Compact optical data processor employing holographic reflective lenses.
A compact optical data processor is described that employs holographic reflective lenses. The processor is inexpensive and requires one-half of the length of the optical bench as that required for using glass lenses. The fabrication of the holographic lenses is described, and the results of optical processing reported. The results show that an inexpensive data processor employing holographic lenses is a feasible project. The processor may find use for onboard optical processing on spacecrafts and satellites. The most distinguishing characteristic of such a processor is its extreme light weight. The angular alignment tolerances for holographic lenses are very low. The processor must, therefore, be made rugged, designed, and mounted to withstand vibrations, shocks, and other environmental problems associated with spacecrafts and satellites.


Role of gastrin-releasing peptide and neuromedin B in anxiety and fear-related behavior.
Bombesin (BB)-like peptides have been implicated in the mediation and/or modulation of the stress response. However, the impact of manipulating this peptidergic system has only been assessed in a limited number of anxiety and fear paradigms. Given that different behavioral paradigms reflect different aspects of anxiety, the objective of the present investigation was to assess the effects of two mammalian BB-related peptides, namely gastrin-releasing peptide (GRP) and neuromedin B (NMB), in paradigms thought to reflect fear and anxiety-related behaviors. To this end, the effects of central (3rd ventricular; i.c.v.) administration of GRP (0.30 nmol), GRP receptor (BB(2)) antagonist, [Leu(13)-(CH(2)NH)Leu(14)]-BN (1.26 nmol), NMB-30 (0.29 nmol), NMB (BB(1)) receptor antagonist, BIM 23127 (1.70 nmol) and a mixed BB(1)/BB(2) receptor antagonist, PD 176252 (0.621 nmol) were assessed in the elevated plus maze (EPM) and in a fear potentiated startle paradigm (a model thought to reflect conditioned fear). The BB(1) receptor antagonist and the mixed BB(1)/BB(2) receptor antagonist elicited anxiolytic effects in the EPM, whereas, the BB(2) receptor antagonist was without effect. In the fear potentiated startle paradigm, pretreatment with either the BB(1) receptor antagonist or the BB(2) receptor agonist attenuated the fear potentiated startle response, without affecting basal startle amplitude. These data suggest that NMB and GRP do affect the stress response. However, whereas NMB manipulations affected both anxiety and fear responses, GRP alterations selectively affected fear-related responses.


The role of the exocyst in matrix metalloproteinase secretion and actin dynamics during tumor cell invadopodia formation.
Invadopodia are actin-rich membrane protrusions formed by tumor cells that degrade the extracellular matrix for invasion. Invadopodia formation involves membrane protrusions driven by Arp2/3-mediated actin polymerization and secretion of matrix metalloproteinases (MMPs) at the focal degrading sites. The exocyst mediates the tethering of post-Golgi secretory vesicles at the plasma membrane for exocytosis and has recently been implicated in regulating actin dynamics during cell migration. Here, we report that the exocyst plays a pivotal role in invadopodial activity. With RNAi knockdown of the exocyst component Exo70 or Sec8, MDA-MB-231 cells expressing constitutively active c-Src failed to form invadopodia. On the other hand, overexpression of Exo70 promoted invadopodia formation. Disrupting the exocyst function by siEXO70 or siSEC8 treatment or by expression of a dominant negative fragment of Exo70 inhibited the secretion of MMPs. We have also found that the exocyst interacts with the Arp2/3 complex in cells with high invasion potential; blocking the exocyst-Arp2/3 interaction inhibited Arp2/3-mediated actin polymerization and invadopodia formation. Together, our results suggest that the exocyst plays important roles in cell invasion by mediating the secretion of MMPs at focal degrading sites and regulating Arp2/3-mediated actin dynamics.


Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study.
The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. The definition persistent postpartum haemorrhage identified women with severe postpartum haemorrhage at an early stage of haemorrhage, unlike definitions based on blood transfusion. It also captured a large majority of adverse maternal outcomes, almost as large as the definition of ≥1 L blood loss, which is commonly applied as a definition of postpartum haemorrhage rather than severe haemorrhage.


Managing food allergies in schools.
Food allergies are estimated to affect as many as 8 % of children with 2.5 % being allergic to peanut products. Based on the results of recent surveys, this prevalence has been increasing over the last few decades for unknown reasons. As children with food allergies reach school age, the issue is becoming more common in schools. For that reason, schools are now required to be prepared to take responsibility for the safety of food-allergic students. This review discusses the common problems surrounding management of food allergies in the school setting along with reasonable recommendations for addressing those problems. The most important component of food allergy management is for the student to get an accurate diagnosis and to then discuss development of an anaphylaxis action plan with their health-care provider. Each school should insist that a copy of such a plan be provided for each student with food allergy and that epinephrine is readily available should a student have an anaphylactic reaction. In addition to epinephrine, it is essential that school personnel be properly trained to recognize and treat allergic reactions should they occur. Known deficiencies in school preparedness have been documented in previous literature, and consequently, both state and the federal government have begun to implement policies to help with school preparedness.


Bronchoalveolar lavage for the evaluation of interstitial lung disease: is it clinically useful?
Although the application of thoracic high-resolution computed tomography (HRCT) to clinical pulmonology has revolutionised the diagnostic approach to patients with suspected interstitial lung disease (ILD), additional testing is often needed to make a confident ILD diagnosis. Bronchoalveolar lavage (BAL) can play a significant role in making an accurate and confident diagnosis of specific forms of ILD. When BAL is used in conjunction with comprehensive clinical information and HRCT, BAL nucleated immune cell patterns can frequently provide useful information for diagnostic evaluation and lessen the need to proceed to more invasive procedures, such as surgical lung biopsy. Additionally, BAL can identify confounding conditions, such as infection or malignancy. However, BAL technique, and protocols for processing and analysing BAL fluid are critically important for providing useful information. This perspective reviews the current status of using BAL as a diagnostic tool for the diagnosis of ILD.


The use of guided imagery to manage pain in an elderly orthopaedic population.
The management of postoperative pain in elderly orthopaedic patients is critical for advancing patient outcomes and improving the use of healthcare resources. Adequate pain control without adverse side effects, such as confusion and sedation, is crucial to promote comfort and participation in rehabilitation therapies among all patients but particularly among elderly joint replacement patients. Without adequate pain control, physical therapy is delayed and the risk of complications increases. One area of investigation that holds promise for improved treatment outcomes involves the use of complementary therapies, such as guided imagery. The purpose of this pilot study was to test the effects of a guided imagery intervention in the older adult patient who has undergone joint replacement surgery. This pilot study used a two-group experimental repeated measures design. A sample of 13 patients, age 55 years and older, were recruited. The control group received usual care and a music audio tape. The experimental group received usual care and a guided imagery audio tape intervention. Trends in this pilot study demonstrated positive outcomes for pain relief, decreased anxiety, and decreased length of stay. Complementary therapy holds the promise of increasing positive outcomes. Further research is needed to validate these findings with a larger postoperative sample and in other populations as well. There is a critical need to incorporate the use of guided imagery and other complementary therapies into all nursing curricula. Nurses must develop expertise and be ready and able to act as patient educators and advocates in the use of these interventions in programs of care and institutional policy.


Molecular regulation of somatic embryogenesis in potato: an auxin led perspective.
Potato internodal segments (INS) treated with the auxin 2,4-dichlorophenoxyacetic acid can be induced to develop somatic embryos upon their transfer to an auxin-free medium, while the continuous presence of auxin in the medium suppresses the progression of embryogenically-induced somatic cells to embryos. We have employed these contrasting pathways, in combination with potato microarrays representing circa 10,000 genes, to profile global gene expression patterns during the progression of somatic embryogenesis in potato. The induction phase, characterised by the presence of auxin, was analysed by the direct comparison of RNA isolated from freshly excised (0 days) and embryogenically induced (14 days) INS explants. RNAs from embryo-forming (withdrawal of auxin after 14 days) and embryo-inhibitory (continuous presence of auxin) conditions, isolated over a range of time-points until the emergence of somatic embryos, were compared in a loop design to identify auxin responsive genes putatively involved in the process of somatic embryogenesis. A total of 402 transcripts were found to be showing significant differential expression patterns during somatic embryogenesis 'induction' phase, 524 during 'embryo-transition' phase, while 44 transcripts were common to both phases. Functional classification of these transcripts, using Gene Ontology vocabularies (molecular and biological), revealed that a significant proportion of transcripts were involved in processes which are more relevant to somatic embryogenesis such as apoptosis, development, reproduction, stress and signal transduction. This is the first study profiling global gene expression patterns during true somatic embryogenesis initiated from mature and completely differentiated explants and has enabled the description of stage-specific expression patterns of a large number of genes during potato somatic embryogenesis (PSE). The significance of the key identified genes during critical stages of somatic embryogenesis is discussed.


Finding common ground in public health nursing education and practice.
Preparation of the public health nursing (PHN) workforce requires public health nurses from academia and practice to collaborate. However, a shortage of PHN clinical sites may lead to competition between schools of nursing for student placements. The Henry Street Consortium, a group of 5 baccalaureate schools of nursing and 13 local health departments in the state of Minnesota, developed a model for collaboration between PHN education and practice. This paper describes the development process--the forming, storming, norming, and performing stages--experienced by the Henry Street Consortium members. The consortium developed a set of entry-level core PHN competencies that are utilized by both education and practice. It developed menus of learning opportunities that were used to design population-based PHN clinical experiences. In addition, the consortium created a model for training and sustaining a preceptor network. The members of the Henry Street Consortium collaborated rather than competed, used consensus for decision making, and respected and accepted different points of view. This collaboration significantly impacted how schools of nursing and local health departments work together. The consortium's ability to retain its relevance, energy, and momentum for both academic and agency partners sustains the collaboration.


The evolution of pharmacy residency training programs and corresponding standards of accreditation.
Practice-based pharmacy training has a long history, particularly in institutional pharmacy practice. Formal pharmacy residency training programs and accreditation standards were first developed in the early 1960s. Practitioners now practice in a much different environment. Residency programs and accreditation standards have changed dramatically to meet the needs of practitioners, patients, and employers. The authors trace the evolution of programs from general internships through clinical practice and specialty residencies and fellowships and the development of standards and competency-based training.


Carotid intima-media thickness and serum paraoxonase-1 activity in patients with Helicobacter pylori.
To evaluate serum paraoxonase(PON)-1 activity and carotid intima-media thickness (CIMT) in patients with Cytotoxin-associated antigen(CagA)-positive and negative Helicobacter pylori strains. The study group included a total of 134 individuals, of whom 103 were H. pylori positive, and 31 were H. pylori negative. Five biopsies were collected from each patient for histological examination: two from the antrum, two from the corpus, and one from the incisura angularis. The presence of H. pylori was determined using a modified Gram staining protocol. Peripheral blood was collected from each patient to determine levels of triglyceride, TC, HDL-cholesterol and LDL-cholesterol. IgG antibodies against CagA protein were analyzed by enzyme immunoassays. PON-1 activity was measured by colorimetric method. Carotid intima-media thickness and atherogenic plaques were measured using a grey scale color Doppler ultrasound. Data were analyzed by descriptive and inferential statistics. The right, the left and the mean CIMT were significantly higher in H. pylori (+) group versus H. pylori (-) group (p < 0.001 for all). However, the mean PON-1 concentration was significantly lower in H. pylori (+) group versus H. pylori (-) group (p < 0.001). The right, the left and the mean CIMT of CagA (+) group were significantly higher than that of CagA (-) group and controls, while PON-1 concentrations of CagA (+) group were significantly lower than that of CagA (-) group and controls (for all p = 0.0001). The right, the left and the mean CIMT of CagA (-) group were significantly higher than that of the control group, while the mean PON-1 concentration were significantly lower (for all p = 0.0001). Decreased PON-1 activity may be an etiopathogenetic factor in increased atherosclerosis in patients with H. pylori infection, especially in those infected with the CagA positive strain.


Protective Mechanism Pathway of Swietenia macrophylla Extract Nanoparticles against Cardiac Cell Damage in Diabetic Rats.
Hyperglycemia causes cardiac cell damage through increasing ROS production during diabetic complications. The current study proves the antioxidant activity of Swietenia macrophylla (S. macrophylla) extract nanoparticles as a protector against streptozotocin (STZ)-induced cardiac cell damage. In this research, high-energy ball milling is used to create S. macrophylla extract nanoparticles. The active chemical compounds in the S. macrophylla extract nanoparticles were analyzed through phytochemical screening and GC-MS. Furthermore, we characterized the size of S. macrophylla extract nanoparticles with Dynamic Light Scattering (DLS). Forty male rats were divided randomly into five groups. In the control group, rats received aqua dest orally; in the diabetic group, rats were injected intraperitoneally with STZ; in the S. macrophylla group, rats were injected with STZ and orally given S. macrophylla extract nanoparticles. The results of phytochemical screening showed that S. macrophylla extract nanoparticles contain saponins, flavonoids, alkaloids, phenolics and tannins. Seven chemical compounds in S. macrophylla extract nanoparticles were identified using GC-MS, including phenol, piperidine, imidazole, hexadecene, heptadecanol, dihexylsulfide and heptanol. DLS showed that the S. macrophylla extract nanoparticles' size was 91.50 ± 23.06 nm. Injection with STZ significantly increased malondialdehyde (MDA) levels in cardiac tissue and creatine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH) levels in serum. STZ also significantly reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the level of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in cardiac tissue compared with the control group (p < 0.05). In contrast, the administration of S. macrophylla extract nanoparticles can prevent STZ-induced cardiac cell damage through decreasing the level of CK-MB and LDH in serum and the level of MDA in cardiac tissue. S. macrophylla extract nanoparticles also significantly increased Nrf2 expression as well as SOD and GPx levels in cardiac tissue. These effects are related to the prevention of cardiac histopathological alteration (degeneration and necrosis) in diabetic rats. These results suggest that S. macrophylla nanoparticles contain active compounds such as flavonoids, phenols, piperidine, imidazole and hexadecene and have strong antioxidant activity. These can act as a potential cardioprotective agent against STZ-induced cardiac cell damage due to its antioxidant properties.


The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress.
Organisms respond to mitochondrial stress by activating multiple defense pathways including the mitochondrial unfolded protein response (UPRmt). However, how UPRmt regulators are orchestrated to transcriptionally activate stress responses remains largely unknown. Here we identified CBP-1, the worm ortholog of the mammalian acetyltransferases CBP/p300, as an essential regulator of the UPRmt, as well as mitochondrial stress-induced immune response, reduction of amyloid-β aggregation and lifespan extension in Caenorhabditis elegans. Mechanistically, CBP-1 acts downstream of histone demethylases, JMJD-1.2/JMJD-3.1, and upstream of UPRmt transcription factors including ATFS-1, to systematically induce a broad spectrum of UPRmt genes and execute multiple beneficial functions. In mouse and human populations, transcript levels of CBP/p300 positively correlate with UPRmt transcripts and longevity. Furthermore, CBP/p300 inhibition disrupts, while forced expression of p300 is sufficient to activate, the UPRmt in mammalian cells. These results highlight an evolutionarily conserved mechanism that determines mitochondrial stress response, and promotes health and longevity through CBP/p300.


Neuroprotective effects depend on the model of focal ischemia following middle cerebral artery occlusion.
The purpose of the present study was to compare the characteristics of the photochemical-induced thrombotic occlusion model and the thermocoagulated occlusion model of the middle cerebral artery in rats. We evaluated the neuroprotective effects of a NMDA receptor antagonist, (+)-MK-801 (dizocilpine, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine), an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, YM90K (6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione monohydrochloride), a Ca2+ channel antagonist, S-312-d (S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)-thieno[2 ,3-b]pyridine-5-carboxylate), the radical scavengers, MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) and EPC-K1 (L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyl-tridecyl)-2H-1-be nzopyran-6yl-hydrogen phosphate] potassium salt), and a calcineurin inhibitor, FK506 (tacrolimus, Prograf). Although all tested agents in the present study attenuated the brain damage in the photochemical-induced thrombotic occlusion model, the radical scavengers did not attenuate the brain damage in the thermocoagulated occlusion model. The time course of brain damage and brain edema formation in the two models was examined. The time course of brain damage was not different in the two models, but the time course of brain edema was quite different. Brain edema formation in the photochemical-induced thrombotic occlusion model was significantly greater (P < 0.01) than that in the thermocoagulated occlusion model at all time point studied until 24 h after occlusion of the middle cerebral artery. The present study suggests that the photochemical-induced thrombotic occlusion model has characteristics of both permanent ischemia and ischemia-reperfusion.


An elementary derivation of the hard/soft-acid/base principle.
The hard/soft-acid/base (HSAB) principle indicates that hard acids prefer binding to hard bases (often forming bonds with substantial ionic character) while soft acids prefer binding to soft bases (often forming bonds with substantial covalent character). Though the HSAB principle is a foundational concept of the modern theory of acids and bases, the theoretical underpinnings of the HSAB principle remain murky. This paper examines the exchange reaction, wherein two molecules, one the product of reacting a hard acid and a soft base and the other the product of reacting a soft acid with a hard base, exchange substituents to form the preferred hard-hard and soft-soft product. A simple derivation shows that this reaction is exothermic, proving the validity of the HSAB principle. The analysis leads to the simple and conceptually appealing conclusion that the HSAB principle is a driven by simple electron transfer effects.


Primary feather follicle ablation in common pintails (Anas acuta acuta) and a white-faced whistling duck (Dendrocygna viduata).
Eight 1-yr-old common pintails (Anas acuta acuta) and one 2-yr-old white-faced whistling duck (Dendrocygna viduata) were presented for the persistence of primary flight feathers 1 yr after pinioning. The birds were housed outdoors in an open enclosure necessitating flight prevention. The birds were placed under general anesthesia, and a diode laser was used to ablate the primary feather follicles of the previously pinioned wing. Swelling was the most common side effect seen in seven out of nine treated birds. Other side effects included ulceration, hyperemia, edema, and serosanguinous discharge. All side effects were resolved by 12 wk postprocedure. Laser feather follicle ablation was successful in 28 of 40 (70%) of the treated common pintail feathers, and flight was not observed 7 mo following the procedure in any of these birds. Feather follicle ablation was successful in two of six (33%) of the treated white-faced whistling duck feathers, and the bird in question was observed flying 5 mo after the procedure. Primary feather follicle ablation with a diode laser was a successful method of flight prevention in common pintails but was not effective for a white-faced whistling duck.


Investigation of the transport and metabolic patterns of oil-displacing bacterium FY-07-G in the microcosm model using X-CT technology.
Microbial enhanced oil recovery (MEOR) is dedicated to enhancing oil recovery by harnessing microbial metabolic activities and their byproducts within reservoir rocks and fluids. Therefore, the investigation of microbial mobility and their extensive distribution within crude oil is of paramount importance in MEOR. While microscale models have been valuable for studying bacterial strain behavior in reservoirs, they are typically limited to 2D representations of porous media, making them inadequate for simulating actual reservoir conditions. Consequently, there is a critical need for 3D models and dependable visualization methods to observe bacterial transport and metabolism within these complex reservoir environments. Bacterial cellulose (bc) is a water-insoluble polysaccharide produced by bacteria that exhibits biocompatibility and biodegradability. It holds significant potential for applications in the field of MEOR as an effective means for selective plugging and spill prevention during oil displacement processes. Conditionally cellulose-producing strain, FY-07-G, with green fluorescent labeling, was engineered for enhanced oil recovery. 3D micro-visualization model was constructed to directly observe the metabolic activities of the target bacterial strain within porous media and to assess the plugging interactions between cellulose and the medium. Additionally, X-ray computed tomography (X-CT) technology was employed for a comprehensive analysis of the transport patterns of the target strain in oil reservoirs with varying permeabilities. The results indicated that FY-07-G, as a microorganism employing biopolymer-based plugging principles to enhance oil recovery, selectively targets and seals regions characterized by lower permeability and smaller pore spaces. This work provided valuable insights into the transport and metabolic behavior of MEOR strains and tackled the limitation of 2D models in faithfully replicating oil reservoir conditions, offering essential theoretical guidance and insights for the further application of oil-displacing bacterial strains in MEOR processes.


Is current preoperative frailty assessment adequate?
Preoperative frailty predicts adverse postoperative outcomes. Recommendations for preoperative assessment of elderly patients include performing a frailty assessment. Despite the advantages of incorporating frailty assessment into surgical settings, there is limited research on surgical health care professionals' perception and use of frailty assessment for perioperative care. We surveyed local health care employees to assess their attitudes toward and practices for frail patients. Nurses and allied health professionals were more likely than surgeons to agree frailty should play a role in planning a patient's care. Lack of knowledge about frailty issues was a prominent barrier to the use of frailty assessments in practice, despite clinicians understanding that frailty affects their patients' outcomes. Results of this survey suggest further training in frailty issues and the use of frailty assessment instruments is necessary and could improve the uptake of such tools for perioperative care planning.


Sequence-based genotyping for marker discovery and co-dominant scoring in germplasm and populations.
Conventional marker-based genotyping platforms are widely available, but not without their limitations. In this context, we developed Sequence-Based Genotyping (SBG), a technology for simultaneous marker discovery and co-dominant scoring, using next-generation sequencing. SBG offers users several advantages including a generic sample preparation method, a highly robust genome complexity reduction strategy to facilitate de novo marker discovery across entire genomes, and a uniform bioinformatics workflow strategy to achieve genotyping goals tailored to individual species, regardless of the availability of a reference sequence. The most distinguishing features of this technology are the ability to genotype any population structure, regardless whether parental data is included, and the ability to co-dominantly score SNP markers segregating in populations. To demonstrate the capabilities of SBG, we performed marker discovery and genotyping in Arabidopsis thaliana and lettuce, two plant species of diverse genetic complexity and backgrounds. Initially we obtained 1,409 SNPs for arabidopsis, and 5,583 SNPs for lettuce. Further filtering of the SNP dataset produced over 1,000 high quality SNP markers for each species. We obtained a genotyping rate of 201.2 genotypes/SNP and 58.3 genotypes/SNP for arabidopsis (n = 222 samples) and lettuce (n = 87 samples), respectively. Linkage mapping using these SNPs resulted in stable map configurations. We have therefore shown that the SBG approach presented provides users with the utmost flexibility in garnering high quality markers that can be directly used for genotyping and downstream applications. Until advances and costs will allow for routine whole-genome sequencing of populations, we expect that sequence-based genotyping technologies such as SBG will be essential for genotyping of model and non-model genomes alike.


Imaging beyond the ballistic limit in coherence imaging using multiply scattered light.
We present an imaging system based on low coherence interferometric detection of multiply scattered light for extended depth imaging into highly scattering media. By incorporating angle-resolved detection, coherence imaging with multiply scattered photons is shown to be both feasible and potentially superior to existing techniques for performing time-resolved measurements of scattered light. Imaging is demonstrated through nearly 100 mean free paths of scattering phantom in a single-ended geometry. The resolution and imaging contrast are compared to those obtained with conventional OCT systems which chiefly detect singly scattered light.


Common ancestry of Escherichia coli pyruvate oxidase and the acetohydroxy acid synthases of the branched-chain amino acid biosynthetic pathway.
A number of enzymes require flavin for their catalytic activity, although the reaction catalyzed involves no redox reaction. The best studied of these enigmatic nonredox flavoproteins are the acetohydroxy acid synthases (AHAS), which catalyze early steps in the synthesis of branched-chain amino acids in bacteria, yeasts, and plants. Previously, work from our laboratory showed strong amino acid sequence homology between these enzymes and Escherichia coli pyruvate oxidase, a classical flavoprotein dehydrogenase that catalyzes the decarboxylation of pyruvate to acetate. We have now shown this homology (i) to also be present in the DNA sequences and (ii) to represent functional homology in that pyruvate oxidase has AHAS activity and a protein consisting of the amino-terminal half of pyruvate oxidase and the carboxy-terminal half of E. coli AHAS I allows native E. coli AHAS I to function without added flavin. The hybrid protein contains tightly bound flavin, which is essential for the flavin substitution activity. These data, together with the sequence homologies and identical cofactors and substrates, led us to propose that the AHAS enzymes are descended from pyruvate oxidase (or a similar protein) and, thus, that the flavin requirement of the AHAS enzymes is a vestigial remnant, which may have been conserved to play a structural rather than a chemical function.


Regulation of laccase biosynthesis in the plant-pathogenic fungus Cryphonectria parasitica by double-stranded RNA.
Transmissible hypovirulence of the chestnut blight fungus, Cryphonectria parasitica, is associated with cytoplasmic double-stranded-RNA (dsRNA) viruses. The fungal laccase has attracted interest because its activity is reduced in hypovirulent dsRNA-containing strains. A laccase cDNA clone was isolated by screening a cDNA expression library with antibodies against the purified extracellular laccase. The amino acid sequence deduced from part of the cDNA clone revealed high homology to other fungal laccases, especially to the Neurospora crassa laccase. A major laccase transcript 2.3 kb in length was detected in Northern (RNA) blots. In liquid culture, extracellular laccase activity was reduced by about 75% in the hypovirulent (dsRNA-free) strain EP155/2. In contrast, production of biomass was not affected by the dsRNA. Northern blot analysis indicated that dsRNA down regulates laccase biosynthesis by reducing laccase mRNA accumulation. The laccase gene is one of several developmentally regulated genes affected by the presence of dsRNA.


The Norwegian version of the Severe Respiratory Insufficiency Questionnaire.
The aims of this study were to translate and adapt the Severe Respiratory Insufficiency (SRI) questionnaire into Norwegians and to test its reliability and validity.Data were collected from a cross-sectional survey and were linked to the Norwegian Registry of patients receiving long-term mechanical ventilation (LTMV). Of 193 potential participants, 127 responded to the SRI questionnaire. Reliability as measured with Cronbach's α varied between 0.68 and 0.88 for the subscales and was 0.94 for SRI-sum score. Construct validity was obtained with high correlations between subscales in SF-36 and SRI. The SRI questionnaire discriminated well between universally accepted clinical differences among categories of patients receiving LTMV by significant dissimilarities in SRI-sum score and SRI subscales. The Norwegian version of SRI has well-documented psychometric properties regarding reliability and validity. It might be used in clinical practice and in international studies for assessing health-related quality of life in patients receiving LTMV.


Macrophage membrane interleukin 1 regulates the expression of acute phase proteins in human hepatoma Hep 3B cells.
To assess the potential role of membrane interleukin 1 (mIL-1) in modulating expression of acute phase proteins, we studied the effect of fixed mouse peritoneal macrophages and isolated cell membranes on the synthesis of C3 and albumin in human hepatoma Hep 3B cells. An increase in C3 synthesis and decrease in albumin synthesis were detected after incubation of Hep 3B cells with fixed stimulated macrophages or with membrane preparations. Estimates of hepatocellular C3 and albumin mRNA indicated that the mIL-1 regulation was exerted at a pretranslational level. The changes in C3 and albumin expression induced by mIL-1 were inhibited by addition of anti-interleukin 1 (IL-1) antiserum to the macrophages, supporting the hypothesis that a form of IL-1 is present on the outer cell membrane of macrophages. Moreover, cell-surface iodination of macrophages allowed the detection of a 33-kDa IL-1 molecule, suggesting that an IL-1 species, similar to the intracellular precursor of IL-1 is present at the outer cell surface of macrophages. The expression of mIL-1 was temporally dissociated from IL-1 release, indicating that the cell-surface associated IL-1 activity is not the result of adsorbed soluble IL-1. These studies provide a basis for further investigation of the role of mIL-1 in modulating monocytes and macrophages function via cell-cell interactions.


Digital questionnaire platform in the Danish Blood Donor Study.
The Danish Blood Donor Study (DBDS) is a prospective, population-based study and biobank. Since 2010, 100,000 Danish blood donors have been included in the study. Prior to July 2015 all participating donors had to complete a paper-based questionnaire. Here we describe the establishment of a digital tablet-based questionnaire platform implemented in blood bank sites across Denmark. The digital questionnaire was developed using the open source survey software tool LimeSurvey. The participants accesses the questionnaire online with a standard SSL encrypted HTTP connection using their personal civil registration numbers. The questionnaire is placed at a front-end web server and a collection server retrieves the completed questionnaires. Data from blood samples, register data, genetic data and verification of signed informed consent are then transferred to and merged with the questionnaire data in the DBDS database. The digital platform enables personalized questionnaires, presenting only questions relevant to the specific donor by hiding unneeded follow-up questions on screening question results. New versions of questionnaires are immediately available at all blood collection facilities when new projects are initiated. The digital platform is a faster, cost-effective and more flexible solution to collect valid data from participating donors compared to paper-based questionnaires. The overall system can be used around the world by the use of Internet connection, but the level of security depends on the sensitivity of the data to be collected.


Empowering Head Start to improve access to good oral health for children from low income families.
Surveys over 20 years have documented worsening in the dental health of preschoolers. Healthy People 2010 Midcourse Review reports the country moving away from oral health goals for young children; the slip is 57%. Exacerbating this is the inability of Medicaid to provide for those in need. Most children receive examinations only: few receive comprehensive care. We urge Head Start grantees to adopt a new approach to oral health goals and in this paper offer: (1) a review of the problem and premises preventing a solution; (2) a proposal that Head Start adopt a public health perspective; and (3) specific roles staff and dental personnel can take to mount aggressive strategies to arrest tooth decay at the grantee site.


The use of an acoustic device to identify the epidural space in cattle.
Twelve healthy cattle (weighing 188-835 kg) were placed in stocks and sedated with xylazine. Caudal epidural puncture was performed using an acoustic device that indicated a decrease in resistance with a change in pitch. Lidocaine was injected to verify correct needle placement by assessing needle prick stimuli applied on the left and right side of the tail root and the perineal region, and the loss of tail and anal sphincter tone. Pressure measurements were recorded during penetration of the different tissue layers and in the epidural space. A clear and sudden decrease in the pitch of the acoustic signal was audible in all 12 cattle. All cows showed clinical effects indicating successful epidural anaesthesia. The pressure in the epidural space after puncture was -19±10 mm Hg. The device may be of assistance in identifying the epidural space in cattle.


Transdermal drug delivery system: patent reviews.
Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. Although the concept of transdermal drug delivery has been known since 1924, it took until 1979, as FDA approved the transdermal delivery of scopolamine, that transdermal delivery systems [TDDS] received broad attention as novel tool for controlled release. These drug delivery systems are designed for controlled release of drug through the skin into systemic circulation maintaining consistent efficacy and reducing dose of the drug and its related side effects. More than 200 patents have been granted by the United State patent alone, of which more than 35 TDD products have now been approved for sale in the US, and approximately 16 active ingredients have been approved for use globally. Statistics reveal a market of $ 12.7 billion in the year 2005 which is expected to increase by $ 21.5 billion in the year 2010 and $ 31.5 billion in the year 2015. Almost all major and minor pharmaceutical companies are developing TDDS. There is not a single review article which describes patents on different types of TDDS. Thus this review is designed for patents on the different type of TDDS which would be helpful for the researcher in the field of TDDS.


Psychological Stress and Stressors Among Clinical Dental Students at Shiraz School of Dentistry, Iran.
The purpose of this study was to assess the level of psychological stress and the perceived stressors among the undergraduate clinical dental students of Shiraz School of Dentistry. This study was conducted during the second semester of the academic year 2018-2019 at Shiraz School of Dentistry, Shiraz University of Medical Sciences, Iran. The study group consisted of 150 dental clinical students. The participants were surveyed via the validated Depression, Anxiety, and Stress Scale (DASS-21) and the Dental Environment Stress (DES) questionnaires. One-way ANOVA, post hoc Tukey's test, repeated measure ANOVA, Holm-Sidak's test, and t-test were performed to analyze the data after the normality of the data was checked by Kolmogorov-Smirnov test. The P values of less than 0.05 were considered as statistically significant. No significant differences were observed among the dental students with different academic levels in terms of depression and anxiety scores (P=0.057 and 0.154, respectively). The lowest and highest stress scores were observed among the sixth- and fifth-year students, respectively (P values <0.05). The scores of the stressors associated with the academic factors were significantly higher than those of the other domains (P<0.05) except for that of the clinical education domain (P=0.070). The females showed significantly higher DES scores (P values <0.05). The highest and lowest stress levels were observed among the fifth- and sixth-year students, respectively. The primary sources of stress were academic factors and clinical education. The females expressed higher levels of stress in certain areas of dental training.


Red phosphorus-single-walled carbon nanotube composite as a superior anode for sodium ion batteries.
Sodium ion batteries (SIBs) have been considered as a top alternative to lithium ion batteries due to the earth abundance and low cost of sodium compared with lithium. Among all proposed anode materials for SIBs, red phosphorus (P) is a very promising candidate because it has the highest theoretical capacity (∼2600 mAh/g). In this study, a red P-single-walled carbon nanotube (denoted as red P-SWCNT) composite, in which red P is uniformly distributed between tangled SWCNTs bundles, is fabricated by a modified vaporization-condensation method. Benefiting from the nondestructive preparation process, the highly conductive and mechanically strong SWCNT network is preserved, which enhances the conductivity of the composite and stabilizes the solid electrolyte interphase. As a result, the red P-SWCNT composite presents a high overall sodium storage capacity (∼700 mAh/gcomposite at 50 mA/gcomposite), fast rate capability (∼300 mAh/gcomposite at 2000 mA/gcomposite), and stable long-term cycling performance with 80% capacity retention after 2000 sodiation-desodiation cycles. The red P-SWCNT composite fabricated by the vaporization-condensation method significantly extends the cycling stability of P/carbon composite from current ∼100 cycles to ∼2000 cycles.


Comparison of abdominal damage control surgery in combat versus civilian trauma.
The majority of individuals who perform damage control surgery in the military arena are trained in civilian venues. Therefore, it is important to compare and contrast damage control performed in civilian and military settings. In contrast to civilian trauma, which is primarily caused by blunt injury and addressed at one or two surgical facilities, combat casualties primarily sustain explosion-related injuries and undergo treatment at multiple levels of care across continents. We aimed to compare patients undergoing abdominal damage control surgery across these two very different settings. Parallel retrospective reviews were conducted over 2 years (2005-2006) in a combat setting and at a US Level I trauma center. Patients were examined during the first 7 days after injury. The civilian population (CP) was older (40 vs. 23; p < 0.01) with a higher injury severity score (35 vs. 27; p < 0.02). The CP experienced greater blunt injury than the military population (MP) (83 vs. 4%; p < 0.01). Explosion-related injury was only present in the MP (64%). At baseline, the CP presented with lower systolic blood pressure (108 vs. 126) and larger base deficit (9.8 vs. 6.5; p < 0.05). The MP underwent more surgeries (3.5 vs. 2.9; p = 0.02) with similar rates of fascial closure (48.7% vs. 70.0%; p = 0.11). Complication rates were similar between the CP and the MP (43% vs. 58%, respectively; p = 0.14). Military and civilian trauma patients who undergo damage control surgery experience similar fascial closure rates despite differing demographics and widely disparate mechanisms of injury. The MP undergoes a greater number of procedures than the CP, but complication rates do not differ between the groups.


A challenging case: Symmetrical drug related intertriginous and flexural exanthem, fixed drug eruption, or both?
We herein report a 12-year-old boy with amoxicillin-induced, recurrent, site-specific, symmetrical, sharply demarcated reddish plaques on the buttocks and the major flexural and intertriginous areas. The lesions resolved with topical corticosteroids, leaving hyperpigmentation. Histopathology showed nonspecific features of inflammation and dermal melanophages. Amoxicillin was the probable inducer based on oral provocation test with Amoksina(®) tablet, however patch testing with amoxicillin on previously affected and unaffected skin remained negative. The diagnosis was challenging because of the overlapping features of symmetrical drug-related intertriginous and flexural exanthema and fixed drug eruption. This one represents a unique and challenging one with overlapping clinical features of symmetrical drug-related intertriginous and flexural exanthem (SDRIFE) and fixed drug eruption (FDE). We discuss the possible immunopathogenetic mechanisms leading to the simultaneous occurrence of different phenotypes of drug eruption in the same patient.


Development of LC-MS/MS analytical method for the rapid determination of Diquat in water and beverages.
This study aimed to develop simple, fast, and sensitive methods for the determination of diquat (DQ) in various matrices such as water and beverages. For water, direct injection was tested first, however, the sensitivity of the incurred samples were too low and couldn't possibly achieve the targeted limit of quantification. Hence, dilution with "weaker" injection solvents were tested, and the final conditions involved the dilution of water with acetonitrile (0.4 % ammonium hydroxide) which increased the sensitivity by more than ten times. Nevertheless, the beverages samples needed further treatment to achieve acceptable spiked recovery. The final conditions involved extraction using the aforementioned solvent, followed by heating and partitioning. Both of the methods satisfied the validation requirements, with an average recovery ranging from 85.9 to115 % and associated relative standard deviation (RSD %) within the range 3-8. Further applications on real samples were done to test the levels of contamination.


Videourodynamic factors predictive of successful onabotulinumtoxinA urethral sphincter injection for neurogenic or non-neurogenic detrusor underactivity.
The aim of the present study was to analyze treatment outcomes and identify videourodynamic factors predictive of successful urethral onabotulinumtoxinA treatment of neurogenic and non-neurogenic detrusor underactivity (DU). Patients with DU refractory to medical treatment were treated with injections totaling 100 U onabotulinumtoxinA into the urethral sphincter. Treatment outcomes were assessed 1 month after treatment using the Global Response Assessment. The videourodynamic parameters evaluated included bladder neck status during voiding, bladder sensation, detrusor pressure, maximum flow rate, and post-void residual volume. Treatment outcome was analyzed by patient and baseline videourodynamic characteristics. In all, 60 patients (27 with non-neurogenic and 33 with neurogenic DU) were included in the study and received urethral sphincter injections of 100 U onabotulinumtoxinA in total. Good outcomes were reported in 36 (60%) patients (20 [74.1%] with non-neurogenic and 16 [48.5%] with neurogenic DU). Treatment outcome was significantly better in patients with non-neurogenic than neurogenic DU (P = .039). However, good treatment outcome was not related to age, gender, or any videourodynamic variables, except for an open bladder neck during voiding vs non-opening bladder neck (94.3% vs. 12.0%; P < .0001). The duration of the therapeutic effect was similar between patients with non-neurogenic and neurogenic DU (mean [± SD] 7.37 ± 3.69 vs. 7.69 ± 3.18 months, respectively; P = .788). In all, 12 patients reported de novo urinary incontinence after urethral onabotulinumtoxinA injection, 4 of whom developed stress urinary incontinence and 8 who had exacerbated urgency urinary incontinence. Urethral sphincter injection of onabotulinumtoxinA is effective in 60% of patients with DU. Careful videourodynamic interpretation of bladder neck opening enables urologists to select appropriate candidates for onabotulinumtoxinA treatment.


Isolation in cell culture of nodavirus from farmed Atlantic halibut Hippoglossus hippoglossus in Norway.
Isolation in cell culture of nodavirus from Atlantic halibut Hippoglossus hippoglossus suffering from viral encephalopathy and retinopathy (VER) is described. The cell line SSN-1 was inoculated with tissue material from affected juveniles (60 d after first feeding). Extensive cytopathic effects (CPE) developed approximately 5 d after inoculation, and were also observed after several passages in the same cell line. Cells from infected cultures showed reactivity with an antiserum against sea bass Dicentrarchus labrax nodavirus in an indirect immunofluorescence test. Analysis of infected cells with reverse transcriptase-polymerase chain reaction (RT-PCR) resulted in a product of the predicted size using primers specific for striped jack Pseudocaranx dentex nodavirus. Electron micrographs of infected SSN-1 cells demonstrated virus particles that were approximately less than 30 nm. Challenge of Atlantic halibut larvae (4 d post-hatching) with supernatants from infected SSN-1 cells resulted in development of VER as verified by immunohistochemistry performed on larvae sampled from Day 9 after challenge. The present results show that a nodavirus from Atlantic halibut has been isolated using the SSN-1 cell line and that virus propagated in cell culture retained virulence.


In vivo analysis of thoracic mechanical response variability under belt loading: specific behavior and relationship to age, gender and body mass index.
Thoracic injuries are a major cause of mortality in frontal collisions, especially for elderly female and obese people. Car occupant individual characteristics like age, gender and Body Mass Index (BMI) are known to influence human vulnerability tolerance in crashes. The objective of the this study was to perform in vivo test experiments to quantify the influence of subject characteristics in terms of age, gender and anthropometry and on thorax mechanical response variability under belt loading. Thirty-nine relaxed volunteers of different anthropometries, genders and age were submitted to non-injurious sled tests (4 g, 8 km/h) with a sled buck representing the environment of a front passenger restrained by a 3-point belt. A resulting shoulder belt force FRes was computed using the external and internal shoulder belt loads and considering shoulder belt geometry. The mid sternal deflection D was calculated as the distance variation between markers placed at mid-sternum and at the 7th vertebra spinous process of the subject. Linear stiffness (K) and damping coefficient (μ) of a spring-dashpot model were identified from the FRes-D curves of each test. The analysis suggests that among subjects over 40 years old, thinness leads to higher K-values.


Modelling the effect of atmospheric nitrogen deposition on marine phytoplankton in the Singapore Strait.
Atmospheric deposition is an important source of nutrients to the ocean, potentially stimulating primary production, but its relative effect on coastal eutrophication remains largely unknown. This paper presents data generated by the 3-D modelling program NEUTRO to assess the proportion of atmospheric nutrient fluxes, allowing a quantification of the relative contribution of atmospheric and ocean fluxes in the Singapore Strait. This work included an assessment of the importance of high concentration episodic inputs of nitrate-nitrogen associated with transport of polluted air onto the surface water. The NEUTRO model features a nutrient-fuelled food web composed of nutrients, plankton, and dissolved oxygen dynamics. Model simulations show that atmospheric deposition fluxes alone might contribute nitrate-nitrogen mass up to 15% into the Singapore Strait. This amount might be a significant contributor toward regional eutrophication when the system is under nutrient-depleted conditions. Model calibrations for temporal and spatial variability of nutrients qualitatively and quantitatively agreed with available measurements.


Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells.
Senescence-associated (beta)-galactosidase is widely used as a biomarker of replicative senescence. However, it remains unknown whether this is a distinct enzyme active at pH 6, and differentially expressed in senescence, or a manifestation of an increase in the classic acid lysosomal (beta)-galactosidase. Here we have investigated the origin of senescence-associated-(beta)-galactosidase activity by modifying the intracellular and lysosomal pH of young and senescent human umbilical vein endothelial cells and examining the effect of these manipulations on the levels of activity, using a flow cytometric assay. Lysosomal alkalinisation with chloroquine or bafilomycin A(1), as well as equilibration of the intracellular milieu to pH 6 with nigericin, caused a profound (92-99%) inhibition of the total intracellular (beta)-galactosidase activity. However, independent of pH alterations, senescent cells showed levels of (beta)-galactosidase activity three- to sixfold higher than young cells. This increase in activity occurred in parallel to an increase in (beta)-galactosidase protein levels. Acridine Orange staining revealed an increase in lysosomal content with replicative age, which correlated with the increase in (beta)-galactosidase. These findings demonstrate that senescence-associated (beta)-galactosidase is a manifestation of residual lysosomal activity at a suboptimal pH, which becomes detectable due to the increased lysosomal content in senescent cells.


Effect of a nationwide program of educational outreach visits to improve the processes of care for patients with type 2 diabetes.
To improve processes of ambulatory care for patients with type 2 diabetes in a nationwide program. Interrupted time-series analysis with audits of practice. To implement selected recommendations of national guidelines, educational outreach visits (office visits or phone discussions) were offered to all French physicians who diagnosed one case of type 2 diabetes during a six-month intervention period. Outcome measures were the number of HBA1c measurements recorded monthly in the medical insurance computer database and the proportion of diabetic patients for whom one test had been reimbursed during the previous six months (HBA1c, fasting blood glucose) or previous twelve months (serum cholesterol, serum creatinine, urine microalbumin, electrocardiogram, ophthalmologic examination). A total of 15,522 office visits and 9,062 telephone discussions were performed among 22,940 physicians. The increase in the monthly proportion of the number of HBA1c tests to the total number of laboratory tests was higher during the intervention period than during the preintervention (p value < .0001) and postintervention periods (p value < .001). Between the first audit (n = 651,574) and the third audit (n = 911,871), HBA1c measurements increased from 41.2% to 60.5% and blood glucose measurements performed alone decreased from 38.8% to 18.7%. Urine microalbumin measurements increased from 10.6% before to 15.3% after intervention. Only a slight increase was observed for other tests. Physician to physician outreach visits can be an effective way to improve the processes of care for diabetes and to routinize nationwide use of practice guidelines.


Cyclin D2, but not cyclin D1, overexpression closely correlates with gastric cancer progression and prognosis.
Expression of cyclins D1 and D2, as well as cyclin-dependent kinase 4 (cdk4), was investigated by means of immunohistochemistry in 455 gastric cancer cases. Additional western blotting was performed for four breast cancer and four gastric cancer cell lines and 35 fresh frozen gastric cancer samples, to confirm the cyclin D1, D2, and cdk4 data. Cyclin D1 was restricted to the nucleus of cancer cells with a few exceptions, whereas cyclin D2 was present in both cell compartments, but predominantly in the cytoplasm. Cdk4 was intermediately expressed. Cyclin D1 was overexpressed in 93 cases (20.4 per cent) and cyclin D2 in 105 (23.0 per cent). In the cyclin D2 cases, this correlated with greater age (p=0.0004), better differentiation (p=0.0023), greater depth of cancer invasion (p=0. 003), the presence of lymph node metastasis (p=0.0014), vascular invasion by cancer cells (p< 0.0001), and poor prognosis (p< 0.0001), while cyclin D1 did not correlate with any of these except age (p=0.00193). Multivariate analysis revealed cyclin D2 overexpression to be an independent prognostic factor, in addition to depth of cancer invasion and lymph node status. Cdk4 overexpression was linked to cyclin D1, but not cyclin D2 overexpression. The results indicate that cyclin D2 up-regulation plays an important role in the progression and prognosis of gastric cancer independently of cdk4, whereas cyclin D1 overexpression does not.


Jejunal diverticulosis. A heterogenous disorder caused by a variety of abnormalities of smooth muscle or myenteric plexus.
We analyzed the clinical, radiographic, esophageal manometric, and pathological features of 10 patients referred with jejunal diverticulosis. Nine patients were over age 59 yr and had symptoms of intestinal pseudoobstruction of 5-43 yr duration. Seven had surgery for mechanical obstruction, although none was found. Eight had diarrhea, steatorrhea, and weight loss. Five had Raynaud's phenomenon and heartburn, and 2 had dysphagia. At radiography, 9 had jejunal diverticula with or without duodenal or ileal diverticula, or both. Two each had abnormal structure or motility of the esophagus or stomach. At manometry, 3 of 7 had a nonspecific motor abnormality, and 1 other had low amplitude peristaltic waves. Light microscopy of small intestinal tissue in 7 patients showed that 4 had fibrosis and decreased numbers of normal-appearing muscle cells, findings consistent with progressive systemic sclerosis. Two others had fibrosis associated with degenerated smooth muscle cells, findings consistent with a visceral myopathy. The seventh patient had neuronal and axonal degeneration and neuronal intranuclear inclusions, findings consistent with a visceral neuropathy. We conclude that (a) intestinal pseudoobstruction is a major clinical manifestation of jejunal diverticulosis, (b) jejunal diverticulosis is a heterogenous disorder associated with at least three abnormalities of the smooth muscle or myenteric plexus, (c) in contrast to intestinal pseudoobstruction without diverticulosis, the esophagus, stomach, and colon are less frequently involved in jejunal diverticulosis, and (d) some patients with jejunal diverticulosis probably have clinically inapparent progressive systemic sclerosis.


Hepatic lipase (LIPC) sequencing in individuals with extremely high and low high-density lipoprotein cholesterol levels.
Common variants in the hepatic lipase (LIPC) gene have been shown to be associated with plasma lipid levels; however, the distribution and functional features of rare and regulatory LIPC variants contributing to the extreme lipid phenotypes are not well known. This study was aimed to catalogue LIPC variants by resequencing the entire LIPC gene in 95 non-Hispanic Whites (NHWs) and 95 African blacks (ABs) with extreme HDL-C levels followed by in silico functional analyses. A total of 412 variants, including 43 novel variants were identified; 56 were unique to NHWs and 234 were unique to ABs. Seventy-eight variants in NHWs and 89 variants in ABs were present either in high HDL-C group or low HDL-C group. Two non-synonymous variants (p.S289F, p.T405M), found in NHWs with high HDL-C group were predicted to have damaging effect on LIPC protein by SIFT, MT2 and PP2. We also found several non-coding variants that possibly reside in the circRNA and lncRNA binding sites and may have regulatory potential, as identified in rSNPbase and RegulomeDB databases. Our results shed light on the regulatory nature of rare and non-coding LIPC variants as well as suggest their important contributions in affecting the extreme HDL-C phenotypes.


Reactive lymphoid hyperplasia of the pancreas: a clinical conundrum.
Localized reactive lymphoid hyperplasia is a rare condition characterized by the presence of lymphoid follicles. We describe a case of a 60-year-old woman who presented with right upper quadrant pain and was found to have a reactive nodular hyperplasia of the pancreas involving the uncinate process, body and tail of the gland. Due to the multifocal distribution of these hypoechoic vascular lesions, a total pancreatectomy was performed since malignancy could not be safely excluded. There have been a handful of cases reporting reactive lymphoid hyperplasia affecting the pancreas; however, it is uncommon to perform such a radical pancreatic resection for this benign condition.


[Nazi Terror against the Danish Medical Profession. The February 20, 1945 Murders in Odense].
On February 20, 1945, during the German occupation of Denmark, members of a notorious Nazi terror organization named the Petergroup murdered four young medical doctors at the city and regional hospital of Odense. On the 70th anniversary of the crime, a symposium was organized at the Odense University Hospital, and a monument revealed close to the site of the murders in commemoration of the four victims of the crime. The young physicians were not known to be connected with the Danish resistance, and they were shot without their murderers even knowing their identities in an attempt to revenge the growing resistance in Denmark's central, third largest city, and as a reprisal for several cases where the hospital had treated wounded resistance fighters, and prevented their being handed over to the German police. The article describes the terror action of February 20, 1945 and its perpetrators, as well as other Nazi attacks on members of the Danish medical profession. It lines out the strong protest voiced by the Danish central administration against the Odense hospital killings which were on the very same day seconded by further killings and a German campaign of blowing up important Odense buildings including two newspaper printing houses. Conclusively, the authors - by way of obituaries and material from relatives of the murdered - portray the four victims of the atrocity Christian Fabricius Møller, Jørgen Hvalkof, Henning Magnus Adelsteen Dalsgaard, and Henning Ørsberg.


Use of stimulant medications in children.
A systematic approach to the use of stimulant medications is required in the treatment of attention deficit disorder and associated learning problems. The diagnosis of attention deficit disorder must be confirmed before drug therapy is started, and parents must be counseled about the use of stimulant medications. The actions and side effects of the various treatment alternatives should be discussed.


[Role of cycloferon and interferon-alphain apoptosis regulation in neuroendocrinal system on aging].
A detailed analysis of the literature data gives contradictory information about the role of interferon-alpha in the regulation of apoptosis, while there are almost no data on the participation of cycloferon in this process. Results of original experiments in recent years showed that exogenous interferon-alpha is not apoptosis protector in hypothalamic neurons on aging. The treatment with interferon-alpha activates dystrophic processes in neurosecretory cells of aged mice. However, endogenous interferon induced by cycloferon leads to a decrease in the apoptosis of hypothalamic neurons in both young and old animals. Antiapoptotic activity of interferon-alpha and cycloferon has been found in aged animals under stress condition. Thus, the role of immunomodulators in apoptosis regulation in hypothalamic neurons depends on the age and the type of immunomodulators. This fact opens new prospects for the clinical use of interferon-alpha and cycloferon.


Immunocytochemical localization of substance P neurokinin-1 receptors in rat gingival tissue.
The distributions of substance P (SP) and the neurokinin-1 receptor (NK1-R), the receptor preferentially activated by SP, were examined in rat gingiva by immunocytochemical methods with light and electron microscopy. SP-immunoreactive nerve fibers were located preferentially in the junctional epithelium (JE) but few in the other oral and oral sulcular epithelia. NK1-R immunoreactivity was found in the endothelial cells (capillaries and postcapillary venules underlying the JE). NK1-R-labeled and -unlabeled unmyelinated nerve fibers were located close to the blood vessels and partially or completely covered by a Schwann cell sheath. In the JE, labeled naked axons without Schwann cell sheaths were observed. Neutrophils and macrophages in the connective tissue underlying the JE and in the JE were also labeled with NK1-R. Furthermore, NK1-R was found in the JE cells. Basically, immunoreaction products for NK1-R were found throughout various cells (endothelial cells, neutrophils, and JE cells) at invaginations of the plasma membrane and in vesicular and granular structures that are probably endosomes and are found close to both the plasma membrane and the nucleus. This is a first report, demonstrating the presence of NK1-R in the gingival tissue in the normal nonstimulated condition. Furthermore, it is thought that SP may modulate the permeability of blood vessels beneath the JE, the production of antimicrobial agents in neutrophils, and the proliferation and endocytotic ability of JE cells through NK1-R.


"Not Unless It's a Life or Death Thing": A Qualitative Study of the Health Care Experiences of Adults Who Stutter.
For adults who stutter, communication difficulties can impact many spheres of life. Previous studies have not examined how stuttering might impact patient's experiences with the medical system. Our objective was to understand the range and depth of experiences with the medical system among adults who stutter. This was a qualitative study using age-stratified focus groups. Sixteen adults who stutter were recruited at a national conference about stuttering. We conducted three focus groups. Participants also completed a written questionnaire about sociodemographic characteristics, health status, and the impact of stuttering on their life [using the St. Louis Inventory of Life Perspectives Scale (SL-ILP-S) Total Effect Score]. We analyzed data using an iterative, thematic analysis, with an inductive approach, at a semantic level. Participants were mostly (75 %) male and resided throughout the United States. The mean SL-ILP-S Total Effect Score was 27.3, indicating that stuttering caused minimal concern in participants' lives. Despite this, we identified five themes that characterize ways in which stuttering affects interactions with the medical system. Participants described (1) discomfort speaking with office staff and physicians, which resulted in (2) avoiding health care interactions because of stuttering, and (3) relying on a third party to navigate the medical system. During visits with physicians, participants felt that (4) discussing stuttering with physicians required trust and rapport, and (5) speaking assertively with physicians required self-acceptance of their stuttering. We identified ways in which stuttering affects medical interactions. These results highlight the need for increased awareness and training for medical staff and physicians when caring for persons who stutter. Future studies among diverse samples of stutterers can determine the effects of stuttering on medical interactions, and inform the development of interventions to provide high quality health care for adults who stutter.


Developmental defects resulting from arginine auxotrophy in Aspergillus nidulans.
A mutant of Aspergillus nidulans, isolated for inability to form asexual spores (conidia) on complete medium, was found to regain the ability to conidiate if the medium was supplemented with arginine. On minimal medium the mutant required arginine for growth but at a much lower concentration than that required for conidiation. This mutant, designated argB12, thus defines a phase-critical gene, i.e. a gene whose function is in greater demand for development than for growth. In addition to its aconidial phenotype, the mutant also exhibited (depending on the medium) aberrant sexual development and a low efficiency of conidial germination. In crosses, each of these developmental phenotypes segregated with arginine auxotrophy. Genetic and biochemical analyses showed the argB12 mutation to be an allele of the previously described argB locus, mutants of which lack ornithine transcarbamylase. Arginine-requiring mutants at at least two other loci were also found to be defective in asexual sporulation, but the germination defect appears to be specific to argB mutants.


New insights into syntrophic ethanol oxidation: Effects of operational modes and solids retention times.
Anaerobic ethanol oxidation relies on syntrophic interactions among functional microorganisms to become thermodynamically feasible. Different operational modes (sequencing batch reactors, SBRs, and continuous flow reactors, CFRs) and solids retention times (SRT, 25 days and 10 days) were employed in four ethanol-fed reactors, named as SBR25d, SBR10d, CFR25d, and CFR10d, respectively. System performance, syntrophic relationships, microbial communities, and metabolic pathways were examined. During the long-term operation, 2002.7 ± 56.0 mg COD/L acetate was accumulated in CFR10d due to the washout of acetotrophic methanogens. Microorganisms with high half-saturation constants were enriched in reactors of 25-day SRT. Moreover, ethanol oxidizing bacteria and acetotrophic methanogens with high half-saturation constants could be acclimated in SBRs. In SBRs, Syner-01 and Methanothrix dominated, and the low SRT of 10 days increased the relative abundance of Geobacter to 38.0%. In CFRs, the low SRT of 10 days resulted in an increase of Desulfovibrio among syntrophic bacteria, and CFR10d could be employed in enriching hydrogenotrophic methanogens like Methanobrevibacter.


Transcriptome profiling reveals the regulatory mechanism underlying pollination dependent and parthenocarpic fruit set mainly mediated by auxin and gibberellin.
Fruit set is a key process for crop production in tomato which occurs after successful pollination and fertilization naturally. However, parthenocarpic fruit development can be uncoupled from fertilization triggered by exogenous auxin or gibberellins (GAs). Global transcriptome knowledge during fruit initiation would help to characterize the molecular mechanisms by which these two hormones regulate pollination-dependent and -independent fruit set. In this work, digital gene expression tag profiling (DGE) technology was applied to compare the transcriptomes from pollinated and 2, 4-D/GA3-treated ovaries. Activation of carbohydrate metabolism, cell division and expansion as well as the down-regulation of MADS-box is a comprehensive regulatory pathway during pollination-dependent and parthenocarpic fruit set. The signaling cascades of auxin and GA are significantly modulated. The feedback regulations of Aux/IAAs and DELLA genes which functioned to fine-tune auxin and GA response respectively play fundamental roles in triggering fruit initiation. In addition, auxin regulates GA synthesis via up-regulation of GA20ox1 and down-regulation of KNOX. Accordingly, the effect of auxin on fruit set is mediated by GA via ARF2 and IAA9 down-regulation, suggesting that both pollination-dependent and parthenocarpic fruit set depend on the crosstalk between auxin and GA. This study characterizes the transcriptomic features of ovary development and more importantly unravels the integral roles of auxin and GA on pollination-dependent and parthenocarpic fruit set.


18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels.
In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of 18F-DOPA, 11 patients with medullary thyroid carcinoma were examined using 18F-DOPA PET. Results of 18F-fluorodeoxyglucose (18F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. 18F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), 18F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: 18F-DOPA PET 63%, 18F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with 18F-DOPA PET. 18F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and 18F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, 18F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence.


Structure reconstruction of TiO2-based multi-wall nanotubes: first-principles calculations.
A new method of theoretical modelling of polyhedral single-walled nanotubes based on the consolidation of walls in the rolled-up multi-walled nanotubes is proposed. Molecular mechanics and ab initio quantum mechanics methods are applied to investigate the merging of walls in nanotubes constructed from the different phases of titania. The combination of two methods allows us to simulate the structures which are difficult to find only by ab initio calculations. For nanotube folding we have used (1) the 3-plane fluorite TiO2 layer; (2) the anatase (101) 6-plane layer; (3) the rutile (110) 6-plane layer; and (4) the 6-plane layer with lepidocrocite morphology. The symmetry of the resulting single-walled nanotubes is significantly lower than the symmetry of initial coaxial cylindrical double- or triple-walled nanotubes. These merged nanotubes acquire higher stability in comparison with the initial multi-walled nanotubes. The wall thickness of the merged nanotubes exceeds 1 nm and approaches the corresponding parameter of the experimental patterns. The present investigation demonstrates that the merged nanotubes can integrate the two different crystalline phases in one and the same wall structure.


Parthenolide, an NF-κB Inhibitor Ameliorates Diabetes-Induced Behavioural Deficit, Neurotransmitter Imbalance and Neuroinflammation in Type 2 Diabetes Rat Model.
Diabetes is associated with behavioural and neurochemical alterations. In this manuscript, we are reporting the beneficial effects of parthenolide, an NF-κB inhibitor on behavioural and neurochemical deficits in type 2 diabetic rat model. Diabetes was induced by high-fat diet followed by low dose of streptozotocin (35 mg/kg). Elevated plus maze, open-field, MWM and passive avoidance test paradigm were used to assess behavioural and cognitive deficits. Three-week treatment of parthenolide (0.25 and 0.50 mg/kg; i.p.) attenuated diabetes-induced alteration in cognitive function in Morris water maze and passive avoidance test. Anxiety-like behaviour was also reduced by parthenolide treatment. Moreover, TNF-α and IL-6 levels were significantly decreased in cortex and hippocampus of parthenolide-treated rats. Three-week parthenolide treatment also toned down the alteration of GABA and glutamate homoeostasis. Results of this study corroborate the involvement of neuroinflammation in the development of behavioural and neurochemical deficits in diabetic animals and point towards the therapeutic potential of parthenolide in diabetes-induced alteration of learning, memory and anxiety behaviour.


Reconstructing images from their most singular fractal manifold.
Real-world images are complex objects, difficult to describe but at the same time possessing a high degree of redundancy. A very recent study on the statistical properties of natural images reveals that natural images can be viewed through different partitions which are essentially fractal in nature. One particular fractal component, related to the most singular (sharpest)transitions in the image, seems to be highly informative about the whole scene. In this paper we will show how to decompose the image into their fractal components.We will see that the most singular component is related to (but not coincident with) the edges of the objects present in the scenes. We will propose a new, simple method to reconstruct the image with information contained in that most informative component.We will see that the quality of the reconstruction is strongly dependent on the capability to extract the relevant edges in the determination of the most singular set. We will discuss the results from the perspective of coding, proposing this method as a starting point for future developments.


Clinical supervision and support: Perspectives of undergraduate nursing students on their clinical learning environment in Malawi.
The nurse educators' role in clinical learning is to define the necessary prerequisites of an ideal clinical learning environment. The purpose of the study was to explore and describe the Kamuzu College of Nursing (KCN) undergraduate nursing students' perspectives on clinical supervision and support in their clinical learning environment and their preferences in the clinical learning environment. A mixed method research approach was used to explore and describe clinical supervision from the students' perspectives on the features of their actual and preferred clinical learning environment. The study's population comprised all third- and fourth-year undergraduate nursing students (n = 219). A sample (n = 125) was randomly selected from the population for the quantitative survey of which 120 questionnaires (96%) were valid for analysis. The data collection for qualitative arm of the study comprised interviews conducted through purposive sampling interviewing 20 participants. Survey results were analysed using the Statistical Package for the Social Science (Version 16) and the qualitative data were analysed using the content analysis approach where themes were generated. The study found that the participants were not satisfied with clinical supervision and support during clinical learning. The participants preferred improved clinical supervision and support in their clinical learning. Comparing the difference between actual and the preferred items of supervision the results were statistically significant at p < 0.05. There is a need to improve students' clinical supervision and support at KCN. Nurse educators need to plan for clinical supervision and support effectively to promote proficient nursing graduates.


Stress change on the temporomandibular joint in mandibular prognathism subjects with asymmetry after orthognathic surgery.
The purpose of this study was to evaluate changes in stress on the temporomandibular joint (TMJ) in 80 Japanese subjects (21 males and 59 females, mean age 23.7 years) with mandibular prognathism, with and without asymmetry after orthognathic surgery using the rigid bodies spring model (RBSM). The asymmetric group consisted of 40 subjects whose Mx-Md midline was more than 3 degrees. The remaining 40 subjects formed the symmetric group. The geometry of the stress analysis model was based on frontal cephalograms of the subjects. Menton (Me), the centre point of occlusal force on a line connecting the bilateral buccal cusps of the second molars, and the most lateral, superior, and medial points on the condyle were plotted on a computer display and stress on the condyle was calculated with the two-dimensional RBSM program, Fortran. The degree (force partition) of the resultant force, the direction (angulation), and the displacement (X, Y) of each condyle were calculated and the horizontal displacement (u), the vertical displacement (v), and rotation displacement (theta) of the mandibular body at Me were calculated pre- and post-operatively. The data was analysed using paired and unpaired t-tests. For the vertical (v) and rotational (theta) displacement, the post-operative value was smaller than the pre-operative value (v: P < 0.001, theta: P = 0.0063) in the asymmetric group. For angulation and the X-component, the post-operative value was smaller than that pre-operatively on the deviated (angulation: P = 0.0074, X-component: P = 0.0003) and non-deviated (angulation: P = 0.0024, X-component: P = 0.001) side in the asymmetric group. However, there was no significant difference between the pre- and post-operative value for any parameter in the symmetric group. These findings suggest that surgical correction of mandibular prognathism, with and without asymmetry, could induce an improvement in stress balance on the TMJ in the frontal aspect.


Use of complementary and alternative medicines among women with gestational trophoblastic diseases: a survey at the Philippine General Hospital.
To determine the prevalence of complementary and alternative medicine (CAM) use among women with gestational trophoblastic disease (GTD) at the University of the Philippines-Philippine General Hospital (UP-PGH). A survey on the use of CAM among women (N = 52) with GTD managed at the UP-PGH Gestational Trophoblastic Disease Center from June to August 2009 was done. The mean age of the participants was 32.3 years, and there were no significant differences in the proportion of CAM users as to educational attainment, diagnosis and treatment type received. Among the participants 96% used CAM, most commonly mental healing/prayer, fruit juices/vegetable diet, banaba/taheebo tea and multivitamins. Reasons for CAM use included safety, improvement of immune system, stress reduction and hope for their condition. Benefits included enhanced quality of life, stress reduction, immune system improvement and a healthier lifestyle. No untoward effect of CAM use was reported. Thirty-six percent of the participants disclosed CAM use to their physician. About 56% percent of the physicians were in favor of the CAM used. The main sources of information on CAM were relatives and friends. To better address patients' needs, physicians should routinely ask patients about their use of CAM and be able to discuss these therapies with them.


Neurological Manifestations in Familial Mediterranean Fever: Results of 22 Children from a Reference Center in Kayseri, an Urban Area in Central Anatolia, Turkey.
Background Familial Mediterranean fever (FMF) is an inherited inflammatory disorder characterized by attacks of fever with polyserositis. Objective The purpose of this study was to evaluate pediatric patients with FMF who had central nervous system (CNS) findings. Materials and Methods Our medical records database for 2003 to 2014 was screened retrospectively. In total, 104 patients with FMF were identified, 22 of whom had undergone neurological examination for CNS symptoms. Results Neurological findings included headache in 16 patients (72.7%), epilepsy in 6 patients (27.3%), pseudotumor cerebri in 2 patients (9.1%), tremor in 2 patients (9.1%), and multiple sclerosis in 1 patient (4.5%). The most common MEFV gene mutation was homozygous M694V (40.9%). Conclusions Patients with FMF can present with various CNS manifestations. Further studies that include large populations are needed to elucidate the neurological manifestations of FMF.


How simple are 'simple renal cysts'?
The increasing use of medical imaging as an investigative tool is leading to the incidental and frequent finding of renal cysts in the general population. The presence of a solitary or multiple renal cysts has been generally considered benign in the absence of a family history of renal cystic disease or evidence of chronic kidney disease. Nonetheless, a number of recent studies have questioned this consensus by reported associations with the development of hypertension or malignant change. For these reasons, some clinicians consider the presence of renal cysts to be a contraindication to kidney donation. The situation is complicated by the different usage of the term 'simple' by some radiologists (to indicate non-complex lesions) or nephrologists (to indicate age-related non-hereditary lesions). We propose that the term 'simple' be replaced with the morphological description, Stage I renal cyst (Bosniak Classification). The presence of a Stage I renal cyst should not preclude kidney donation. However, occult renal disease should be excluded and appropriate donor assessment performed.


Hyperthermia treatment planning guided applicator selection for sub-superficial head and neck tumors heating.
In this study, we investigated the differences in hyperthermia treatment (HT) quality between treatments applied with different hyperthermia systems for sub-superficial tumours in the head and neck (H&N) region. In 24 patients, with a clinical target volume (CTV) extending up to 6 cm from the surface, we retrospectively analysed the predicted HT quality achievable by two planar applicator arrays or one phased-array hyperthermia system. Hereto, we calculated and compared the specific absorption rate (SAR) and temperature distribution coverage of the CTV and gross tumour volume (GTV) for the Lucite cone applicator (LCA: planar), current sheet applicator (CSA: planar) and the HYPERcollar (phased-array). The HYPERcollar provides better SAR coverage than planar applicators if the target region is fully enclosed by its applicator frame. For targets extending outside the HYPERcollar frame, sufficient SAR coverage (25% target coverage, i.e. TC25 ≥ 75%) can still be achieved using the LCA when the target is fully under the LCA aperture and not deeper than 50 mm from the patient surface. Simulations predict that the HYPERcollar (hence also its successor the HYPERcollar3D) is to be preferred over planar applicators such as LCA and current sheet applicator in sub-superficial tumours in the H&N region when used within specifications.


Vaccination Status in Pediatric Solid-Organ Transplant Recipients and Their Household Members.
Vaccine-preventable diseases remain a major cause of morbidity and mortality in solid-organ transplant candidates and recipients. Newer recommendations include vaccination of all household members to create a herd immunity around the transplant recipient. This study evaluated the vaccination status of pediatric solid-organ transplant recipients and their household members. We evaluated 30 pediatric solid-organ transplant recipients (14 kidney, 13 liver, 3 heart) and their household members (26 siblings, 30 parents) at time of transplant. Fourteen recipients (47%) received scheduled vaccinations before solid-organ transplant and were up to date for their age with their diphtheria, tetanus, pertussis; hepatitis B virus; poliomyelitis; Haemophilus influenzae type B; Streptococcus pneumoniae conjugate vaccine; and measles, mumps, and rubella vaccinations. Another 7 recipients (23%) had partially completed their schedules, only missing the second dose of the measles, mumps, and rubella vaccine. Fifteen siblings (58%) had either completed (n = 13, 50%) or partially completed (n = 2, 8%) their vaccinations. All 30 parents were either unaware of their vaccination status (n = 10, 33%) or had only incomplete vaccination records (n = 20, 67%). We found that most pediatric solid-organ transplant recipients to be appropriately vaccinated. However, vaccination status in household members, especially in parents, was disappointing.


Childhood maltreatment experiences and problematic sexual outcomes in adult males who have sexually offended: Further evidence of the potency of male caregiver psychological abuse.
Although research on the developmental antecedents of sexual offending has tended to focus on sexual abuse, recent research in juveniles and adults who have sexually offended suggests that psychological abuse perpetrated by a male caregiver may be a particularly important factor in the development of problematic sexual interests and behaviors. This study aimed to extend previous findings by investigating the association between psychological abuse by a male caregiver and problematic sexual outcomes in a sample of adult males who had sexually offended. Participants were 529 adult males incarcerated for sexual offenses, 21% of whom were civilly committed. Childhood maltreatment and problematic sexual outcomes were assessed using the Multidimensional Assessment of Sex and Aggression, a contingency-based inventory that assesses domains related to sexual aggression. Hierarchical regressions were calculated examining the association between childhood abuse types and sexual outcomes. Childhood sexual abuse was associated with child sexual (β = .247, p < .001) and other paraphilic interests (β = .189, p < .001). Male caregiver psychological abuse also emerged as marginally associated with child sexual interest (β = .100, p = .059), even after controlling for other abuse types. These results partially replicate recent findings in a juvenile sample and challenge conventional developmental theories of sexual offending, by suggesting that male caregiver psychological abuse may play a role in the etiology of child sexual interest among males who have sexually offended. This study also suggests a possible gender symmetry effect moderating the developmental consequences of abuse.


Downsizing antibodies: Towards complementarity-determining region (CDR)-based peptide mimetics.
Monoclonal antibodies emerged as an important therapeutic drug class with remarkable specificity and binding affinity. Nonetheless, these heterotetrameric immunoglobulin proteins come with high manufacturing and therapeutic costs which can take extraordinary proportions, besides other limitations such as their limited in cellulo access imposed by their molecular size (ca. 150 kDa). These drawbacks stimulated the development of downsized functional antibody fragments (ca. 15-50 kDa), together with smaller synthetic peptides (ca. 1-3 kDa) derived from the antibodies' crucial complementarity-determining regions (CDR). Despite the general lack of success in the literal translation of CDR loops in peptide mimetics, rational structure-based and computational approaches have shown their potential for obtaining functional CDR-based peptide mimetics. In this review, we describe the efforts made in the development of antibody and nanobody paratope-derived peptide mimetics with particular focus on the used design strategies, in addition to highlighting the challenges associated with their development.


Laparoscopic resection of colonic cancer.
Laparoscopic resection of colonic cancer can be regarded as a safe and efficacious procedure. Short-term outcome is better after laparoscopic colectomy than after open colectomy. Long-term results of the first published randomized clinical trial indicate improved cancer related survival following laparoscopic resection of colonic cancer. However, patients included in this single center study were operated on by highly experienced laparoscopic surgeons and included relative small numbers of patients. Results of other large randomized controlled trials have to be awaited before laparoscopic resection can be recommended for colonic cancer. Higher in-hospital costs and a long learning curve hinder rapid implementation of laparoscopic colectomy into general surgical practice. Integration of laparoscopic surgery into surgical training programs is mandatory.


Oncogene-targeting T cells reject large tumors while oncogene inactivation selects escape variants in mouse models of cancer.
The genetic instability of cancer cells frequently causes drug resistance. We established mouse cancer models, which allowed targeting of an oncogene by drug-mediated inactivation or monospecific CD8(+) effector T (T(E)) cells. Drug treatment of genetically unstable large tumors was effective but selected resistant clones in the long term. In contrast, T(E) cells completely rejected large tumors (≥500 mm(3)), if the target antigen was cancer-driving and expressed in sufficient amounts. Although drug-mediated oncogene inactivation selectively killed the cancer cells and left the tumor vasculature intact, which likely facilitated survival and growth of resistant clones, T(E) cell treatment led to blood vessel destruction and probably "bystander" elimination of escape variants, which did not require antigen cross-presentation by stromal cells.


Restriction pattern of the major outer-membrane protein gene provides evidence for a homogeneous invasive group among ruminant isolates of Chlamydia psittaci.
Thirty-six ruminant isolates of Chlamydia psittaci, previously classified as invasive or non-invasive in a mouse model of virulence, were compared by analysing AluI restriction patterns of the major outer-membrane protein (MOMP) gene after DNA amplification by the polymerase chain reaction. The 24 invasive isolates, although from various origins, all belonged to serotype 1 and represented a strictly homogeneous group sharing a specific MOMP-gene restriction pattern that was not observed in the non-invasive strains. On the other hand, the 12 non-invasive strains, although all belonging to serotype 2, constituted a heterogeneous group with eight distinct MOMP-gene restriction patterns. However, all eight patterns shared a 180 bp fragment or the corresponding restricted fragments of 110 and 70 bp. MOMP-gene restriction patterns also clearly distinguished the ruminant strains from an avian C. psittaci isolate, a C. pneumoniae isolate and two C. trachomatis isolates which were studied for comparison. The homogeneous character of the invasive C. psittaci strains argues strongly for their genetic relatedness. Our results illustrate the usefulness of the MOMP-gene restriction mapping in typing chlamydiae.


A genetically myeloablated MPS VII model detects the expansion and curative properties of as few as 100 enriched murine stem cells.
Causes of transplantation failures are often difficult to assess due to our inability to monitor hematopoietic stem cell (HSC) homing, distribution, and amplification in situ. We have developed a mouse model that permits histochemical localization of 1000-fold enriched HSC and quantification of their long-term expanded progeny in situ. The mice are genetically myeloablated (c-kit receptor mutated, W41/W41) and are beta-glucuronidase null (GUSB ; gus(mps)/gus(mps)). The GUSB- mice with mucopolysaccharidosis type VII (MPS VII), like a large number of human patients with similar diseases, have systemic lysosomal storage disease that leads to premature death. Congenic GUSB+, Lineage(lo), Sca-1(hi), c-Kit(hi), Hoechst(lo) HSC, at doses of 30, 100, 250, and 425 cells, implanted and amplified in adult W41/W41, gus(mps)/gus(mps) recipients in a dose-dependent manner. At autopsy, primary recipients of 100 and 425 donor cells had histologically identifiable donor GUSB+ cells in multiple sites and showed both myeloid and lymphoid expansion in bone marrow. Donor cells were rare in the liver and spleen of 100-cell recipients, but lysosomal storage was significantly reduced. The life span was significantly extended in engrafted recipients of 250 (36.7 +/- 3.84 weeks,p = 0.0316) and 425 (40.7 +/-1.53 weeks,p = 0.0033) cells compared to untreated mice (26.4 +/- 1.53 weeks). Secondary hosts of marrow from the recipients of 425 cells demonstrated continued expansion of the GUSB+ cells. Results indicate the genetically myeloablated MPS VII mice can be used to trace and enumerate donor cells long-term and to follow early engraftment events in situ.