Nonlinear effect of GdnHCl on hydration dynamics of proteins: a 1H magnetic relaxation dispersion study.
Proton magnetic relaxation dispersion investigations with aqueous solutions of lysozyme and bovine serum albumin (BSA) in the 0-5 M range of guanidine hydrochloride (GdnHCl), pH 4.4, 27 degrees C, were taken up with the objective of examining the hydration dynamics of internal cavity waters as the protein is held under increasingly destabilizing conditions. Field cycling NMR and conventional pulsed NMR techniques were employed to cover a frequency range of 100 kHz to 50 MHz. Analyses of dispersion profiles at different concentrations of GdnHCl were carried out considering the contributions from internal and surface waters. The denaturant-dependent variation of internal water contribution indicates that the reorientational disorder of internal waters decreases with increments of the denaturant up to its subdenaturing limit. For both proteins, the variation of effective correlation time with GdnHCl apparently shows a marginal shrink in hydrodynamic volumes under the subdenaturing condition. These results suggest that subdenaturing amounts of GdnHCl restrict the motional freedom of the internal waters, and can have considerable influence on the surface hydration. On increasing the denaturant concentration further, the dispersion amplitude drops sharply, indicating that the chaotropic action of the denaturant now runs over its own cavity water-ordering effect operative in the subdenaturing limit. The results are fundamentally important for the understanding of the susceptibility of protein structure and hydration to denaturants.


Cytoplasmic free Ca2+ in Arabidopsis roots changes in response to touch but not gravity.
Changes in cytoplasmic Ca2+ concentration ([Ca2+]i) have been proposed to be involved in signal transduction pathways in response to a number of stimuli, including gravity and touch. The current hypothesis proposes that the development of gravitropic bending is correlated with a redistribution of [Ca2+]i in gravistimulated roots. However, no study has demonstrated clearly the development of an asymmetry of this ion during root curvature. We tested this hypothesis by quantifying the temporal and spatial changes in [Ca2+]i in roots of living Arabidopsis seedlings using ultraviolet-confocal Ca(2+)-ratio imaging and vertical stage fluorescence microscopy to visualize root [Ca2+]i. We observed no changes in [Ca2+]i associated with the graviresponse whether monitored at the whole organ level or in individual cells in different regions of the root for up to 12 h after gravistimulation. However, touch stimulation led to transient increases in [Ca2+]i in all cell types monitored. The increases induced in the cap cells were larger and longer-lived than in cells in the meristematic or elongation zone. One millimolar La3+ and 100 microM verapamil did not prevent these responses, whereas 5 mM EGTA or 50 microM ruthenium red inhibited the transients, indicating an intracellular origin of the Ca2+ increase. These results suggest that although touch responses of roots may be mediated through a Ca(2+)-dependent pathway, the gravitropic response is not associated with detectable changes in [Ca2+]i.


Diffraction of a plane, finite-radius wave by a spiral phase plate.
We derive analytical expressions containing a hypergeometric function to describe the Fresnel and Fraunhofer diffraction of a plane wave of circular and ringlike cross section by a spiral phase plate (SPP) of an arbitrary integer order. Experimental diffraction patterns generated by an SPP fabricated in resist through direct e-beam writing are in good agreement with the theoretical intensity distribution.


Delinquent Medical Records: Who Are the Stakeholders for Timely Medical Documentation?
The explosion of electronic documentation associated with Meaningful Use-certified electronic health record systems has led to a massive increase in provider workload for completion and finalization of patient encounters. Delinquency of required documentation affects multiple areas of hospital operations. We present the major stakeholders affected by delinquency of the electronic medical record and examine the differing perspectives to gain insight for successful engagement to reduce the burden of medical record delinquency.


Recovery of silver nanoparticles synthesized on AOT/C(12)E(4) mixed reverse micelles by antisolvent CO(2).
Silver nanoparticles were synthesized in sodium bis(2-ethylhexyl)sulfosuccinate (AOT) reverse micelles in isooctane with tetraethylene glycol dodecyl ether (C(12)E(4)) as a cosurfactant. Recovery of the Ag particles from the reverse micelles by dissolving antisolvent CO(2) in the micellar solution was investigated. All the Ag particles in the reverse micelles could be precipitated by compressed CO(2) at suitable pressures, while the surfactants remained in the isooctane continuous phase, and well-dispersed Ag nanoparticles were obtained. The effects of operating conditions on the size and size distribution of the Ag particles were investigated. The particle size decreased with decreasing molar ratio (w) of water to surfactant. A higher CO(2) pressure in the recovery process favored production of smaller particles. A decrease in the molar ratio of reductant KBH(4) to AgNO(3) resulted in larger Ag particles with higher polydispersity.


Behavioral Patterns in Breaking Bad News Communication: An Ethnographic Study with Hematologists.
Hematologists adequately disclosing bad news is a critical point precluding patient-centered communication. Specific courses on communication for hematologists seem to be rare, as well as research exploring their communicative skills and patterns. We aim at describing the hematologists' behavior during difficult conversations to account for behavioral patterns in communication and provide new insights regarding teaching skills to communicate bad news. We employed a focused visual ethnography to answer the following research: "what are hematologists' behavioral patterns in communicating bad news to patients and families?" The collected data included (1) video recordings, (2) observational field notes, (3) interviews with hematologists. The analysis highlighted four patterns: (1) a technical-defensive pattern, (2) an authoritative pattern, (3) a relational-recursive pattern, and (4) a compassionate sharing pattern. Hematologists seem to have difficulty expressing compassionate caring and empathetic comprehension. Communication skills remain a challenge for hematologists. The study of behavioral patterns can lead to increasingly targeted training interventions for this specific learner population.


Additive-Assisted Growth of Scaled and Quality 2D Materials.
2D materials are increasingly becoming key components in modern electronics because of their prominent electronic and optoelectronic properties. The central and premise to the entire discipline of 2D materials lie in the high-quality and scaled preparations. The chemical vapor deposition (CVD) method offers compelling benefits in terms of scalability and controllability in shaping large-area and high-quality 2D materials. The past few years have witnessed development of numerous CVD growth strategies, with the use of additives attracting substantial attention in the production of scaled 2D crystals. This review provides an overview of different additives used in CVD growth of 2D materials, as well as a methodical demonstration of their vital roles. In addition, the intrinsic mechanisms of the production of scaled 2D crystals with additives are also discussed. Lastly, reliable guidance on the future design of optimal CVD synthesis routes is provided by analyzing the accessibility, pricing, by-products, controllability, universality, and commercialization of various additives.


Circular RNA circ0007360 Attenuates Gastric Cancer Progression by Altering the miR-762/IRF7 Axis.
Gastric cancer is a major health burden worldwide. Circular RNAs (circRNAs) are a novel family of noncoding RNAs that are involved in multiple types of cancers, including gastric cancer. As biological functions and the underlying molecular mechanisms of the newly identified circRNA circ0007360 have not been investigated, our present study focused on the role of circ0007360 in the progression of gastric cancer. After characterizing circ0007360 as a cytoplasmic circRNA, we revealed the inhibitory effects of circ0007260 on the survival, migration, invasion, and stemness of gastric cancer cells. Subsequently, miR-762 was identified as a direct target microRNA (miRNA) of circ0007360 and was proved to act as a vital downstream transcript to fulfill the tumor-promoting effects in the absence of circ0007360. Furthermore, we demonstrated that interferon regulatory factor 7 (IRF7), which was validated as a target gene of miR-762, serves as an indirect target of circ0007360 to attenuate the progression of gastric cancer. Moreover, in vivo experiments confirmed the potentiation of gastric cancer cell growth and stemness upon depletion of circ0007360. In summary, our results revealed that activation of the circ0007360/miR-762/IRF7 axis is a novel mechanism for the attenuation of gastric cancer progression. Our study unveils the diagnostic and therapeutic values of circ0007360 in patients with gastric cancer.


Convenient microfluidic cartridge for single-molecule droplet PCR using common laboratory equipment.
We have previously established a cost-efficient in-house system for single-molecule droplet polymerase chain reaction (PCR) using a polydimethylsiloxane microfluidic cartridge and common laboratory equipment. However, the microfluidic cartridge was only capable of generating monodisperse water-in-oil droplets. Therefore, careful and time-consuming manual droplet handling using a micropipette was required to transfer droplets between the three discrete steps involved in the workflow of droplet PCR-i.e., (1) droplet generation; (2) PCR amplification; and (3) determination of the fluorescence intensity of the thermocycled droplets. In the current study, we developed a new microfluidic cartridge consisting of four layers, with a thin glass slide as the bottom layer. In this cartridge, droplets generated in the uppermost polydimethylsiloxane microfluidic layer are delivered to the glass slide in an online fashion. After the accumulation of many droplets on the glass slide, the cartridge is placed on the flatbed heat block of a thermocycler for PCR amplification. Direct fluorescence imaging of the thermocycled droplets on the glass slide is then carried out using a conventional fluorescence microscope. Efficient heat transfer from the heat block to the settled droplets through the thin glass slide was confirmed by successful PCR amplification inside the droplets, even from single template molecules. The new cartridge eliminates the need for manual droplet transfer between the major steps of droplet PCR analysis, allowing more convenient single-molecule droplet PCR than in our previous studies.


[Clinical application of left ventricular volume and ejection fraction derived from gated SPECT data].
Left ventricular (LV) volume and ejection fraction (LVEF) derived from ECG-gated myocardial SPECT data are reproducible and objective. Those quantitative values, however, interacted according to varied factors such as a frame number per R-R interval, tracers, and processing-algorisms. A decrease of frame number per R-R interval yields underestimation of end-diastolic volume and overestimation of end-systolic volume, resulting in underestimation of LVEF. Thus, it is important to change a frame number per R-R interval by the examination purpose. A good correlation of LVEF is usually obtained, independent of a combination of tracer and processing-algorism. On the other hand, LV volume does not always show linearity between combinations of tracer and processing-algorism. An extraction of myocardial edge using QGS program is deteriorating in patients with small LV below 20 ml. It is crucial to assess LV functional values derived from ECG-gated SPECT data as clinical indices, taking the varied effects into consideration.


Selection of T lymphocytes bearing limited T-cell receptor beta chains in the response to a human pathogen.
Delayed-type hypersensitivity (DTH) is a classic measure of T-cell responsiveness to foreign antigen. To estimate the extent of the T-cell repertoire in the DTH response to a human pathogen, we measured T-cell receptor (TCR) beta-chain variable-region (V beta) gene usage in reversal reactions in leprosy. Reversal reactions represent naturally occurring DTH responses in leprosy, in which augmentation of T-cell responses to Mycobacterium leprae is concomitant with clearance of bacilli from lesions. T cells using the V beta 6-, V beta 12-, V beta 14-, and V beta 19-encoded TCRs were strikingly overrepresented in the lesions of patients as compared to blood and pre-DTH lesions from the same individuals. Furthermore, these data indicate a possible association between the predominant expression of a V beta gene segment in lesions and the major histocompatibility complex class II haplotype of the individual. V beta 6 was prominent in the lesions of four patients who were DR15, a marker of resistance in leprosy infection. Sequence analysis of V beta 6 TCRs showed frequent use of V beta 6.1 and J beta 2.7 gene segments and a conserved amino acid motif in the V-J junction in a reversal-reaction lesion, but not in blood from the same patient. The limited TCR repertoire expressed by the infiltrating T cells suggests that a limited set of antigens is recognized in the DTH response to a human pathogen. We suggest that the mechanism by which major histocompatibility complex haplotype influences DTH in this disease involves the presentation of specific peptides, with subsequent selection of specific TCRs followed by local oligoclonal expansion.


A novel mannose-binding lectin from Liparis nervosa with anti-fungal and anti-tumor activities.
Plant lectins are carbohydrate-binding proteins with nonimmune origin, which can reversibly bind with carbohydrates, agglutinate cells, and precipitate polysaccharides and glycoconjugates. Plant lectins have attracted much attention for their anti-virus, anti-proliferation, and pro-apoptosis properties. Thus the exploration of new lectins has received special attention. Here we purified a mannose-binding lectin from the rhizomes of Liparis nervosa by ion exchange chromatography on DEAE-Sepharose, affinity chromatography on Mannose-Sepharose 4B, and gel filtration chromatography on Sephacryl S-100. The purified L. nervosa lectin (LNL) was identified to be a monomeric protein with a molecular mass of 13 kDa. LNL exhibited hemagglutinating activity towards rabbit erythrocytes, and its activity could be strongly inhibited by D-mannose, N-acetyl glucosamine and thyroglobulin. In vitro experiments showed that LNL exhibited a comparable anti-fungal activity against Piricularia oryzae (Cavara), Bipolaris maydis, Fusarium graminearum, and Sclerotium rolfsii, and anti-proliferation activity against tumor cells by inducing apoptosis. The full-length cDNA sequence of LNL is 715 bp in length and contains a 525 bp open reading frame (ORF) encoding a 110-residue mature protein. It was predicted to have three mannose-binding conserved motifs 'QXDXNXVXY'. The binding pattern of LNL was further revealed by homology modeling and molecular docking. We demonstrated that LNL is not only a potential therapeutic candidate against tumor but also a new anti-fungal agent.


Carboxyl Methyltransferase Catalysed Formation of Mono- and Dimethyl Esters under Aqueous Conditions: Application in Cascade Biocatalysis.
Carboxyl methyltransferase (CMT) enzymes catalyse the biomethylation of carboxylic acids under aqueous conditions and have potential for use in synthetic enzyme cascades. Herein we report that the enzyme FtpM from Aspergillus fumigatus can methylate a broad range of aromatic mono- and dicarboxylic acids in good to excellent conversions. The enzyme shows high regioselectivity on its natural substrate fumaryl-l-tyrosine, trans, trans-muconic acid and a number of the dicarboxylic acids tested. Dicarboxylic acids are generally better substrates than monocarboxylic acids, although some substituents are able to compensate for the absence of a second acid group. For dicarboxylic acids, the second methylation shows strong pH dependency with an optimum at pH 5.5-6. Potential for application in industrial biotechnology was demonstrated in a cascade for the production of a bioplastics precursor (FDME) from bioderived 5-hydroxymethylfurfural (HMF).


Grandfathers' and grandmothers' satisfaction with the grandparenting role: seeking new answers to old questions.
A total of 146 Australian grandparents rated their level of satisfaction with grandparenthood as an overall experience and ranked the satisfaction they gained from this role relative to other significant roles in adult life including parenthood, marriage and career. In contrast to the results of a seminal study conducted in the United States three decades ago (Neugarten & Weinstein, 1964), only a small minority (8%) were more dissatisfied than satisfied with the grandparenting role. On the other hand, in line with Neugarten and Weinstein's results, but in contrast to the results of two intervening studies of North American grandparents (Thomas 1986, 1989), there were no significant differences between grandfathers' and grandmothers' levels of satisfaction with grandparenting. Frequent contact with grandchildren predicted high levels of satisfaction in grandparents of both genders, whereas there were no effects of the grandparent's own age or marital status, or of the grandchildren's gender, age or number. In addition to the two main gratifications of biological renewal and emotional fulfillment reported by Neugarten and Weinstein, these older Australians frequently reported the opportunities to observe their grandchildren's development and share in their activities as the best features of grandparenthood, while lack of frequent enough contact was the worst feature.


Genome-wide profiling of long non-coding RNA expression patterns in the EGFR-TKI resistance of lung adenocarcinoma by microarray.
Mutations in the epidermal growth factor receptor (EGFR) make lung adenocarcinoma cells sensitive to EGFR tyrosine kinase inhibitors (TKIs). Long-term cancer therapy may cause the occurrence of acquired resistance to EGFR TKIs. Long non-coding RNAs (lncRNAs) play important roles in tumor formation, tumor metastasis and the development of EGFR-TKI resistance in lung cancer. To gain insight into the molecular mechanisms of EGFR-TKI resistance, we generated an EGFR-TKI-resistant HCC827-8-1 cell line and analyzed expression patterns by lncRNA microarray and compared it with its parental HCC827 cell line. A total of 1,476 lncRNA transcripts and 1,026 mRNA transcripts were dysregulated in the HCC827‑8-1 cells. The expression levels of 7 chosen lncRNAs were validated by real-time quantitative PCR. As indicated by functional analysis, several groups of lncRNAs may be involved in the bio-pathways associated with EGFR-TKI resistance through their cis- and/or trans‑regulation of protein-coding genes. Thus, lncRNAs may be used as novel candidate biomarkers and potential targets in EGFR-TKI therapy in the future.


Application of ultrasound-guided intranodal lymphangiography and embolisation in cancer patients with postoperative lymphatic leakage.
Traumatic lymphatic leakage is a rare but potentially life-threatening complication. The purpose of this study was to introduce ultrasound-guided intranodal lymphangiography and embolisation techniques for postoperative lymphatic leakage in patients with cancer. From January 2018 through June 2020, seven cancer patients (three males, four females, aged 59-75 years [mean 67.57 ± 6.11 years]) developed lymphatic leakage after abdominal or pelvic surgery, with drainage volumes ranging from 550 to 1200 mL per day. The procedure and follow-up of ultrasound-guided intranodal lymphangiography and embolisation were recorded. This study retrospectively analysed the technical success rate, operative time, length of hospital stay, clinical efficacy, and complications. The operation was technically successful in all patients. Angiography revealed leakage, and embolisation was performed in all seven patients (7/7, 100%). The operative time of angiography and embolisation was 41 to 68 min, with an average time of 53.29 ± 10.27 min. The mean length of stay was 3.51 ± 1.13 days. Lymph node embolisation was clinically successful in five patients (5/7, 71.43%), who had a significant reduction in or disappearance of chylous ascites. The other two patients received surgical treatment 2 weeks later due to poor results after embolisation. All patients were followed for 2 weeks. No serious complications or only minor complications were found in all the patients. Ultrasound-guided intranodal lymphangiography and embolisation were well tolerated by the patients, who experienced a low incidence of complications. Early intervention is recommended for cancer patients with postoperative lymphatic leakage.


Stable silver(I) hydride complexes supported by diselenophosphate ligands.
The first stable structure of silver(I) cluster cations [Ag(8)(mu(4)-H){Se(2)P(OR)(2)}(6)](+) [R = (i)Pr, 1; Et, 2] containing Ag(I)-hydride bridges (Ag-mu-H-Ag) in T symmetry was reported. The clusters having an interstitial hydride were composed of an octanuclear silver core in tetracapped tetrahedral geometry, which was inscribed within a Se(12) icosahedron represented by six dialkyl diselenophosphate ligands in a tetrametallic-tetraconnective (mu(2), mu(2)) bonding mode. The presence of hydride was unequivocally corroborated by both (1)H and (109)Ag NMR spectroscopies of which a nonet in the (1)H NMR spectrum for the hydride resonance coupled with a doublet peak observed in the (109)Ag NMR spectrum clearly suggests that eight silver nuclei are equivalent in the NMR time scale and a fast exchange of the positions between the vertex and capping silver atoms in solution must occur. The hypothesis was also supported by a density functional theory (DFT) investigation on a simplified model [Ag(8)(H)(Se(2)PH(2))(6)](+), which confirmed that the Ag(8)H cubic core of T(h) symmetry may not be formed as it is energetically highly unfavorable (0.67 eV less stable than the T structure).


Cultural, behavioral, social, and psychological perceptions of saliva: relevance to clinical diagnostics.
The search for a resource that can be used to detect a broad range of diseases easily and reliably is akin to a search for the diagnostic Holy Grail. Yet, each of us may have inside our mouths, a key to the pathological and disease biomarker library hidden inside our bodies. Saliva--the source of all this information--is the secretory product of glands located in or around the oral cavity. If one could read the stories of diagnostic information present within saliva, then the abundance of information waiting to be found could be comparable to a vast vault of information, such as the Internet. Upon dissection of this data, it would be seen that the source of this information is from saliva's origin as a filtrate of blood, and that the validity of both mediums should be equal. Although one day this may be the view, most people's hold of saliva, current and past cultures, have fared much more diverse meanings to the secretion. Ivan Pavlov's experiments has shown how closely tied salivation is with the thought of food, one of life's primary indulgences. The relationship between salivation and behaviors within our daily lives is undeniable. Yet most people never appreciate the uniqueness of saliva. Throughout the world, saliva carries definite positive and negative connotations, based upon its social, psychological, behavioral, and cultural settings. The thought of saliva may be viewed as grotesque in one population, yet may be the vehicle of blessing in other cultures. Saliva's double nature brings up some interesting cultural, social, behavioral, and psychological points about how saliva is perceived in the world, some of which are subsequently stated in order to present saliva as the spirited fluid it is.


Expression of p53 in premalignant and malignant squamous epithelium.
Using three antibodies (JG8, CM-1 and 1081) directed to the p53 protein, strong positivity was found in 16/47 (34.0%) of mucosal squamous cell carcinomas of the head and neck and in two squamous carcinoma cell lines (LICR-LON- HN5 and HN6Rr). The presence of the mutant p53 was confirmed in the cell lines as substitutions in exon 7 (codon 238, TGT greater than AGT) and exon 5 (codon 152, CCG greater than CTG) respectively. Positive staining was seen only in the undifferentiated cells and progressively lost as the cells keratinized, both in the tumour specimens and in the cell lines. Similar results were seen in areas of dysplasia, well removed from the site of the primary tumour. Staining of epidermal lesions showed positivity in 2/12 (16.6%) cases of Bowen's disease, 0/12 (0.0%) cases of solar keratosis, 0/10 (0.0%) basal cell carcinomas and in 3/20 (15.0%) squamous cell carcinomas. These results are discussed in relation to the multifocal origin of squamous cell carcinomas, the role of p53 mutations in squamous cell carcinomas from different sites and the significance of the 'basal' distribution of p53 as a normal growth regulator. The possible significance of the distribution of p53 in squamous epithelium as it relates to papilloma virus infection is also considered.


Green Chemistry in the Extraction of Natural Dyes from Colored Food Waste, for Dyeing Protein Textile Materials.
The beetroot peels can be a sustainable source of betalains that can dye the wool materials through green processes based on low water and energy consumption. Green chemistry in the extraction of betalains from colored food waste/peels from red beetroot involved the use of water as a solvent, without other additives. In order for the extract obtained to be able to dye the wool, it was necessary to functionalize betalains or even the wool. Three types of sustainable functionalizations were performed, with (1) acetic acid; (2) ethanol; and (3) arginine. For each functionalization, the mechanism that can justify dyeing the wool in intense colors was elucidated. The characterization of the extract was performed with the data provided by UV-VIS and HPLC-MS analyses. The characterization of the wool dyed with the extract obtained from the red beetroot peels was possible due to the information resulting from the FTIR and CIELab analyses. The functionalizations of betalains and wool in acid environments lead to the most intense red colors. The color varies depending on the pH and the concentration of betalains.


UDP-glucose: Glucan Synthetase in Developing Cotton Fibers: II. Structure of the Reaction Product.
The solubility properties, composition, and structure of the radioactive product synthesized from UDP-[(14)C]glucose by a highly active cotton fiber glucan synthetase have been determined. Product obtained under the following three different conditions was analyzed: at high and low substrate concentrations by detached fibers, and at high substrate concentrations with an isolated particulate preparation. The results of acetic and nitric acid digestion, enzyme digestion, total acid hydrolyses, periodate oxidation, partial acid hydrolyses, and methylation analyses all support the conclusion that the product of the glucan synthetase produced under all three assay conditions is a linear beta-(1-->3)-glucan.


Primary extragastrointestinal stromal tumors in the omentum and mesentery: a clinicopathological and immunohistochemical study.
This study aimed to describe the clinical, histological and immunohistochemical characteristics of primary extragastrointestinal stromal tumors (EGISTs) of the omentum and mesentery diagnosed in the Hospital 12 de Octubre, in Madrid, Spain, from 1993-2005. The clinical data and histological and immunohistochemical findings of primary mesenchymal neoplasias were revised using the Department of Pathological Anatomy databases. Six EGISTs were identified. Three were primarily of the omentum and 3 mesenteric. They were found in 4 males and 2 females with an average age of 65.16 years. All were c-KIT positive, and the majority CD34 positive, while 3 were positive for muscle-specific actin. The 3 omentum cases had a mixed spindle/epithelioid pattern and low mitotic rate, while the 3 mesenteric cases had a spindle pattern, with a high mitotic rate in 2 cases, where hepatic metastasis appeared at 6 and 32 months respectively. The 3 omentum cases were alive at the time of writing, and free of disease at 16, 21 and 34 months of follow-up. EGISTs represent 11.9% of GIST cases diagnosed in the hospital over the period 2000-2005. In this study primary EGISTs of the omentum and mesentery showed clinicopathological and immunohistochemical characteristics similar to those previously in the literature for GISTs of the digestive tract, which supports the hypothesis that these tumors originate from extragastrointestinal c-KIT positive cells. Mesenteric location appears to be associated with a poorer prognosis.


Expectancy and risk for alcoholism: the unfortunate exploitation of a fundamental characteristic of neurobehavioral adaptation.
Psychological investigations of alcohol expectancies over the last 20 years, using primarily verbal techniques, have strongly supported expectancies as an important mediator of biological and environmental antecedent variables that influence risk for alcohol use and abuse. At the same time, rapid developments in neuroscience, cognitive science, affective science, computer science, and genetics proved to be compatible with the concept of expectancy and, in some cases, used this concept directly. By using four principles that bear on the integration of knowledge in the biological and behavioral sciences-consilience, conservation, contingency, and emergence-these developments are merged into an integrated explanation of alcoholism and other addictions. In this framework, expectancy is seen as a functional approach to adaptation and survival that has been manifested in multiple biological systems with different structures and processes. Understood in this context, addiction is not a unique behavioral problem or special pathology distinct from the neurobehavioral substrate that governs all behavior, but is rather a natural (albeit unfortunate) consequence of these same processes. The ultimate intent is to weave a working heuristic that ties together findings from molecular and molar levels of inquiry and thereby might help direct future research. Such integration is critical in the multifaceted study of addictions.


Alprazolam in the treatment of panic disorders.
An open clinical trial of alprazolam therapy of patients with panic disorder or agoraphobia with panic attacks was undertaken to clarify certain issues not resolved by previous studies. These included the proportion of patients who significantly improve with alprazolam; the relative time courses for improvement in panic attacks, anticipatory anxiety, and phobic avoidance; whether successful alprazolam treatment alters vulnerability to panic with sodium lactate infusion; and what factors predict response to alprazolam in panic patients. Thirty patients meeting DSM-III criteria for panic disorder or agoraphobia with panic attacks completed a 12-week open clinical trial, and 22 were considered responders. In responders, panic attacks showed rapid improvement, whereas improvement of anticipatory anxiety and phobic avoidance was more variable. Successful alprazolam therapy appeared to block lactate vulnerability. High pretreatment Hamilton Anxiety Scale scores were associated with poor treatment response. The data suggest that alprazolam is an effective treatment for panic disorder and agoraphobia with panic attacks, and acts by directly blocking panic attacks.


Primary Cutaneous Interdigitating Dendritic Cell Sarcoma: A Case Report and Review of the Literature.
Interdigitating dendritic cell sarcoma (IDCS) is defined as a neoplastic proliferation of spindle to ovoid cells with phenotypic features similar to those of interdigitating dendritic cells, which are present in the T cell-rich areas of lymphoid organs and participate as antigen-presenting cells responsible for initiating primary T lymphocyte immune response. IDCS usually presents with lymphadenopathy. Solitary lymph node involvement is often seen. Extra nodal presentation has been described as well. Cutaneous lesions are extremely rare, and less than 10 cases have been previously documented in medical literature. Here, the authors describe another primary cutaneous IDCS in a 42-year-old patient and review the literature.


Recent advances in post-kala-azar dermal leishmaniasis.
Post-kala-azar dermal leishmaniasis (PKDL) is a challenge for clinicians and researchers, because its burden is poorly investigated and pathogenesis is disputable. However, recent studies contributed to understanding of the pathogenesis of PKDL especially its association with host immunological factors, and also how to improve its diagnosis and treatment. This review focuses on recent advances in diagnosis, new insights into pathogenesis and case management. Information regarding the burden of PKDL, especially in Bangladesh, is now available. Association between skin parasite burden and different clinical forms of PKDL has been explored. The diagnostic importance of detection of Leishmania donovani DNA in the peripheral blood buffy coat and in skin specimens by PCR has been studied. Variable effects of different antileishmanial drugs on immune response have been observed. Finally, high efficacy of miltefosine for treatment of PKDL has been demonstrated. The incidence of PKDL is reducing in India after introduction of miltefosine and amphotericin B for treatment of visceral leishmaniasis. It remains higher in Bangladesh and in Sudan. Parasite burden is higher in nodular and papular forms of PKDL compared to the macular form of the disease. The demonstration of Leishmania DNA in peripheral blood buffy coat and in skin specimens can help to diagnose 40-75% clinically suspected PKDL individuals. An initial cure rate of 95% has been achieved with miltefosine for treatment of PKDL. However, the efficacy of combination therapy should be explored to reduce the treatment duration and hence to improve treatment compliance.


Negative regulation of the adeno-associated virus (AAV) P5 promoter involves both the P5 rep binding site and the consensus ATP-binding motif of the AAV Rep68 protein.
Transcript levels from the P5 promoter of adeno-associated virus type 2 (AAV) are negatively regulated by the AAV Rep78 and Rep68 proteins in the absence of helper virus. We have identified a Rep-responsive negative cis element of the P5 promoter between the P5 TATA box and transcription start site by using 5' and 3' deletions of the P5 promoter fused to the chloramphenicol acetyltransferase gene. This element contains four imperfect GAGC repeats similar to the Rep recognition sequences (RRSs) in the AAV inverted terminal repeats and in the AAV preferred integration locus in chromosome 19. Band shift analyses showed that human 293 cell nuclear extracts containing Rep68 or Rep68/K340H, a putative nucleoside triphosphate (NTP)-binding-site mutant of Rep68, formed Rep-specific complexes with this P5 RRS DNA. Within the P5 RRS, mutation of a cytosine at position 273 in the AAV sequence to guanine abolished Rep68 binding to the DNA. A mutation in the P5 RRS within a full-length AAV genome, which abolished Rep binding, resulted in a 40 to 50% reduction in the ability of wild-type Rep68 to inhibit the accumulation of P5 transcripts in vivo. In contrast, the Rep68/K340H mutant was unable to down-regulate this mutated promoter. These results indicate that there are at least two mechanisms involved in the negative regulation of P5 transcript levels by Rep68; one involves Rep68 binding to the P5 RRS, and another requires the region of Rep68 containing the consensus NTP-binding motif. Furthermore, our studies of AAV genomes containing mutated RRS- and/or YY1-binding elements suggest that transcription factor YY1 binding to the transcription start site of P5 interferes with Rep68 repression of the P5 promoter.


Adenine nucleotide content of corn roots as affected by injury and subsequent washing.
The adenine nucleotide content of the 2-centimeter segments excised from tray-grown corn (Zea mays L., WF9 x Mo17) roots declines for the first hour after excision. Concomitant with the loss of adenine nucleotides is a decline in respiration and a leakage of K(+). With continued washing, these parameters partially or completely recover and increased phosphate influx develops. Increasing the wound effect by cutting 0.5-centimeter segments gives a more rapid and pronounced degradation of adenine nucleotides and slower recovery. Conversely, the mild injury caused by submerging intact roots induces less degradation and produces greater net adenine nucleotide synthesis during recovery; adding auxin to the washing medium produces a similar result. With all treatments, there is stabilization of energy charge at about 0.85.Brief submersion or rubbing of intact roots, as well as recutting washed and recovered root segments, will initiate the transient loss of adenine nucleotides but will not induce increased phosphate influx.It is suggested that the loss in adenine nucleotides may reflect homeostasis in energy charge via catabolism arising from membrane permeability changes.


Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process.
The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution.


Virtual assessments of knee and wrist joint range motion have comparable reliability with face-to-face assessments.
There has been increased usage of virtual telerehabilitation approach during the COVID-19 pandemic. It is crucial to establish reliability of conducting virtual assessments for musculoskeletal conditions. This research determined the intra- and interrater reliability of measuring knee and wrist range of motion (ROM) assessed virtually and obtained face-to-face (F2F) using a goniometer (UG) for a student and an experienced examiner. Knee and wrist joint ROM for 54 healthy participants was assessed virtually and F2F by a student examiner and an experienced physical therapist. Intra- (virtual vs. UG assessment) and inter-rater (virtual or UG assessment between examiners) reliabilities were examined for all ROM using Intraclass correlation coefficient (ICC). The ICC values were considered good (>0.75) or excellent (>0.90). Bland and Altman plots determined the limits of agreement (LOA) in assessing joint ROM. Student examiner had good reliability in virtually estimating knee extension (ICC = 0.79), wrist flexion (ICC = 0.82) and wrist extension (ICC = 0.78), whereas the experienced examiner had excellent reliability in virtually estimating all knee and wrist ROM (ICC > 0.90). The LOA in assessing knee and wrist ROM for the student examiner were wider indicating higher disagreement between virtual and UG-obtained ROM in some cases. Virtual estimation of knee and wrist ROM is a reliable technique, however experience level impacts the precision of measurement. It is suggested that the same examiner conducts all the ROM assessments throughout the clinical course of a patient receiving virtual interventions for knee or wrist pathologies.


Detection of clonal evolution in hematopoietic malignancies by combining comparative genomic hybridization and single nucleotide polymorphism arrays.
Array comparative genomic hybridization (aCGH) has become a powerful tool for analyzing hematopoietic neoplasms and identifying genome-wide copy number changes in a single assay. aCGH also has superior resolution compared with fluorescence in situ hybridization (FISH) or conventional cytogenetics. Integration of single nucleotide polymorphism (SNP) probes with microarray analysis allows additional identification of acquired uniparental disomy, a copy neutral aberration with known potential to contribute to tumor pathogenesis. However, a limitation of microarray analysis has been the inability to detect clonal heterogeneity in a sample. This study comprised 16 samples (acute myeloid leukemia, myelodysplastic syndrome, chronic lymphocytic leukemia, plasma cell neoplasm) with complex cytogenetic features and evidence of clonal evolution. We used an integrated manual peak reassignment approach combining analysis of aCGH and SNP microarray data for characterization of subclonal abnormalities. We compared array findings with results obtained from conventional cytogenetic and FISH studies. Clonal heterogeneity was detected in 13 of 16 samples by microarray on the basis of log2 values. Use of the manual peak reassignment analysis approach improved resolution of the sample's clonal composition and genetic heterogeneity in 10 of 13 (77%) patients. Moreover, in 3 patients, clonal disease progression was revealed by array analysis that was not evident by cytogenetic or FISH studies. Genetic abnormalities originating from separate clonal subpopulations can be identified and further characterized by combining aCGH and SNP hybridization results from 1 integrated microarray chip by use of the manual peak reassignment technique. Its clinical utility in comparison to conventional cytogenetic or FISH studies is demonstrated.


Modifications of the mouse zona pellucida during oocyte maturation and egg activation: effects of newborn calf serum and fetuin.
A precocious but limited loss of cortical granules (CG) occurs during mouse oocyte maturation both in vivo and in vitro. Although CG loss during maturation in vivo is not associated with changes in the zona pellucida (ZP), a maturation-associated conversion of ZP2 to ZP2f occurs during oocyte maturation in vitro in serum-free medium. We now demonstrate that a maturation-associated change of ZP3 to ZP3f, as assessed by a reduction in sperm binding, also occurs during maturation in vitro in serum-free medium, and that both newborn calf serum (NCS) and fetuin, each of which inhibits the ZP2 conversion, also inhibit the ZP3 conversion. The concentration-dependence of the NCS- and fetuin-mediated inhibition of the ZP2 conversion, coupled with the concentration of fetuin present in NCS, is consistent with fetuin being the component present in NCS that is primarily responsible for this inhibition. Although NCS can inhibit the ZP modifications that occur during oocyte maturation in vitro, ionophore treatment of eggs, which results in an extensive release of CGs over a short period of time, overcomes the inhibitory effect of NCS on the ZP2 conversion. Results of these studies suggest a potential regulatory function of serum-derived components in the formation of a fertilizable egg.


p21Waf1 expression is regulated by nuclear intermediate filament vimentin in neuroblastoma.
Human neuroblastoma (NB) cell lines may present with either one of the so-called S-and N-subtypes. We have previously reported a strong correlation between protein expression levels of vimentin, an S-subtype marker, and the p21Waf1 cyclin-dependent kinase inhibitor. We here investigated whether this correlation extend to the mRNA level in NB cell lines as well as in patients' tumors. We also further explored the relationship between expression of vimentin and p21, by asking whether vimentin could regulate p21 expression. Vimentin and p21 mRNA levels in NB cell lines as well as in patients' tumors (n = 77) were quantified using Q-PCR. Q-PCR data obtained from tumors of high risk NB patients (n = 40) were analyzed in relation with the overall survival using the Log-rank Kaplan-Meier estimation. siRNA-mediated depletion or overexpression of vimentin in highly or low expressing vimentin cell lines, respectively, followed by protein expression and promoter activation assays were used to assess the role of vimentin in modulating p21 expression. We extend the significant correlation between vimentin and p21 expression to the mRNA level in NB cell lines as well as in patients' tumors. Overall survival analysis from Q-PCR data obtained from tumors of high risk patients suggests that lower levels of p21 expression could be associated with a poorer outcome. Our data additionally indicate that the correlation observed between p21 and vimentin expression levels results from p21 transcriptional activity being regulated by vimentin. Indeed, downregulating vimentin resulted in a significant decrease in p21 mRNA and protein expression as well as in p21 promoter activity. Conversely, overexpressing vimentin triggered an increase in p21 promoter activity in cells with a nuclear expression of vimentin. Our results suggest that p21 mRNA tumor expression level could represent a refined prognostic factor for high risk NB patients. Our data also show that vimentin regulates p21 transcription; this is the first demonstration of a gene regulating function for this type III-intermediate filament.


Evaluation of factors promoting astaxanthin production by a unicellular green alga, Haematococcus pluvialis, with fractional factorial design.
Factors affecting the astaxanthin production by a unicellular green alga, Haematococcus pluvialis UTEX 16, were evaluated with sequential fractional factorial design. To simulate an actual production mode, a two-stage process was adapted for astaxanthin production: the alga was first cultivated under vegetative growth conditions, and then astaxanthin production was induced by applying various induction methods. A high dose of irradiation was most effective for the production of astaxanthin both in weight (mg/g) and in cellular (pg/cell) contents. A combination of nitrogen deficiency and acetate addition also significantly increased the astaxanthin content of cells on a dry weight basis. Meanwhile, the acetate addition alone increased only the cellular content of astaxanthin. Although the addition of ferrous ion alone had a negative effect on the weight content of astaxanthin, simultaneous addition of ferrous ion and acetate was effective for increasing the cellular content of astaxanthin.


MagicFinger: 3D Magnetic Fingerprints for Indoor Location.
Given the indispensable role of mobile phones in everyday life, phone-centric sensing systems are ideal candidates for ubiquitous observation purposes. This paper presents a novel approach for mobile phone-centric observation applied to indoor location. The approach involves a location fingerprinting methodology that takes advantage of the presence of magnetic field anomalies inside buildings. Unlike existing work on the subject, which uses the intensity of magnetic field for fingerprinting, our approach uses all three components of the measured magnetic field vectors to improve accuracy. By using adequate soft computing techniques, it is possible to adequately balance the constraints of common solutions. The resulting system does not rely on any infrastructure devices and therefore is easy to manage and deploy. The proposed system consists of two phases: the offline phase and the online phase. In the offline phase, magnetic field measurements are taken throughout the building, and 3D maps are generated. Then, during the online phase, the user's location is estimated through the best estimator for each zone of the building. Experimental evaluations carried out in two different buildings confirm the satisfactory performance of indoor location based on magnetic field vectors. These evaluations provided an error of (11.34 m, 4.78 m) in the (x; y) components of the estimated positions in the first building where the experiments were carried out, with a standard deviation of (3.41 m, 4.68 m); and in the second building, an error of (4 m, 2.98 m) with a deviation of (2.64 m, 2.33 m).


Regulation of neuroinflammation by B cells and plasma cells.
The remarkable success of anti-CD20 B cell depletion therapies in reducing the burden of multiple sclerosis (MS) disease has prompted significant interest in how B cells contribute to neuroinflammation. Most focus has been on identifying pathogenic CD20+ B cells. However, an increasing number of studies have also identified regulatory functions of B lineage cells, particularly the production of IL-10, as being associated with disease remission in anti-CD20-treated MS patients. Moreover, IL-10-producing B cells have been linked to the attenuation of inflammation in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. In addition to IL-10-producing B cells, antibody-producing plasma cells (PCs) have also been implicated in suppressing neuroinflammation. This review will examine regulatory roles for B cells and PCs in MS and EAE. In addition, we speculate on the involvement of regulatory PCs and the cytokine BAFF in the context of anti-CD20 treatment. Lastly, we explore how the microbiota could influence anti-inflammatory B cell behavior. A better understanding of the contributions of different B cell subsets to the regulation of neuroinflammation, and factors that impact the development, maintenance, and migration of such subsets, will be important for rationalizing next-generation B cell-directed therapies for the treatment of MS.


How many social workers are needed in primary care? A patient-based needs assessment example.
This study measured levels of self-reported social need in a sample of 684 veterans seen in four primary care clinics of a large Veterans Affairs health care system, using the Social Needs Checklist, and calculated levels of social work staffing to meet these needs. Data were obtained on the presence and severity of 15 areas of social needs, housing status, patient requests for social work services, and current access to other providers for social services. Data were also obtained from primary care social workers who estimated the average time needed to provide basic social work services. Nearly two-thirds of the sample had problems related to finances and personal stress. Three in four patients reported multiple needs. One-third requested social work services. Social work staffing needed for highest acuity patients was estimated to be 61 percent higher than actual staffing available. The study presents a method of estimating staffing levels based on social needs reported by patients.


Array-enhanced coherence resonance and forced dynamics in coupled FitzHugh-Nagumo neurons with noise.
Nonlinear dynamics of coupled FitzHugh-Nagumo neurons subject to independent noise is analyzed. A kind of self-sustained global oscillation with almost synchronous firing is generated by array-enhanced coherence resonance. Further, forced dynamics of the self-sustained global oscillation stimulated by sinusoidal input is analyzed and classified as synchronized, quasiperiodic, and chaotic responses just like the forced oscillations in nerve membranes observed by in vitro experiments with squid giant axons. Possible physiological importance of such forced oscillations is also discussed.


Phenytoin overdose treated with hemodialysis using a high cut-off dialyzer.
We describe the case of a 52-year-old man who presented after having ingested an unknown quantity of phenytoin. Peak phenytoin concentration was 51.2 mg/L (therapeutic range 10-20 mg/L). Five days after admission, the patient became comatose and was intubated. Because of persistent toxic phenytoin levels and unchanged clinical status for 12 days, hemodialysis (HD) was prescribed to enhance elimination of phenytoin. HD was performed using a Gambro TheraliteTM filter (Baxter International Inc., Deerfield, USA), a high cut-off filter that allows the removal of molecules of up to 45 kDa. Phenytoin concentration readily decreased during the 8-hour HD treatment from 38.9 mg/L to 27.8 mg/L (28.5% decrease); during HD, phenytoin half-life was 18.5h (compared to 1109.8h before HD and 56.3h after HD), phentyoin clearance averaged 80.1 mL/min and a total of 1.1 g of phenytoin was removed. Albumin removal from the Theralite filter was most important at the beginning of HD. The high clearance of phenytoin obtained with this filter was likely due to its high surface area rather than its capacity to remove the albumin-phenytoin complex.


Success of cardiopulmonary resuscitation after heart attack in hospital and outside hospital.
To determine factors associated with cardiopulmonary resuscitation being attempted after cardiac arrest from myocardial infarction, in or outside hospital, and estimate short term and long term survival rates. Descriptive cross sectional and cohort study. Community based register of all suspected heart attacks and sudden cardiac deaths in Lower Hunter region of New South Wales, Australia. 4924 men and women aged 25-69. Rates of attempted cardiopulmonary resuscitation and survival after successful resuscitation. Cardiopulmonary resuscitation was attempted in 41% of cases of cardiac arrest after myocardial infarction outside hospital and 63% of cases in hospital. Survival rates at 28 days were 12% and 39% respectively. Among the survivors, although 41% had another myocardial infarction (or coronary death), 81% of both groups were still alive two years later. Younger and better educated people were more likely to receive cardiopulmonary resuscitation in either setting, and being married predicted cardiopulmonary resuscitation being attempted outside hospital. Younger age predicted better survival rates after attempted resuscitation in hospital. The reasons for better education to predict cardiopulmonary resuscitation being attempted need explanation. The higher survival rate after cardiopulmonary resuscitation in hospital compared with outside hospital and the good long term prognosis for survivors in both settings suggest that attempts to improve success of cardiopulmonary resuscitation outside hospital may be worth while.


[Alcohol withdrawal syndrome in the hospital].
Contrary to widely held belief, physical dependency is not systematic in alcohol dependence. Alcohol withdrawal syndrome can appear even without stopping (or sharply decreasing) high or chronic alcohol intake. It occurs through revelation of a physicochemical cerebral response (membrane changes and decrease in modulation systems) to chronic intoxication. Given the differences in severity, the lability of symptoms and the rapid evolution of the syndrome, the repeated use of scales to evaluate intensity is suggested. Management should be based on this index in order to treat minor forms and to avoid a course to severe forms, which should be transferred to the intensive care unit.


Postprandial lipoprotein composition in pigs fed diets differing in type and amount of dietary fat.
To determine the effects of diet on postprandial lipoprotein composition, growing pigs were fed diets containing 20 or 40% of energy as soybean oil, tallow or a 50:50 blend of soybean oil and tallow. At the end of wk 6, a blood sample was drawn from pigs fasted for 12 h. Pigs were then fed, and blood samples were drawn 1 and 4 h later. In LDL, concentrations of free and total cholesterol were greater in pigs fed 40% of energy as fat than in pigs fed 20% of energy as fat (P less than 0.02). Pigs fasted for 12 h had lesser concentrations of triacylglycerol and greater concentrations of phospholipid in LDL and HDL than did pigs fasted for 1 and 4 h (P less than 0.05). In HDL, total cholesterol and phospholipid concentrations were greater in pigs fed 40% of energy as fat than in pigs fed 20% of energy as fat (P less than 0.01). A greater concentration of triacylglycerol was found in VLDL of pigs fed 40% of energy as fat than in pigs fed 20% of energy as fat (P less than 0.01). Amount of dietary fat had a greater effect than did type of dietary fat on composition of lipoproteins from postprandial pigs.


Combination of sustained off-resonance irradiation and on-resonance excitation in FT-ICR.
Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry is becoming more widely used among the mass spectrometric techniques and has excellent figures of merit. Ion activation and fragmentation via sustained off-resonance irradiation (SORI) collision-induced dissociation (CID) is commonly used in FT-ICR. However, one of the limitations of SORI-CID is that only low-energy processes are typically observed in the product ion spectra. Here we present another option for performing CID in FT-ICR, a combination of SORI and on-resonance excitation (RE), termed SORI-RE. In comparison to SORI, this method produces more abundant ions resulting from higher energy fragmentation pathways. The result is the observation of a significant abundance of both higher and lower energy fragmentation pathways in the same mass spectrum. The comparison of SORI, RE, and SORI-RE spectra may lead to mechanistic insights as the relative abundances of certain fragment ions change as a function of internal energy deposition. This technique is simple to incorporate in existing instruments, does not require hardware or software modification, and requires only an additional 20-40 ms acquisition time. The technique is illustrated for a peptide (YGGFL), two disaccharides differing in the position of the glycosidic linkage (2alpha-mannobiose, 3alpha-mannobiose), an oligosaccharide (Alditol XT), a small protein (ubiquitin), and an inorganic cation (UO2+). Examples of higher energy fragmentation pathways enhanced by SORI-RE include the formation of immonium ions and oligosaccharide cross-ring cleavages.


Immunohistochemical diagnosis of systemic bovine zygomycosis by murine monoclonal antibodies.
Murine monoclonal antibodies (Mabs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Rhizopus arrhizus (Rhizopus oryzae) were produced in vitro by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. Supernatants reacting only with homologous antigens in an enzyme-linked immunosorbent assay were subsequently screened for reactivity with homologous fungi in immunohistochemical techniques. All four Mabs raised against the WF of A. arrhizus failed to react on tissues. However, four of the Mabs raised against the WSSA of R. arrhizus (Mab-WSSA-RA-1 through Mab-WSSA-RA-4) revealed a high homologous reactivity on tissues and the cross-reactivity of these were subsequently evaluated on tissues containing other members of the family Mucoraceae and other unrelated fungi. On tissues and on immunoblots all four Mabs reacted identically and specifically with members of the family Mucoraceae, i.e., Absidia corymbifera, R. arrhizus, and Rhizomucor pusillus. The Mabs were all isotyped as IgM antibodies, were nonprecipitating, and reacted with homologous antigens with molecular masses from I4 to 110 kDa. With WSSA from A. corymbifera and R. pusillus the four Mabs were bound to antigens from 14 to 52 kDa and from 20 to 28 kDa, respectively. The diagnosis of 145 bovine lesions obtained by one of the specific Mabs (Mab-WSSA-RA-1) were compared to results obtained by heterologously absorbed polyclonal antibodies. In most lesions (n = 140 [approximately 97%]) the Mab and the polyclonal antibodies reacted in a similar pattern, i.e., positively for zygomycosis in 89 lesions, negatively in 41 aspergillosis lesions, and negatively in 10 undiagnosed lesions. Hyphae within two of four lesions in lymph nodes, which were not stained by the polyclonal antibodies, reacted with the specific Mab. However, in another three lesions of lymph nodes stained by the polyclonal antibodies no reactivity was seen with the Mab-WSSA-RA-1. The immunoreactivity of the Mabs (Mab-WSSA-RA-1 through Mab-WSSA-RA-4) raised against WSSA of R. arrhizus justify their application for the in situ diagnosis of systemic bovine zygomycosis.


[A case of schistosomiasis suspected by circumoval precipitin test and diagnosed by rectal biopsy].
A forty-year-old female from Brazil was admitted to Teikyo Hospital because of easy fatigability, fullness of the abdomen and left hyochondralgia. She was anxious about Schistosoma mansoni infection, because three of her relatives died of the infection. Physical examinations revealed a tenderness at the left hypochondrium. Laboratory data showed no abnormal finding. No egg of S. mansoni was found in the stool. A circumoval precipitin test (COPT) with the serum showed a deposite around the egg. Enzyme-linked immunosorbent assay (ELISA) revealed the presence of antibody against S. mansoni in the serum. A colonoscopy showed no abnormal finding macroscopically. The rectal biopsy showed the existence of mild procitis. The diagnosis was made by finding the characteristic lateral-spined eggs in the biopsy specimens from the rectum. Treatment of 3 g of prazicantel per day for three days was started. She complained of mild nausea at the first dosing. A month later, another three-day-treatment was given. In the case where there are no eggs found in the stool, COPT and ELISA are usefull in detecting the disease, and colonoscopy is recommended in diagnosing the disease.


A case report of the management of demodicosis in the golden hamster.
A 1.6 year-old male golden hamster was presented with alopecia on the back. The animal's physical condition was slightly below normal, and moderate pruritus was observed. Examination of skin scraping revealed mites identified as Demodex sp. Initially, combined therapy using 1% of selenium sulfide shampoo and a topical application of 0.013% amitraz was carried out, although this was not completely successful. Repeated use of 0.017% coumaphos was effective in achieving a complete cure of the alopecia associated with demodicosis. No adverse side effects were recognized during the treatment of this case.


Different patterns of BK and JC polyomavirus reactivation following renal transplantation.
Reactivation of latent BK polyomavirus (BKV) infection is relatively common following renal transplantation and BKV-associated nephropathy has emerged as a significant complication. JC polyomavirus (JCV) reactivation is less well studied. The aim of the study was to determine reactivation patterns for these polyomaviruses in renal transplant recipients using an in-house quantitative real-time multiplex PCR assay and IgG serological assays using recombinant BK and JC virus-like particles. Retrospective analysis of urine and plasma samples collected from 30 renal transplant patients from February 2004 to May 2005 at Leeds Teaching Hospitals NHS Trust. Samples were collected at 5 days and thereafter at 1, 3, 6 and 12 months post-transplantation. Eight patients (26.7%) were positive for BK viruria; three of these patients submitted plasma samples and two had BK viraemia. Five patients (16.7%) were positive for JC viruria. A corresponding rise in BKV and JCV antibody titres was seen in association with high levels of viruria. Different patterns of reactivation were observed: BK viruria was detected after 3-6 months, and JC viruria was observed as early as 5 days post-transplantation. One patient had biopsy-proven BKV nephropathy. No dual infections were seen. In order to ensure better graft survival, early diagnosis of these polyomaviruses is desirable.


Neuroimaging diagnosis of Tolosa-Hunt syndrome: MRI contribution.
To present our experience in the neuroradiological diagnosis of six patients with Tolosa-Hunt syndrome. Computerized tomograms and MRI, with and without contrast enhancement, of the cranium and orbits of patients fulfilling IHS criteria for the diagnosis of Tolosa-Hunt syndrome were analyzed. Standard CT scan, with and without contrast enhancement, disclosed an enlarged cavernous sinus in one patient and was normal in the remaining five. In comparison, MRI was clearly abnormal in the four patients on whom it was performed, showing a convex enlargement of the symptomatic cavernous sinus by an abnormal tissue isointense with gray matter on short TR/TE images and iso-hypointense on long TR/TE scans. This abnormal tissue markedly increased in signal intensity after contrast injection and, in two patients, extended into contiguous regions, mainly the orbital apex and subtemporal fossa ipsilaterally. One patient had follow-up studies after successful treatment with corticosteroids. Although diminished in size, the abnormal tissue was still visible on MRI after 3 months of treatment and only disappeared after 6 months of treatment. These MRI findings help in the differential diagnosis of the Tolosa-Hunt syndrome from conditions such as meningioma, lymphoma, and sarcoidosis, as well as confirming the similarities of the Tolosa-Hunt syndrome and orbital pseudotumor. In the presence of painful ophthalmoplegia, the finding by MRI of cavernous sinus enlargement, with the herein described signal and extension characteristics and slow resolution with corticosteroid treatment, is highly suggestive of the Tolosa-Hunt syndrome.


Synthetic polyamines activating autophagy: effects on cancer cell death.
The ability of symmetrically substituted long chain polymethylene tetramines, methoctramine (1) and its analogs 2-4 to kill cancer cells was studied. We found that an elevated cytotoxicity was correlated with a 12 methylene chain length separating the inner amine functions (6-12-6 carbon backbone), together with the introduction of diphenylethyl moieties on the terminal nitrogen atoms (compound 4) of a tetramine backbone. Compound 4 triggered dissipation of mitochondrial transmembrane potential and increased intracellular peroxide levels, leading to a caspase-independent HeLa cell death associated with a rapid activation of autophagy. The antioxidant N-acetylcysteine inhibited cell death and activation of autophagy, indicating a link between oxidative stress and autophagy. Autophagy was rapidly triggered even by tetramines 2 and 3, indicating that is related to their polyamine structure. Autophagy did not protect HeLa cells against cytotoxicity elicited by compound 4. The present study shows that, by modifications of the methoctramine structure, it is possible to design polyamine derivatives highly cytotoxic against tumor cells and that the appropriate design of molecules bearing polyamine-like structures leads to powerful inducers of autophagy.


Factors Impacting the Control of Rabies.
Rabies is a classical zoonosis that has been known to man for ages. The disease can be caused by several viral species in the Lyssavirus genus, but the type species, rabies virus (RABV), is by far the most important from a zoonosis perspective. The extreme neurotropism of RABV and the evolutionarily conserved elements and structures of the mammalian brain suggest that this virus evolved an ultimate niche for replication, simultaneously exploiting classical social behavior of a wide diversity of hosts among the chiropters and carnivores. There is substantial evidence that RABV originated in bats and later switched hosts to yield globally disseminated canine rabies. Following the revolutionary work of Louis Pasteur, control and elimination of dog rabies was achieved in Europe, but widespread colonial introduction of European strains of dog RABV to other parts of the world occurred. Thus, dog rabies spread rapidly in the 1900s, and today the vast majority of the tens of thousands of annual human rabies cases stem from dog rabies, which has become endemic in the entire developing world. The fact that human rabies is preventable, through control in the dog reservoir on one hand and through effective prophylaxis in cases of exposure on the other hand, is an indictment of public health strategies and practices. This article discusses some of the drivers that have contributed to the recurrent neglect of rabies in the modern world, as well as evolving One Health-based rabies control partnerships and initiatives that have been progressive, productive, and promising of true global benefits.


Future non-invasive imaging to detect vascular plaque instability and subclinical non-obstructive atherosclerosis.
Atherosclerosis underlies the major causes of death in the Western World. Our main goal is to detect early changes of atherosclerosis and to identify subjects at highest cardiovascular risk that may aid in the development of prevention approaches and better management that will decrease cardiovascular morbidity and mortality. The new methods that are of interest include the advanced vascular ultrasound methods, the infra red and near infra red imaging techniques, the EndoPat device that reflects peripheral arterial tone, the electron beam computed tomography, the magnetic resonance imaging, and the molecular imaging techniques. In this review we will focus on the future of advanced imaging techniques that are being developed to detect early (pre-clinical) development of atherosclerosis.


Causes and Diagnosis of Abnormal Vaginal Bleeding.
Abnormal vaginal bleeding in a postmenarchal adolescent patient is most often related to dysfunctional uterine bleeding. However, there are other potential etiologies, including hematologic disorders, infections, and oncologic problems. We present a 12-year-old girl who presented with prolonged vaginal bleeding and was ultimately diagnosed with rhabdomyosarcoma. In this article, we discuss the approach to a patient with vaginal bleeding along with a more in-depth review of risk stratification in rhabdomyosarcoma, including treatment options such as chemotherapy, surgery, and radiation therapy.


[Role and movement of the toes during walking].
In order to understand the function of toes during free walking, movements of the toes of 30 normal adults were measured with the electrogoniometers. The angular changes of the interphalangeal (IP) joint of the 1st toe and the distal interphalangeal (DIP) joints of the 2nd to 4th toes, the ground reaction force, foot switch signal and the pressure changes in the forefoot were recorded simultaneously. The relationships between these measurements were then investigated. During the foot-flat phase, the IP joint of the 1st toe stayed at a flexed position, while the DIP joints of the 2nd to 4th toes remained at a slightly extended or neutral position but there was scarcely any pressure on the toe tips (0-0.3 kg/cm3). After the heel-off, the pressure on the 1st toe tip gained with increasing flexion of the IP joint of the 1st toe. The mean of the maximum angles was 13 +/- 5 (mean +/- SD) degrees. After the heel-off, the DIP joints of the 2nd and 3rd toes remained in the extended position in 16 cases (6.6 +/- 3.1 and 6.3 +/- 3.4 degrees) and appeared to stay at a flexed position in 14 cases (10.0 +/- 7.8 and 8.0 +/- 5.3 degrees). The DIP joint of the 4th toe remained in the extended position in all cases (9.2 +/- 8.5 degrees). The pressure of the toe tips increased. The magnitude of the pressure of the extended toe tips was higher than that in the flexed toe tips. The pressure of the toe tips of the 1st to 4th toes reached the maximum much earlier than that of the toe-off. From these observations, we conclude that the function of the toes during free walking seems to stabilize the foot by extending a contact area with floor mainly after the heel-off.


Migratory conventional dendritic cells in the induction of peripheral T cell tolerance.
Conventional DCs are an extremely heterogeneous cell population that comprises several different subsets. A major distinction can be made between lymphoid-resident DCs that are present in the lymphoid tissues and the blood and migratory DCs that reside in the nonlymphoid tissues and migrate to the lymph nodes, both in homeostatic conditions and during the course of an infection. Migratory DCs differ from tissue to tissue but share the unique ability to transport antigens to the draining lymph nodes-in particular, tissue-restricted antigens in homeostatic conditions and microbial antigens after an infection. Recently, steady-state migratory DCs have gained much attention after the discovery of their high tolerogenic potential. The purpose of this review is to give a picture of the recent finding regarding steady-state migratory DCs with particular interest in their role in inducing T cell tolerance.


PaperChase: computerized bibliographical retrieval for the physician.
PaperChase is a computer program that permits any physician or scientist to search the National Library of Medicine's MEDLINE data base of references to the biomedical literature. Written for the clinician rather than for the search librarian, PaperChase permits the user to search the entire MEDLINE collection of over 5,000,000 references published in 4,000 biomedical journals dating back to 1966. PaperChase is now available throughout the world to anyone who has a computer terminal or personal computer, and a modem. No special training is needed for a successful search. There is no user's manual. Users can search by title word, Medical Subject Heading, author's name, journal title, year of publication, language of publication, or any combination of the above. Users can read abstracts online, and they can request that a photocopy of the full text of any article be mailed to them.


Are giant clams (Tridacna maxima) distractible? A multi-modal study.
To properly assess risk, an animal must focus its attention on relevant external stimuli; however, attention can be reallocated when distracting stimuli are present. This reallocation of attention may interfere with an individual's ability to effectively assess risk and may impede its response. Multiple stimuli presented together can have additive effects as distractors, and these include stimuli in different modalities. Although changes in noise and water flow are detectable by some bivalves, this has not been studied in the context of risk assessment or distraction. We experimentally exposed giant clams (Tridacna maxima) to changes in water particle movement through underwater sound (motorboat noise) and increased water flow to determine whether these stimuli, individually or together, modified risk assessment or caused distraction. We found that clams responded to sound, flow, and their combination by increasing frequency of mantle retractions (a potential anti-predator response) when exposed to a stimulus. Sound alone did not change risk assessment in either the latency to close or to reemerge following closure. However, when exposed to both stimuli simultaneously, clams increased their latency to close. We suggest that clams perceive sound and flow in an additive way, and are thus distracted. Interestingly, and uniquely, clams discriminate these multimodal stimuli through a single sensory modality. For sessile clams, anthropogenic noise is detectable, yet unavoidable, suggesting that they be especially vulnerable to marine noise pollution.


Prior image constrained compressed sensing: implementation and performance evaluation.
Prior image constrained compressed sensing (PICCS) is an image reconstruction framework which incorporates an often available prior image into the compressed sensing objective function. The images are reconstructed using an optimization procedure. In this paper, several alternative unconstrained minimization methods are used to implement PICCS. The purpose is to study and compare the performance of each implementation, as well as to evaluate the performance of the PICCS objective function with respect to image quality. Six different minimization methods are investigated with respect to convergence speed and reconstruction accuracy. These minimization methods include the steepest descent (SD) method and the conjugate gradient (CG) method. These algorithms require a line search to be performed. Thus, for each minimization algorithm, two line searching algorithms are evaluated: a backtracking (BT) line search and a fast Newton-Raphson (NR) line search. The relative root mean square error is used to evaluate the reconstruction accuracy. The algorithm that offers the best convergence speed is used to study the performance of PICCS with respect to the prior image parameter α and the data consistency parameter λ. PICCS is studied in terms of reconstruction accuracy, low-contrast spatial resolution, and noise characteristics. A numerical phantom was simulated and an animal model was scanned using a multirow detector computed tomography (CT) scanner to yield the projection datasets used in this study. For λ within a broad range, the CG method with Fletcher-Reeves formula and NR line search offers the fastest convergence for an equal level of reconstruction accuracy. Using this minimization method, the reconstruction accuracy of PICCS was studied with respect to variations in α and λ. When the number of view angles is varied between 107, 80, 64, 40, 20, and 16, the relative root mean square error reaches a minimum value for α ≈ 0.5. For values of α near the optimal value, the spatial resolution of the reconstructed image remains relatively constant and the noise texture is very similar to that of the prior image, which was reconstructed using the filtered backprojection (FBP) algorithm. Regarding the performance of the minimization methods, the nonlinear CG method with NR line search yields the best convergence speed. Regarding the performance of the PICCS image reconstruction, three main conclusions can be reached. (1) The performance of PICCS is optimal when the weighting parameter of the prior image parameter is selected to be near α = 0.5. (2) The spatial resolution measured for static objects in images reconstructed using PICCS from undersampled datasets is not degraded with respect to the fully-sampled reconstruction for α near its optimal value. (3) The noise texture of PICCS reconstructions is similar to that of the prior image, which was reconstructed using the conventional FBP method.


Do diurnal changes in loading affect the interpretation of MRI scans of the lumbar spine?
We tested the hypothesis that the visual interpretation of magnetic resonance imaging (MRI) scans of the asymptomatic lumbar spine are affected by diurnal changes in fluid exchange in the intervertebral discs. Ten male subjects carried a 20-kg backpack in the intervening 3-h period between two MRI scans of the lumbar spine. After the subjects arrived at the MRI center (within 45 min of awakening), they lay on a bed for 45 min. The first set of MRI scans were obtained. Each subject was then fitted with a 20-kg backpack. After they walked for 3 h, the pack was removed, and a second set of MRI scans were obtained immediately. The sets of MRI scans were reviewed by three radiologists: none of the three radiologists found differences in the interpretation of the MRI scans. On the basis of these results, diurnal changes in fluid exchange in the asymptomatic intervertebral disc (exaggerated in our case by the backpack) are undetectable by visual reading of MRI scans.


Colorectal cancer and the blood loss paradox.
Faecal occult blood (FOB) positivity and iron deficiency anaemia (IDA) are common manifestations of colorectal cancer (CRC) and both potentially facilitate diagnosis at an earlier, more treatable stage. It has been assumed that both are the consequence of low-grade blood loss from the tumour bed. A retrospective analysis of 1121 cases of CRC diagnosed at a single centre between 2010 and 2016, comparing cases presenting via FOB-based Bowel Cancer Screening Programme (BCSP) and IDA pathways for a series of variables including age, sex, tumour location and prevalence of anaemia. The BCSP and IDA pathways each accounted for about 15% of the total case load. There were significant differences between the BCSP and IDA sub-groups in median age (68 vs 78 years: p<0.001), median haemoglobin (138 vs 89 g/L: p<0.001) and proportion of lesions in right colon (31.1% vs 82.5%: p<0.001). The major disparity in the prevalence of anaemia (overall 20.0% vs 98.2%: p<0.001) persisted when controlled for tumour location. Paradoxically, CRC screening through the detection of FOB positivity and IDA identifies distinctly different sub-populations of cases. The theoretical implication is that an additional mechanism may be required to explain the development of IDA in CRC. The practical implication is that detection of IDA may have a complementary role to the BCSP in population screening for CRC.


Interleukin-6 receptor gene polymorphisms and periodontitis in a non-smoking Japanese population.
The indispensable role of interleukin-6 receptor (IL-6R) in regulating IL-6 responses has been clearly established. We have previously reported that IL6R polymorphisms strongly influenced the serum levels of soluble IL-6R. In this study, we investigated the association between these genetic variations and periodontitis. Among the seven novel IL6R single-nucleotide polymorphisms (SNPs) reported, we genotyped two important sites: the +48892 A/C in exon 9 and the -183 G/A in the promoter region. The SNP in exon 9 results in Asp-->Ala substitution in the proteolytic cleavage site of IL-6Ralpha. In total, 212 periodontitis cases and 210 healthy controls were genotyped using polymerase chain reaction, restriction fragment length polymorphisms and direct sequencing methods. Analysis of the genotype distribution of the +48892 A/C SNP in periodontitis patients and in controls revealed a suggestive association with aggressive (p = 0.04) and chronic periodontitis (p = 0.04). In addition, the carriage rate for the A allele was significantly higher in chronic periodontitis patients [p = 0.02, odds ratio (OR) = 2.25]. No association was found in the -183 G/A SNP. The two markers were in linkage disequilibrium (LD) (|D'| = 0.53). The IL6R+48892 A/C polymorphism could act as a risk factor for periodontitis; however, further association and biological studies are needed.


[Great elongation of uterine cervix: retrospective study of 20 cases].
The aim of the study was to evaluate the safety and efficacy of the Musset Poitout surgical procedure consisting in an anterior uterosacral ligament transposition and a cervix amputation. The main indication is an uterovaginal prolapse with an isolated elongation of the cervix. A retrospective consecutive series of 20 women with an elongation of uterine cervix undergoing Musset Poitout procedure over a 10 year period between 1990 and 2001 with analysis of per and post operative complications and success. Four Kelly urethral plications were performed in the same time. The patient's ages, time under anesthesia, change in hemoglobin, days of hospitalization, medical illnesses, complications and follow-up were assessed. Failure was defined as a symptomatic elongation of the cervix or a third degree hysterocele on examination. and discussion. The median age of Musset Poitout procedure was 43.9 years (range 23-83). General anaesthesia could be performed in all patients. Mean operation time was 67 minutes (range 40-130). No major per or post operative complications occurred. The average of post-operative bladder cathetherisation was 3.65 days, the average hospital stay was 6.3 days. Complications were insignificant: urinary tract infection in 2, voiding dysfunction in 2. All the patients but 2 were followed for a mean 59 months (range 6-127). There was one recurence (5.5%). In this preliminary assessment the Musset Poitout procedure offered significant avantages in a genital prolapse with elongation of the cervix.


Low-Power Photodetectors Based on PVA-Modified Reduced Graphene Oxide Hybrid Solutions.
Photodetectors based on reduced graphene oxide (rGO) have attracted much attention owing to their simple and low-cost fabrication process. However, the aggregation and defects of rGO flakes still limit the performance of rGO photodetectors. Controlling the composition of rGO has become a vital factor for its prospective applications. For example, the interconnection between rGO and polymers for modified morphologies of rGO films leads to an enhanced performance of devices. In this work, a practical approach to engineer surface uniformity and enhance the performance of a photodetector by modifying the rGO film with hydrophilic polymers poly(vinyl alcohol) (PVA) is reported. Compared with the rGO photodetector, the on/off ratio for the PVA/rGO photodetector shows 3.5 times improvement, and the detectivity shows 53% enhancement even when the photodetector is operated at a low bias of 0.3 V. This study provides an effective route to realize PVA/rGO photodetectors with a low-power operation which shows promising opportunities for the future development of green systems.


Anti-Müllerian hormone and ovarian dysfunction.
Anti-Müllerian hormone (AMH) has important roles in postnatal ovarian function. Produced by ovarian granulosa cells, AMH is involved in initial follicle development. In fact, serum AMH level correlates with ovarian follicle number. In patients with polycystic ovary syndrome (PCOS), AMH levels are elevated, which indicates its potential relevance in PCOS diagnosis and management. AMH represents a useful clinical marker for the assessment of ovarian reserve in cases of subfertility caused by advanced age in women. A potential role for AMH in dominant follicle selection has also been suggested. Future challenges comprise the availability of a well-standardized assay and the development of AMH agonists and antagonists as possible tools to manipulate ovarian function for contraception or ovarian longevity.


Community coalitions for prevention and health promotion: factors predicting satisfaction, participation, and planning.
Coalitions currently are a popular tool for promoting community-based solutions to health problems, such as alcohol, tobacco, and other drug (ATOD) abuse. Private foundations, granting agencies, and other public health organizations assume that participation of community members in health promotion coalitions will increase the likelihood of program success. This article examines whether key characteristics of coalitions are related to effectiveness as measured by member satisfaction, commitment to the coalition, and the quality of planning efforts. Member survey data from the first year evaluation of an ATOD coalition were analyzed using factor analysis, chi-square, and multiple regression techniques at both the individual and group levels. The results suggest that community leadership, shared decision making, linkages with other organizations, and a positive organizational climate were key determinants of member satisfaction and participation. These same factors were not related to the quality of coalition plans. However, the significance of coalitions for community empowerment and health promotion is discussed.


Imaging of small nanoparticle-containing objects by finite-element-based photoacoustic tomography.
We present semiquantitative photoacoustic images of small nanoparticle-containing objects having a wide range of contrast levels relative to the background. The images are obtained by a finite-element reconstruction algorithm that is based on the Helmholtz-like photoacoustic wave equation in the frequency domain. Our reconstruction approach is an iterative Newton method coupled with combined Marquardt and Tikhonov regularizations that can extract the spatial distribution of relative optical absorption property in heterogeneous media. We demonstrate experimental images in single- and multiple-object configurations with a circular scanning photoacoustic tomographic system. The results obtained show that millimeter-size nanoparticle-containing objects can be clearly detected in terms of position, size, and relative optical properties.


[The Relevance of Surgeon-performed Ultrasound For the Detection of Acute Appendicitis: a Review of the Literature and a Practical Diagnostic Algorithm].
Background The relevance of ultrasound (US) in diagnosing acute appendicitis is controversial. The validity of US in comparison with other imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), is unclear, as is the difference between surgeon-performed ultrasound (SPUS) and radiologist-performed ultrasound (RPUS). On the basis of a review of current literature, our study aimed to develop a US-based algorithm to simplify the choice between additional diagnostic measures and surgery. Methods MEDLINE (PubMed®) was searched for literature published between 2010 and 2016. A total of 53 relevant full-text articles were eventually evaluated. Results Ultrasound (US) is an established part of algorithms used to diagnose acute appendicitis and has already replaced CT as the imaging technique of choice. The differences between SPUS and RPUS with regard to sensitivity, specificity, and positive and negative predictive values (PPV, NPV) are not statistically significant. The benefit of SPUS over RPUS is the simultaneous clinical assessment of the patient by the surgeon while the sonogram is performed (sonopalpation), which can increase diagnostic accuracy even further. Radiation exposure as a result of CT could be avoided or significantly reduced through the routine use of US, which is increasingly being used and is widely available. Conclusions SPUS should be the first imaging technique used to diagnose patients with suspected appendicitis. Additional diagnosis using CT or MRI is only recommended if sonographic imaging of the appendix is impossible in combination with specific clinical and laboratory criteria. A structured diagnostic approach with obligatory use of (SP)US, as described in the diagnostic algorithm, should be used for detection of acute appendicitis.


Polyinosinic acid as a carrier in the microscale purification of total RNA.
Three different RNA carriers were compared for use in microscale RNA isolation and subsequent cDNA synthesis and amplification via the polymerase chain reaction. E.coli rRNA alone gave considerable cDNA synthesis which under standard carrier conditions overwhelmed cDNA synthesis from lymphocyte mRNA. Yeast tRNA caused inhibition of mRNA primed cDNA synthesis, giving low levels of cDNA synthesis when used without cellular RNA. In contrast, commercially available poly I alone did not prime detectable cDNA synthesis nor did it inhibit such synthesis primed by cellular mRNA. When RNA preparations were made using these three carriers and decreasing numbers of starting lymphocytes, poly I allowed the detection of cDNA from two orders of magnitude fewer lymphocytes than the other carriers. Thus poly I was found to be a superior carrier molecule for microscale RNA preparations suitable for reverse transcription and subsequent amplification using the polymerase chain reaction.


Magnetostructural Transition Kinetics in Shocked Iron.
A generalized Heisenberg model is implemented to study the effect of thermal magnetic disorder on kinetics of the Fe α-ε transition. The barrier to bulk martensitic displacement remains large in α-Fe shocked well past the phase line but is much reduced in the [001] α-ε boundary. The first result is consistent with observed overdriving to metastable α, while the second suggests structural instability, as implied by observation of a [001] shock transformation front without plastic relaxation. Reconciling both behaviors may require concurrent treatment of magnetic and structural order.


Experts' Misinterpretation of Box Plots - a Dual Processing Approach.
Recent studies have shown that students often misinterpret the area of the box in box plots as representing the frequency or proportion of observations in that interval, while it actually represents density. This misinterpretation has been shown to be based on the saliency of this area and can be explained by heuristic reasoning as defined by dual process theories. In this study we tested whether expert users of box plots also display this misinterpretation and show signs of the same heuristic reasoning as found in students. Using a reaction time test, we found signs of heuristic reasoning in experts, both with respect to accuracy and reaction times. If even experts have difficulty interpreting box plots, one can question whether these are an appropriate form of representation to use when reporting data and deserve the prominent place they currently have in the statistics curriculum.


Steal from skeletonized internal thoracic artery graft during hemodialysis after coronary artery bypass grafting.
We used transthoracic Doppler echocardiography to evaluate the potential for flow variation in a skeletonized internal thoracic artery (ITA) graftc ipsilateral to an upper-extremity arteriovenous fistula during postoperative hemodialysis. Between October 2008 and May 2009, 7 patients in chronic hemodialysis underwent coronary artery bypass grafting. We selected 5 of these patients according to the following inclusion criteria: patients who were undergoing chronic hemodialysis via a left upper-extremity arteriovenous fistula and in whom the skeletonized left ITA was anastomosed to the left anterior descending artery as an in situ graft; the right ITA was not used as a graft; postoperative multidetector computed tomography evaluation of the coronary artery demonstrated patency of the left ITA. The following parameters were calculated at baseline, after the dialysis pump was on, before the pump was turned off, and after the pump was off: peak systolic velocity, end-diastolic velocity, time-averaged mean velocity, pulsatility index, and ITA diameter. Flow was calculated with the following formula: Flow = Time-Averaged Mean Velocity x (Half the Diameter of the ITA)2 x 60 x pi. When the hemodialysis pump was started, there was a significant reduction in the flow of the left ITA (P = .01), whereas there was no variation in the flow of the right ITA (P = .54). During dialysis, no patients experienced hypotension, arrhythmia, or angina. Just after the end of dialysis, the left ITA flow significantly increased (P = .01). Flow reduction of the ITA graft ipsilateral to an upper-extremity arteriovenous fistula develops during postoperative hemodialysis, even when the skeletonization technique is used.


Selective expansion of polyfunctional pathogen-specific CD4(+) T cells in HIV-1-infected patients with immune reconstitution inflammatory syndrome.
Since the introduction of highly active antiretroviral therapies (ART), the prognosis for HIV-1 patients has improved immensely. However, approximately 25% of patients can experience a variety of inflammatory symptoms that are collectively known as immune reconstitution inflammatory syndrome (IRIS). Studying the etiology and immunopathology of IRIS has been hampered by the fact that the symptoms and associated opportunistic infections are highly varied. We hypothesized that there is a common mechanism underlying IRIS pathogenesis and investigated a patient group with IRIS related to different pathogens. Functional and phenotypic characterization of PBMC samples was performed by polychromatic flow cytometry after in vitro stimulation with relevant antigenic preparations. In most patients, IRIS events were characterized by the robust increase of preexisting polyfunctional, highly differentiated effector CD4(+) T-cell responses that specifically targeted the antigens of the underlying co-infection. T-cell responses to HIV-1 or other underlying infections were not affected and did not differ between IRIS and non-IRIS patients. These data suggest that patients with IRIS do not have a generalized T-cell dysfunction; instead, IRIS represents a dysregulated CD4(+) T-cell response against residual opportunistic infection antigen. These studies were registered at www.clinical-trials.gov as NCT00557570 and NCT00286767.


Potential confounding in evaluating infection-control interventions in hospital settings: changing antibiotic prescription.
The colonization dynamics of antibiotic-resistant pathogens in hospital settings are complex, with multiple and continuously interacting variables (e.g., introduction of resistance, infection-control practices, antibiotic use). Quantification of these variables is indispensable in the evaluation of intervention studies, because these variables represent potential confounders. In this article, the complexity of colonization dynamics is described. Through a systematic review, we identified studies that evaluated the modification of antibiotic prescription to reduce antibiotic resistance in intensive care units (n=19), and the extent of confounding-control was determined. Most studies evaluated antimicrobial restriction/substitution (n=12) or antibiotic rotation (n=4). Sixteen studies had a prospective cohort design (before-after), of which 12 were without a control group. Introduction of antibiotic resistance was determined in 10 studies. The relative importance of colonization routes and adherence to infection-control measures were not determined in any study. Therefore, it remains uncertain whether observed changes in the prevalence of antibiotic resistance after intervention were causally related to the intervention. Appropriate choices of study design, primary end point (colonization rates rather than infection rates) and statistical tests, determination of colonization routes, and control of potential confounders are needed to increase validity of intervention studies.