The P2Y1 receptor, necessary but not sufficient to support full ADP-induced platelet aggregation, is not the target of the drug clopidogrel.
Recently we showed that the P2Y1 receptor coupled to calcium mobilization is necessary to initiate ADP-induced human platelet aggregation. Since the thienopyridine compound clopidogrel specifically inhibits ADP-induced platelet aggregation, it was of interest to determine whether the P2Y1 receptor was the target of this drug. Therefore we studied the effects of clopidogrel and of the two specific P2Y1 antagonists A2P5P and A3P5P on ADP-induced platelet events in rats. Although clopidogrel treatment (50 mg/kg) greatly reduced platelet aggregation in response to ADP as compared to untreated platelets, some residual aggregation was still detectable. In contrast, A2P5P and A3P5P totally abolished ADP-induced shape change and aggregation in platelets from both control and clopidogrel-treated rats. A2P5P and A3P5P (100 microM) totally inhibited the [Ca2+]i rise induced by ADP (0.1 microM) in control and clopidogrel-treated platelets, whereas clopidogrel treatment had no effect. Conversely, the inhibition of adenylyl cyclase induced by ADP (5 microM) was completely blocked by clopidogrel but not modified by A2P5P or A3P5P (100 microM). A3P5P (1 mM) reduced the number of [33P]2MeSADP binding sites on control rat platelets from 907 +/- 50 to 611 +/- 25 per platelet. After clopidogrel treatment, binding of [33P]2MeSADP decreased to 505 +/- 68 sites per platelet and further decreased to 55 +/- 12 sites in the presence of A3P5P (1 mM). In summary, these results demonstrate that the platelet P2Y1 receptor responsible for the initiation of aggregation in response to ADP is not the target of clopidogrel. Platelets may express another, as yet unidentified, P2Y receptor, specifically coupled to the inhibition of adenylyl cyclase and necessary to induce full platelet aggregation, which could be the target of this drug.


Defects in protein folding in congenital hypothyroidism.
Primary congenital hypothyroidism (CH) is the most common endocrine disease in children and one of the most common preventable causes of both cognitive and motor deficits. CH is a heterogeneous group of thyroid disorders in which inadequate production of thyroid hormone occurs due to defects in proteins involved in the gland organogenesis (dysembryogenesis) or in multiple steps of thyroid hormone biosynthesis (dyshormonogenesis). Dysembryogenesis is associated with genes responsible for the development or growth of thyroid cells: such as NKX2-1, FOXE1, PAX8, NKX2-5, TSHR, TBX1, CDCA8, HOXD3 and HOXB3 resulting in agenesis, hypoplasia or ectopia of thyroid gland. Nevertheless, the etiology of the dysembryogenesis remains unknown for most cases. In contrast, the majority of patients with dyshormonogenesis has been linked to mutations in the SLC5A5, SLC26A4, SLC26A7, TPO, DUOX1, DUOX2, DUOXA1, DUOXA2, IYD or TG genes, which usually originate goiter. About 800 genetic mutations have been reported to cause CH in patients so far, including missense, nonsense, in-frame deletion and splice-site variations. Many of these mutations are implicated in specific domains, cysteine residues or glycosylation sites, affecting the maturation of nascent proteins that go through the secretory pathway. Consequently, misfolded proteins are permanently entrapped in the endoplasmic reticulum (ER) and are translocated to the cytosol for proteasomal degradation by the ER-associated degradation (ERAD) machinery. Despite of all these remarkable advances in the field of the CH pathogenesis, several points on the development of this disease remain to be elucidated. The continuous study of thyroid gene mutations with the application of new technologies will be useful for the understanding of the intrinsic mechanisms related to CH. In this review we summarize the present status of knowledge on the disorders in the protein folding caused by thyroid genes mutations.


Genetic variation in the cannabinoid receptor gene (CNR1) (G1359A polymorphism) and their influence on anthropometric parameters and metabolic parameters under a high monounsaturated vs. high polyunsaturated fat hypocaloric diets.
An intragenic polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism in Caucasian populations (rs1049353). Intervention studies with this polymorphism have yield contradictories results. We decide to investigate the role of polymorphism (G1359A) of (CNR1) gene on metabolic parameters and weight loss secondary to a high monounsaturated fat and high polyunsaturated fat hypocaloric diets in obese subjects. A population of 258 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 3-month period in which subjects received 1 of 2 diets (diet M: high monounsaturated fat diet vs diet P: high polyunsaturated fat diet). One hundred and sixty five patients (63.9%) had the genotype G1359G and 93 (36.1%) patients (A allele carriers) had G1359A (78 patients,30.3%) or A1359A (15 patients,5.8%) genotypes. In subjects with both genotypes, body mass index, weight, fat mass, waist circumference and systolic blood pressures decreased with both diets. With the diet-type M and in both genotype groups, biochemical parameters remained unchanged. After the diet type P and in subjects with both genotypes, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, insulin and homeostasis model assessment for insulin resistance (HOMA-IR) levels decreased. In G1359G genotype subjects after both diets, leptin levels decreased. The finding of this study is the association of the A allele with a lack of improvement on leptin levels. Subjects with both genotypes and after a high polyunsaturated fat hypocaloric diet showed a significant improvement of LDL cholesterol, total cholesterol, HOMA-IR and insulin levels.


Photosensitized 2-amino-3-hydroxypyridine-induced mitochondrial apoptosis via Smac/DIABLO in human skin cells.
The popularity of hair dyes use has been increasing regularly throughout the world as per the demand of hair coloring fashion trends and other cosmetic products. 2-Amino-3-hydroxypyridine (A132) is widely used as a hair dye ingredient around the world. We are reporting first time the phototoxicity mechanism of A132 under ambient environmental UV-B radiation. It showed maximum absorption in UV-B region (317 nm) and forms a photoproduct within an hour exposure of UV-B irradiation. Photocytotoxicity of A132 in human keratinocytes (HaCaT) was measured by mitochondrial (MTT), lysosomal (NRU) and LDH assays which illustrated the significant reduction in cell viability. The role of reactive oxygen species (ROS) generation for A132 phototoxicity was established photo- chemically as well as intracellularly. Noteworthy, formation of tail DNA (comet assay), micronuclei and cyclobutane pyrimidine dimers (CPDs) (immunocytochemistry) formation confirmed the photogenotoxic potential of dye. Cell cycle study (sub-G1peak) and staining with EB/AO revealed the cell cycle arrest and apoptosis. Further, mitochondrial mediated apoptosis was corroborated by reduced MMP, release of cytochrome c and upregulation of caspase-3. Release of mitochondrial Smac/DIABLO in cytoplasm demonstrated the caspase dependent apoptotic cell death by photolabile A132 dye. In-addition increased Bax/Bcl2 ratio again proved the apoptosis. Thus, study suggests that A132 induces photogenotoxicity, phototoxicity and apoptotic cell death through the involvement of Smac/DIABLO in mitochondrial apoptosis via caspase dependent manner. Therefore, the long term use of A132 dye and sunlight exposure jointly increased the oxidative stress in skin which causes premature hair loss, damage to progenitor cells of hair follicles.


Identification of novel rhoptry neck protein of Plasmodium falciparum.
The clinical symptoms of malaria are attributed to the blood stage life cycle of parasite in which merozoite invades erythrocyte, undergoes multiplication and exit to re-invade into new erythrocyte to continue its life cycle. The interaction of repertoire of parasite proteins with host cell receptors is essential for invasion process. Identification, characterization and localization of the proteins involved in invasion will enrich our understanding of this complex process. In the present study we have identified a novel Apical Rhoptry Neck Protein in Plasmodium falciparum, which harbours a predicted signal and transmembrane domain and is conserved across the species. The transcription and translation analysis confirmed its expression in schizont stage of asexual cycle of P. falciparum. Immunoflouresence microscopy in schizonts and merozoites revealed its localization in the neck of rhoptries of P. falciparum. Furthermore, PfARNP has been found at the tight junction during invasion of P. falciparum merozoite to erythrocyte.


The effects of chewing-gum stick size and duration of chewing on salivary flow rate and sucrose and bicarbonate concentrations.
The objectives were to determine (1) the relations between salivary flow rate and the sample weights of chewing-gum and gum base, (2) whether any reduction in salivary flow rate with duration of chewing is due to a reduction in hardness of gum base with chewing, and (3) the sucrose and bicarbonate concentrations in saliva elicited by different weights of chewing-gum containing sucrose. Ten subjects chewed, for 20 min, samples of 1, 2, 3, 6 and 9 g of gum base and of a sucrose-containing chewing-gum. With each sample, salivary flow rates peaked initially and then fell to a relatively constant value. Flow rates during the periods of 1-2 and 15-20 min were linearly related to the logarithm of sample weight. With the chewing-gum samples, virtually all the sucrose was released into the saliva during the 20 min of chewing, with peak concentrations (201-666 mM) at 1-2 min, and bicarbonate concentrations were higher with the 9-g than the 3-g samples. Six subjects chewed 3 g of gum base and within 45 min the weight of base had increased to 122% of the original, presumably due to the uptake of saliva. The hardness of gum base was determined at 21 and 36 degrees C, 21 and 36 degrees C after it had been chewed, and 21 degrees C after it had been chewed without exposure to saliva, and gave Brinell values of 0.277, 0.038, 0.022, 0.002 and 0.061, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Surgery in patients with advanced germ cell malignancy following a clinical partial response to chemotherapy.
Twenty-one patients with metastatic germ cell tumors achieved only partial clinical tumor regression following chemotherapy, and underwent surgical biopsy or resection of the residual tumor deposits. Sixteen (76%) are at present clinically disease-free after a median 30 + months (range 17-50 months) from the time of surgery, and five (24%) died after 9-29 months. Adverse prognostic signs were the finding of persistent cancer at histopathological examination of the resected tumor masses, and the presence of elevated serum tumor markers at the time of surgery. Postchemotherapy surgery in this setting provides tissue for the prognostically important histopathological examination on which a decision regarding further chemotherapy may be based. In addition, it provides tumor bulk reduction in the cases of differentiated teratoma and persistent cancer.


Defective bone formation by Hyp mouse bone cells transplanted into normal mice: evidence in favor of an intrinsic osteoblast defect.
The hypophosphatemic (Hyp) mouse is an animal model for human hypophosphatemic vitamin D-resistant rickets. We have reported that bone cells isolated from Hyp mice born to homozygous mutant females produce abnormal bone when transplanted into normal mice. To test whether an environmentally acquired defect of the mutant cells contributed to the impaired bone formation observed in transplants, periostea and osteoblasts from normal and Hyp littermates were transplanted intramuscularly into normal animals. To test more specifically for an hypophosphatemia-induced cell alteration before transplantation, bone cells isolated from phosphate-depleted normal mice were transplanted into normal animals. The bone nodules formed in 2 week transplants were characterized by measuring their osteoid thickness and volume. Impaired bone formation was evidenced in Hyp transplants compared to normal littermate transplants by increased osteoid thickness and volume. In contrast to cells from mutant mice, cells isolated from normal mice with comparable hypophosphatemia produced normal bone. These results indicate that the inability of Hyp osteoblasts to produce normal bone when placed in a normal environment is not the consequence of prior exposure to an altered environmental but likely of an intrinsic cellular abnormality. These observations add further support to the concept that the osteoblast is an important target for the Hyp mutation.


The PPAR alpha agonist gemfibrozil is an ineffective treatment for spinal cord injured mice.
Peroxisome Proliferator Activated Receptor (PPAR)-α is a key regulator of lipid metabolism and recent studies reveal it also regulates inflammation in several different disease models. Gemfibrozil, an agonist of PPAR-α, is a FDA approved drug for hyperlipidemia and has been shown to inhibit clinical signs in a rodent model of multiple sclerosis. Since many studies have shown improved outcome from spinal cord injury (SCI) by anti-inflammatory and neuroprotective agents, we tested the efficacy of oral gemfibrozil given before or after SCI for promoting tissue preservation and behavioral recovery after spinal contusion injury in mice. Unfortunately, the results were contrary to our hypothesis; in our first attempt, gemfibrozil treatment exacerbated locomotor deficits and increased tissue pathology after SCI. In subsequent experiments, the behavioral effects were not replicated but histological outcomes again were worse. We also tested the efficacy of a different PPAR-α agonist, fenofibrate, which also modulates immune responses and is beneficial in several neurodegenerative disease models. Fenofibrate treatment did not improve recovery, although there was a slight trend for a modest increase in histological tissue sparing. Based on our results, we conclude that PPAR-α agonists yield either no effect or worsen recovery from spinal cord injury, at least at the doses and the time points of drug delivery tested here. Further, patients sustaining spinal cord injury while taking gemfibrozil might be prone to exacerbated tissue damage.


A neurodevelopmental disorder associated with an activating de novo missense variant in ARF1.
ADP-ribosylation factor 1 (ARF1) is a small GTPase that regulates membrane traffic at the Golgi apparatus and endosomes through recruitment of several coat proteins and lipid-modifying enzymes. Here, we report a pediatric patient with an ARF1-related disorder because of a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. Neuroimaging revealed a hypoplastic corpus callosum and subcortical white matter abnormalities. Notably, this patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis of the R99H-ARF1 variant protein revealed that it was expressed at normal levels and properly localized to the Golgi apparatus; however, the expression of this variant caused swelling of the Golgi apparatus, increased the recruitment of coat proteins such as coat protein complex I, adaptor protein complex 1 and GGA3 and altered the morphology of recycling endosomes. In addition, we observed that the expression of R99H-ARF1 prevented dispersal of the Golgi apparatus by the ARF1-inhibitor brefeldin A. Finally, protein interaction analyses showed that R99H-ARF1 bound more tightly to the ARF1-effector GGA3 relative to wild-type ARF1. These properties were similar to those of the well-characterized constitutively active Q71L-ARF1 mutant, indicating that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations. The absence of periventricular nodular heterotopias in this R99H-ARF1 subject also indicates that this finding may not be a consistent phenotypic expression of all ARF1-related disorders.


The next Black America: Obstacles amidst opportunities for Black families.
In this article, the author offers personal accounts on how she feels about the current Black America and obstacles that people face reaching for opportunities for Black families. Focus relies on the current state of Black America, poverty, schools, academic achievement, raising children in the next Black America and much more. (PsycINFO Database Record


Preparation of biocompatible molecularly imprinted shell on superparamagnetic iron oxide nanoparticles for selective depletion of bovine hemoglobin in biological sample.
Bovine hemoglobin (BHb), as one of the high-abundance proteins, could seriously mask and hamper the analysis of low-abundance proteins in serum. To selectively deplete BHb, we design a simple and effective strategy for preparation of biocompatible molecularly imprinted shell on superparamagnetic iron oxide nanoparticles through surface imprinting technique combined with template immobilization strategy. Firstly, template proteins are immobilized on the directly aldehyde-functionalized magnetic nanoparticles through imine bonds. Then, with gelatin as functional monomer, a polymeric network molded around the immobilized template proteins is obtained. Finally, the specific cavities for BHb are fabricated after removing the template proteins. The effects of imprinting conditions were investigated and the optimal imprinting conditions are found to be 40mg of BHb, 150mg of gelatin, and 8h of polymerization time. The resultant materials exhibit good dispersion, high crystallinity, and satisfactory superparamagnetic property with a high saturation magnetization (33.43emug(-1)). The adsorption experiments show that the imprinted nanomaterials have high adsorption capacity of 93.1mgg(-1), fast equilibrium time of 35min, and satisfactory selectivity for target protein. Meanwhile, the obtained polymers could be used without obvious deterioration after six adsorption-desorption cycles. In addition, the resultant polymers are successfully applied in the selective isolation BHb from bovine blood sample, which could provide an alternative solution for the preparatory work of proteomics.


Development and validation of a single robust HPLC method for the characterization of a pharmaceutical starting material and impurities from three suppliers using three separate synthetic routes.
Novel approaches to the development of analytical procedures for monitoring incoming starting material in support of chemical/pharmaceutical processes are described. High technology solutions were utilized for timely process development and preparation of high quality clinical supplies. A single robust HPLC method was developed and characterized for the analysis of the key starting material from three suppliers. Each supplier used a different process for the preparation of this material and, therefore, each suppliers' material exhibited a unique impurity profile. The HPLC method utilized standard techniques acceptable for release testing in a QC/manufacturing environment. An automated experimental design protocol was used to characterize the robustness of the HPLC method. The method was evaluated for linearity, limit of quantitation, solution stability, and precision of replicate injections. An LC-MS method that emulated the release HPLC method was developed and the identities of impurities were mapped between the two methods.


Oral Health-Related Quality of Life in Persian-Speaking Elementary Schoolers in Iran: A Psychometric Study of Child Perception Questionnaire.
Background and Purpose: The study aims to examine the validity and reliability of the impact of 16-item Short-Form Child Perception Questionnaire (CPQ11-14-ISF:16) in Persian-speaking elementary schoolers. Methods: From two main cities in Iran, 708 mother-child dyads were enrolled in 2018. Decayed, missing, and filled teeth (DMFT/dmft) indexes were examined for divergent validity. Two built-in indexes of overall oral health and overall impacted well-being were used for concurrent validity. Exploratory factor analysis (EFA) with Geomin rotation, Cronbach's α, and Spearman's correlation were executed. Results: The total Cronbach's α was 0.71. EFA indicated CPQ11-14-ISF:11 (α = 0.66) to compose three eligible factors (α = 0.66), including oral problems (α = 0.54), emotional problems (α = 0.66), and social problems (α = 0.41). The concurrent/divergent validity of CPQ11-14-ISF:11 and the subscales was partially confirmed. Conclusions: The use of CPQ11-14-ISF:11 to multidimensionally address dental care for children requires further investigations.


Development and validation of dust exposure prevention questionnaire for cardiovascular patients based on the health belief model.
Many cardiovascular patients suffer from respiratory failure. Environmental conditions can exacerbate symptomatology. It is necessary to prevent exposure to dust by taking educational steps to identify and modify patient behavior. This study aimed to develop and validate a dust exposure behavior questionnaire based on the Health Belief Model. A mixture of qualitative and quantitative methods was employed to design and develop the desired tool. Qualitative methods were used to identify the preventive behaviors needed by cardiovascular patients at risk of dust exposure using the opinions of two expert panels and a literature review. The quantitative phase of the research was performed to evaluate the psychometric properties of the research tool. The research population comprised 417 people with cardiovascular disease referred to a heart hospital in Bushehr, Iran in 2018. Consenting participants entered the study through consecutive sampling. The final version of the questionnaire included 27 items across six domains, namely perceived susceptibility, perceived barriers, perceived severity, perceived benefits, cues to action, and self-efficacy. The mean values of the content validity ratio and content validity index were 0.93 and 0.9, respectively. In addition, all items had a good correlation with the total score of their parent domain (P < 0.01). The model fit was initially unsuitable, according to the related indices. Hence, to achieve a better model fit, the model was improved by releasing some parameters based on the modifications suggested by the AMOS software. The modified model featured an acceptable fit (χ2/df = 2.2, P < 0.001). Cronbach's alpha coefficients also confirmed appropriate reliability for all six domains. The Dust Exposure Prevention questionnaire has desirable psychometric properties and appropriate validity to determine the behavioral factors involved in harm from dust exposure among cardiovascular disease patients. This marks an effective step toward evaluating the factors effective in preventing complications related to dust exposure among such patients.


Semiconducting Polymer Nano-regulators with Cascading Activation for Photodynamic Cancer Immunotherapy.
Combination photoimmunotherapy holds promise for tumor suppression; however, smart phototherapeutic agents that only activate their immune pharmaceutical action in tumors have been rarely developed. Herein, we report a semiconducting polymer (SP) nano-regulator (SPNT ) with cascading activation for combinational photodynamic cancer immunotherapy. SPNT comprises an immunoregulator (M-Trp: 1-methyltryptophan) conjugating to the side chain of the SP backbone via an apoptotic biomarker-cleavable linker. Under near-infrared photoirradiation, SPNT produces singlet oxygen to induce immunogenic apoptosis. Concurrently, an apoptotic biomarker is upregulated, which triggers the specific cleavage of M-Trp for indoleamine 2,3-dioxygenase (IDO) activity inhibition, regulatory T cells reduction and cytotoxic T lymphocytes infiltration. SPNT -mediated combination photodynamic immunotherapy thus reprograms the tumor immune microenvironment, resulting in efficient suppression of tumors, and inhibition of lung metastasis.


Structure and function of the PsbP protein of photosystem II from higher plants.
PsbP is a membrane extrinsic subunit of Photosystem II (PS II), which is involved in retaining Ca2+ and Cl-, two inorganic cofactors for the water-splitting reaction. In this study, we re-investigated the role of N-terminal region of PsbP on the basis of its three-dimensional structure. In previous paper [Ifuku and Sato (2002) Plant Cell Physiol 43: 1244-1249], a truncated PsbP lacking 19 N-terminal residues (Delta19) was found to bind to NaCl-washed PS II lacking PsbP and PsbQ without activation of oxygen evolution at all. Three-dimensional (3D) structure of PsbP suggests that deletion of 19 N-terminal residues would destabilize its protein structure, as indicated by the high sensitivity of Delta19 to trypsin digestion. Thus, a truncated PsbP lacking 15 N-terminal residues (Delta15), which retained core PsbP structure, was produced. Whereas Delta15 was resistant to trypsin digestion and bound to NaCl-washed PS II membranes, it did not show the activation of oxygen evolution. This result indicated that the interaction of 15-residue N-terminal flexible region of PsbP with PS II was important for Ca2+ and Cl- retention in PS II, although the 15 N-terminal residues were not essential for the binding of PsbP to PS II. The possible N-terminal residues of PsbP that would be involved in this interaction are discussed.


Studies on the inhibition by chlorpromazine of myotonia induced by ion channel modulators in mouse skeletal muscle.
The myotonic activity of mouse soleus and extensor digitorum longus muscles induced by either a combination of K+ channel blockers (4-aminopyridine) and a Cl- channel blocker (9-anthracene carboxylic acid) or a Cl- channel blocker in low Ca2+ (0.25 mM) Krebs or a Na+ channel activator (veratridine) was characterized in this paper. Myotonic activity was characterized by an increase in both the contraction amplitude and contraction duration accompanied by stimulus-related repeated action potentials. The slow soleus and fast extensor digitorum longus muscles appeared to differ in their responses to these ion channel modifiers. Nevertheless, chlorpromazine at a low concentration of 1 microM significantly inhibited all kinds of myotonic activity; it reduced the prolonged contraction duration and attenuated the stimulus-related repeated action potential firing. This depressant action of chlorpromazine was apparently not correlated with inhibition of either calmodulin or phospholipase A2 activity, since the myotonic depressant action of calmodulin inhibitors, such as dibucaine, flunarizine, chlorpromazine, trifluoperazine and diltiazem, was unrelated to their potency in inhibiting the activity of calmodulin or phospholipase A2. However, phosphatidylcholine was found to inhibit the myotonic depressant action of chlorpromazine. It is therefore, tentatively concluded that chlorpromazine interacted with membrane phospholipids, thereby changing membrane ion channel activity and depressing myotonic activity. These findings indicate that chlorpromazine might be useful in the management of clinical myotonia.


Antiviral drugs in aquatic environment and wastewater treatment plants: A review on occurrence, fate, removal and ecotoxicity.
The environmental release of antiviral drugs is of considerable concern due to potential ecosystem alterations and the development of antiviral resistance. As a result, interest on their occurrence and fate in natural and engineered systems has grown substantially in recent years. The main scope of this review is to fill the void of information on the knowledge on the worldwide occurrence of antiviral drugs in wastewaters and natural waters and correlate their levels with their environmental fate. According to the conducted literature survey, few monitoring data exists for several European countries, such as Germany, France, and the UK. Lesser data are available for Asia, where approximately 80% of the studies focus on Japan. Several articles study the occurrence of mostly antiretroantivirals in sub-Saharan African countries, while there is a lack of data for other developing regions of the world, including the rest of Africa, South America, and the biggest part of Asia. An importantly smaller number of studies exists for North America, while no studies exist for Oceania. The against innfluenza drug oseltamivir along with its active carboxy metabolite is found to be the most studied antiviral drug. The distribution of antiviral drugs across all geographic regions varies from low ng L-1 to high μg L-1 levels, in some cases, even in surface waters. This overarching review reveals that monitoring of antiviral drugs is necessary, and some of those compounds may require toxicological attention, in the light of either spatial and temporal high concentration or potential antiviral resistance. Based on the information provided herein, the need for a better understanding of the water quality hazards posed by antiviral drugs existence in wastewater outputs and freshwater ecosystems is demosntrated. Finally, the future challenges concerning the occurrence, fate, and potential ecotoxicological risk to organisms posed by antiviral drug residues are discussed.


Caring science and the science of unitary human beings: a trans-theoretical discourse for nursing knowledge development.
Two dominant discourses in contemporary nursing theory and knowledge development have evolved over the past few decades, in part by unitary science views and caring theories. Rogers' science of unitary human beings (SUHB) represents the unitary directions in nursing. Caring theories and related caring science (CS) scholarship represent the other. These two contemporary initiatives have generated two parallel, often controversial, seemingly separate and unrelated, trees of knowledge for nursing science. This paper explores the evolution of CS and its intersection with SUHB that have emerged in contemporary nursing literature. We present a case for integration, convergence, and creative synthesis of CS with SUHB. A trans-theoretical, trans-disciplinary context emerges, allowing nursing to sustain its caring ethic and ontology, within a unitary science. The authors critique and review the seminal, critical issues that have separated contemporary knowledge developments in CS and SUHB. Foundational issues of CS, and Watson's theory of transpersonal caring science (TCS), as a specific exemplar, are analysed, alongside parallel themes in SUHB. By examining hidden ethical-ontological and paradigmatic commonalities, trans-theoretical themes and connections are explored and revealed between TCS and SUHB. Through a creative synthesis of TCS and SUHB we explicate a distinct unitary view of human with a relational caring ontology and ethic that informs nursing as well as other sciences. The result: is a trans-theoretical, trans-disciplinary view for nursing knowledge development. Nursing's history has been to examine theoretical differences rather than commonalities. This trans-theoretical position moves nursing toward theoretical integration and creative synthesis, vs. separation, away from the 'Balkanization' of different theories. This initiative still maintains the integrity of different theories, while facilitating and inviting a new discourse for nursing science. The result: Unitary Caring Science that evokes both science and spirit.


Electroencephalography as a localizing tool.
1. The immature brain is not a miniature adult brain, and adult-epilepsy concepts and protocols do not necessarily apply to infant-epilepsy surgery. 2. The epileptogenic zone is conceptually, and often also topographically, distinct from both the ictal-onset zone and the irritative zone (interictal spiking). This distinction is especially important in pediatric evaluations. 3. In partial seizure disorders, the best strategy at present for demarcating the epileptogenic zone seems to be a weighted confluence of an epileptogenic lesion (if present), the ictal-onset zone, and the irritative zone. If these zones are not perfectly convergent (as is usually the case), they are given relative weights according to individual patient factors and variations in philosophy among epilepsy centers. This approach leaves much to be desired, especially in extratemporal nonlesional cases; it is hoped that future research will identify more reliable interictal markers for the epileptogenic zone. 4. Some cases of catastrophic generalized epilepsies or multifocal independent partial seizures are due to localized pathology (ZCA) and respond to resection of the offending lesion (often multilobar or hemispheric). In this context, the epileptogenic zone is coincident with the epileptogenic lesion and is best demarcated by the confluence of interictal indicators of structural pathology. The most reliable localizing aspects of the EEG are, therefore, interictal nonepileptiform abnormalities traditionally associated with structural lesions.


What do people with type 2 diabetes want from a brief messaging system to support medication adherence?
Many people with type 2 diabetes do not take their treatment as prescribed. Brief messages to support medication use could reach large numbers of people at a very low cost per person, but current interventions using brief messages rarely adequately describe the content of the messages, nor base these messages on explicit behavior change principles. This study reports the views of people with type 2 diabetes concerning the acceptability of 1) a messaging system and 2) proposed messages based on behavior change techniques (BCTs) and beliefs and concerns around taking medication. The proposed system and brief messages were discussed in focus groups of people with type 2 diabetes recruited through general practices in England. Transcripts were analyzed thematically. Twenty-three participants took part in one of five focus group discussions. All participants were over 18 years, were taking tablet medication for their diabetes, and had access to a mobile phone. Key exclusion criteria were recent hospitalization for hyper- or hypoglycemia or diagnosis with a terminal illness. Four themes were identified as relating to the acceptability of the messaging system: "opportunities and limitations of technology", "us and them (who is the system for?)", "responsibility for adherence", and "diabetes management beyond medication". Participants recognized the benefit of using technology. Those with high confidence in their ability to adhere were keen to make a distinction between themselves and those who did not adhere; participants were more comfortable taking responsibility for medication than diet and exercise. Acceptability of the messages hinged on avoiding "preaching to the converted". These findings show that brief messaging could be acceptable to the target population for a range of diabetes-related behaviors but highlight the need for such a system to be perceived as personally relevant. Acceptable messages would need to maintain novelty for the target population.


Molecular and cellular biology of von Willebrand factor.
von Willebrand factor (VWF) is a plasma protein that performs 2 main functions in hemostasis: it mediates platelet adhesion to the injured vessel wall, and it carries and protects coagulation factor VIII. VWF is synthesized through a multistep process in endothelial cells and megakaryocytes as a very large polymer composed of identical disulfide-linked 250-kd subunits. In endothelial cells, VWF not only directs the formation of its own storage granules, the Weibel-Palade bodies, but it also acts as a chaperone molecule to direct other proteins, such as P-selectin, into these granules. Upon stimulation of the endothelium, the Weibel-Palade bodies will be translocated to the plasma membrane, and their contents will be secreted into the plasma milieu. The expression of VWF can be regulated at different levels by a number of genetic and environmental factors, resulting in control of its activity. New roles for VWF, especially in inflammatory processes, have recently been suggested, indicating that some aspects of this well-studied protein remain to be investigated.


Changes in regional cerebral blood flow and functional connectivity in the cholinergic pathway associated with cognitive performance in subjects with mild Alzheimer's disease after 12-week donepezil treatment.
Acetylcholinesterase inhibitors (AChEIs), such as donepezil, have been shown to improve cognition in mild to moderate Alzheimer's disease (AD) patients. In this paper, our goal is to determine the relationship between altered cerebral blood flow (CBF) and intrinsic functional network connectivity changes in mild AD patients before and after 12-week donepezil treatment. An integrative neuroimaging approach was employed by combining pseudocontinuous arterial spin labeling (pCASL) MRI and resting-state functional MRI (R-fMRI) methods to determine the changes in CBF and functional connectivity (FC) in the cholinergic pathway. Linear regression analyses determined the correlations of the regional CBF alterations and functional connectivity changes with cognitive responses. These were measured with the Mini-Mental Status Examination (MMSE) scores and Alzheimer's disease Assessment Scale-Cognitive subscale (ADAS-cog) scores. Our results show that the regional CBF in mild AD subjects after donepezil treatment was significantly increased in the middle cingulate cortex (MCC) and posterior cingulate cortex (PCC), which are the neural substrates of the medial cholinergic pathway. In both brain regions, the baseline CBF and its changes after treatment were significantly correlated with the behavioral changes in ADAS-cog scores. The intrinsic FC was significantly enhanced in the medial cholinergic pathway network in the brain areas of the parahippocampal, temporal, parietal and prefrontal cortices. Finally, the FC changes in the medial prefrontal areas demonstrated an association with the CBF level in the MCC and the PCC, and also were correlated with ADAS-cog score changes. These findings indicate that regional CBF and FC network changes in the medial cholinergic pathway were associated with cognitive performance. It also is suggested that the combined pCASL-MRI and R-fMRI methods could be used to detect regional CBF and FC changes when using drug treatments in mild AD subjects.


[Nonspecific means of increasing the sensitivity of the passive hemagglutination reaction].
The effect of some methods of preliminary treatment of erythrocytes on the PHAT depended on the sensitin náture and the method of erythrocyte load. In case of erythrocyte load with nonprotein and immunoglobulin sensitins without any conjugating agents the simulating effect of heating and periodate treatment was caused not by increase of stable sensitin binding, but by the reduction of physico-chemical resistance of erythrocytes. This effect of erythrocyte treatment permitted to increase the sensitivity of the antibodies and antigens determination. In loading the erythrocytes with the aid of conjugating agents and in sensitization with protein antigens after Boyden no stimuating effect of the treatment was noted.


Differential roles of extracellular signal-regulated kinase 1/2 and p38MAPK in mechanical load-induced procollagen alpha1(I) gene expression in cardiac fibroblasts.
We have previously demonstrated that mechanical loading of cardiac fibroblasts leads to increased synthesis and gene expression of the extracellular matrix protein collagen. We hypothesised that the upregulation of procollagen gene expression in cardiac fibroblasts, in response to cyclic mechanical load, is mediated by one or more members of the MAP kinase family. To test this hypothesis, the effect of mechanical load on the activation of extracellular signal-regulated kinase (ERK) 1/2, p46/54JNK, and p38MAPK was examined in rat cardiac fibroblasts. Peak phosphorylation of ERK 1/2, p38MAPK kinases, and p46/54JNK was observed following 10-20 min of continuous cyclic mechanical load. Mechanical load significantly increased procollagen alpha1(I) mRNA levels up to twofold above static controls after 24 h. This increase was completely abolished by the MEK 1/2 inhibitor U0126, with no effect on basal levels. In contrast, SB203580, a specific inhibitor of p38MAPK, enhanced both basal and stretch-stimulated levels of procollagen mRNA. Consistent with this finding, selective activation of the p38MAPK signalling pathway by expression of MKK6(Glu), a constitutive activator of p38MAPK, significantly reduced procollagen alpha1(I) promoter activity. SB203580-dependent increase in procollagen alpha1(I) was accompanied by ERK 1/2 activation, and inhibition of this pathway completely prevented SB203580-induced procollagen alpha1(I) expression. These results suggest that mechanical load-induced procollagen alpha1(I) gene expression requires ERK 1/2 activation and that the p38MAPK pathway negatively regulates gene expression in cardiac fibroblasts. These pathways are likely to be key in events leading to matrix deposition during heart growth and remodelling induced by mechanical load.


Body image and genital self-image in pre-menopausal women with dyspareunia.
With a prevalence of 15-21%, dyspareunia is one of the most commonly reported sexual dysfunctions in pre-menopausal women under the age of 40. Studies to date have focused primarily on clinical samples, showing that women with dyspareunia report overall sexual impairment, anxiety, and feelings of sexual inadequacy. However, little is known about their body image and genital self-image and few studies have sampled women exclusively from the general population. The aim of the present, controlled study was to investigate body image and genital self-image in a community sample of pre-menopausal women with self-reported dyspareunia. In total, 330 women completed an online survey, of which 192 (58%) had dyspareunia and 138 (42%) were pain-free control women. In comparison to pain-free control women, women with dyspareunia reported significantly more distress about their body image and a more negative genital self-image. Moreover, findings from a logistic regression, in which trait anxiety was controlled for, showed that a more negative genital self-image was strongly and independently associated with an increased likelihood of reporting dyspareunia. These results suggest that, in women with dyspareunia, body image and genital self-image are significantly poorer and would benefit from more attention from both clinicians and researchers.


[Endoscopic palliation of dysphagia due to anastomotic recurrences after esophageal surgery and total gastrectomy due to carcinoma].
Dysphagia is the main symptom of locally recurrent esophageal and gastric carcinoma and generally suggests extensive disease. The safety and efficacy of endoscopic palliation in patients who developed locally recurrent disease after surgery is evaluated. Twenty-six males and 12 females, with an average age of 63.5 years were included in the patients group. In 12 patients there was an esophago-gastric anastomosis, in 26 an esophago-jejunostomy, after total gastrectomy. Anastomotic recurrences were divided into predominantly polypoid (16 cases) and predominantly stenosing (22 cases). Three treatment modalities were employed: endoscopic dilation (6 cases), Nd-Yag laser therapy (16 cases) and prostheses (16 cases). Successful endoscopic treatment was obtained in 33 out of 38 patients (86.8%). Major complications occurred in 5 patients (15%) with a mortality rate of 6%. The endoscopic palliation is effective. Technically, endoscopic treatment is easier to perform, with better results, when dealing with polypoid rather than stenosing recurrences.


Hospital-based home care for children with cancer: feasibility and psychosocial impact on children and their families.
To assess the feasibility and psychosocial impact of a hospital-based home care (HBHC) program for children with cancer. A HBHC program was carried out with 51 children (0-18 years) with cancer to assess its feasibility in terms of satisfaction, care preferences, safety, and cost. A controlled trial was conducted to assess children's health-related quality of life (HRQOL) using the parent-reported and self-reported PedsQL generic core scale and PedsQL cancer module, and the psychosocial impact on the family by PedsQL family impact module comprising a subsample of 28 children and 43 parents in the home care group, and 47 children and 66 parents receiving standard hospital care. All parents in the HBHC program were satisfied and preferred home care. There were no serious adverse events associated with HBHC, and costs did not increase. When adjusting for age, gender, diagnosis and time since diagnosis, we found significant higher HRQOL scores in parent-reported physical health (P = 0.04; 95% confidence interval (CI): -0.2-19.5) and worry (P = 0.04; 95% CI: -0.4-20.6) in the home-care group indicating better physical health and less worry for children in the home-care group. No significant difference was found in the Family Impact Module. This study indicates that HBHC is a feasible alternative to hospital care for children with cancer, and is greatly preferred by parents. Specific aspects of children's HRQOL may be improved with HBHC and the psychosocial burden on the family does not increase.


Influence of caffeine on sparing effect of dose fractionation in housefly larvae.
Caffeine, given during interfraction interval, abolishes the sparing effect of dose fractionation observed for delay of pupariation in Musca domestica larvae. When given as postirradiation treatment after single exposure, caffeine increases the delay in the synergistic manner. Pretreatment of the larvae with ascorbic acid for 3 h protects from radiation-induced delay whereas pretreatment with caffeine does not have any effect. Combination of ascorbic acid and caffeine pretreatment protects the larvae only at low concentration (0.05%) and not at high concentration (0.1%).


A Dual, Systematic Approach to Malaria Diagnostic Biomarker Discovery.
The emergence and spread of Plasmodium falciparum parasites that lack HRP2/3 proteins and the resulting decreased utility of HRP2-based malaria rapid diagnostic tests (RDTs) prompted the World Health Organization and other global health stakeholders to prioritize the discovery of novel diagnostic biomarkers for malaria. To address this pressing need, we adopted a dual, systematic approach by conducting a systematic review of the literature for publications on diagnostic biomarkers for uncomplicated malaria and a systematic in silico analysis of P. falciparum proteomics data for Plasmodium proteins with favorable diagnostic features. Our complementary analyses led us to 2 novel malaria diagnostic biomarkers compatible for use in an RDT format: glyceraldehyde 3-phosphate dehydrogenase and dihydrofolate reductase-thymidylate synthase. Overall, our results pave the way for the development of next-generation malaria RDTs based on new antigens by identifying 2 lead candidates with favorable diagnostic features and partially de-risked product development prospects.


No clinical advantages of coblation tonsillectomy compared with traditional tonsillectomy.
Tonsillectomy may be performed by several methods. It is continuously being discussed which method is preferable with regard to postoperative haemorrhage, pain, activity and nutrition. The present study is a prospective non-randomized study of tonsillectomy. It included 198 patients aged 14-40 years who either underwent coblation tonsillectomy or traditional "cold" tonsillectomy after random allocation to different surgeons. A total of 51 patients underwent coblation tonsillectomy and 147 patients underwent traditional tonsillectomy. We tested the hypothesis that there is no difference in postoperative pain experience between the two surgical techniques. The patients were followed for nine days postoperatively. They filled in a questionnaire on postoperative pain score, activity level and food intake. We found no statistically significant difference in pain perception between the two groups and there was no difference in their levels of activity. The intraoperative haemorrhage was significantly reduced in the coblation tonsillectomy group, but there was no difference in postoperative haemorrhage between the two groups. The overall results of this study suggest that neither coblation tonsillectomy nor traditional tonsillectomy enjoys an advantage over the other in patients aged 14-40 years. not relevant. not relevant.


Commercially pure titanium implants with surfaces modified by laser beam with and without chemical deposition of apatite. Biomechanical and topographical analysis in rabbits.
The purpose of this study was to evaluate the surfaces of commercially pure titanium (cp Ti) implants modified by laser beam (LS), without and with hydroxyapatite deposition by the biomimetic method (HAB), without (HAB) and with thermal treatment (HABT), and compare them with implants with surfaces modified by acid treatment (AS) and with machined surfaces (MS), employing topographical and biomechanics analysis. Forty-five rabbits received 75 implants. After 30, 60, and 90 days, the implants were removed by reverse torque and the surfaces were topographically analyzed. At 30 days, statistically significant difference (P < 0.05) was observed among all the surfaces and the MS, between HAB/HABT and AS and between HAB and LS. At 60 days, the reverse torque of LS, HAB, HABT, and AS differed significantly from MS. At 90 days, difference was observed between HAB and MS. The microtopographic analysis revealed statistical difference between the roughness of LS, HAB, and HABT when compared with AS and MS. It was concluded that the implants LS, HAB, and HABT presented physicochemical and topographical properties superior to those of AS and MS and favored the osseointegration process in the shorter periods. In addition, HAB showed the best results when compared with other surfaces.


Value of early follow-up CT in paediatric tuberculous meningitis.
The value of CT in the diagnosis of tuberculous meningitis (TBM) in children is well reported. Follow-up CT scanning for these patients is, however, not well described and, in particular, the value of early follow-up CT has not been addressed for children with TBM. To assess the value of early follow-up CT in children with TBM in identifying diagnostic, prognostic and therapeutically relevant features of TBM. A retrospective 4-year review of CT scans performed within 1 week and 1 month of initial CT in children with proven (CSF culture-positive) and probable TBM (CSF profile-positive but culture-negative) and comparison with initial CT for the diagnostic, prognostic and therapeutic CT features of TBM. The CT scans of 50 children were included (19 "definite" TBM; 31 "probable" TBM). Of these, 30 had CT scans performed within 1 week of the initial CT. On initial CT, 44 patients had basal enhancement. Only 24 patients had contrast medium-enhanced follow-up scans. Important findings include: 8 of 29 patients (who were not shunted) developed new hydrocephalus. New infarcts developed in 24 patients; 45% of those who did not have infarction initially developed new infarcts. Three of the six patients who did not show basal enhancement on initial scans developed this on the follow-up scans, while in seven patients with pre-existing basal enhancement this became more pronounced. Two patients developed hyperdensity in the cisterns on non-contrast medium scans. Eight patients developed a diagnostic triad of features. Three patients developed CT features of TBM where there was none on the initial scans. Early follow-up CT is useful in making a diagnosis of TBM by demonstrating features that were not present initially and by demonstrating more sensitive, obvious or additional features of TBM. In addition, follow-up CT is valuable as a prognostic indicator as it demonstrates additional infarcts which may have developed or become more visible since the initial study. Lastly, follow-up CT has therapeutic value in demonstrating hydrocephalus, which may develop over time and may require drainage. We advise routine follow-up CT in patients with suspected TBM within the first week of initial CT and optionally at 1 month.


Relationship between toilet training process and primary nocturnal enuresis in children and adolescents - A systematic review.
Primary nocturnal enuresis (PNE) affects the quality of life of children and families and may lead to low self-esteem and social isolation. The pathophysiology of enuresis is multifactorial. This systematic review aimed to investigate the relationship between toilet training (TT) and PNE in children and adolescents. We searched for articles about TT and PNE in MEDLINE (via PubMed), SCOPUS and WEB of SCIENCE databases. The Preferred Reporting Items for Systematic Reviews (PRISMA) statement was used to guide the systematic review. Prior to the study, the review protocol was registered and approved in PROSPERO under the protocol CRD42021270976. The Risk of Bias in Non-Randomized Studies of Exposures (ROBINS-E) was used to analyze the biases of the select studies. A total of 570 studies were initially selected. Of these, eight articles were included in this systematic review, with a total number of 5990 participants aged between 5 and 18 years diagnosed with PNE. Seven of the eight articles reported that prolonged use of disposable diapers for more than one-year, late initiation of the TT process or non-acceptance of the Assisted Infant TT or Elimination Communication approach, use of coercive approaches, and complete of TT after 24 months of age increase the risk of enuresis. Only one of the selected studies did not find an association between the start of TT after 24 months of age and the presence of isolated PNE. Three studies did not mention the approach used in the TT process. Most of the articles reviewed showed that prolonged diaper use, delay in the start or completion of the TT and use of coercive approaches increase the risk of enuresis. On the other hand, one study showed no relationship between the start of TT after 24 months of age and the presence of isolated enuresis.


Effect of paracetamol (acetaminophen) on body temperature in acute stroke: A meta-analysis.
The objective of this study was to assess the efficacy of paracetamol (acetaminophen) on body temperature in acute stroke. Medline, Cochrane Central Register of Controlled Trials, EMBASE, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the World Health Organization (WHO) International Clinical Trials Registry Platform were searched electronically. Relevant journals and references of studies included were hand-searched for randomized controlled trials (RCT) and controlled clinical trials (CCT) regarding the efficacy of paracetamol (acetaminophen) on body temperature in acute stroke. Two reviewers independently performed data extraction and quality assessment. Data were analyzed using RevMan 5.3 software by the Cochrane Collaboration. Five studies were included. To compare the efficacy of paracetamol (acetaminophen) in acute stroke, the pooled RR (Risk Ratio) and its 95% CI of body temperature reduction at 24h from the start of treatment were -0.3 (95% CI: -0.52 to -0.08), with statistical significance (P=0.007). Consistently, the pooled RR (Risk Ratio) and its 95% CI of body temperature at 24h from the start of treatment were -0.22 (-0.29, -0.15), with statistical significance (P<0.00001). When analyzing the body temperature reduction after 5days from the start of treatment, the pooled RR (Risk Ratio) and its 95% CI were 0.04 (95% CI: -0.20 to 0.29), with no statistical significance (P=0.73). For functional outcome (mRS≤2) analysis, the pooled RR and its 95% CI were 1.08 (0.88, 1.32), with no statistical significance (P=0.45). In addition, the difference of serious adverse events between acetaminophen and placebo was 0.86 (95% CI: 0.62 to 1.2), with no statistical significance (P=0.27). Acetaminophen was revealed to have some favorable influence in body temperature reduction in acute stroke, but showed no important effect on improving functional outcome and reducing adverse events of patients. What is already known on this subject? Paracetamol (acetaminophen) is one of the most commonly used antipyretic drugs and has some capability to reduce body temperature through acting on central nervous system. Acetaminophen showed some capability to decrease body temperature for acute stroke. Acetaminophen could not improve functional outcome and reduce adverse events of patients with acute stroke.


Oral contraceptive agents: current status.
Oral contraceptives are the most widely prescribed and ingested drug in human history. The difficulty in establishing their clear-cut side effects is compounded by the rarity of these side effects and their occurrence with multiple other factors and cofactors that may be etiologically more important. For the prudent surgeon, suffice it to say that should operation require bedrest postoperatively, oral contraceptives should be stopped at least 2 weeks preoperatively and barrier methods begun. Barrier methods should also be used when drugs that interfere with oral contraceptives are prescribed. Oral contraceptives and anticoagulants should not be given together because of the chemical changes in the blood caused by the steroid content of the contraceptive. As surgeons, we must remember the contraindications noted herein and become familiar with the current literature as new developments unfold in the dynamic field of conception control.


Basic response properties of auditory nerve fibers: a review.
All acoustic information from the periphery is encoded in the timing and rates of spikes in the population of spiral ganglion neurons projecting to the central auditory system. Considerable progress has been made in characterizing the physiological properties of type-I and type-II primary auditory afferents and understanding the basic properties of type-I afferents in response to sounds. Here, we review some of these properties, with emphasis placed on issues such as the stochastic nature of spike timing during spontaneous and driven activity, frequency tuning curves, spike-rate-versus-level functions, dynamic-range and spike-rate adaptation, and phase locking to stimulus fine structure and temporal envelope. We also review effects of acoustic trauma on some of these response properties.


Evaluation of a newly developed tobacco cessation program for people with disabilities.
Tobacco use is the single most preventable cause of morbidity and mortality, accounting for at least 480,000 deaths in the United States annually. People with disabilities smoke at a rate 1.5 times greater than the able-bodied population. Higher incidence of tobacco use among people with disabilities has been directly related to both unique and universal cessation barriers. Despite increased prevalence of tobacco use and cessation obstacles, evidence is lacking on the development of successful interventions targeting people with disabilities. We aimed to assess the feasibility, acceptability, and potential effectiveness of a cessation intervention tailored to people with disabilities. Eighteen tobacco users with disabilities (56% African American, 64% male) participated in a 4-week, 8-session tobacco cessation program consisting of group sessions on managing addiction, relapse, and lifestyle changes specific to people with disabilities. Semi-structured interviews were conducted at the conclusion of the program. A follow-up measure of smoking status, triggers, and nicotine replacement therapy usage was completed at 4 weeks and 6 months. Sixteen participants completed the intervention (89%), with participants on average attending 86% of sessions. Most participants rated the program as excellent (83%) or good (8%). Qualitative interviews revealed participants value social support, accessibility, and a tailored program. Four participants (22%) reported abstinence at six months, which is greater than the standard quit rate. This study suggests tailoring a cessation program to the characteristics unique to people with disabilities may be critical in delivering meaningful and effective cessation interventions among this population.


Malignant fibrous histiocytoma of bone and osteosarcoma. A comparative light and electron microscopic study.
Malignant fibrous histiocytomas are well-described tumors of the soft tissues. Recent investigations have shown that malignant histiocytoma may also occur as a primary bone tumor. However, difficulties may arise to distinguish malignant histiocytoma of bone from other malignant bone tumors, such as osteosarcoma. In the present study, the ultrastructure of five cases of malignant fibrous histiocytoma of bone is compared with that of osteosarcoma. The results show that malignant fibrous histiocytoma is composed mainly of histiocytic cells and fibroblastic cells. In addition, xanthomatous cells, undifferentiated cells, and giant cells may be observed. By contrast, the predominant cell type in osteosarcoma is the neoplastic osteoblast, characterized by abundant rough endoplasmic reticulum. Signs of matrix calcification in the intercellular matrix between the collagen fibrils are regularly observed in osteosarcoma, but not in malignant histiocytoma. From these results it is concluded that the ultrastructure of malignant fibrous histiocytoma arising in bone is morphologically identical with the soft tissue counterpart of this tumor. The components of the tumor are derived from neoplastic histiocytes. This cytogenesis differs from that of osteosarcoma, which is derived from neoplastic osteoblasts. Therefore, from the ultrastructural point of view, malignant fibrous histiocytoma of bone should be accepted as a distinct histologic entity among bone tumors.


Preventing leaf identity theft with hormones.
Genetic analysis of plant development has begun to demonstrate the importance of hormone synthesis and transport in regulating morphogenesis. In the case of leaf development, for example, auxin pooling determines where a primordium will emerge and leads to the activation of transcription factors, which determine leaf identities by modulating abscisic acid (ABA) and gibberellic acid (GA) concentrations. Signal transduction studies suggest that negative regulation of transcription factors through protein turnover is commonly used as a mechanism of hormone action. Together, these findings suggest that auxin might degrade a repressor that allows the activation of genes that modulate ABA/GA ratios in emerging leaves. With our increased understanding of the molecular basis of hormone signaling, it is becoming possible to overlay important regulators onto signaling modules that determine morphological outputs.


Transmission of Pandora neoaphidis in the presence of co-occurring arthropods.
Transmission of the entomopathogenic fungus Pandora neoaphidis to the nettle aphid Microlophium carnosum was assessed in the presence of arthropods that co-exist with the fungus within the habitat but do not compete for aphid hosts. The presence of a parasitoid significantly enhanced transmission, and transmission rates were similar for both enemy and non-enemy parasitoids. Although herbivory of nettle leaves by Peacock butterfly (Inchis io) caterpillars indirectly reduced the number of M. carnosum by >30% due to a reduction in leaf area for feeding, the addition of I. io significantly increased transmission of P. neoaphidis in the remaining aphids. It is likely that enhanced transmission in the presence of A. rhopalosiphii and I. io is due to disturbance and subsequent movement of the aphid, resulting in contact with conidia deposited on the leaf surface. The presence and impact of co-occurring arthropods should be taken into consideration when assessing the transmission of fungal entomopathogens.


Large Congenital Hydrocephalus:Extended Survival without Neurosurgery.
This work was presented at the 57th Quarterly Grand Rounds at Fairview Developmental Center, Costa Mesa, California on October 17, 2012. Authors are grateful to Stephan Reynolds CRT, and Indira Makwana for records. None of the authors has any conflict of interest with the information provided in this article. We report the case of a 45-year-old patient with large congenital hydrocephalus. Patient was born prematurely at 26-weeks' gestation with a weight of 1.14Kg. His head-circumferences have been: Birth, 27.9 cms; age 3-months, 40.6 cms; 18-months, 74 cms; 36-months, 80 cms; current, 88.4 cms (normal adult: 52-58 cms). During infancy, his prognosis was considered "terminal" due to rapid progression of severe hydrocephalus; therefore no neurosurgical intervention was undertaken. At 18-months' age, he was admitted to our developmental center where he is presently comfortable and clinically stable. Due to habitual unilateral decubitus, his head is now markedly flattened on the right (deformational plagiocephaly), and disproportionately long and narrow (scaphocephaly: occipitofrontal length 36.8 cms, biparietal width 12.5; ratio 2.9). We credit patient's extended survival to diligent professional care. PubMed.


[Accelerated atherosclerosis in rheumatoid arthritis].
Cardiovascular manifestations are frequent in rheumatoid arthritis (RA) and significantly contribute to morbidity and mortality in this disorder. Premature atherosclerosis is responsible for these complications, as supported by autopsy studies. Moreover, a high prevalence of sub-clinical atherosclerosis--evaluated by imaging and instrumental parameters--has been reported. Traditional risk factors cannot completely account for accelerated atherosclerosis in RA. The presence of RA by itself and the immunosuppressive therapy (especially corticosteroids) represent non-traditional risk factors for premature atherosclerosis. Additional factors playing a synergistic role in the atherosclerotic process are systemic chronic inflammation frequently associated with RA and both humoral and cellular specific autoimmune responses. Herein we review and discuss atherosclerosis in rheumatoid arthritis, with special emphasis on clinical presentations, pathogenesis and therapy.


Oral delivery of oil-based formulation for a novel synthetic cationic peptide of GnRH (gonadotropin-releasing hormone) antagonist for prostate cancer treatment.
LXT-101, a cationic peptide is a novel antagonist of gonadotropin-releasing hormone (GnRH) for prostate cancer treatment. However, effective delivery of peptide drugs into the body by the oral route remains a major challenge due to their origin properties with high molecular weights, strong polarity and low stability in the gastrointestinal (GI) tract. In this study, we have developed a novel oral delivery of oil-based formulation in which therapeutic peptide LXT-101 are solubilized in oils and with this solution as oil phase, an optimum formulation of self-microemulsifying drug delivery system (SMEDDS) was developed. The peptide stability with the SMEDDS formulation in artificial gastric and intestinal fluid was tested in vitro. On the other hand, the testosterone level and plasma concentration of LXT-101 in rats after oral administration of the SMEDDS formulation were investigated in vivo. The data in vitro indicated that LXT-101 in the SMEDDS formulation was stable over 8 h in artificial gastric and intestinal fluid. LXT-101 can be absorbed in vivo and suppression of testosterone maintained in castration level within 12 h can be achieved effectively after SMEDDS formulation administered orally at a dose of 3.5 mg/kg. The approach can provide a potential way for delivery peptides by oral.


Galectin-1 promotes gastric cancer peritoneal metastasis through peritoneal fibrosis.
Peritoneal metastasis is one of the main causes of death in patients with gastric cancer (GC). Galectin-1 regulates various undesirable biological behaviors in GC and may be key in GC peritoneal metastasis. In this study, we elucidated the regulatory role of galectin-1 in GC cell peritoneal metastasis. GC and peritoneal tissues underwent hematoxylin-eosin (HE), immunohistochemical (IHC), and Masson trichrome staining to analyze the difference in galectin-1 expression and peritoneal collagen deposition in different GC clinical stages. The regulatory role of galectin-1 in GC cell adhesion to mesenchymal cells and in collagen expression was determined using HMrSV5 human peritoneal mesothelial cells (HPMCs). Collagen and corresponding mRNA expression were detected with western blotting and reverse transcription PCR, respectively. The promoting effect of galectin-1 on GC peritoneal metastasis was verified in vivo. Collagen deposition and collagen I, collagen III, and fibronectin 1 (FN1) expression in the peritoneum of the animal models were detected by Masson trichrome and IHC staining. Galectin-1 and collagen deposition in the peritoneal tissues was correlated with GC clinical staging and were positively correlated. Galectin-1 enhanced the ability of GC cells to adhere to the HMrSV5 cells by promoting collagen I, collagen III, and FN1 expression. The in vivo experiments confirmed that galectin-1 promoted GC peritoneal metastasis by promoting peritoneal collagen deposition. Galectin-1-induced peritoneal fibrosis may create a favorable environment for GC cell peritoneal metastasis.


Observing Atoms at Work by Controlling Beam-Sample Interactions.
Functional behavior can be initiated and captured in series of images with previously unknown details using a successful effort to effectively control beam-sample interactions in high-resolution transmission electron microscopy. The approach uses tunable electron dose rates that can be chosen to be as low as attoamperes per square-Ångstrom to delay sample degradation to an unexplored end. Dose rates can be systematically increased to stimulate and observe dynamic object responses. Observations can be made in real time with deep sub-Ångstrom resolution and single-atom sensitivity, even if radiation-sensitive matter is probed and either pressure or temperature is raised in the electron microscope.


[Subphrenic abscess and suppurative pericarditis as complications in children with perforated appendicitis].
The combination of subphrenic abscess with purulent pericarditis is a rare postoperative complication of perforated appendicitis in children, with severe clinical course, difficult to diagnose and high case fatality rate. A 7-year-old child with this complication, successfully diagnosed and treated is reported. The importance of complex therapy--surgical and intensive and collaboration between pediatric surgeons, anesthesiologists, cardiac surgeons and cardiologists for the favourable outcome is emphasized.


Ageist comments by colleagues need to be challenged.
I was horrified to read about a senior nurse leaving because of colleagues' unkind ageist comments in 'Age discrimination by fellow nurses is forcing me to leave' (letters, April 27).


Enhanced Scenedesmus sp. growth in response to gibberellin secretion by symbiotic bacteria.
Microalgae usually co-exist with bacteria, which may influence the microalgal growth, in aquatic environment. In this study, thirteen strains that can promote microalgal growth were isolated from Scenedesmus sp. LX1 culture. Additional results showed that these strains could secrete gibberellin (GA), which is a phytohormones, promoting the growth and metabolism of the Scenedesmus sp. LX1. Low concentration (0.1 mg L-1) of GA can increase the microalgae biomass by 51% after 4 days. GA could enhance the photosynthetic activity by increasing the photosynthetic pigment content, such as culture after 2 h with low GA concentration (0.1 mg L-1), chlorophyll a and β-carotene increased from 0.59 μg per 106 cells to 0.72 μg per 106 cells and from 0.20 μg per 106 cells to 0.38 μg per 106 cells, respectively. In addition, GA could also stimulate the dehydrogenase activity, ATP accumulation, and carbonic anhydrase activity to increase the metabolic activity of the microalgae. Interestingly, the microalgae can selectively enhance the bacterial GA secretion in turn, indicating that there was a specific feedback regulation mechanism between the microalgae and the bacteria. The results of this study show a new mechanism of symbiotic-bacteria that enhances microalgal growth. It's a great significance to understand the microalgal growth and water bloom in aquatic environment.


How do old dogs learn new tricks: teaching a technological skill to brain injured people.
Little is known about the way people learn technological skills. This investigation was carried out to see how 100 brain injured, 50 controls and two amnesic patients performed on a task requiring them to learn a six-step programme for an electronic memory aid. Performance was correlated with other measures of memory to determine whether the technological skill was similar to a procedural learning task, a spatial memory task, a visual task, a verbal task or an amalgam of these. All controls but only 59 percent of the patients learned the task within three trials. The two amnesic patients also failed to learn the new skill. There was a high correlation between overall performance on a standardized test of everyday memory (the Rivermead Behavioural Memory Test) but little evidence that the technological skill was similar to a procedural learning task; nor was it specifically related to visual, verbal or spatial memory. It is concluded that a combination of skills is required to learn the technological task. Implications for the concept of procedural learning are discussed.


Visible light photoactivity of Polypropylene coated Nano-TiO2 for dyes degradation in water.
The use of Polypropylene as support material for nano-TiO2 photocatalyst in the photodegradation of Alizarin Red S in water solutions under the action of visible light was investigated. The optimization of TiO2 pastes preparation using two commercial TiO2, Aeroxide P-25 and Anatase, was performed and a green low-cost dip-coating procedure was developed. Scanning electron microscopy, Atomic Force Microscopy and X-Ray Diffraction analysis were used in order to obtain morphological and structural information of as-prepared TiO2 on support material. Equilibrium and kinetics aspects in the adsorption and successive photodegradation of Alizarin Red S, as reference dye, are described using polypropylene-TiO2 films in the Visible/TiO2/water reactor showing efficient dyes degradation.


Identification of Central Symptoms in Depression of Older Adults With the Geriatric Depression Scale Using Network Analysis and Item Response Theory.
This study aimed to identify the central symptoms of late-life depression using network analysis and the item response theory. A total of 3,472 older adults were enrolled and the Geriatric Depression Scale-15 (GDS-15) was used to evaluate the depressive symptoms. To identify the central symptoms and the network structures among the individual symptoms, the analyses of symptom network structures and item response theory were performed. Among items on the GDS-15, "Happy," "Hopeless," "Empty," "Bored," "Worthless," and "Good spirits" showed significantly higher strength centrality than the other symptoms. Among all the edges, the edge between "Empty" and "Bored" was the strongest; however, these two symptoms were not connected strongly to other symptoms. In the analysis of item response theory, "Empty," "Bored," "Hopeless," "Worthless," "Happy," "Helpless," and "Satisfied" presented a very high value on the discrimination parameter. Our study identified the central symptoms and the network structures among symptoms listed on the GDS-15. Most of central symptoms identified by network analysis and item response theory coincided. Our results suggest that these central symptoms need to be prioritized as highly comorbid symptoms and can contribute to the development of a brief screening tool for the elderly.


Antibody response to infection in multiple myeloma. Implications for vaccination.
We report the humoral immune response of a patient with multiple myeloma to rapidly successive episodes of meningococcal and pneumococcal meningitis. Specific antibody responses included a high bactericidal titer (1:640) against the infecting meningococcus and a sharp increase (from 198 to 8,097 ng/ml antibody nitrogen) in antibody to the type-specific capsular polysaccharide of the infecting pneumococcus. These data, showing the production of protective antibodies against the two pathogens, suggest that some patients with multiple myeloma might also respond to appropriately administered bacterial vaccines. This fact should be ascertained because vaccination could potentially reduce the high rate of bacterial infections associated with this disease.


Baclofen (Lioresal) intoxication report of 4 cases and review of the literature.
4 cases of baclofen intoxication were reported to the Vienna Poison Information Center during the years 1974-1982. These cases are presented and are discussed along with previously published cases of baclofen intoxication. A review of symptomatology and therapy is given.


Evaluation of the average of patients: application to endocrine assays.
Recent work (Cembrowski et al, Am J Clin Pathol 1984;81:492-499) has shown that the average of selected patient data can theoretically be used to demonstrate systematic errors. We formerly demonstrate that the sensitivity or power of the 'average of patients' (AOP) is related to the index (NpSw2)/Sp2 where Np is the number of patient results averaged, Sw the within-run component of the standard deviation of the analytical method and Sp the standard deviation of the trimmed population. The utility of the AOP can therefore be assessed rapidly without power function curves or the calculation of the daily AOP itself. The index showed that, for 12 radioimmunoassays done in our laboratory, the power of the AOP was greatest for T3 uptake, then FTI, then T4. Daily AOP were followed for these tests with control results on parallel Shewhart plots. We also applied an exponential smoothing procedure on the AOP and control results to improve trend detection. These analyses demonstrated that the AOP can improve the detection of systematic errors and the differentiation of true errors from errors affecting only control specimens.


Comparison of diafiltration and size-exclusion chromatography to recover hemicelluloses from process water from thermomechanical pulping of spruce.
Hemicelluloses constitute one of the most abundant renewable resources on earth. To increase their utilization, the isolation of hemicelluloses from industrial biomass side-streams would be beneficial. A method was investigated to isolate hemicelluloses from process water from a thermomechanical pulp mill. The method consists of three steps: removal of solids by microfiltration, preconcentration of the hemicelluloses by ultrafiltration, and purification by either size-exclusion chromatography (SEC) or diafiltration. The purpose of the final purification step is to separate hemicelluloses from small oligosaccharides, monosaccharides, and salts. The ratio between galactose, glucose, and mannose in oligo- and polysaccharides after preconcentration was 0.8:1:2.8, which is similar to that found in galactoglucomannan. Continuous diafiltration was performed using a composite fluoro polymer membrane with cutoff of 1000 Da. After diafiltration with four diavolumes the purity of the hemicelluloses was 77% (gram oligo- and polysaccharides/gram total dissolved solids) and the recovery was 87%. Purification by SEC was performed with 5, 20, and 40% sample loadings, respectively and a flow rate of 12 or 25 mL/min (9 or 19 cm/h). The purity of hemicelluloses after SEC was approx 82%, and the recovery was above 99%. The optimal sample load and flow rate were 20% and 25 mL/min, respectively. The process water from thermomechanical pulping of spruce is inexpensive. Thus, the recovery of hemicelluloses is not of main importance. If the purity of 77%, obtained with diafiltration, is sufficient for the utilization of the hemicelluloses, diafiltration probably offers a less expensive alternative in this application.


N-(2,3,5,6-Tetrafluoropyridin-4-yl)formamide.
The title compound, C6H2F4N2O, displays amide bond lengths of 1.218 (3) Å and 1.366 (3) Å for the C=O and C-N bonds, respectively. The Cp-N-C-O (p = pyridine) torsion angle of 179.0 (2)° indicates an anti-conformation for the grouping. Inter-molecular hydrogen bonding is observed between the amine N-H group and the carbonyl O atom, which generates chains of mol-ecules propagating along the b-axis direction.


In vitro model of bone to facilitate measurement of adhesion forces and super-resolution imaging of osteoclasts.
To elucidate processes in the osteoclastic bone resorption, visualise resorption and related actin reorganisation, a combination of imaging technologies and an applicable in vitro model is needed. Nanosized bone powder from matching species is deposited on any biocompatible surface in order to form a thin, translucent, smooth and elastic representation of injured bone. Osteoclasts cultured on the layer expressed matching morphology to ones cultured on sawed cortical bone slices. Resorption pits were easily identified by reflectance microscopy. The coating allowed actin structures on the bone interface to be visualised with super-resolution microscopy along with a detailed interlinked actin networks and actin branching in conjunction with V-ATPase, dynamin and Arp2/3 at actin patches. Furthermore, we measured the timescale of an adaptive osteoclast adhesion to bone by force spectroscopy experiments on live osteoclasts with bone-coated AFM cantilevers. Utilising the in vitro model and the advanced imaging technologies we localised immunofluorescence signals in respect to bone with high precision and detected resorption at its early stages. Put together, our data supports a cyclic model for resorption in human osteoclasts.


Single Ion-Channel Analysis in Droplet Interface Bilayer.
Droplet interface bilayer (DIB) is a method of fabricating lipid bilayer membrane by contacting two aqueous droplets coated with a monolayer of lipid molecules in oil media. Lipids coat the droplet surface either by vesicles fusing to the water-oil interface from the droplet side or diffusing toward the interface from the oil side, thereby forming a lipid monolayer. With the DIB technique, nanoliter amounts of aqueous solution is needed and one may obtain two different compositions of monolayers to form asymmetric bilayer which is difficult to replicate by other in vitro lipid membrane methods. Here, a DIB-based protocol is reported to fabricate a stable lipid bilayer membrane to perform single-channel electrophysiology on a pore-forming toxin.


Cloning and expression of three new Aazotobacter vinelandii genes closely related to a previously described gene family encoding mannuronan C-5-epimerases.
The cloning and expression of a family of five modular-type mannuronan C-5-epimerase genes from Azotobacter vinelandii (algE1 to -5) has previously been reported. The corresponding proteins catalyze the Ca2+-dependent polymer-level epimerization of beta-D-mannuronic acid to alpha-L-guluronic acid (G) in the commercially important polysaccharide alginate. Here we report the identification of three additional structurally similar genes, designated algE6, algE7, and algY. All three genes were sequenced and expressed in Escherichia coli. AlgE6 introduced contiguous stretches of G residues into its substrate (G blocks), while AlgE7 acted as both an epimerase and a lyase. The epimerase activity of AlgE7 leads to formation of alginates with both single G residues and G blocks. AlgY did not display epimerase activity, but a hybrid gene in which the 5'-terminal part was exchanged with the corresponding region in algE4 expressed an active epimerase. Southern blot analysis of genomic A. vinelandii DNA, using the 5' part of algE2 as a probe, indicated that all hybridization signals originated from algE1 to -5 or the three new genes reported here.


Late-onset Pompe disease associated with polyneuropathy.
Late-onset Pompe disease is caused by a glycogen deposition involving mainly striated muscle. It may also target many other tissues such as liver, smooth muscles or spine anterior horn. Glycogen accumulation in Schwann cells and in the perineurium of peripheral nerves was shown in Pompe's disease mouse models. Moreover two late-onset Pompe disease patients were reported as having a small fiber neuropathy. To the best of our knowledge an involvement of large nerve fibers was never depicted. We describe four late-onset Pompe disease patients having a concomitant polyneuropathy of undetermined etiology. Our observations reinforce the proof-of-concept supporting a potential involvement of peripheral nerves as additional organ targeted by late-onset Pompe disease. It has clinical care consequences since peripheral neuropathy in late-onset Pompe disease could worsen patient's disability and needs particular care such as proprioceptive physiotherapy.


Neurotrophic factors as a therapeutic target for Parkinson's disease.
The search for therapeutic agents that might alter the disease course in Parkinson's disease (PD) is ongoing. One area of particular interest involves neurotrophic factors (NTFs), with those of the glial cell line-derived neurotrophic factor (GDNF) family showing greatest promise. The safety and efficacy of these therapies has recently come into question. Furthermore, many of the key questions pertaining to such therapies, such as the optimal method of delivery, timing of treatment and selection of patients most likely to benefit, remain unanswered. In this review we sought to evaluate the therapeutic potential of NTFs in the treatment of PD. We appraised the evidence provided by both in vitro and in vivo work before proceeding to a critical assessment of the relevant clinical trial data. Relevant literature was identified using a PubMed search of articles published up to October 2007. Search terms included: 'Parkinson's disease', 'Neurotrophic factors', 'BDNF' (Brain-derived neurotrophic factor), 'GDNF' and 'Neurturin'. Original articles were reviewed, and relevant citations from these articles were also appraised. NTF therapy has potential in the treatment of nigrostriatal dysfunction in PD but numerous methodological and safety issues will need to be addressed before this approach can be widely adopted. Furthermore PD is now recognized as being more than a pure motor disorder, and one in which neuronal loss is not just confined to the dopaminergic nigrostriatal system. Non-motor symptomatology in PD is unlikely to benefit from therapies that target only the nigrostriatal system, and this must inform our thinking as to the maximal achievable benefit that NTFs are ever likely to provide.


Glucose alters rat liver S9-mediated mutagenesis, metabolism and DNA-binding of aflatoxin B1.
The administration of 30% glucose in drinking water to rats for 48 h caused a significant increase in the hepatic S9-mediated mutagenicity of aflatoxin B1, in Salmonella typhimurium TA100 and in the binding of alfatoxin B1, to calf thymus DNA in vitro. These effects correlated with a reduction in the metabolism and detoxification of aflatoxin B1, by S9 from glucose-treated rats and suggest that the oral intake of sugar may affect the hepatocarcinogenicity of aflatoxin B1.


Computed tomography demonstration of a hypothalamic metastasis.
This case report describes a patient who presented with panhypopituitarism secondary to hypothalamic metastasis. A primary hypothalamic abnormality was suggested by computed tomographic (CT) demonstration of a small enhancing circular mass centered within the hypothalamus. Sellar radiographs and cerebral angiography were normal.


[Transbronchial needle aspiration of hilar and mediastinal lymph nodes].
Besides clarifying the etiology of unidentified lymphadenomegaly, puncturing hilar and mediastinal lymph nodes by a flexible bronchoscopic needle is an aid in diagnosing and staging broncho- genic cancer or other metastatic cancers. Our study had the principal objective to evaluate the positivity of transbronchial needle aspiration (TBNA). We evaluated retrospectively the effectiveness of all TBNA done in 74 consecutive patients. Forty-nine patients were male and the median age was 59. We used Wang-needles, 21-gauge (Bard, USA), and the same technique described for different authors. Of the 74 patients evaluated, 11(15%) showed mediastinal mass and 65 (85%) hilar mass. We observed 76 endoscopic abnormalities. According to the classification of the specimens, we had 32/74 (43%) unsatisfactory specimens, 34/74 (46%) satisfactory and diagnostic specimens, and 8/74(11%) satisfactory and non-diagnostic specimens. Thirty four (46%) of the examinations were found to be positive out of the total amount of specimens. Of the positive results, 30/34 specimens (88%) contained malignant disease. Small-cell carcinoma was the most frequent finding, with 10/34 cases (29%); squamous cell carcinoma 7/34 (21%); adenocarcinoma 7/34 (21%), non- -small cell carcinoma 6/34 (17%); sarcoidosis 2/34 (6%) and tuberculosis 2/34 (6%). Our study indicated that this method is safe, easy to per- form, with a minimum of complications and useful for the diagnosis and staging of pulmonary neoplasms.


Stand-Alone Personalized Normative Feedback for College Student Drinkers: A Meta-Analytic Review, 2004 to 2014.
Norms clarification has been identified as an effective component of college student drinking interventions, prompting research on norms clarification as a single-component intervention known as Personalized Normative Feedback (PNF). Previous reviews have examined PNF in combination with other components but not as a stand-alone intervention. To investigate the degree to which computer-delivered stand-alone personalized normative feedback interventions reduce alcohol consumption and alcohol-related harms among college students and to compare gender-neutral and gender-specific PNF. Electronic databases were searched systematically through November 2014. Reference lists were reviewed manually and forward and backward searches were conducted. Outcome studies that compared computer-delivered, stand-alone PNF intervention with an assessment only, attention-matched, or active treatment control and reported alcohol use and harms among college students. Between-group effect sizes were calculated as the standardized mean difference in change scores between treatment and control groups divided by pooled standard deviation. Within-group effect sizes were calculated as the raw mean difference between baseline and follow-up divided by pooled within-groups standard deviation. Eight studies (13 interventions) with a total of 2,050 participants were included. Compared to control participants, students who received gender-neutral (dbetween = 0.291, 95% CI [0.159, 0.423]) and gender-specific PNF (dbetween = 0.284, 95% CI [0.117, 0.451]) reported greater reductions in drinking from baseline to follow-up. Students who received gender-neutral PNF reported 3.027 (95% CI [2.171, 3.882]) fewer drinks per week at first follow-up and gender-specific PNF reported 3.089 (95% CI [0.992, 5.186]) fewer drinks. Intervention effects were small for harms (dbetween = 0.157, 95% CI [0.037, 0.278]). Computer-delivered PNF is an effective stand-alone approach for reducing college student drinking and has a small impact on alcohol-related harms. Effects are small but clinically relevant when considered from a public health perspective. Additional research is needed to examine computer-delivered, stand-alone PNF as a population-level prevention program.


Automated antigen assays display a high heterogeneity for the detection of SARS-CoV-2 variants of concern, including several Omicron sublineages.
Diagnostic tests for direct pathogen detection have been instrumental to contain the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Automated, quantitative, laboratory-based nucleocapsid antigen (Ag) tests for SARS-CoV-2 have been launched alongside nucleic acid-based test systems and point-of-care (POC) lateral-flow Ag tests. Here, we evaluated four commercial Ag tests on automated platforms for the detection of different sublineages of the SARS-CoV-2 Omicron variant of concern (VoC) (B.1.1.529) in comparison with "non-Omicron" VoCs. A total of 203 Omicron PCR-positive respiratory swabs (53 BA.1, 48 BA.2, 23 BQ.1, 39 XBB.1.5 and 40 other subvariants) from the period February to March 2022 and from March 2023 were examined. In addition, tissue culture-expanded clinical isolates of Delta (B.1.617.2), Omicron-BA.1, -BF.7, -BN.1 and -BQ.1 were studied. These results were compared to previously reported data from 107 clinical "non-Omicron" samples from the end of the second pandemic wave (February to March 2021) as well as cell culture-derived samples of wildtype (wt) EU-1 (B.1.177), Alpha VoC (B.1.1.7) and Beta VoC (B.1.351)). All four commercial Ag tests were able to detect at least 90.9% of Omicron-containing samples with high viral loads (Ct < 25). The rates of true-positive test results for BA.1/BA.2-positive samples with intermediate viral loads (Ct 25-30) ranged between 6.7% and 100.0%, while they dropped to 0 to 15.4% for samples with low Ct values (> 30). This heterogeneity was reflected also by the tests' 50%-limit of detection (LoD50) values ranging from 44,444 to 1,866,900 Geq/ml. Respiratory samples containing Omicron-BQ.1/XBB.1.5 or other Omicron subvariants that emerged in 2023 were detected with enormous heterogeneity (0 to 100%) for the intermediate and low viral load ranges with LoD50 values between 23,019 and 1,152,048 Geq/ml. In contrast, detection of "non-Omicron" samples was more sensitive, scoring positive in 35 to 100% for the intermediate and 1.3 to 32.9% of cases for the low viral loads, respectively, corresponding to LoD50 values ranging from 6181 to 749,792 Geq/ml. All four assays detected cell culture-expanded VoCs Alpha, Beta, Delta and Omicron subvariants carrying up to six amino acid mutations in the nucleocapsid protein with sensitivities comparable to the non-VoC EU-1. Overall, automated quantitative SARS-CoV-2 Ag assays are not more sensitive than standard rapid antigen tests used in POC settings and show a high heterogeneity in performance for VoC recognition. The best of these automated Ag tests may have the potential to complement nucleic acid-based assays for SARS-CoV-2 diagnostics in settings not primarily focused on the protection of vulnerable groups. In light of the constant emergence of new Omicron subvariants and recombinants, most recently the XBB lineage, these tests' performance must be regularly re-evaluated, especially when new VoCs carry mutations in the nucleocapsid protein or immunological and clinical parameters change.


Analysis of Photoprotection and Apparent Non-photochemical Quenching of Chlorophyll Fluorescence in Tradescantia Leaves Based on the Rate of Irradiance-Induced Changes in Optical Transparence.
The kinetics of irradiation-induced changes in leaf optical transparence (ΔT) and non-photochemical quenching (NPQ) of chlorophyll fluorescence in Tradescantia fluminensis and T. sillamontana leaves adapted to different irradiance in nature was analyzed. Characteristic times of a photoinduced increase and a dark decline of ΔT in these species were 12 and 20 min, respectively. The ΔT was not confirmed to be the main contributor to the observed middle phase of NPQ relaxation kinetics (τ = 10-28 min). Comparison of rate of photoinduced increase in ΔT and photosystem II quantum yield recovery showed that the former did not affect the tolerance of the photosynthetic apparatus (PSA) to irradiances up to 150 µmol PAR·m-2·s-1. Irradiance tolerance correlated with the rate of "apparent NPQ" induction. Considering that the induction of apparent NPQ involves processes significantly faster than ΔT, we suggest that the photoprotective mechanism induction rate is crucial for tolerance of the PSA to moderate irradiance during the initial stage of light acclimation (first several minutes upon the onset of illumination).


Comparison of methods for evaluating bacterial contamination of ultrasound probes.
To determine suitable methods for evaluating bacterial contamination of ultrasound probes. We compared probe imprinting, swab streaking, and swab suspension methods for evaluating bacterial contamination of ultrasound probes. Experimental and clinical investigations showed that the sensitivity for detecting bacterial contamination of ultrasound probes was higher with probe imprinting than with swab methods. Probe imprinting was very simple and required only agar plates. Probe imprinting was the most suitable method for evaluating bacterial contamination of ultrasound probes.