Mesoporous, Three-Dimensional Wood Membrane Decorated with Nanoparticles for Highly Efficient Water Treatment.
Wood, an earth-abundant material, is widely used in our everyday life. With its mesoporous structure, natural wood is comprised of numerous long, partially aligned channels (lumens) as well as nanochannels that stretch along its growth direction. This wood mesostructure is suitable for a range of emerging applications, especially as a membrane/separation material. Here, we report a mesoporous, three-dimensional (3D) wood membrane decorated with palladium nanoparticles (Pd NPs/wood membrane) for efficient wastewater treatment. The 3D Pd NPs/wood membrane possesses the following advantages: (1) the uniformly distributed lignin within the wood mesostructure can effectively reduce Pd(II) ions to Pd NPs; (2) cellulose, with its abundant hydroxyl groups, can immobilize Pd NPs; (3) the partially aligned mesoporous wood channels as well as their inner ingenious microstructures increase the likelihood of wastewater contacting Pd NPs decorating the wood surface; (4) the long, Pd NP-decorated channels facilitate bulk treatment as water flows through the entire mesoporous wood membrane. As a proof of concept, we demonstrated the use and efficiency of a Pd NPs/wood membrane to remove methylene blue (MB, C16H18N3ClS) from a flowing aqueous solution. The turnover frequency of the Pd NPs/wood membrane, ∼2.02 molMB·molPd-1·min-1, is much higher than the values reported in the literature. The water treatment rate of the 3D Pd NPs/wood membrane can reach 1 × 105 L·m-2·h-1 with a high MB removal efficiency (>99.8%). The 3D mesoporous wood membrane with partially aligned channels exhibits promising results for wastewater treatment and is applicable for an even wider range of separation applications.


Yeast Transcriptome and In Vivo Hypoxia Detection Reveals Histoplasma capsulatum Response to Low Oxygen Tension.
Although there is growing understanding of the microenvironmental conditions fungal pathogens encounter as they colonize their host, nothing is known about Histoplasma capsulatum's response to hypoxia. Here we characterized hypoxia during murine histoplasmosis using an in vivo hypoxia detection agent, Hypoxyprobe-2 (HP-2); and analyzed H. capsulatum's transcriptional profile in response to in vitro hypoxia. Immunohistopathology and flow cytometry analyses revealed distinct regions of hypoxia during infection. Granuloma cells, enriched with macrophages and T-cells isolated from infected livers were 66-76% positive for HP-2, of which, 95% of macrophages and 55% of T-cells were hypoxic. Although inhibited, H. capsulatum was able to survive under in vitro hypoxic conditions (<1% O2), and restored growth when replaced in normoxia. Next-generation sequencing (RNA-seq) analysis after 24 hours of hypoxia demonstrated a significant increase in NIT50 (swirm domain DNA binding protein), a predicted ABC transporter (ABC), NADPH oxidoreductase (NADP/FAD), and guanine nucleotide exchange factor (RSP/GEF); and other genes with no known designated function. Computational transcription factor binding site analysis predicted human sterol regulatory element binding protein (SREBP) binding sites upstream of NIT50, ABC, NADP/FAD and RSP/GEF. Hypoxia resulted in a time-dependent increase in the H. capsulatum homolog of SREBP, here named Srb1. Srb1 peaked at 8 hours and returned to basal levels by 24 hours. Our findings demonstrate that H. capsulatum encounters and survives severe hypoxia during infection. Additionally, the hypoxic response may be regulated at the level of transcription, and these studies contribute to the understanding of hypoxic regulation and adaptation in H. capsulatum.


Vesicles Cytoplasmic Injection: An Efficient Technique to Produce Porcine Transgene-Expressing Embryos.
The use of vesicles co-incubated with plasmids showed to improve the efficiency of cytoplasmic injection of transgenes in cattle. Here, this technique was tested as a simplified alternative for transgenes delivery in porcine zygotes. To this aim, cytoplasmic injection of the plasmid alone was compared to the injection with plasmids co-incubated with vesicles both in diploid parthenogenic and IVF zygotes. The plasmid pcx-egfp was injected circular (CP) at 3, 30 and 300 ng/μl and linear (LP) at 30 ng/μl. The experimental groups using parthenogenetic zygotes were as follows: CP naked at 3 ng/μl (N = 105), 30 ng/μl (N = 95) and 300 ng/μl (N = 65); Sham (N = 105); control not injected (N = 223); LP naked at 30 ng/μl (N = 78); LP vesicles (N = 115) and Sham vesicles (N = 59). For IVF zygotes: LP naked (N = 44) LP vesicles (N = 94), Sham (N = 59) and control (N = 79). Cleavage, blastocyst and GFP+ rates were analysed by Fisher's test (p < 0.05). The parthenogenic CP naked group showed lower cleavage respect to control (p < 0.05). The highest concentration of plasmids to allow development to blastocyst stage was 30 ng/μl. There were no differences in DNA fragmentation between groups. The parthenogenic LP naked group resulted in high GFP rates (46%) and also allowed the production of GFP blastocysts (33%). The cytoplasmic injection with LP vesicles into parthenogenic zygotes allowed 100% GFP blastocysts. Injected IVF showed higher cleavage rates than control (p < 0.05). In IVF zygotes, only the use of vesicles produced GFP blastocysts. The use of vesicles co-incubated with plasmids improves the transgene expression efficiency for cytoplasmic injection in porcine zygotes and constitutes a simple technique for easy delivery of plasmids.


Glucocorticoids inhibit cell death in ovarian cancer and up-regulate caspase inhibitor cIAP2.
Almost all patients with epithelial ovarian cancer receive chemotherapy and, concurrently, the synthetic steroid hormone dexamethasone to alleviate the side effects. This study aims to test the impact of steroid hormones on the apoptosis of epithelial ovarian cancer cells and to identify its mediators. Tumor cell lines from 19 patients with advanced epithelial ovarian cancer were analyzed for glucocorticoid receptor, estrogen receptor, progesterone receptor, and androgen receptor expression. Cells were incubated with corresponding steroid hormones at serum-equivalent doses in hormone-depleted medium. Apoptosis was induced by application of tumor necrosis factor-related apoptosis-inducing ligand or staurosporine and determined by poly(ADP-ribose)polymerase cleavage and cell survival. Microarray with 8K cDNA chips including apoptosis-relevant genes was used to study genes regulated by glucocorticoids. In cell culture, tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in OV-MZ-30 and OV-MZ-31 cells was reduced after treatment with dexamethasone or cortisol, but not with estradiol, progesterone, or androstenedione. Microarray analysis revealed a 7-fold up-regulation of the caspase inhibitor cIAP2 by dexamethasone in OV-MZ-30 and OV-MZ-31 cells. cIAP2 up-regulation by glucocorticoids was confirmed by RT-PCR and Western blot analysis in OV-MZ-30, OV-MZ-31, OV-CAR3, and SK-OV-3 cells. Down-regulation of cIAP2 expression by small interfering RNA sensitized SK-OV-3 cells to apoptosis inducer staurosporine. Under clinical conditions, treatment with dexamethasone was associated with significant up-regulation of cIAP2 in the ascites cells. Activation of the glucocorticoid receptor in epithelial ovarian cancer cells caused an anti-apoptotic effect associated with the enhanced cellular expression level of cIAP2. Dexamethasone pretreatment of epithelial ovarian cancer patients receiving apoptosis-inducing chemotherapy raises questions about a negative effect on antitumor efficacy.


Structural and Topological Evolution in SixSe1-x Glasses: Results from 1D and 2D 29Si and 77Se NMR Spectroscopy.
The coordination environments of Si and Se atoms and their connectivity in binary SixSe1-x glasses with 0.05 ≤ x ≤ 0.33 are investigated using a combination of one- and two-dimensional 29Si and 77Se nuclear magnetic resonance (NMR) and Raman spectroscopy. The high-resolution correlated isotropic and anisotropic 29Si and 77Se NMR spectra allow for the identification and quantitation of a variety of Si and Se environments. The results suggest that the structure of these glasses are characterized by a network with essentially perfect short-range chemical order, but with strong clustering at the intermediate range. Initial addition of Si to Se results in cross-linking of Se chain segments with nanoclusters of corner- and edge-shared SiSe4/2 tetrahedra. These clusters percolate via coalescence near x ≥ 0.2 to finally form a low-dimensional network with high molar volume, at the stoichiometric composition (x = 0.33) that is composed of chains of edge-sharing tetrahedra cross-linked by corner-shared tetrahedra. This structural evolution is shown to be consistent with the compositional variation of the glass transition temperature and the molar volume of these glasses.


Insulin Allergy to Detemir Followed by Rapid Onset of Diabetic Ketoacidosis: A Case Report and Literature Review.
The management of diabetes mellitus in an insulin-dependent patient is challenging in the setting of concomitant antibody-mediated-insulin hypersensitivity. We report a case of a 62-year-old woman with pre-existing type 2 diabetes mellitus of 10 years duration who developed type 3 hypersensitivity reaction to insulin analogue detemir, and subsequently, severe diabetic ketoacidosis (DKA). She was C-peptide negative and was diagnosed with insulin-dependent diabetes. Despite increasing dose adjustments, insulin-meal matching, and compliance with insulin, she experienced episodes of unexpected hyperglycaemia and hypoglycaemia. The development of rash after detemir initiation and rapid progression to DKA suggests an aberrant immune response leading to the insulin allergy and antibody-induced interference with insulin analogues. Glycaemic control in the patient initially improved after being started on subcutaneous insulin infusion pump with reduced insulin requirements. However, after a year on pump therapy, localised insulin hypersensitivity reactions started, and glycaemic control gradually deteriorated.


What information do parents want from the antenatal consultation?
To explore whether the information content, process and social interaction of the antenatal consultation satisfies the informational needs of women admitted to hospital in preterm and threatened preterm labour. Fifty women with pregnancies of gestational ages of between 25 and 32 weeks were admitted to a tertiary care perinatal referral centre and provided with an antenatal consultation about the medical risks and treatments relative to their potentially premature infant. Within 48 h following the consultation, patients were asked to respond to a questionnaire to assess their recall of the information provided, their information expectations and their anxiety level. The majority of respondents (92%) thought that the antenatal consultation increased their knowledge and understanding of what might happen if their infant was born preterm. Although the mean state anxiety score was high, 78% agreed that the consultation relieved some of their worry and anxiety about their baby. In rank order, respondents wanted information about chances of survival, likely medical problems and the risk for disability, followed by medical treatments and breastfeeding. They consistently recalled receiving information about chances of survival, likely medical problems and medical treatments. Following the antenatal consultation, respondents were generally satisfied with the information provided but remained highly anxious. Recall of the discussion about disability was inconsistent. They reported needing an opportunity to express their feelings, and to talk about their baby and their anticipated interaction with their baby. Recognizing these aspects can help to improve physician-patient communication.


Experimental Study on the Central Mechanism of Penehyclidine Hydrochloride against Relapse Behavior in Morphine-Dependent Rats.
This article is mainly to study the central mechanism of penehyclidine hydrochloride against relapse behavior in morphine-dependent rats. The rats were randomly divided into the blank control group (k), PHC low-dose group (LP according to a body weight of 0.22 mg/kg), middle-dose group (MP according to a body weight of 0.55 mg/kg), high-dose group (HP according to a body weight of 1.38 mg/kg), and administration group, with 40 rats in each group. Each group was randomly divided into 5 subgroups (n = 10): 4 h after administration, 7 h after administration, 13 h after administration, 25 h after administration (K48, LP48, MP48, and HP48), and 37 h after administration, and then, Morris water maze experiment and immunohistochemical detection of the rat brain hippocampus were carried out. 4 and 7 hours after administration, compared with group 1, the TchE activity increased and Ach level decreased in groups 2, 3, and 4 and the difference was significant (P < 0.05), so the principle of penehyclidine hydrochloride against morphine-dependent rats is that penehyclidine hydrochloride causes cognitive impairment in the brain of mice, thereby achieving antimorphine effects.


Recent patents in siRNA delivery employing nanoparticles as delivery vectors.
Small interfering RNAs (siRNAs) are rapidly emerging as new therapeutic tools for the treatment of some of the deadly diseases such as cancer. However, poor cellular uptake and instability in physiological milieu limit its therapeutic potential, hence there arises a need of a delivery system which can efficiently and repeatedly deliver siRNA to the target cells. Nanoparticles have shown immense potential as suitable delivery vectors with enhanced efficacy and biocompatibility. These delivery vectors are usually few nanometers in size, which not only protects siRNA against enzymatic degradation but also leads to tissue and cellular targeting. Nanoparticles prepared from various cationic polymers like polyethylenimine, and chitosan have been largely exploited as they bear several advantages such as, ease of manipulation, high stability, low cost and high payload. This review summarizes some of the recent patents on siRNA delivery employing polymer or lipid-based nano-vectors for therapeutic applications.


Rotational therapy with a colchicine analog in chronic granulocytic leukemia.
9 patients with chronic granulocytic leukemia were treated sequentially with busulfan, 6-mercaptopurine, and trimethylcolchicinic acid methyl ether d-tartrate (TMCA; NSC-36354). Smoothness of control of the disease was similar with busulfan and 6-mercaptopurine, but it was significantly poorer with TMCA. Toxic effects of therapy and median survival were similar to those observed with conventional therapy.


Clinician distress in seriously ill patient care: A dimensional analysis.
Caring for patients with serious illness may severely strain clinicians causing distress and probable poor patient outcomes. Unfortunately, clinician distress and its impact historically has received little attention. The purpose of this article was to investigate the nature of clinician distress. Qualitative inductive dimensional analysis. After review of 577 articles from health sciences databases, a total of 33 articles were eligible for analysis. This study did not require ethical review and the authors adhered to appropriate academic standards in their analysis. A narrative of clinician distress in the hospital clinician in the United States emerged from the analysis. This included clinicians' perceptions and sense of should or the feeling that something is awry in the clinical situation. The explanatory matrix consequence of clinician distress occurred under conditions including: the recognition of conflict, the recognition of emotion, or the recognition of a mismatch; followed by a process of an inability to feel and act according to one's values due to a precipitating event. This study adds three unique contributions to the concept of clinician distress by (1) including the emotional aspects of caring for seriously ill patients, (2) providing a new framework for understanding clinician distress within the clinician's own perceptions, and (3) looking at action outside of a purely moral lens by dimensionalizing data, thereby pulling apart what has been socially constructed. For clinicians, learning to recognize one's perceptions and emotional reactions is the first step in mitigating distress. There is a critical need to understand the full scope of clinician distress and its impact on the quality of patient-centered care in serious illness.


Association Between Neighborhood Disadvantage and Functional Well-being in Community-Living Older Persons.
Neighborhood disadvantage is a novel social determinant of health that could adversely affect the functional well-being of older persons. Deficiencies in resource-poor environments can potentially be addressed through social and public health interventions. To evaluate whether estimates of active and disabled life expectancy differ on the basis of neighborhood disadvantage after accounting for individual-level socioeconomic characteristics and other prognostic factors. This prospective longitudinal cohort study included 754 nondisabled community-living persons, aged 70 years or older, who were members of the Precipitating Events Project in south central Connecticut from March 1998 to June 2020. Disability in 4 essential activities of daily living (bathing, dressing, walking, and transferring) was assessed each month. Scores on the Area Deprivation Index, a census-based socioeconomic measure with 17 education, employment, housing quality, and poverty indicators, were obtained through linkages with the 2000 Neighborhood Atlas. Area Deprivation Index scores were dichotomized at the 80th state percentile to distinguish neighborhoods that were disadvantaged (81-100) from those that were not (1-80). Among the 754 participants, the mean (SD) age was 78.4 (5.3) years, and 487 (64.6%) were female. Within 5-year age increments from 70 to 90, active life expectancy was consistently lower in participants from neighborhoods that were disadvantaged vs not disadvantaged, and these differences persisted and remained statistically significant after adjustment for individual-level race and ethnicity, education, income, and other prognostic factors. At age 70 years, adjusted estimates (95% CI) for active life expectancy (in years) were 12.3 (11.5-13.1) in the disadvantaged group and 14.2 (13.5-14.7) in the nondisadvantaged group. At each age, participants from disadvantaged neighborhoods spent a greater percentage of their projected remaining life disabled, relative to those from nondisadvantaged neighborhoods, with adjusted values (SE) ranging from 17.7 (0.8) vs 15.3 (0.5) at age 70 years to 55.0 (1.7) vs 48.1 (1.3) at age 90 years. In this prospective longitudinal cohort study, living in a disadvantaged neighborhood was associated with lower active life expectancy and a greater percentage of projected remaining life with disability. By addressing deficiencies in resource-poor environments, new or expanded social and public health initiatives have the potential to improve the functional well-being of community-living older persons and, in turn, reduce health disparities in the US.


Animal model of thermal injuries.
Experimental studies of burns require the use of different animal models with the aim to imitate and reproduce pathophysiological conditions. The aim of this work was to establish experimental model of thermal injury. New Zealand rabbits, weighted from 1.8 kg to 2.3 kg, were utilised during our study. Another, also utilized, animal types were laboratory Rattus rats, species Wistar, albino type, females with body weight of about 232 g. All animals were from our own litter (Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine in Sarajevo). During the experiment, animal were properly situated in adequate cages and rooms, at the controlled temperature (22 +/- 2 degrees C), and in the air with normal humidity level. All animals took food and water ad libitum. Rabbits received anesthesia--intravenous pentobarbital sodium in a dose of 60 mg/kg, and then, hair from the upper side of the each rabbit ear was removed and burns were caused by a metal seal in the same manner as in rats. Rats were primarily anesthesied by intraperitoneal pentobarbital sodium in a dose of 35 mg/kg, and then, their hair was removed from the scapula zone (5 cm x 5 cm). Burns were caused by contact with a round metal seal, heated at 80 degrees C in a water bath, during the period of 14 seconds together with contact thermometer control. Round metal seal (radius: 2.5 cm; weight: 100 g; surface: 5 cm2) was just placed on the rat skin without any additional pressure. In order to maintain the microcirculation in the burn wound and to reduce the conversion of partial-thickness skin burns to the burns of the full-thickness skin, all burn wounds were immediately sunk in the 4 degrees C water. Subsequent to that procedure, all animals were individually situated in the proper cages, and left to rest for 4 hours with a constant cautious monitoring of the wound development and animal general state.


Respiratory effects of chronic intrathoracic vagotomy in rabbits.
Respiratory variables were recorded in 29 anaesthetized, chronic rabbits after bilateral vagotomy in the chest. The Hering-Breuer reflex was absent. Their breathing frequency was lowered and they became hypoxaemic compared to prevagotomy values. Movements of the vocal cords remained undisturbed and the laryngeal resistances were similar to those in the group of intact rabbits. Laryngeal palsy after midcervical vagotomy in these rabbits increased the tracheal pressures to lower values than in the group of intact, acutely vagotomized rabbits. This demonstrates the less adducted position of the paralyzed vocal cords due to the sequence of denervation steps and consequent glottal aperture proportional to increased respiratory airflow.


Copper Catalyzed One-Pot Three-Component Imination-Alkynylation-aza-Michael Sequence: Enantio- and Diastereoselective Syntheses of 1,3-Disubstituted Isoindolines and Tetrahydroisoquinolines.
An enantio- and diastereoselective syntheses of 1, 3-disubstituted isoindolines and tetrahydroisoquinolines via CuI-Pybox-diPh catalyzed one-pot imination-alkynylation-aza-Michael sequence has been reported. The three-component reaction produces one C-C and two C-N bonds sequentially with high yield (up to 92%), enantioselectivity (up to 99%), and diastereoselectivity (up to 9:1) in a single operation. Furthermore, the synthetic utility of the product has been demonstrated by LiAlH4 reduction of ester and hydrogenation of alkyne functionality without losing the stereoselectivity.


Performance assessment of two lysis methods for direct identification of yeasts from clinical blood cultures using MALDI-TOF mass spectrometry.
In cases of fungal infection of the bloodstream, rapid species identification is crucial to provide adapted therapy and thereby ameliorate patient outcome. Currently, the commercial Sepsityper kit and the sodium-dodecyl sulfate (SDS) method coupled with MALDI-TOF mass spectrometry are the most commonly reported lysis protocols for direct identification of fungi from positive blood culture vials. However, the performance of these two protocols has never been compared on clinical samples. Accordingly, we performed a two-step survey on two distinct panels of clinical positive blood culture vials to identify the most efficient protocol, establish an appropriate log score (LS) cut-off, and validate the best method. We first compared the performance of the Sepsityper and the SDS protocols on 71 clinical samples. For 69 monomicrobial samples, mass spectrometry LS values were significantly higher with the SDS protocol than with the Sepsityper method (P < .0001), especially when the best score of four deposited spots was considered. Next, we established the LS cut-off for accurate identification at 1.7, based on specimen DNA sequence data. Using this LS cut-off, 66 (95.6%) and 46 (66.6%) isolates were correctly identified at the species level with the SDS and the Sepsityper protocols, respectively. In the second arm of the survey, we validated the SDS protocol on an additional panel of 94 clinical samples. Ninety-two (98.9%) of 93 monomicrobial samples were correctly identified at the species level (median LS = 2.061). Overall, our data suggest that the SDS method yields more accurate species identification of yeasts, than the Sepsityper protocol.


The influence of perceptual and knowledge-based familiarity on the neural substrates of face perception.
This study examined the neural substrates of facial familiarity and person-knowledge. Based on current neural models of face perception, it was hypothesized that distinct extended networks of brain regions differentiate the perception of (a) novel faces, (b) novel faces associated with person-knowledge, (c) perceptually familiar faces and (d) familiar faces for which person-knowledge was learned. To test this hypothesis, we conducted an event-related functional magnetic resonance imaging experiment during which participants viewed faces experimentally manipulated to represent these different levels of familiarity. Results confirmed that distinct networks of brain regions, particularly the medial prefrontal cortex, underlie the perception of faces for which person-knowledge is available.


Safety and tolerability of the implantable recurrent laryngeal nerve stimulator.
The recurrent laryngeal nerve (RLN) stimulator has been implanted on a limited basis since 1988 for control of spasmodic dysphonia. A similar vagus nerve stimulator has been implanted in a larger series of patients to control epilepsy. The safety and tolerability of these two stimulators were evaluated. In 113 patients implanted with the vagus nerve stimulator, the complication rate was 0.9%. All patients were monitored for vital signs, electrocardiographic changes, and adverse effects. The absence of changes in vital signs and electrocardiograms during vagal stimulation establishes the safety of this treatment. Since placement of the electrode around the vagus nerve is an easier surgical technique than placement deep to the RLN, it seems reasonable to change the technique to implant the stimulator on the vagus in patients with spasmodic dysphonia.


Lavandula Reduces Heart Injury via Attenuating Tumor Necrosis Factor-Alpha and Oxidative Stress in A Rat Model of Infarct-Like Myocardial Injury.
Lavender is used in herbal medicine for different therapeutic purposes. Nonetheless, potential therapeutic effects of this plant in ischemic heart disease and its possible mechanisms remain to be investigated. In this experimental study, lavender oil at doses of 200, 400 or 800 mg/kg was administered through gastric gavage for 14 days before infarct-like myocardial injury (MI). The carotid artery and left ventricle were cannulated to record arterial blood pressure (BP) and cardiac function. At the end of experiment, the heart was removed and histopathological alteration, oxidative stress biomarkers as well as tumor necrosis factor-alpha (TNF-α) level were evaluated. Induction of M.I caused cardiac dysfunction, increased levels of lipid peroxidation, TNF-α and troponin I in heart tissue (P<0.001). Pretreatment with lavender oil at doses of 200 and 400 mg/kg significantly reduced myocardial injury, troponin I and TNF-α. In addition, it improved cardiac function and antioxidant enzyme activity (P<0.01). Our finding showed that lavender oil has cardioprotective effect through inhibiting oxidative stress and inflammatory pathway in the rat model with infarct-like MI. We suggest that lavender oil may be helpful in prevention or attenuation of heart injury in patients with high risk of myocardial infarction and/or ischemic heart disease.


Intestinal absorption of lysozyme, an egg-white allergen, in rats: kinetics and effect of NSAIDs.
The absorption pathway(s) of a representative food allergen, lysozyme, and the mechanisms of lysozyme absorption facilitated by non-steroidal anti-inflammatory drugs were examined by intestinal closed-loop and re-circulating perfusion methods in rats. The absorption rate of fluorescein isothiocyanate (FITC)-labeled lysozyme in the proximal intestine was higher than that for a marker of non-specific absorption, FD-10, and was suppressed by colchicine (endocytosis inhibitor). Aspirin increased the absorption of FITC-lysozyme in the proximal intestine with no effects on tissue accumulation. Diclofenac facilitated FITC-lysozyme absorption, but meloxicam and loxoprofen exerted no effects on absorption. Co-administration of misoprostol (synthetic prostaglandin-E1 analog) with aspirin significantly ameliorated the aspirin-facilitated absorption of FITC-lysozyme to the same level as that seen with controls. Thus, lysozyme absorption was mediated by endocytic and paracellular pathways in the proximal intestine, and was facilitated by aspirin and diclofenac after impairment of the paracellular pathway. Misoprostol may suppress the allergen absorption facilitated by aspirin.


The Impact of Chronic Urticaria from the Patient's Perspective: A Survey in Five European Countries.
Chronic spontaneous urticaria (CSU) is associated with considerable burden, but data from European patients are limited. This study is a retrospective, cross-sectional analysis of National Health and Wellness Survey data from the five largest EU countries (5EU: France, Germany, Italy, Spain, and the UK) collected between 2010 and 2013. Burden of disease for patients with CSU was estimated by comparing individuals currently treated for chronic urticaria (proxy CSU cases) with controls selected from respondents without chronic urticaria. Matching and regression models were used to quantify the impact of chronic urticaria on health-related quality of life, self-reported psychological complaints, work and activity impairment, and healthcare use. The sample included 175,923 respondents. Prevalence of diagnosed chronic urticaria was 0.5 and 0.2% were treating the condition with a prescription. Cases (N = 369) had substantially lower (worse) regression-adjusted mean Mental Component Summary (40.2 vs. 45.4), Physical Component Summary (44.6 vs. 49.9), and SF-6D health utility scores (0.63 vs. 0.71; all p < 0.001) relative to controls (N = 1476), differences that exceed accepted minimally important differences for these measures. Depression, anxiety, and sleep difficulties were approximately twice as prevalent among those currently receiving treatment for chronic urticaria (all p < 0.001). Cases also had elevated presenteeism (31 vs. 17%), overall work impairment (37 vs. 20%), and impairment in non-work activities (42 vs. 26%; all p < 0.01) relative to controls. Physician visits (9.1 vs. 4.9), emergency room visits (0.8 vs. 0.3), and hospitalizations (0.3 vs. 0.2) were more frequent than in controls (all p < 0.01). This research adds to the existing evidence showing significant burden of CSU.


Expression of basement membrane zone antigens at the dermo-epibolic junction in organ cultures of human skin.
Using the epithelial outgrowth in organ cultures of human skin ("epiboly") as a model system for basement membrane zone neogenesis, the emergence of various antigenic determinants of the junction zone (bullous pemphigoid antigen, type IV collagen and laminin) was studied and the time sequence of their appearance assessed. All 3 antigens were found at the newly built dermo-epibolic junction; their synthesis, however, followed a distinct time sequence: bullous pemphigoid antigens emerged synchronously with the advancing tip of the migrating epithelium, whereas type IV collagen and to a greater extent, laminin, appeared with considerable delay. At the ultrastructural level, the formation of basal lamina accompanied the emergence of type IV collagen and laminin.


[Research on induced differentiation of human bone marrow mesenchymal stem cells into vascular endothelial cells].
To analyze gene expression difference between human mesenchymal stem cells and umbilical vein endothelial cells, to discuss the feasibility of inducing hMSCs to differentiate into endothelial cells through in vitro gene transfection as well as the use and prospective as a seeding cell source of vascular tissue engineering. hMSCs and hUVECs were isolated, expanded in culture, and characterized by flow-cytometry, immunocytochemistry, immunofluorescence and transmission electron microscopy (TEM). Differential analysis of gene expression profiles between them was performed by Biostar H-40 cDNA microarrays. The properties of VEGF 165 transfected were also detected with RT-PCR, ELISA et al. Nearly 86% genes were coexpressed in both cells and hMSCs expressed typical endothelial antigen marker of EC. After VEGF165 transfection, hMSCs (or committed hMSCs) were positive for CD31. To different extent, the expression of CD44 was down regulated and CD34, FVIIIAg, Flt-1 up regulated. Generation of functional EC or tissue engineered blood vessels from human MSCs is feasible utilizing an in vitro environment gene transfection.


Recent advances in veterinary applications of structural vaccinology.
The deployment of effective veterinary vaccines has had a major impact on improving food security and consequently human health. Effective vaccines were essential for the global eradication of Rinderpest and the control and eradication of foot-and-mouth disease in some regions of the world. Effective vaccines also underpin the development of modern intensive food production systems such as poultry and aquaculture. However, for some high consequence diseases there are still significant challenges to develop effective vaccines. There is a strong track record in veterinary medicine of early adoption of new technologies to produce vaccines. Here we provide examples of new technologies to interrogate B cell responses and using structural biology to improve antigens.


Membrane fouling and dialysate flow pattern in an internal filtration-enhancing dialyzer.
For efficient removal of large molecular weight solutes by dialysis, several types of internal filtration-enhancing dialyzers (IFEDs) are commercially available. However, in a pressure-driven membrane separation process (i.e., filtration), membrane fouling caused by adhesion of plasma proteins is a severe problem. The objective of the present study is to investigate the effects of internal filtration on membrane fouling based on the membrane's pure-water permeability, diffusive permeability, and sieving coefficient. Hemodialysis experiments were performed with two different dialyzers, IFEDs and non-IFEDs. Local membrane fouling in each dialyzer was evaluated by measuring the pure-water permeability, the diffusive permeability, and the sieving coefficient of native membranes and membranes treated with bovine blood. The effects of packing ratio on dialysate flow pattern were also evaluated by measuring the time required for an ion tracer to reach electrodes placed in the dialyzers. In the IFED, membrane fouling caused by protein adhesion is increased because of enhanced internal filtration only at the early stage of dialysis, and this fouling tends to occur only near the dialysate outlet port. However, enhanced internal filtration has little effect on measured membrane transfer parameters.


Avian influenza H5N1 in a great white pelican (Pelecanus onocrotalus), Mauritania 2022.
In February 2022, mortalities among great white pelicans (Pelecanus onocrotalus) were reported in the Parc National de Diawling, southwestern Mauritania. Samples were collected and processed, indicating the presence of high pathogenicity avian influenza subtype H5N1. A nearly complete genome was generated for one sample, revealing a high similarity [> 99.5% (H5) nucleotide sequence identity] with Clade 126.96.36.199b H5N1 identified in Europe in 2022.


PS1 Alzheimer's disease family with spastic paraplegia: the search for a gene modifier.
PS1 mutations are associated with classic Alzheimer's disease (AD); however, some families develop AD and spastic paraplegia (SP) with brain pathology characterized by Abeta cotton wool plaques. The authors report a variant AD family with the E280Q PS1 mutation. The fact that the same PS1 mutation can be found in patients with either variant or classic AD argues in favor of the presence of a genetic modifier. The authors have excluded that this modifier effect originates from coding sequence variations in three SP genes or from a second mutation in the other AD genes.


Work from home or office during the COVID-19 pandemic: The different chain mediation models of perceived organizational support to the job performance.
With the coronavirus pandemic in 2019 (COVID-19), work from home (WFH) has become a frequent way of responding to outbreaks. Across two studies, we examined how perceived organizational support influences job performance when employees work in office or work from home. In study 1, we conducted a questionnaire survey of 162 employees who work in office. In study 2, we conducted a questionnaire survey of 180 employees who work from home. We found that perceived organizational support directly affected job performance when employees work in office. When employees work from home, perceived organizational support could not affect job performance directly. However, it could influence job performance indirectly through the separate mediating effects of job satisfaction and work engagement. These findings extend our understanding of the association of perceived organizational support and job performance and enlighten enterprises on improving employees' job performance during the COVID-19 pandemic.


Resistance to 5-fluorouracil associated with increased cytidine triphosphate levels in V79 Chinese hamster cells.
Clones stably resistant to the toxic effects of 5-fluorouracil have been isolated from V79.5 Chinese hamster fibroblast cells by a single-step selection procedure. The 5-fluorouracil-resistant lines were found to (a) have an auxotrophic requirement when grown in dialyzed fetal calf serum that was satisfied by the addition of either thymidine, deoxyuridine, or deoxycytidine to the medium, (b) be cross-resistant to the toxic effects of 1-beta-D-arabinofuranosylcytosine and to high concentrations of thymidine, (c) have increased intracellular levels of cytidine 5'-triphosphate (CTP) and deoxycytidine 5'-triphosphate and decreased levels of uridine 5'-triphosphate, (d) also be resistant to 5-fluorouridine but not to 5-fluorodeoxyuridine, and (e) incorporate less 5-fluorouracil into RNA than do the wild-type cells. The primary lesion in these mutant appears to be an altered CTP synthetase activity which is no longer sensitive to negative regulation by CTP. The resulting increased CTP levels appear to be responsible for the various phenotypic characteristics of these mutants, including the resistance to 5-fluorouracil.


Physics-Constraint Variational Neural Network for Wear State Assessment of External Gear Pump.
Most current data-driven prognosis approaches suffer from their uncontrollable and unexplainable properties. To address this issue, this article proposes a physics-constraint variational neural network (PCVNN) for wear state assessment of the external gear pump. First, a response model of the pressure pulsation of the gear pump is constructed via a spectral method, and a compound neural network is utilized to extract features from the pressure pulsation signal. Then, the response model is formulated into an objective function to softly constrain the learning process of the neural network, forcing the learned features to have explicit physics meaning. Meanwhile, to characterize the system uncertainty, the variational inference is utilized to extend a Kullback-Leibler ( KL) divergence into the objective function. Finally, the wear state is evaluated based on the distance of learned physics features. Experimental results on an external gear pump validate the merits of the proposed method in explainable representation learning and system uncertainty estimation. It also offers a controllable and explainable perspective to understand the dynamic behavior of the system.


Cardiac computed tomography: diagnostic utility and integration in clinical practice.
Cardiac applications of computed tomography (CT) is a rapidly growing diagnostic area because of the ability to visualize plaque burden (coronary artery calcification [CAC]) and luminal obstruction (computed tomographic angiography [CTA]) noninvasively. Coronary artery calcification has been validated in over 1,000 studies over the last 20 years, primarily with electron beam tomography. Studies demonstrate several indications that could aid physicians in the management of symptomatic and asymptomatic patients. Determining that a symptomatic patient has no CAC is associated with both a lower risk of an abnormal nuclear study and angiographic obstruction. The ability to detect subclinical atherosclerosis (CAC) with minimal radiation and no contrast makes this an attractive method for risk stratification. New studies demonstrate a 10-fold risk of cardiovascular events with increasing amounts of coronary calcification. The invasive nature, expense, and risk resulting from invasive angiography have been instrumental in encouraging the development of new diagnostic methods that allow the coronary arteries to be visualized noninvasively. Multislice CT, with its advanced spatial and temporal resolution, has opened up new possibilities in the imaging of the heart and major vessels of the chest, including the coronary arteries. The last decade has seen great strides in the field of cardiac imaging, particularly in the ability to visualize the coronary lumen with sufficient diagnostic accuracy. Possessing that qualification, CTA is now being used increasingly in clinical practice. As a result of having high spatial and improved temporal resolutions, this imaging modality not only allows branches of the coronary artery to be evaluated, but also allows simultaneous analysis of other cardiac structures, making it extremely useful for other cardiac applications. This paper reviews the diagnostic utility and limitations of cardiac CT and how it could be integrated into clinical practice.


[Are we testing the right people? Results of a patient questionnaire in the STD and HIV counselling office of the local health authority in the city of Cologne].
HIV testing and counselling is offered free of charge in most local health offices in Germany. During 2003, a survey was performed among German-speaking clients of the Cologne local health office to look at socio-demographic background, reasons for testing and sexual risk behaviour. All German-speaking clients attending the HIV counselling office from March to July 2003 were asked to fill in an anonymous standardised questionnaire. Questions included demographic characteristics, social status, STI history, reasons for HIV testing, sexual orientation and number of sexual partners. Data were compared to the general Cologne population regarding demographic characteristics. Female respondents were compared to heterosexual men and men who have sex with men (MSM); German respondents were compared to migrants using SPSS 14.0. A total of 457 female and 488 male clients participated (response rate 93.9 %). Average age was 28.4 years. Of all participants, 17.7 % were of non-German origin. The respondents had a high school degree in 80.8 % of the cases compared to 33.5 % in the general Köln population (p < 0.001). Among men, 30.2 % were MSM. Having a "new partner" or "unprotected sex with a person with unknown HIV status" were reported by 483 (39.8 %) and 373 (30.8 %) as reasons for testing. 38.7 % of the respondents reported choosing the local health office for HIV testing because it was free of charge and 24.5 % because it was anonymous. Women and heterosexual men had a median of 1, MSM a median of 3 sexual partners within the past 6 months (p < 0.001). Vaccination against hepatitis B was reported by 34.4 % of the clients, the proportion was higher among MSM (46.9 % p < 0.001) and lower among migrants. 112 (11.9 %) persons reported having had a previous STI. With the exception of MSM, the offer of free and anonymous HIV testing and counselling does not reach persons who carry a higher risk for HIV. As the risk for STI is higher than for HIV in Germany and there is a low public awareness, HIV counselling should be used for comprehensive sexual health counselling and include the offer for STI testing, Further outreaching efforts and other settings are necessary to reach persons with a low education level and highly vulnerable persons.


Recovery of intellectual function after a brain injury: a comparison of longitudinal and cross-sectional approaches.
The goal of this study was to investigate recovery of intellectual function as a function of age at the time of a brain lesion. Participants with unilateral cortical lesions were selected from an initial data base of 685 patients. Ninety-six participants formed a longitudinal cohort for a first study and 314 participants formed a cross-sectional cohort for a second study. Participants of each study were split into two age groups according to the age at the time of the lesion: (1) before 7 years, (2) 7 years or more. Results showed a significantly different recovery profile as a function of age in the longitudinal study. Older participants manifested recovery on VIQ and PIQ, while younger participants presented stable profiles. The longitudinal and cross-sectional studies revealed differing recovery profiles as a function of age. Results are discussed in the context of the Kennard principle and with regard to the methodological approaches.


Fluorogenic squaraine dimers with polarity-sensitive folding as bright far-red probes for background-free bioimaging.
Polarity-sensitive fluorogenic dyes raised considerable attention because they can turn on their fluorescence after binding to biological targets, allowing background-free imaging. However, their brightness is limited, and they do not operate in the far-red region. Here, we present a new concept of fluorogenic dye based on a squaraine dimer that unfolds on changing environment from aqueous to organic and thus turns on its fluorescence. In aqueous media, all three newly synthesized dimers displayed a short wavelength band characteristic of an H-aggregate that was practically nonfluorescent, whereas in organic media, they displayed a strong fluorescence similar to that of the squaraine monomer. For the best dimer, which contained a pegylated squaraine core, we obtained a very high turn-on response (organic vs aqueous) up to 82-fold. Time-resolved studies confirmed the presence of nonfluorescent intramolecular H-aggregates that increased with the water content. To apply these fluorogenic dimers for targeted imaging, we grafted them to carbetocin, a ligand of the oxytocin G protein-coupled receptor. A strong receptor-specific signal was observed for all three conjugates at nanomolar concentrations. The probe derived from the core-pegylated squaraine showed the highest specificity to the target receptor together with minimal nonspecific binding to serum and lipid membranes. The obtained dimers can be considered as the brightest polarity-sensitive fluorogenic molecules reported to date, having ∼660,000 M(-1) cm(-1) extinction coefficient and up to 40% quantum yield, whereas far-red operation region enables both in vitro and in vivo applications. The proposed concept can be extended to other dye families and other membrane receptors, opening the route to new ultrabright fluorogenic dyes.


Pain Management Using Acupuncture Method in Migraine Headache Patients; A Single Blinded Randomized Clinical Trial.
There were numerous studies using acupuncture for pain relief and in most, the effect of this technique on preventing migraine attacks has been investigated. In those several studies that surveyed the effect of acupuncture on treatment of migraine headaches, the conclusion was not completely persuaded and they suggested further researches on this topic. The purpose of this study is to examine the effect of acupuncture on controlling acute migraine attacks. This study was a single blinded randomized clinical trial that was conducted on patients with a diagnosis of acute migraine attacks. At the time of reference, the patient's pain intensity was measured and recorded in a written checklist. Acupuncture was done in the intervention group with thin metallic needles, which enter certain points in the ear's skin; including shen men, autonomic, thalamus, frontal, and temple. In the placebo group, similar needles were used, however, they were inserted into unusual points. Thereafter, in 30 minutes, one, two, and four hours after the treatment, the pain intensity was also asked and compared with the reference time's score. A total of 60 patients with the mean age of 31.4 ± 7.6 years were enrolled and 83.3% of them were women. There was no significant difference between two groups in terms of the baseline characteristics of participants including age, sex and pain duration before admission (P > 0.05). According to the results, there was a significant difference between the two groups on the checkpoints of 15, 30, 45, and 60 minutes after acupuncture (P < 0.05); however, the pain scores were not statistically different between the two groups on two, three, and four hours after intervention (P > 0.05). Based on the findings of our study, although the pain score was lower in the intervention group than the control group during first hour after the acupuncture, there was no significant change in pain score thereafter. Comparison of the two groups showed no differences between acupuncture and placebo acupuncture on decreasing the mean pain score.


A brief review of adolescents and tobacco: what we know and don't know.
Smoking among teenagers is a major public health problem, and the purpose of this article is to review the literature concerning etiological factors of teen smoking, effects of prevention programs on reducing rates of teenage smoking, and the efficacy of smoking cessation treatment. Peer, family, and intrapersonal factors all play a role in the continuum of initiation to regular use. Prevention programs focusing on social norms governing teenage smoking are particularly effective in reducing onset of smoking behavior. Finally, behavioral cessation programs have been shown to be effective in reducing teenage smoking. Future directions concerning prevention and cessation research are discussed.


Academic Achievement of American Indian and Alaska Native Students: Does Social Emotional Competence Reduce the Impact of Poverty.
Social-emotional competence may be a protective factor for academic achievement among American Indian and Alaska Native (AI/AN) students. This study used Fisher's r to Z transformations to test for group differences in the magnitude of relationships between social-emotional competence and achievement. Hierarchical linear modeling was used to determine the variance in academic achievement explained by student race, poverty, and social-emotional competence, and the schoolwide percentage of students by race. Data are from 335 students across 6 schools. This study suggests that promoting social-emotional competence among AI/AN students could be a strategy for reducing disparities in academic achievement and the consequences of these disparities.


Immunohistologic differential diagnosis of basal cell carcinoma, squamous cell carcinoma, and trichoepithelioma in small cutaneous biopsy specimens.
The distinction between squamoid basal cell carcinoma and basaloid squamous cell carcinoma (or between BCC and trichoepithelioma variants) is usually made readily on the basis of defined histological criteria. However, these differential diagnoses occasionally can pose difficult morphological problems. The stated distinctions are clinically important because the risk of progressive disease is significantly higher with squamous carcinoma of the skin than with basal cell carcinoma (BCC), and a trichoepithelioma misinterpreted as BCC burdens the patient with an inaccurate diagnosis that may result in inappropriate surgery. Recent reports have suggested that reactivity with the monoclonal antibody Ber-EP4 is capable of separating histologically similar basal cell and squamous carcinomas, and that the expression of bcl-2 or CD34 antigen is able to distinguish BCC from trichoepithelioma. However, corroborative studies of these contentions are few in number. In order to investigate the usefulness of the stated immunostains in the above-cited differential diagnoses, the authors analyzed 45 basal cell carcinomas and 22 squamous carcinomas, as well as 36 trichoepitheliomas. The monoclonal antibodies Ber-EP4, My10 (CD34), and anti-bcl-2 were applied to formalin-fixed paraffin sections in all cases, using a standard avidin-biotin-peroxidase complex method. Most BCCs demonstrated strong, diffuse cytoplasmic labeling with Ber-EP4 and anti-bcl-2. In contrast, the squamous carcinomas were uniformly negative for the former marker and only focally reactive for the latter in four examples. 'Peripheral' bcl-2 staining of trichoepitheliomas was noted in 24 of 33 of the immunoreactive tumors, but the remainder were marked diffusely and similarly to most BCCs. Among the latter, immature trichoepitheliomas were diffusely reactive for this marker in 6 of 8 cases. Labeling of epithelium for CD34 failed to discriminate between any of the tumor types under evaluation, whereas staining of peritumoral stroma was characteristic of the majority of trichoepitheliomas and more than one-third of metatypical basal cell carcinomas. These data support the suggestion that Ber-EP4 and bcl-2 are useful in the separation of BCC from squamous carcinomas. Nevertheless, they also serve to caution against reliance upon bcl-2 and CD34 immunostains in attempting to distinguish BCC from trichoepithelioma in histologically enigmatic cases. There is currently no certain method other than conventional microscopy that can be applied successfully to the latter problem.


Numb modulates the paracellular permeability of intestinal epithelial cells through regulating apical junctional complex assembly and myosin light chain phosphorylation.
Numb is highly expressed throughout the crypt-villus axis of intestinal mucosa and functions as cell fate determinant and integrator of cell-to-cell adhesion. Increased paracellular permeability of intestinal epithelial cells is associated with the epithelial barrier dysfunction of inflammatory bowel diseases (IBDs). The apical junctional complex (AJC) assembly and myosin light chain (MLC) phosphorylation regulate adherens junctions (AJ) and tight junctions (TJ). We determined whether and how Numb modulate the paracellular permeability of intestinal epithelial cells. Caco-2 intestinal epithelial cells and their Numb-interfered counterparts were used in the study for physiological, morphological and biological analyses. Numb, expressed in intestinal epithelial cells and located at the plasma membrane of Caco-2 cells in a basolateral to apical distribution, increased in the intestinal epithelial cells with the formation of the intestinal epithelial barrier. Numb expression decreased and accumulated in the cytoplasm of intestinal epithelial cells in a DSS-induced colitis mouse model. Numb co-localized with E-cadherin, ZO-1 and Par3 at the plasma membrane and interacted with E-cadherin and Par3. Knockdown of Numb in Caco-2 cells altered the F-actin structure during the Ca(2+) switch assay, enhanced TNFα-/INF-γ-induced intestinal epithelial barrier dysfunction and TJ destruction, and increased the Claudin-2 protein level. Immunofluorescence experiments revealed that NMIIA and F-actin co-localized at the cell surface of Caco-2 cells. Numb knockdown in Caco-2 cells increased F-actin contraction and the abundance of phosphorylated MLC. Numb modulated the intestinal epithelial barrier in a Notch signaling-independent manner. These findings suggest that Numb modulates the paracellular permeability by affecting AJC assembly and MLC phosphorylation.


Entropy of pseudo-random-number generators.
Since the work of Phys. Rev. Lett. 69, 3382 (1992)]] some pseudo-random-number generators are known to yield wrong results in cluster Monte Carlo simulations. In this contribution the fundamental mechanism behind this failure is discussed. Almost all random-number generators calculate a new pseudo-random-number x(i) from preceding values, x(i) =f( x(i-1), x(i-2), ..., x(i-q) ). Failure of these generators in cluster Monte Carlo simulations and related experiments can be attributed to the low entropy of the production rule f() conditioned on the statistics of the input values x(i-1), ..., x(i-q). Being a measure only of the arithmetic operations in the generator rule, the conditional entropy is independent of the lag in the recurrence or the period of the sequence. In that sense it measures a more profound quality of a random-number generator than empirical tests with their limited horizon.


Neural tissue engineering: strategies for repair and regeneration.
Nerve regeneration is a complex biological phenomenon. In the peripheral nervous system, nerves can regenerate on their own if injuries are small. Larger injuries must be surgically treated, typically with nerve grafts harvested from elsewhere in the body. Spinal cord injury is more complicated, as there are factors in the body that inhibit repair. Unfortunately, a solution to completely repair spinal cord injury has not been found. Thus, bioengineering strategies for the peripheral nervous system are focused on alternatives to the nerve graft, whereas efforts for spinal cord injury are focused on creating a permissive environment for regeneration. Fortunately, recent advances in neuroscience, cell culture, genetic techniques, and biomaterials provide optimism for new treatments for nerve injuries. This article reviews the nervous system physiology, the factors that are critical for nerve repair, and the current approaches that are being explored to aid peripheral nerve regeneration and spinal cord repair.


[Beta-1 and beta-4 integrins, and laminin 67 kDa receptors in interaction between A431 cells and laminin isoforms ].
Laminins, as basal membrane glycoproteins, are able to stimulate cell adhesion and migration, and to influence gene expression. The laminin molecule has a set of bioactive sites that interact with different integrin and nonintegrin receptors, and, as a result, the reaction of the same cell type to different laminin isoforms may be different. The aim of this study was to determine the contributions of both integrins with beta 1 and beta 4 chains and 67 kDa laminin receptor in the interaction of A431 cells with two laminin isoforms: laminin-1 and laminin-2/4. The obtained data show that integrin alpha 6 beta 4 is more specific for interaction with laminin-2/4 than with laminin-1 and takes part in the stage of attachment of A431 cells to laminin. 67 kDa receptor promotes cell spreading on laminin-2/4 and inhibits cell spreading on laminin-1. An assumption was made about the complex action of receptors for interaction of A431 cells with laminins ("integrin alpha 6 beta 4--67 kDa receptors" complex).


Evaluation of the RAMS continuous monitor for determination of PM2.5 mass including semi-volatile material in Philadelphia, PA.
The real-time ambient mass sampler (RAMS) is a continuous monitor based on particle concentrator, denuder, drier, and tapered element oscillating microbalance (TEOM) monitor technology. It is designed to measure PM2.5 mass, including the semi-volatile species NH4NO3 and semi-volatile organic material, but not to measure PM2.5 water content. The performance of the RAMS in an urban environment with high humidity was evaluated during the July 1999 NARSTO-Northeast Oxidant and Particles Study (NEOPS) intensive study at the Baxter water treatment plant in Philadelphia, PA. The results obtained with the RAMS were compared to mass measurements made with a TEOM monitor and to constructed mass obtained with a Particle Concentrator-Brigham Young University Organic Sampling System (PC-BOSS) sampler designed to determine the chemical composition of fine particles, including the semi-volatile species. An average of 28% of the fine particulate material present during the study was semi-volatile organic material lost from a filter during particle collection, and 1% was NH4NO3 that was also lost from the particles during sampling. The remaining mass was dominantly nonvolatile (NH4)2SO4 (31%) and organic material (37%), with minor amounts of soot, crustal material, and nonvolatile NH4NO3. Comparison of the RAMS and PC-BOSS results indicated that the RAMS correctly monitored for fine particulate mass, including the semivolatile material. In contrast, the heated filter of the TEOM monitor did not measure the semi-volatile material. The comparison of the RAMS and PC-BOSS data had a precision of +/-4.1 microg/m3 (+/-9.6%). The precision of the RAMS data was limited by the uncertainty in the blank correction for the reversible adsorption of water by the charcoal-impregnated cellulose sorbent filter of the RAMS monitor. The precision of the measurement of fine particulate components by the PC-BOSS was +/-6-8%.


Association of Proteomics Changes with Al-Sensitive Root Zones in Switchgrass.
In this paper, we report on aluminum (Al)-induced root proteomic changes in switchgrass. After growth in a hydroponic culture system supplemented with 400 μM of Al, plants began to show signs of physiological stress such as a reduction in photosynthetic rate. At this time, the basal 2-cm long root tips were harvested and divided into two segments, each of 1-cm in length, for protein extraction. Al-induced changes in proteomes were identified using tandem mass tags mass spectrometry (TMT-MS)-based quantitative proteomics analysis. A total of 216 proteins (approximately 3.6% of total proteins) showed significant differences between non-Al treated control and treated groups with significant fold change (twice the standard deviation; FDR adjusted p-value < 0.05). The apical root tip tissues expressed more dramatic proteome changes (164 significantly changed proteins; 3.9% of total proteins quantified) compared to the elongation/maturation zones (52 significantly changed proteins, 1.1% of total proteins quantified). Significantly changed proteins from the apical 1-cm root apex tissues were clustered into 25 biological pathways; proteins involved in the cell cycle (rotamase FKBP 1 isoforms, and CDC48 protein) were all at a reduced abundance level compared to the non-treated control group. In the root elongation/maturation zone tissues, the identified proteins were placed into 18 pathways, among which proteins involved in secondary metabolism (lignin biosynthesis) were identified. Several STRING protein interaction networks were developed for these Al-induced significantly changed proteins. This study has identified a large number of Al-responsive proteins, including transcription factors, which will be used for exploring new Al tolerance genes and mechanisms. Data are available via ProteomeXchange with identifiers PXD008882 and PXD009125.


Human papillomavirus vaccines for the treatment of cervical cancer.
Human papillomavirus (HPV) infection is a major cause of cervical cancer, the second most common cancer in women worldwide. Currently, a HPV L1-based virus-like particle has been approved as a prophylactic vaccine against HPV infection, which will probably lead to a reduction in cervical cancer incidence within a few decades. Therapeutic vaccines, however, are expected to have an impact on cervical cancer or its precursor lesions, by taking advantage of the fact that the regulatory proteins (E6 and E7) of HPV are expressed constantly in HPV-associated cervical cancer cells. Vaccine types targeting these regulatory proteins include the recombinant protein and DNA vaccines, peptide vaccines, dendritic-cell vaccines, and viral and bacterial vector deliveries of vaccines, and these may provide an opportunity to control cervical cancer. Further approaches incorporating these vaccine types with either conventional therapy modalities or the modulation of CD4(+) regulatory T cells appear to be more promising in achieving increased therapeutic efficacy. In this review, we summarize current and future therapeutic vaccine strategies against HPV-associated malignancies at the animal and clinical levels.


Serum IgA and secretory IgA levels in bronchial lavages from patients with a variety of respiratory diseases.
The secretory immunoglobulin A (IgA) system plays an important role in the protection of epithelial surfaces. The aim of this study was to evaluate whether the measurement of the primary airway Ig (sIgA) concentration in bronchial washings is clinically useful in patients with airway epithelial injury or inflammation. We measured serum IgA levels and sIgA concentrations in the bronchial lavages of patients with chronic bronchitis (n = 10), bronchiectasis (n = 15), lung cancer (n = 15) and in healthy control subjects (n = 10). Absolute sIgA levels of bronchial lavage fluids in the chronic bronchitis, bronchiectasis and lung cancer groups were higher than the controls, but there was no significant difference between the groups. sIgA/ml recovered bronchial fluid ratios were similar in the all groups. Standardisation of samples by means of albumin concentration ratios (sIgA/alb) showed that the bronchial lavages of the patients with lung cancer, chronic bronchitis and bronchiectasis were generally similar and demonstrated a significantly decreased sIgA/alb ratio compared to that of control subjects (p = 0.001, p < 0.05 and p < 0.05). sIgA/alb ratios in bronchial lavages recovered from involved lung of the patients with lung cancer and bronchiectasis were lower as compared to uninvolved lung (p < 0.001 and p < 0.05). There was no significant difference in serum IgA levels between all groups. As a result, although our findings seem partly to confirm the hypothesis that local bronchial IgA secretion is impaired in areas of bronchial epithelial injury or inflammation, we thought that sIgA would be useless as a marker of respiratory epithelial injury or inflammation in patients with chronic bronchitis, bronchiectasis and lung cancer.


Resistant mechanisms and molecular epidemiology of imipenem-resistant Acinetobacter baumannii.
The aim of the study was to investigate the resistant mechanisms and homology of imipenem-resistant Acinetobacter baumannii (A. baumannii). A total of 46 non-duplicate imipenem‑resistant A. baumannii clinical isolates were collected from three tertiary hospitals between July, 2011 and June, 2012. The minimal inhibitory concentrations (MICs) of antimicrobial agents were determined using the agar dilution method. Phenylalanine‑arginine β-naphthylamide was used to detect the presence of the efflux pump-mediated resistant mechanism. Polymerase chain reaction was employed to amplify genes associated with drug resistance, including β‑lactamase genes, efflux pump genes and outer membrane protein gene CarO. A few amplicons were randomly selected and sequenced. Multilocus sequence analysis (MLST) was employed in typing A. baumanni. A. baumannii was resistant to imipenem, simultaneously showing resistance to several other antimicrobials. In addtition, 13 A. baumannii were found to mediate drug resistance through operation of the efflux pump. Of the various drug resistance genes tested, blaOXA‑51 was present in 46 isolates, blaOXA‑23 gene was present in 44 isolates and blaNDM gene was found in only one strain. Other drug resistant‑associated genes, including blaKPC, blaIMP, blaOXA-24, blaOXA‑58, blaSHV, blaGIM and blaVIM were not detected. Mutation of adeS and outer membrane protein gene CarO were found in a few of the imipenem‑resistant isolates. The MLST analysis revealed that all 46 clinical isolates were clustered into 11 genotypes and the most frequent genotype was ST208. In conclusion, β‑lactamase genes, genes involved in efflux pump and mutation of outer membrane protein encoding gene may be important in mediating imipenem resistance in A. baumannii. Of the 11 different genotypes, ST11 was shared by the majority of A. baumannii, which may be due to horizontal transfer of patients from hospitals.


Reliability and responsiveness of the Self-Efficacy in Assessing, Training and Spotting wheelchair skills (SEATS) outcome measure.
The aim of this study was to evaluate the internal consistency, test-retest reliability and responsiveness of the Self-Efficacy in Assessing, Training and Spotting manual wheelchair skills (SEATS-M) and Self-Efficacy in Assessing, Training and Spotting power wheelchair skills (SEATS-P). A 2-week test-retest design was used with a convenience sample of occupational and physical therapists who worked at a provincial rehabilitation centre (inpatient and outpatient services). Sixteen participants completed the SEATS-M and 18 participants completed the SEATS-P. For the SEATS-M assessment, training, spotting and documentation sections, Cronbach's alpha coefficients ranged from 0.90 to 0.97, the 2-week intraclass correlation coefficients (ICC1,1) ranged from 0.81 to 0.95, the standard error of measurements (SEM) ranged from 5.06 to 8.70 and the smallest real differences (SRD) ranged from 6.24 to 8.18. For the SEATS-P assessment, training, spotting and documentation sections, Cronbach's alpha coefficients ranged from 0.83 to 0.92, the ICCs ranged from 0.72 to 0.86, the SEMs ranged from 4.54 to 8.91 and the SRDs ranged from 5.90 to 8.27. There is preliminary evidence that both the SEATS-M and the SEATS-P have high internal consistency, good test-retest reliability and support for responsiveness. These tools can be used in evaluating clinician self-efficacy with assessing, training, spotting and documenting wheelchair skills included on the Wheelchair Skills Test. Implications for Rehabilitation There is preliminary evidence that the SEATS-M and SEATS-P are reliable and responsive outcome measures that can be used to evaluate the self-efficacy of clinicians to administer the Wheelchair Skills Program. Measurement of clinicians' self-efficacy in this area of practice may enable an enhanced understanding of the areas in which clinicians lack self-efficacy, thereby informing the development of improved knowledge translation interventions.


Sex differences and similarities in urban home ranges and in the accuracy of cognitive maps.
Former research has examined potential human sex differences in spatial abilities or home range size. Both are assumed to have an adaptive function. In this study we combined the investigation of home range size in an urban environment and spatial abilities by accuracy analysis of cognitive maps. Participants (n = 87) drew a sketch of their home range in Vienna depicting all places regularly visited in every-day life. We used the sketches' geographical locations to calculate the size of the home range. With the Geometric Morphometric Methodology, we quantified the accuracy of cognitive maps by measuring Euclidean distances between corresponding landmarks in the sketches and the geographical maps of home ranges. Our results showed a non-significant trend for men to have a larger home range. Overall, participants' cognitive maps were fairly accurate. However, men sketched their home range more precisely than women. Female map accuracy increased as a function of residency duration. In addition, accuracy of cognitive maps was influenced by home range size and number of frequently visited places. In summary, findings indicate that sex differences in home range size and spatial abilities may still persist in humans living in urbanized Western societies, but are also influenced by environmental experience.


Identify miRNA-mRNA regulation pairs to explore potential pathogenesis of lung adenocarcinoma.
MicroRNA (miRNA) function via base-pairing with complementary sequences within mRNA molecules. This study aims to identify critical miRNA-mRNA regulation pairs contributing to lung adenocarcinoma (LUAD) pathogenesis. MiRNA and mRNA microarray and RNA-sequencing datasets were downloaded from gene expression omnibus (GEO) and the cancer genome atlas (TCGA) databases. Differential miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were screened by the GEO2R tool and R packages. DAVID, DIANA, and Hiplot tools were used to perform gene enrichment analysis. The pairs of miRNA-mRNA were screened from the experimentally validated miRNA-target interactions databases (miRTarBase and TarBase). External validation was carried out in 30 pairs of LUAD tissues by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). The diagnostic value of the miRNA-mRNA regulation pairs was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). Biological function assay was were also performed to confirm the function of miRNA-mRNA axis in LUAD progression. The study also performed the clinical, survival and tumor-associated phenotypic analysis of miRNA-mRNA pairs. A total of 7 miRNA and 13 mRNA expression datasets from GEO were analyzed, and 11 DE-miRNAs (5 down-regulated and 6 up-regulated in LUAD tissues) and 128 DE-mRNAs (30 up-regulated and 98 down-regulated in LUAD tissues) were identified. The pairs of miR-1-3p(down) and CENPF(up) and miR-126-5p(down) and UGT8(up) were verified in the external validation cohort (30 LUAD vs. 30 NC) using qRT-PCR. Areas under the ROC curve of the two miRNA-mRNA regulation pairs panel were 0.973 in TCGA-LUAD and 0.771 in the external validation. The DCA also showed that the miRNA-mRNA regulation pairs had an excellent diagnostic performance distinguishing LUAD from normal controls. The expression of the regulation pairs is different in different ages, TNM stages, and gender. The overexpression of miR-1-3p and miR-126-5p significantly inhibited the proliferation and migration of LUAD cells. Correlation analysis showed that CENPF correlated with prognosis and tumor immunity. The research identified potential miRNA-mRNA regulation pairs, providing a new idea for exploring the genesis and development of LUAD.


Perivascular epithelioid cell neoplasm of the colon.
A 17-year-old female presented with rectal bleeding from an ulcerated sigmoid mass in 1994. Initial pathological evaluation revealed a rare clear cell neoplasm of the colon, possibly originating from kidneys, adrenals, lung or a gynecologic source as a metastatic lesion. Extensive imaging studies were negative, and over the next 15 years, she remained well with no recurrence. The original resected neoplasm was reviewed and re-classified as a perivascular epithelioid cell neoplasm (PEComa). Although the long-term natural history of PEComas requires definition, increased clinical and pathological awareness should lead to increased recognition of an apparently rare type of colonic neoplasm that likely occurs more often than is currently appreciated.


Human rights and correctional health policy: a view from Europe.
Purpose Correctional healthcare should promote the protection of human rights. The purpose of this paper is to bring a discussion of human rights into debates on how such policy should be best organized. Design/methodology/approach The paper achieves its aim by providing an analysis of European prison law and policy in the area of prison health, through assessing decisions of the European Court of Human Rights, as well as policies created by the European Committee for the Prevention of Torture. Findings The paper describes the position of the European Court of Human Rights on the topics of access to healthcare, ill health and release from prison, mental illness in prison, and the duty to provide rehabilitative programming for those seeking to reduce their level of "risk." It also argues that human rights law can be a source of practical reform, and that legal frameworks have much to offer healthcare leaders seeking to uphold the dignity of those in their care. Originality/value This paper will provide a rare example of the engagement of human rights law with correctional health policy. It provides practical recommendations arising out of an analysis of European human rights law in the area of prisons.


Chlamydia pneumoniae infection in polarized epithelial cell lines.
We set up a polarized cell culture model to study the pathogenicity of a common respiratory tract pathogen, Chlamydia pneumoniae. Immunofluorescence staining of ZO-1 (a tight junction protein) and Na(+)K(+) ATPase (a protein pump localized at the basolateral membrane in the polarized epithelial cells), as well as TER measurements, suggested that the filter-grown Calu-3 cells, but not the A549 cells, were polarized when grown on collagen-coated membranes. Both the flat and the filter-grown cultures were infected with C. pneumoniae. Infection in the polarized Calu-3 cultures produced more C. pneumoniae genome equivalents than infection in the flat cultures. However, this progeny was not as infective as that in the flat cultures. The maximum amount of C. pneumoniae was detected at 6 days postinfection in the filter-grown A549 cells, indicating a slower developmental cycle than that observed in the flat A549 cultures. The effect of cycloheximide on the growth of C. pneumoniae in the polarized cells was negligible. Furthermore, the infection in the polarized Calu-3 cells was resistant to doxycycline, and several cytokines were released mainly on the apical side of the polarized cells in response to C. pneumoniae infection. These findings indicate that the growth of chlamydiae was altered in the filter-grown epithelial culture system. The diminished production of infective progeny of C. pneumoniae, together with the resistance to doxycycline and polarized secretion of cytokines from the infected Calu-3 cells, suggests that this model is useful for examining epithelial cell responses to C. pneumoniae infection, and it might better resemble in vivo infection in respiratory epithelial cells.


[ANISAKIASIS. REPORT OF A CASE AND REVIEW OF THE LITERATURE]
We present the case of a 38 year-old woman, who attended the Gastroenterology Service of a private hospital in Lima, complaining of a one week history of retroesternal "burning" sensation and mild, sporadic right lower quadrant abdominal pain. Laboratory test within normal limits were obtained and an upper endoscopic study was done. A white, mobile, 30 mm length parasite found attached to the gastric mucosa. Which was removed and identified as Anisakis spp. Taking into account how unusual is the report of this type of findings, the authors decided to review the literature and present it to the medical community. We suspect this parasitosis is subregistered in our country.


Long-Term Effect of an Interdisciplinary Supportive Care Intervention for Lung Cancer Survivors After Surgical Procedures.
Surgical procedures provide the best chance for cure and long-term survival in non-small cell cancer (NSCLC). Persistent symptoms after surgical procedures are common, and they can negatively affect health-related quality of life (HRQOL). The purpose of this study was to examine the long-term effect of an interdisciplinary supportive care intervention to improve HRQOL, psychological distress, and symptoms in lung cancer survivors who were treated surgically. Patients undergoing curative intent resection for NSCLC were enrolled in a prospective sequential design whereby the control group was accrued first, followed by the intervention group. Patients in the intervention group were assessed and presented by nurses at weekly interdisciplinary care meetings before surgical procedures, and received four educational sessions (physical, psychological, social, and spiritual well-being) after surgical procedures. Appropriate symptom management, social work, rehabilitation, and spiritual support interventions were coordinated by the study nurse. In both groups, HRQOL, psychological distress, and symptom severity were assessed at baseline and at 6, 12, 24, 36, and 52 weeks with the use of surveys that included the validated Functional Assessment of Cancer Therapy-Lung (FACT-L), Lung Cancer Subscale (LCS), and Distress Thermometer. Mean survey scores were analyzed with factorial analysis of covariance at 12 months. A total of 71 survivors (control = 33; intervention = 38) were accrued. No difference was found in age, baseline performance status, or stage of disease between groups. Patients in the intervention group had significantly less distress (mean, 1.0 versus 4.0; range, 0 to 10; p < 0.001) and more favorable mean FACT-L scores (126.1 versus 98.7; range, 0 to 140; p < 0.001) and LCS scores (29.4 versus 23.6; range, 0 to 32; p < 0.001) at 12 months. The mean scores of all categories of questions in FACT-L (physical, social/family, emotional, and functional well-being) were considerably more favorable in the intervention group at 12 months. An interdisciplinary supportive care intervention improves psychological distress and HRQOL at 12 months after lung cancer surgical procedures. This study has important implications in improving HRQOL of lung cancer survivors after surgical procedures. Further study is warranted on incorporating the interdisciplinary personalized interventions used in this study into clinical practice for lung cancer survivors.


Ocular surface problems following topical medication.
Adverse effects following topical medication account for a significant ocular morbidity. Toxic and allergic reactions are second in frequency among all external eye diseases (after keratokonjunctivitis sicca). Knowledge on the clinical background that predisposes to such reactions is scarce. This study aims to identify the factors that render commonly used topical medications to powerful ocular irritants. 168 consecutive tertiary referrals with external eye disease problems were studied. The adverse effects on the ocular surface were analysed using a modified Wilson's classification (1983). At least 39 out of 168 (24 %) patients had problems related to topical medication. Factors that predisposed to adverse reactions included a compromised ocular surface in 17 patients (43 %), long-term drug exposure in 8 (21 %), intensified treatment in 8 (21 %), concomitant acute disorders in 4 (10 %), and additive drug toxicity (> 3 medications) in 2 patients (5 %). Toxic papillary keratokonjunctivitis was the most common adverse reaction (n = 31; 80 %) and was associated in 13 patients with epithelial defects, in 2 with keratinisation of the ocular surface and in one with conjunctival scarring. Aminoglycoside antibiotics were the drugs that were most frequently involved in adverse ocular surface reactions. Toxic reactions are far more common than allergic ones. They are frequent in eyes with compromised surface, and after long-term or intensified therapy.


Incontinentia pigmenti: a newborn with characteristic skin lesions and bilateral optic atrophy: case report and review of literature.
Incontinentia Pigmenti (IP) is a rare X-linked dominant disorder with skin, eye, central nervous system (CNS) and tooth abnormalities. According to the reported cases, it is estimated that there have been nearly 900-1200 affected individuals. In this article, the literature is reviewed and a case of IP with characteristic skin lesions and optic atrophy is presented.


Stable Au-C bonds to the substrate for fullerene-based nanostructures.
We report on the formation of fullerene-derived nanostructures on Au(111) at room temperature and under UHV conditions. After low-energy ion sputtering of fullerene films deposited on Au(111), bright spots appear at the herringbone corner sites when measured using a scanning tunneling microscope. These features are stable at room temperature against diffusion on the surface. We carry out DFT calculations of fullerene molecules having one missing carbon atom to simulate the vacancies in the molecules resulting from the sputtering process. These modified fullerenes have an adsorption energy on the Au(111) surface that is 1.6 eV higher than that of C60 molecules. This increased binding energy arises from the saturation by the Au surface of the bonds around the molecular vacancy defect. We therefore interpret the observed features as adsorbed fullerene-derived molecules with C vacancies. This provides a pathway for the formation of fullerene-based nanostructures on Au at room temperature.


Expression of alternatively spliced epidermal growth factor-like domains in aggrecans of different species. Evidence for a novel module.
The carboxyl-terminal globular domain of human aggrecan has been shown previously to contain an alternatively spliced epidermal growth factor (EGF)-like module. We have used reverse transcription/polymerase chain reactions on cartilage-derived RNAs to investigate the heterogeneity in the EGF-like domain content of aggrecans from five species (mouse, rat, dog, bovine, and human). A novel alternatively spliced EGF-like module was detected in human aggrecan, establishing the presence of two of these domains. Highly homologous domains are present in aggrecans of other species, and the expression of these modules is identical (4-8%). They share significant homology with EGF-like domains of differentiation proteins and coagulation factors and have a putative calcium binding site. In contrast to this novel domain (EGF2), the previously described EGF-like module (EGF1) is expressed at a high level exclusively in human aggrecan. The expression of the two EGF-like domains in human aggrecan appears to be independent. Although the function of these domains is not understood, the uniform expression of the EGF2 domain may indicate a general role of this aggrecan module, while the expression of the EGF1 domain may reflect species specificity.


Anti-senescence role of heterozygous fumarate hydratase gene knockout in rat lung fibroblasts in vitro.
Abnormalities in tricarboxylic acid (TCA) cycle function were related to a variety of pathological processes. Fumarate hydratase (FH) is a required enzyme in the TCA cycle. To explore the general influence of FH knockout, we isolated FH+/- rat and normal rat lung fibroblasts and cultured these cells in vitro. The isolated fibroblasts with the current method were rather homogeneous and were confirmed spindle in morphology, positive for vimentin and negative for α-SMA (α-smooth muscle actin). Sequencing of the PCR (polymerase chain reaction) products flanking the FH gene mutation verified the FH+/- status, and the FH gene and protein expression were confirmed to be reduced in the FH+/- cells. No sign of ageing for the FH+/- cells after 61 passages was observed, but the controls died out at this stage. Flow cytometry revealed increased S-phase and decreased G1/G0 proportions with significantly less early apoptosis in FH+/- cells compared to that in control cells. At the same time, increased glucose consumption, intracellular fumarate production and extracellular lactate secretion were verified in the FH+/- cells. Correspondingly, FH+/- cells showed a lower basal oxygen consumption rate (OCR) but a higher level of reactive oxygen species (ROS) production. Single cell cloning and cell line establishment were successfully performed with the FH+/- cells at the 84th passage. All the above results indicate an important role for FH+/- in the longevity or immortality of the FH+/- cells, in which increased p53 and TERT (telomerase reverse transcriptase) protein expression, decreased p21 and p16 protein expression and negative SA-β-Gal (senescence-associated beta-galactosidase) were verified along with metabolic reprogramming.


Stereotactic amygdalotomy in the management of severe aggressive behavioral disorders.
Stereotactic amygdalotomy has been utilized as a surgical treatment for severe aggressive behavioral disorders. Several clinical studies have been reported since the first description of the procedure. In the current study, the authors reviewed the literature and evaluated the surgical results, neuropsychological outcome, and complication rate in patients who had undergone stereotactic amygdalotomy for severe aggressive behavioral disorders. The PubMed database was searched using the following terms: "amygdalotomy," "amygdalectomy," "amygdaloidectomy," "psychosurgery," "aggressive disorder," and "behavioral disorder." Clinical series with more than 5 patients undergoing stereotactic amygdalotomy for aggressive or other behavioral disorders were included in this review. The surgical technique, anatomical target, improvement in psychiatric symptomatology, postoperative employment and social rehabilitation, postoperative neurocognitive function, procedure-related complications, and long-term follow-up were evaluated. Thirteen clinical studies met our inclusion criteria. Reported postoperative improvement in aggressive behavior varied between 33 and 100%. Procedure-related complication rates ranged from 0 to 42%, whereas the mortality rate was as high as 3.8%. In the majority of the reviewed clinical series, the performance of stereotactic amygdalotomy did not compromise a patient's learning, language, and intellectual capabilities. The long-term follow-up, although very limited, revealed that initially observed improvement was maintained in most cases. Stereotactic amygdalotomy can be considered a valid surgical treatment option for carefully selected patients with medically refractory aggressive behavioral disorders. Recent advances in imaging and stereotactic navigation can further improve outcome and minimize the complication rate associated with this psychosurgical procedure.


Synthesis and antiviral evaluation of certain novel pyrazinoic acid C-nucleosides.
Pyrazine (1,4-diazine) C-nucleosides constitute a rare class of nucleic acid analogues that has only recently been reported in the literature. As part of our ongoing investigation into the synthesis and reactivity of these compounds, we have developed an electrophilic esterification of a lithiated pyrazine C-nucleoside (1) to give, following deprotection, the versatile intermediate ethyl 3,5-dichloro-6-(beta-d-ribofuranosyl)pyrazine-2-carboxylate (4). This intermediate was subjected to a variety of reaction conditions to generate a series of pyrazinoic acid C-nucleosides. These compounds, along with 3, 5-dichloro-2-(beta-d-ribofuranosyl)pyrazine (2) and 4, were evaluated for antiviral activity and cytotoxicity. No significant activity was observed for compounds 2 and 5-9, but 4 was active against two herpes viruses and cytotoxic in the micromolar range.


Rational Design of Multi-Stimuli-Responsive Nanoparticles for Precise Cancer Therapy.
Stimuli-responsive nanoparticles with target capacity are of great interest in drug delivery for cancer therapy. However, the challenge is to achieve highly smart release with precise spatiotemporal control for cancer therapy. Herein, we report the preparation and properties of multi-stimuli-responsive nanoparticles through the co-assembly of a 3-arm star quaterpolymer with a near-infrared (NIR) photothermal agent and chemotherapeutic compound. The nanoparticles can exhibit NIR light/pH/reduction-responsive drug release and intracellular drug translocation in cancer cells, which further integrate photoinduced hyperthermia for synergistic anticancer efficiency, thereby leading to tumor ablation without tumor regrowth. Thus, this rational design of nanoparticles with multiple responsiveness represents a versatile strategy to provide smart drug delivery paradigms for cancer therapy.


Safety and efficacy of once-per-cycle pegfilgrastim in support of ABVD chemotherapy in patients with Hodgkin lymphoma.
The objective of this prospective study was to examine the safety and efficacy of pegfilgrastim in support of chemotherapy regimens that are administered every 14 d. Patients with Hodgkin lymphoma receiving standard ABVD (doxorubicin, bleomycin, vinblastine, and decarbazine) chemotherapy every 14 d were eligible for the study. All patients received one fixed dose of 6 mg pegfilgrastim approximately 24h after each ABVD infusion. Absolute neutrophil counts (ANCs) were measured weekly while on therapy. After completion of therapy, ANCs were measured every 3-4 months for 2 years, and every 6 months thereafter. Twenty-three patients received 115 courses (230 doses) of ABVD. Nadir ANC below 0.5 x 10(9)/L was observed only in two cases (1.1%), and ANC counts on the day of ABVD therapy below 1 x 10(9)/L was observed only once (0.4%). No neutropenic fever was observed. Two hundred and fifteen (93.5%) doses of ABVD were given on time as scheduled. Grade 3/4 bone pain was observed after 0.4% of ABVD doses, and bleomycin lung toxicity was observed in two patients. With a median follow-up of 29 months after completion of ABVD, no myelodysplastic syndrome was observed. Two patients relapsed and subsequently underwent successful stem cell collection and transplantation. Pegfilgrastim was found to be safe in support of ABVD chemotherapy that is administered every 14 d. Pegfilgrastim was also effective in maintaining ABVD dose intensity, and keeping planned dose of chemotherapy on schedule.


Locus for elevated apolipoprotein B levels on chromosome 1p31 in families with familial combined hyperlipidemia.
Familial combined hyperlipidemia (FCH), a common cause of premature coronary artery disease, is genetically complex and poorly understood. Recently, a major locus on chromosome 1q21-23 exhibiting highly significant linkage was identified in Finnish FCH families by use of a parametric analysis. We now report highly significant evidence of linkage (maximum LOD score 3.8, recombination fraction 0) of an important FCH phenotype, elevated apolipoprotein B (apoB) levels, to a distinctly separate locus on chromosome 1p31 in Dutch pedigrees. ApoB is the major protein on very low density and low density lipoproteins, and elevated apoB levels have been used as a surrogate trait for FCH. Additional microsatellite markers in the 1p31 region were genotyped, and evidence of linkage improved (maximum LOD score 4.7) in a multipoint analysis of two markers in the peak region. The leptin receptor gene resides within this locus and is involved in obesity and insulin/glucose homeostasis. However, there was no evidence of an association between leptin receptor and apoB levels, raising the possibility that another gene on this chromosomal region contributes to elevated apoB levels in this Dutch population. This is one of the first loci identified for apoB levels in humans and is the second major locus implicated in the genetic etiology of FCH.


Can we finally target the leukemic stem cells?
Two key issues must be addressed in the discussion of targeting leukemic stem cells: (1) can the leukemic stem cell be targeted in vivo, and (2) how to assess whether the leukemic stem cell is actually being targeted. Currently several small molecule and antibody- or ligand-based agents have shown activity in selectively targeting the leukemic stem cell. However, there is debate about how to use these targeted agents and how to identify and quantitate the leukemic stem cell to determine whether or not it is being targeted. Parameters are suggested here to help identify and quantitate leukemic stem cells in the clinical context.


[Human herpesvirus 7].
Human herpesvirus 7 known since 1990 is closely related to herpesvirus 6B. It replicates in human cells only after binding CD4 receptor. It establishes lifelong latency in infected cells, and its frequent reactivations result in asymptomatic virus shedding through saliva. Most children acquire infection by age 3 and 4, but in any later age group seronegative individuals are at risk of infection. Rarely, exanthema subitum or convulsions with fever in children, pityriasis rosea in young adults, lethal complications in immunocompromised persons with concomitant herpesvirus 6B and cytomegalovirus reactivation occur. The most important pathogenic changes are due to the altered cytokine and growth factor secretion from infected lymphocytes with subsequent chain reaction on immune and other cells. Antiviral antibodies are detected by commercial kits (immunofluorescence, ELISA, immunoblot), nucleic acid by nested polymerase chain reaction. The majority of conditions due to infection do not require antiviral medication, but the severe complications are treated with ganciclovir and its derivates or foscarnet and cidofovir.


[Impact of the removal of A2 test erythrocytes and the anti-AB reactant on the interpretation of the ABO blood grouping].
This work evaluates the impact of the removal of the anti-AB reagents and A2 test-red blood cells on the interpretation of ABO blood grouping. The first step of the work was a multicentric study concerning the interpretation of "all coming" blood groupings, reporting the results of 105 195 ABO blood groupings of donors and patients carried out on microplates using an automated or a half-automated technique. Their interpretation was performed following four different methods, in order to appreciate the impact on the results of the removal of either anti-AB test-serum, A2 test-red blood cells, or the combination of both. Moreover, a qualitative and quantitative analysis of the interpretations of the blood groupings that were initially not performed (rejections), was carried out in order to determine the most often implied reagent and to quantify a possible gain in interpretation after removing it. A complementary study of the same type concerning more specifically weak ABO phenotypes was carried out to evaluate, in terms of sanitary risks, the consequences of a possible non-interpretation of these phenotypes in patients who would be potential receivers of blood cell products, and in blood donors.