. This study evaluates whether participation in the FRP is associated with a decrease in medical spending. Using a difference-in-differences approach, we estimate multivariate regression models of average monthly medical expenditures for 2006 through 2008. We find positive benefits from reduced medical spending among highly persistent FRP exercisers. However, the results are sensitive to the inclusion or exclusion of individuals who had very high medical expenditures in any year. Offering exercise-focused wellness initiatives may have economic benefits for employers, but further research is needed to understand the sensitivity of results to the inclusion of outliers.


Shared vision, shared vulnerability: A content analysis of corporate social responsibility information on tobacco industry websites.
Tobacco companies rely on corporate social responsibility (CSR) initiatives to improve their public image and advance their political objectives, which include thwarting or undermining tobacco control policies. For these reasons, implementation guidelines for the World Health Organization's Framework Convention on Tobacco Control (FCTC) recommend curtailing or prohibiting tobacco industry CSR. To understand how and where major tobacco companies focus their CSR resources, we explored CSR-related content on 4 US and 4 multinational tobacco company websites in February 2014. The websites described a range of CSR-related activities, many common across all companies, and no programs were unique to a particular company. The websites mentioned CSR activities in 58 countries, representing nearly every region of the world. Tobacco companies appear to have a shared vision about what constitutes CSR, due perhaps to shared vulnerabilities. Most countries that host tobacco company CSR programs are parties to the FCTC, highlighting the need for full implementation of the treaty, and for funding to monitor CSR activity, replace industry philanthropy, and enforce existing bans.


Colorimetric assay for protein detection based on "nano-pumpkin" induced aggregation of peptide-decorated gold nanoparticles.
Small peptide can be used as an effective biological recognition element and provide an alternative tool for protein detection. However, the development of peptide-based detecting strategy still remains elusive due to the difficulty of signal transduction. Herein, we report a peptide-based colorimetric strategy for the detection of disease biomarker by using vascular endothelial growth factor receptor 1 (Flt-1) as an example. In this strategy, N-terminal aromatic residue-containing peptide modified gold nanoparticles (GNPs) can form bulky aggregate by the introduction of cucurbit[8]uril (CB[8]) that can selectively accommodate two N-terminal aromatic residue of peptides simultaneously regardless of their sequences. However, in the presence of Flt-1, the peptide can specifically bind to the protein molecule and the N-terminal aromatic residue will be occupied, resulting in little aggregation of GNPs. By taking advantage of the highly affinitive peptide and efficiency cross-linking effect of CB[8] to GNPs, colorimetric assay for protein detection can be achieved with a detection limit of 0.2 nM, which is comparable with traditional methods. The feasibility of our method has also been demonstrated in spiked serum sample, indicating potential application in the future.


New image processing and noise reduction technology allows reduction of radiation exposure in complex electrophysiologic interventions while maintaining optimal image quality: a randomized clinical trial.
Despite their carcinogenic potential, X-rays remain indispensable for electrophysiologic (EP) procedures. The purpose of this study was to evaluate the dose reduction and image quality of a novel X-ray technology using advanced image processing and dose reduction technology in an EP laboratory. In this single-center, randomized, unblinded, parallel controlled trial, consecutive patients undergoing catheter ablation for complex arrhythmias were eligible. The Philips Allura FD20 system allows switching between the reference (Allura Xper) and the novel X-ray imaging technology (Allura Clarity). Primary end-point was overall procedural patient dose, expressed in dose area product (DAP) and air kerma (AK). Operator dose, procedural success, and necessity to switch to higher dose settings were secondary end-points. A total of 136 patients were randomly assigned to the novel imaging group (n = 68) or the reference group (n = 68). Baseline characteristics were similar, except patients in the novel imaging group were younger (58 vs 65 years, P < .01). Median DAP and AK were 43% and 40% lower in the novel imaging group, respectively (P < .0001). A 50% operator dose reduction was achieved in the novel imaging group (P < .001). Fluoroscopy time, number of exposure frames, and procedure duration were equivalent between the two groups, indicating that the image quality was similarly adequate in both groups. Procedural success was achieved in 91% of patients in both groups; one pericardial tamponade occurred in the novel imaging group. The novel imaging technology, Allura Clarity, significantly reduces patient and operator dose in complex EP procedures while maintaining image quality.


Baricitinib vs tocilizumab treatment for hospitalized adult patients with severe COVID-19 and associated cytokine storm: a prospective, investigational, real-world study.
Our aim was to compare outcomes of hospitalized adults with severe COVID-19 and cytokine storm treated with tocilizumab or baricitinib. A prospective, investigational, real-world study was performed from April 2020 to April 2021 at our center. COVID-19 severity was classified by World Health Organization criteria, and cytokine storm was documented along predefined criteria. Eligible patients were enrolled at diagnosis if they fulfilled a priori inclusion criteria and received standard-of-care plus tocilizumab or baricitinib for >48 hours. Patients were followed per protocol for 28 days post-diagnosis. The primary outcome was all-cause mortality; secondary outcomes were invasive mechanical ventilation and major infectious complications. Of 463 patients, 102/463 (22.1%) received tocilizumab, and 361/463 (77.9%) baricitinib. Baseline characteristics were balanced. At 28 days, there was no difference in all-cause mortality (22/102, 21.6% vs 64/361, 17.7%; P-value = 0.38). Requirement for invasive mechanical ventilation was more frequent after tocilizumab (52/102, 50.9% vs 96/361, 26.6%; P <0.01), rate of major infectious complications was similar (32/102, 31.4% vs 96/361, 26.6%; P-value = 0.34). In logistic regression, the immunomodulatory drug was not retained as a predictor of all-cause mortality. Kaplan-Meier analysis revealed statistically similar survival distributions. All-cause mortality was similar between adults treated with baricitinib or tocilizumab for severe COVID-19 with cytokine storm.


Fossils from the Middle Jurassic of China shed light on morphology of Choristopsychidae (Insecta, Mecoptera).
Choristopsychidae, established by Martynov in 1937 with a single isolated forewing, is a little known extinct family in Mecoptera. Since then, no new members of this enigmatic family have been described. Based on 23 well-preserved specimens with complete body and wings from the Middle Jurassic of northeastern China, we report one new genus and three new species of Choristopsychidae, two new species of the genus Choristopsyche Martynov, 1937: Choristopsyche perfecta sp. n. and Choristopsyche asticta sp. n.; one new species of Paristopsyche gen. n.: Paristopsyche angelineae sp. n.; and re-describe Choristopsyche tenuinervis Martynov, 1937. In addition, we emend the diagnoses of Choristopsychidae and Choristopsyche. Analyzing the forewing length/width ratios of representative species in Mecoptera, we confirm that choristopsychids have the lowest ratio of forewing length/width, meaning broadest forewings. These findings, the first fossil choristopsychids with well-preserved body structure and the first record of Choristopsychidae in China, shed light on the morphology of these taxa and broaden their distribution from Tajikistan to China, while increasing the diversity of Mesozoic Mecoptera in China.


Biotechnologically generating 'super chickpea' for food and nutritional security.
Chickpea productivity is affected by various constraints that are biotic (Helicoverpa, Aphids, Callosobruchus, Bromus and Orobanche) and abiotic (drought and salinity). In addition, the grains of this legume are deficient in sulfur amino acids, methionine and cysteine. The possibilities for genetic improvement by marker-assisted breeding and selection approaches are limited in chickpeas due to their sexually incompatible gene pool. Transgenic chickpeas expressing either the cry1Ac/b or the cry2Aa gene and the bean α-amylase inhibitor gene are resistant to Helicoverpa and bruchids, respectively, but these chickpeas have yet to be commercialized. Unfortunately, attempts to generate transgenic chickpeas with increased tolerance to drought and salinity or with increased methionine content have been less successful. The commercialization of transgenic chickpeas containing a single transgene may not give adequate yield advantage, as chickpeas are affected by many production constraints in the field and in storage. Gene pyramiding by incorporating two or more genes may be useful because improving one trait at a time will be time-consuming, labor-intensive and costly. Use of modern multi-gene vectors that contain recognition sites for zinc finger nucleases (ZFNs) and homing endonucleases may simplify the incorporation of multiple genes into chickpeas. This approach necessitates a collaborative effort between individuals, public and private organizations to generate 'super chickpeas' that harbor multiple transgenic traits.


[Assessment among German urologists of various conservative treatment modalities for Peyronie's disease. Results of a survey].
The aim of this study was to evaluate the frequency and the assessment of the different conservative modalities of treatment in Peyronie's disease. A representative survey among 3187 German urologists was performed using a standardized questionnaire comprising currently used concepts of therapy, their efficacy, and their tolerability. A total of 636 urologists participated in the study. Altogether they had treated 6019 patients with Peyronie's disease in 2003. The majority of urologists treated between 3 and 15 patients per year. The most frequent treatment modality was the administration of potassium paraaminobenzoate, followed by vitamin E and extracorporeal shock wave therapy. Other oral drugs and intralesional drug administrations were used considerably less frequently. The most commonly used treatment modalities were assessed for the best results in terms of efficacy and tolerability. However, this outcome is contradictory to the few controlled studies regarding the efficacy of the different drugs. The large number of patients treated demonstrates the importance of conservative therapy for Peyronie's disease. Therefore, it is unfortunate that no conservative treatment modality is currently available that cures the symptoms of this disorder in all patients affected.


Valuing urban air quality: a hedonic price analysis in Beijing, China.
Although Chinese government has implemented a series of laws, regulations, and policies to deal with air pollutants, air pollution is still one of the biggest concerns in China. Most of the cities in China suffered from extremely high air pollution levels and cannot meet the national air quality standards. In this study, we attempt to measure individuals' average marginal willingness to pay (MWTP) in Beijing with the hedonic price model. We combine an extensive housing transaction dataset with emission data of six air pollutants from 2013 to 2016 in Beijing, China. When estimating the hedonic price function, we apply both ordinary least squares (OLS) and panel model with various fixed effects to better control for unobservables. The empirical results reveal that the concentrations of CO, NO2, PM2.5, and PM10 are significantly negatively correlated with housing prices. However, we found an insignificant relationship with the concentration of SO2 and the concentration of O3 appears to positively increase the housing values. Policy implications based on these results were also discussed.


Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects.
Bosentan (Ro 47-0203) is a potent and mixed ETA-and ETB-receptor antagonist. Its activity has been studied in a variety of preclinical disease models. Two double-blind placebo-controlled studies were performed to investigate the pharmacokinetics and pharmacodynamics of bosentan after single oral and intravenous doses in healthy volunteers; doses of 3, 10, 30, 100, 300, 600, 1200, and 2400 mg were given in a single ascending oral dose study, and doses of 10, 50, 250, 500, and 750 mg were given in a single ascending intravenous dose study (six subjects received active drug and two received placebo at each dose level). In an open-label crossover added to the second study, six subjects received a single oral dose of 600 mg and a single intravenous dose of 250 mg in randomized order. At regular intervals, blood pressure, pulse rate, and skin responses to intradermally injected endothelin-1 (ET-1) were recorded, and plasma levels of ET-1, proendothelin-1 (big ET-1), and ET-3, and drug and urinary levels of ET-1 and drug were determined. Systemic plasma clearance and volume of distribution decreased with increasing dose to limiting values of around 6 L/hr and 0.2 L/kg, respectively. The absolute bioavailability was 50% and appeared to decrease with doses above 600 mg. Plasma ET-1 increased maximally twofold (oral) and threefold (intravenous), and this increase was directly related to bosentan plasma concentrations according to an Emax model. Bosentan reversed the vasoconstrictor effect of ET-1 measured in the skin microcirculation. There was a tendency toward decreased blood pressure (approximately 5 mm Hg) and increased pulse rate (approximately 5 beats/min), neither was clearly dose dependent. Oral bosentan was well tolerated. Vomiting and local intolerability was observed at the higher intravenous doses. Bosentan is an orally bioavailable, well-tolerated, and active ET-1 antagonist with a low clearance and a moderate volume of distribution. Its intravenous use is limited because of local intolerability.


Prominent Intrapulmonary Shunt Vessels and Altered Lung Development in Infants With Sudden Unexplained Infant Death.
The purpose of this study was to evaluate intrapulmonary arteriovenous shunts in patients with and without sudden unexplained infant death. We identified open intrapulmonary bronchopulmonary anastomoses as potential pathways for right-to-left shunt in a subset of infants with sudden unexplained infant death.


[Intravitreal ranibizumab (Lucentis®) in the treatment of choroidal neovascular membrane secondary to punctate inner choroidopathy].
A 25 year old patient with high myopia diagnosed of metachronic choroidal neovascularisation in both eyes secondary to punctate inner choroidopathy leading to visual impairment and metamorphopsia. First eye was treated with four injections of ranibizumab after photodynamic therapy and the second eye only with charge dose of ranibizumab, reaching inactivity with good final visual acuity in both eyes. Ranibizumab is useful in the treatment of this illness. Prospective studies are needed to investigate the usefulness of a combination with adjuvant therapies such as photodynamic therapy.


Neurotensin and neurotensin receptors: characteristic, structure-activity relationship and pain modulation--a review.
Neurotensin (NT) is a tridecapeptide, which - since its discovery in 1973--has been demonstrated to be involved in the control of various physiological activities in both the central nervous system and in the periphery. Its biological effects are mediated by four receptor types. Exogenously administered NT exerts different behavioral effects, including antinociception. Structure-activity relationship studies performed in recent years resulted in development of several peptidomimetic receptor agonists and non-peptidic receptor antagonists that are useful tools for studies of NT mechanisms in tissue and on cellular level. This may result in design of new generation of analgesics based on neurotensin. NT antinociceptive effects are distinct from opioid analgesia. This creates opportunity of development of hybride analgesics that may simultaneously activate both opioid and NT antinociceptive pathways.


Frequency of detection of respiratory viruses in the lower respiratory tract of hospitalized adults.
Respiratory infections are the most common infections in humans. The prevalence of respiratory viruses in adults is largely underestimated, and relevant data mostly concern infants and children. To evaluate the prevalence of respiratory viruses in adults hospitalized in Italy. During April 2004--May 2005, 510 consecutive lower respiratory tract samples were prospectively collected. These were evaluated with a molecular panel that detected 12 respiratory viruses. Two hundred and fifteen samples were positive for at least one viral pathogen, with an overall sample prevalence of 42.2%. Human rhinoviruses (HRVs) were the most commonly detected viruses (32.9%), followed by influenza virus (FLU)-A (9.0%); the other viruses were 2% or less. Multiple agents were detected in 30 samples from 29 patients, resulting in a co-infection rate of 6.7%. This study shows a high prevalence of viruses in the lower respiratory tract samples of hospitalized adults, mostly HRV and FLU-A. It is not possible to establish the role of viruses detected at low frequency, but our findings suggest the necessity to consider them as potential causes or precursors of lower respiratory tract infections (LRTIs).


Raynaud's phenomenon.
Raynaud's phenomenon can be either primary (idiopathic) or secondary to underlying disease including systemic sclerosis. Primary Raynaud's phenomenon is very common, affecting approximately 3%-5% of the general population. Although much rarer, systemic sclerosis-related Raynaud's phenomenon can be particularly severe, progressing to digital ulceration in approximately 50% of patients. Raynaud's phenomenon can have a major impact on quality of life. This review has a focus on the systemic sclerosis-related Raynaud's phenomenon (which is the most researched form of Raynaud's phenomenon and probably the most challenging to treat) and on recent advances. Epidemiology (including transition from 'isolated' to systemic sclerosis-related Raynaud's phenomenon), pathogenesis, diagnosis and assessment are discussed, followed by the treatment of both 'uncomplicated' and 'complicated' Raynaud's phenomena (i.e. Raynaud's phenomenon which has progressed to digital ulceration and/or critical ischaemia). Finally, some of the major challenges for the next 5-10 years are highlighted.


MRI of transplanted surface-labeled pancreatic islets with heparinized superparamagnetic iron oxide nanoparticles.
Transplantation of insulin-secreting pancreatic islets can provide real-time regulation of blood glucose in patients with type 1 diabetes mellitus. Currently, noninvasive and repetitive monitoring of islet engraftment and function is an emerging and promising modality for successful islet transplantation. Here we report a new technique for highly sensitive in vivo magnetic resonance (MR) imaging of transplanted pancreatic islets. To this end, heparinized superparamagnetic iron oxide (heparin-SPIO) nanoparticle was newly synthesized for chemical conjugation onto islet surface. Compared to typical cellular labeling of Feridex(®) via random endocytosis, chemical conjugation of heparin-SPIO was stable and improved the hypointensity of transplanted islets due to surface modification of every islet. These heparin-SPIO-conjugated islets showed normal viability and insulin secretion, and were quantified by spin echo T(2)-weighted MR imaging with linear correlation depending on transplanted islet mass in vitro and in vivo for 30 days. Also, from the immunohistochemistry, we confirmed the existence of heparin-SPIO and insulin biosynthesis in transplanted islets. However, Feridex-uptake islets showed late glucose responsiveness according to changing glucose concentration although they could normally control the blood glucose levels in diabetic mouse. Thus, we anticipate that this surface labeling with heparin-SPIO can be directly applicable for MR imaging of transplanted islets.


Cerebral infarction associated with vasculitis due to varicella zoster virus in patients infected with the human immunodeficiency virus.
Cases of herpes zoster ophtalmicus (HZO) with delayed contralateral hemiparesis caused by hemispheric stroke secondary to granulomatous angiitis have been reported and are a well-recognized complication of herpes zoster. Similar cases have been reported more recently during infection with human immunodeficiency virus (HIV). We describe two HIV+ patients without any clinical history of zoster dermatitis who developed a sudden hemiparesis followed 2 weeks later for one by an acute retinal necrosis. Computerized tomography (CT) scan, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) were performed and showed a hemispheric stroke with evidence of a segmental arteritis of the carotid syphon. Varicella zoster virus (VZV) was found in the cerebro spinal fluid (CSF) in the two patients and after puncture of the vitreous fluid of the patient with the acute retinal necrosis. These two cases exemplify the difficulty of diagnosis of stroke in HIV+ patients, which seems to be more frequent than in similarly aged non-infected patients and demonstrates that VZV needs to be taken in consideration and identified even without any past history of zoster dermatitis.


A simple method for recording single-channel activity from synaptic plasma membranes.
Due to the small size of most nerve terminals, the ion channels which underlie presynaptic currents are usually inaccessible to investigation by conventional electrophysiological techniques. Here we describe a simple method for obtaining single-channel recordings from synaptic plasma membranes that does not require exposure of the native membranes to exogenous lipids or fusogens. To illustrate the method, we have recorded single-channel activity from rat cerebrocortical synaptosomal membranes. Under conditions designed to isolate calcium-independent currents, we describe three channel types that are most commonly observed.


Multiple sclerosis by phenotype in Germany.
A diagnosis of multiple sclerosis (MS) can be categorized based on its disease course into the following phenotypes: relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). With one exception, studies of MS by phenotype either provide only prevalence data or if describing drug utilization, the emphasis is on patients with RRMS; while drug utilization by phenotype tends to be examined over the course of a year. No recent studies have comprehensively evaluated MS phenotypes by prevalence, drug utilization, and comorbidities over time from a population-based perspective, which is essential for understanding the disease burden and identifying unmet needs in MS. Germany is one of the few countries where specific MS phenotypes are commonly recorded in routine clinical practice. The purpose of this study was to compare MS phenotypes with respect to changes in their population-based prevalence rates and the types of MS treatments prescribed over time, as well as the frequency of clinical conditions associated with MS based on data from a German health insurance database. This retrospective, observational, cohort study used data from a German health insurance database for the period 2010 to 2017. Patients aged 18+ years with a specified phenotype of MS based on ICD-10 diagnosis coding were included in the analysis. In 2010, RRMS was reported in 73%, PPMS in 8%, and SPMS in 19% of patients with MS with a known phenotype. The mean ages of patients were 41.4, 53.6, and 52.8 years, respectively, and all phenotypes were associated with a female predominance (69%, 63% and 63%, respectively). The prevalence rate of each phenotype markedly increased during the study period (RRMS +113%, PPMS +40%, SPMS +54%; in 2017 the rates were 183, 14, and 34 per 100,000, respectively). The mean age of patients reporting each phenotype also increased (p<0.01), while the female:male proportion remained stable in RRMS and SPMS, the proportion of females significantly declined over time in the PPMS group. The overall percentage of patients prescribed a disease-modifying drug increased across the phenotypes from 51% to 57%. Prescription of interferon-based therapies declined in each phenotype, with the greatest declines observed in RRMS and PPMS. The PPMS and SPMS groups had significantly more prescriptions for symptom management than the RRMS group. Depression was the most prevalent clinical condition associated with each phenotype. There was a significant difference in the percentage of patients with depression across the phenotypes (p = 0.03), with the highest among SPMS (44%) compared with RRMS (35%) or PPMS (37%). Significant differences (p<0.05) across the phenotypes were also observed for the composite prevalence of cardiovascular conditions (highest in PPMS) and cognitive dysfunction (highest in SPMS). The increasing numbers of patients across each MS phenotype, aging population in patients with MS regardless of phenotype, gender differences and variations across the types of treatments prescribed, and clinical conditions associated with each MS phenotype present new insight into the disease burden and treatment strategies of MS. These should be considered when developing healthcare strategies and optimizing care for patients with MS.


Amiloride and 5-N,N-dimethylamiloride inhibit the carrier mediated uptake of choline in Ehrlich ascites tumor cells.
Amiloride and 5-N,N-dimethylamiloride (DMA) inhibit the choline uptake of Ehrlich ascites tumor cells. The inhibition by DMA is competitive with a KI value of 20 microM. The apparent KM value for choline was determined as 15 microM. Amiloride is approximately three times less potent. Amiloride uptake is not antagonized by choline or impaired in cells characterized by a deficient choline carrier. This indicates that amiloride is not transported into the cell by the choline carrier. The inhibition of the choline uptake by DMA cannot be attributed to a depression of choline kinase (EC 22.214.171.124) and is therefore considered to be due to a direct interaction between DMA and the choline carrier. DMA does not compete with sodium ions for its effect on the choline carrier. It is suggested that the choline carrier of Ehrlich ascites tumor cells exhibits a binding site for DMA similar to the one on the Na+/H+ antiporter.


The Value of Changing Position in the Detection of CSF Leakage in Spontaneous Intracranial Hypotension Using Tc-99m DTPA Scintigraphy: Two Case Reports.
Radionuclide Cisternography (RNC) is of potential value in pointing out the sites of cerebrospinal fluid (CSF) leakage in patients with spontaneous intracranial hypotension (SIH). In the current report, we present two patients who underwent RNC for suspected CSF leakage. Both patients underwent magnetic resonance imaging (MRI) and RNC for evaluation. We describe a simple method to increase the detection ability of RNC for CSF leakage in patients with SIH.


A Scoping Review of the Use of Machine Learning in Health Economics and Outcomes Research: Part 2-Data From Nonwearables.
Despite the increasing interest in applying machine learning (ML) methods in health economics and outcomes research (HEOR), stakeholders face uncertainties in when and how ML can be used. We reviewed the recent applications of ML in HEOR. We searched PubMed for studies published between January 2020 and March 2021 and randomly chose 20% of the identified studies for the sake of manageability. Studies that were in HEOR and applied an ML technique were included. Studies related to wearable devices were excluded. We abstracted information on the ML applications, data types, and ML methods and analyzed it using descriptive statistics. We retrieved 805 articles, of which 161 (20%) were randomly chosen. Ninety-two of the random sample met the eligibility criteria. We found that ML was primarily used for predicting future events (86%) rather than current events (14%). The most common response variables were clinical events or disease incidence (42%) and treatment outcomes (22%). ML was less used to predict economic outcomes such as health resource utilization (16%) or costs (3%). Although electronic medical records (35%) were frequently used for model development, claims data were used less frequently (9%). Tree-based methods (eg, random forests and boosting) were the most commonly used ML methods (31%). The use of ML techniques in HEOR is growing rapidly, but there remain opportunities to apply them to predict economic outcomes, especially using claims databases, which could inform the development of cost-effectiveness models.


Bone mineral density and the risk of peripheral arterial disease: the Rotterdam Study.
Low estrogen exposure throughout life is thought to result in low bone mineral density (BMD) and an increased incidence of cardiovascular disease. In the Rotterdam Study we cross-sectionally examined the relation between BMD and peripheral arterial disease (PAD), as assessed by an ankle-arm index (AAI) of <0.9 in either leg. Data on BMD and PAD were available for 5268 individuals (3053 women, 2215 men). From the BMD, Z-scores were calculated and subsequently divided into tertiles. Logistic regression analysis was used to compute odds ratios (OR) for PAD in tertiles of BMD, using the upper tertile as a reference. When adjusting for age, women with a low femoral neck BMD had a significantly increased risk of PAD (OR = 1.49, 95% CI 1.16-1.91). This could not be found for men (1.14, 0.84-1.53). The mid-tertile did not differ from the reference in either men or women. In women, additional adjustment for several potential confounders resulted in a somewhat lowered risk estimate (1.35, 1.02-1.79). In contrast, no association between lumbar spine BMD and PAD could be observed in either men or women. Our study shows an association between low femoral neck BMD and PAD in women only, an association unlikely to be causal. Estrogen deficiency may be the common denominator in osteoporosis and PAD, resulting in clustering of these two major diseases in postmenopausal women.


Internal limiting membrane staining with various concentrations of indocyanine green dye under air in macular surgeries.
To determine the effective minimal concentration of indocyanine green (ICG) for staining the internal limiting membrane (ILM) under air in macular surgeries and to report the clinical outcome of these patients. Prospective, randomized clinical trial. Consecutive cases of macular hole (17 cases) and epiretinal membrane (ERM) (11 cases) undergoing primary surgery with ICG-stained ILM peeling were randomized to receive one of the three concentrations (mg/ml) of ICG (1): 0.25, (2) 0.5, and (3) 1.25. The number of ICG injections, visual quality of the stained ILM, and time used for ILM peeling were recorded. Internal limiting membrane specimens were subsequently examined under electron microscopy. Preoperative and postoperative clinical data with fluorescein angiography were recorded. There was a significantly smaller number of eyes with poor ILM staining in the 1.25-mg/ml group compared with the 0.25- to 0.5-mg/ml group (Fisher exact test, P =.04). The mean time required for ILM peeling was 4.2 minutes (range, 2.0-8.1 minutes). There was no significant difference in the time required for ILM peeling among the three concentration groups (one-way analysis of variance, P =.18) or between the macular hole and ERM group (two-tailed t test, P =.34). No ICG toxicity was found clinically or angiographically, except in one suspected case with ERM formation at the edge of ILM peeling. Electron microscopy of ILM specimens did not reveal any retinal elements. 1.25-mg/ml ICG under air stains the macular ILM consistently well for its removal in macular surgeries. The safety of ICG-stained ILM peeling needs further evaluation.


[Multimodal magnetic resonance imaging of brain tumors].
Magnetic resonance imaging arose as a reference for diagnosis, pre-therapeutic and follow-up of brain tumors. Among parameters obtained from standard MRI (of low specificity), only volumetric growth allows prognostic information. The multiple "advanced" sequences have leaded to increase both sensitivity and specificity of brain MRI. Yet, perfusion-weighted imaging and spectroscopy provide metabolic information, and diffusion tensor imaging and cortical activation provide functional information. Characterization, grading, therapeutic management and follow-up have improved, with prognostic information.


Basic fibroblast growth factor in cells derived from Dupuytren's contracture: synthesis, presence, and implications for treatment of the disease.
Dupuytren's contracture (DC) is associated with fibroblast and endothelial cell proliferation. We have identified a fibroblast and endothelial cell mitogen, basic fibroblast growth factor (FGF), in cells derived from this tissue and characterized the effects of this growth factor on DC cells. Northern blot analysis of DC cells reveals the presence of basic FGF mRNA species, and the DC cells coexpress multiple forms of basic FGF. Radioreceptor assays establish that the DC cells have high-affinity binding sites for basic FGF and proliferate in response to exogenous recombinant basic FGF. Furthermore, a conjugate between saporin (a ribosome-inactivating protein) and basic FGF, which is cytotoxic to cells possessing the basic FGF receptor, is also cytotoxic to DC cells. The possibility that basic FGF-saporin could be a potential therapeutic agent for prevention of recurrence of the disease after surgery is discussed.


CpG oligodeoxynucleotide-specific goose TLR21 initiates an anti-viral immune response against NGVEV but not AIV strain H9N2 infection.
Toll-like receptors (TLRs) recognize components of pathogens and mediate the host innate immune response. TLR21 is a TLR that specifically recognizes exogenous double-stranded DNA and rapidly signals to downstream innate immune factors. This study reports the cDNA of goose TLR21 and identifies its immune characteristics. The goose TLR21 is 3161 base pairs and encodes a 975 amino acid protein. As predicted, the goose transmembrane protein TLR21 has a signal peptide, leucine-rich repeat regions, a transmembrane domain, and a Toll/interleukin-1 receptor domain. Multiple sequence alignments and phylogenetic analyses showed that goose TLR21 has homology to chicken TLR21. The tissue distribution of TLR21 suggested that it has high transcript levels in immune-associated tissues, especially in the bursa of Fabricius, the Hadrian gland, and the thymus. After challenge with agonist ODN2006 and new type gosling viral enteritis virus (NGVEV), significant induction of TLR21 production, pro-inflammatory cytokines IL-1β and IL-6, and interferons were observed in peripheral blood mononuclear cells. Both synthetic DNA (ODN2006) and viral DNA (NGVEV) can be recognized by goose TLR21, which leads to a rapid up-regulation of pro-inflammatory cytokines and anti-viral molecules. In vivo, avian influenza A virus H9N2 and NGVEV were used to infect goslings, which was followed by a significant up-regulation of TLR21 mRNA transcripts in multiple tissues of NGVEV-infected geese. In general, goose TLR21 plays an important role in binding invading pathogenic DNA viruses, which subsequently triggers an innate immune response; furthermore, it acts as a functional homologue of mammalian TLR9, as TLR21 recognizes a mammalian TLR9 agonist.


Long-term outcome 19 years after childhood IgA nephritis: a retrospective cohort study.
We evaluated the natural long-term outcome after childhood IgA nephritis. Altogether 55 patients with biopsy-proven IgA nephritis were identified, 37 (67%) responded to the health questionnaire and 31 (56%) participated in the medical examination after a mean follow-up of 18.7 years (SD 6.2; range 8.5-29.8). The results of medical examination, onset data and the re-analysis of original biopsies of 31 participants were used when analyzing the predictive factors for persistent nephropathy, i.e. constant proteinuria/hematuria or end-stage renal disease (ESRD). All patients' medical history data were obtained from regional hospitals and renal survival data from the national kidney register. Six (11%) of the 55 identified patients had developed ESRD. Sixteen (52%) of the 31 participants were not attending for regular follow-up visits after the acute phase. Twenty-two (71%) had renal symptoms and 12 (39%) were receiving drugs for hypertension/proteinuria at their latest follow-up visit. The chronicity index and total biopsy score in the first renal biopsy were higher in patients with persistent nephropathy or ESRD than in those without (p=0.022 and p=0.014, respectively). Nine (69%) of the 13 subjects who had been over 16 years of age at diagnosis had persistent nephropathy or ESRD, compared with 4 (22%) of the 18 subjects who had been under 16 years of age (relative risk 3.1, 95% CI 1.2-8.0). Pregnancy complications were common: 12 (55%) of the 22 pregnancies had been complicated by proteinuria and/or hypertension, and the prematurity rate was 30%. Long-term follow-up during adulthood is needed even after mild childhood IgA nephritis, especially in women during and after pregnancy.


Significantly Lower Infection Risk for Anterior Cruciate Ligament Grafts Presoaked in Vancomycin Compared With Unsoaked Grafts: A Systematic Review and Meta-analysis.
To compare postoperative infection rates following ACL reconstruction performed with grafts presoaked in vancomycin versus those without vancomycin. A systematic review was performed using PRISMA guidelines. PubMed, SCOPUS, and Cochrane Central Register of Controlled Trials were searched for therapeutic level I to III studies that compared outcomes of presoaking ACL grafts with vancomycin versus without vancomycin in human patients. Included graft types were tendon autografts or allografts, and included studies documented infection with a minimum follow-up of 30 days. Postoperative infection rates and knee-specific patient-reported outcome scores were extracted from each study and compared between groups. Study methodological quality was analyzed using the Methodological Index for Non-Randomized Studies (MINORS) and Modified Coleman Methodology Score (MCMS). Infection rates and retear rates were pooled and weighted for meta-analysis using a random-effects model. All P values were reported with an α level of 0.05 set as significant. The initial search yielded 144 articles (44 duplicates, 100 screened, 29 full-text review). Ten articles (21,368 subjects [7,507 vancomycin and 13,861 no vancomycin], 67% males, mean ± standard deviation age 29.5 ± 1.5 years) were included and analyzed. Eight of the 10 studies included only autografts, with 94.5% of grafts being hamstring autografts. Soaking grafts in vancomycin resulted in significantly fewer infections (0.013% versus 0.77%; odds ratio 0.07; 95% confidence interval 0.03, 0.18; P < .001). Only 2 studies included patient-reported outcomes, and both demonstrated no difference in International Knee Documentation Committee scores 1 year after surgery for patients with grafts presoaked in vancomycin versus without vancomycin. Soaking ACL tendon grafts with vancomycin before implantation is associated with a nearly 15 times decrease in odds of infection compared with grafts not soaked in vancomycin. Few studies investigated patient-reported outcomes and retear rates after soaking ACL grafts in vancomycin. III, systematic review of level III studies.