Arthroscopic meniscus repair with a posterior incision.
The transarticular arthroscopic approach with a posterior incision provided a method of repairing more than 98% of unstable meniscus tears encountered between November 1983 and November 1986. A clinically stable bond was obtained in most of these tears with a subjective failure rate of 2% or less. There was a trend towards better healing of isolated meniscus repairs and lateral meniscus tears less than eight weeks old associated with ACL reconstruction when a blood clot injection was used to supplement the rasp abrasion of the parameniscal synovium. Healing of rim widths to 5 mm can be obtained with these methods. Indications for meniscus repair include all lateral meniscus tears and all medial meniscus tears except when repair of a stump would not replace 25% or more of the missing area. In our experience, this includes more than 98% of all unstable meniscus tears. Contraindications to meniscus repair include short (10 mm or less) stable tears, partial thickness (less than 50% of vertical height), and shallow radial tears (3 mm or less in depth). The posterior incision and popliteal retractor are necessary to protect the popliteal neurovascular structures.


Potential antitumor agents. 17. 9-Anilino-10-methylacridinium salts.
9-Anilino-10-methylacridinium salts result from reaction of substituted anilines and 9-chloro-10-methylacridinium salts in turn prepared from the 10-methyl-9(10H)-acridones and SOCl2 or POCl3. Antileukemic (L1210) activities of the quaternary salts were uniformly depressed compared to their unquaternized counterparts. If drug-solvent partition properties (log P) of the cations were considered, log P-activity relationships were similar for both base and quaternary salt series. Substituent effects on antitumor activity were similar in both series.


Mechanisms of platelet activation in cancer-associated thrombosis: a focus on myeloproliferative neoplasms.
Platelets are anucleate blood cells that play key roles in thrombosis and hemostasis. Platelets are also effector cells in malignancy and are known to home into the microenvironment of cancers. As such, these cells provide central links between the hemostatic system, inflammation and cancer progression. Activation of platelets by cancers has been postulated to contribute to metastasis and progression of local tumor invasion. Similarly, cancer-activated platelets can increase the risk of development of both arterial and venous thrombosis; a major contributor to cancer-associated morbidity. Platelet granules secretion within the tumor environment or the plasma provide a rich source of potential biomarkers for prediction of thrombotic risk or tumor progression. In the case of myeloproliferative neoplasms (MPNs), which are characterized by clonal expansion of myeloid precursors and abnormal function and number of erythrocytes, leukocytes and platelets, patients suffer from thrombotic and hemorrhagic complications. The mechanisms driving this are likely multifactorial but remain poorly understood. Several mouse models developed to recapitulate MPN phenotype with one of the driving mutations, in JAK2 (JAK2V617F) or in calreticulin (CALR) or myeloproliferative leukemia virus oncogene receptor (MPL), have been studied for their thrombotic phenotype. Variability and discrepancies were identified within different disease models of MPN, emphasizing the complexity of increased risk of clotting and bleeding in these pathologies. Here, we review recent literature on the role of platelets in cancer-associated arterial and venous thrombosis and use MPN as case study to illustrate recent advances in experimental models of thrombosis in a malignant phenotype. We address major mechanisms of tumor-platelet communication leading to thrombosis and focus on the role of altered platelets in promoting thrombosis in MPN experimental models and patients with MPN. Recent identification of platelet-derived biomarkers of MPN-associated thrombosis is also reviewed, with potential therapeutic implications.


Neural pathways for visual speech perception.
This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody) can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns of activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1) The visual perception of speech relies on visual pathway representations of speech qua speech. (2) A proposed site of these representations, the temporal visual speech area (TVSA) has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS). (3) Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA.


Legal considerations in cosmetic laser surgery.
Cosmetic laser surgery is a continuously evolving field of medicine. According to the American Society for Dermatologic Surgery, over 100 million laser and light source cosmetic procedures were performed by its members. Procedures including hair removal, nonablative treatments, as well as removal of pigmented lesions, tattoos, and unwanted vascular lesions have revolutionized this field. With an increasing number of physicians and nonphysicians performing these procedures, and with the availability of increasingly powerful laser technologies, the potential for problems and their legal consequences continue to increase. This chapter will deal with the concept of negligence and the potential for a resultant medical malpractice that may arise in such a setting. An understanding of the basic principles of a cause of action in medical malpractice will likely protect a physician from losing such a case in a court of law.


Measurement of brain metabolites in patients with type 2 diabetes and major depression using proton magnetic resonance spectroscopy.
Type 2 diabetes and major depression are disorders that are mutual risk factors and may share similar pathophysiological mechanisms. To further understand these shared mechanisms, the purpose of our study was to examine the biochemical basis of depression in patients with type 2 diabetes using proton MRS. Patients with type 2 diabetes and major depression (n=20) were scanned along with patients with diabetes alone (n=24) and healthy controls (n=21) on a 1.5 T MRI/MRS scanner. Voxels were placed bilaterally in dorsolateral white matter and the subcortical nuclei region, both areas important in the circuitry of late-life depression. Absolute values of myo-inositol, creatine, N-acetyl aspartate, glutamate, glutamine, and choline corrected for CSF were measured using the LC-Model algorithm. Glutamine and glutamate concentrations in depressed diabetic patients were significantly lower (p<0.001) in the subcortical regions as compared to healthy and diabetic control subjects. Myo-inositol concentrations were significantly increased (p<0.05) in diabetic control subjects and depressed diabetic patients in frontal white matter as compared to healthy controls. These findings have broad implications and suggest that alterations in glutamate and glutamine levels in subcortical regions along with white matter changes in myo-inositol provide important neurobiological substrates of mood disorders.


On the Provision of Health Services and Protection of Health Workers in War: A Review of Leonard Rubenstein's Perilous Medicine.
This review critiques Johns Hopkins professor Leonard Rubenstein's Perilous Medicine: The Struggle to Protect Health Care from the Violence of War, and offers the reader a military medical officer's perspective on these important concepts. Rubenstein's tome is essential reading for military officers who must understand how the laws of armed conflict and the ideals of humanitarian protection apply in twenty-first-century conflict. This review adds that military officers may, at times, need to also consider a less ideal but more consequential framework.


Ergonomic interventions for office workers with musculoskeletal disorders: a systematic review.
Ergonomic interventions designed for office and computer work have become widely available and heavily marketed but there is little evidence to support their use with workers who already have a musculoskeletal disorder (MSD). The purpose of any ergonomic intervention can be to improve worker comfort, safety and/or productivity. The ergonomic research in secondary prevention typically focuses outcomes on improved worker comfort but less if any emphasis has been put on productivity and safety. The purpose of this study was to determine the level and quality of evidence supporting ergonomic interventions to improve the comfort, safety and/or productivity of office workers with symptoms of MSDs. A search of the ergonomic intervention literature based on MSDs of four body areas (low back, upper limb, eye and neck) was employed. The studies underwent two levels of analysis for inclusion in a best-evidence synthesis approach, which included a priori evaluation of specific interventions relative to outcomes of comfort, safety and/or productivity. Twenty-seven out of 202 articles were synthesized based on relevance, quality and significant results. Only 8 articles were determined high quality and no strong levels of evidence were identified. Levels of evidence for specific ergonomic interventions ranged from insufficient to moderate. Generally outcomes were focused mostly on improved comfort of workers. There is still limited quality research that addresses ergonomic interventions designed for secondary prevention. Further high quality studies are needed to support evidence-based ergonomic interventions in practice. For all stakeholders to fully evaluate the usefulness of the ergonomic intervention studies need to attend to outcomes not only of worker comfort but also to productivity and safety.


Characterization of interleukin-10 receptor expression on B-cell chronic lymphocytic leukemia cells.
B-cell chronic lymphocytic leukemia (B-CLL) cells accumulate in vivo in the G0/G1 phase of the cell cycle, suggesting that their malignant expansion is due, at least in part, to a delay in cell death. However, the cellular or molecular factors responsible for a delay in B-CLL cell death are unknown. B-CLL cells do express receptors for interferon-alpha (IFN-alpha) and IFN-gamma, and activation of both has been shown to promote B-CLL survival in vitro by preventing apoptosis. The interleukin-10 (IL-10) receptor is another member of the IFN receptor family, but its ligand, IL-10, has been reported to induce apoptosis in B-CLL cells. In the current study, we undertook a biochemical analysis of IL-10 receptor expression on freshly isolated B-CLL cells and characterized the functional responsiveness of IL-10 binding to its constitutively expressed receptor. We show that B-CLL cells bind IL-10 with significant specificity and express between 47 and 127 IL-10 receptor sites per cell, with a dissociation constant in the range of 168 to 426 x 10(-12) mol/L. Ligand binding and activation of the IL-10 receptor expressed on B-CLL cells results in the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 proteins. This pattern of STAT protein phosphorylation is identical to IL-10 receptor activation on normal cells and similar to IFN-alpha (STAT1 and STAT3) and IFN-gamma (STAT1) receptor activation in CLL. Further, in consecutive samples of fresh blood obtained from patients with B-CLL cells, the addition of IL-10 inhibited B-CLL proliferation, enhanced B-CLL differentiation, but did not induce apoptosis. Indeed, IL-10, like IFN-gamma, was able to significantly reduce the amount of B-CLL cell death caused by hydrocortisone-induced apoptosis. We conclude that cytokines, which signal through the interferon family of receptors, have comparable functional effects on B-CLL cells.


The Selective Phosphoinoside-3-Kinase p110δ Inhibitor IPI-3063 Potently Suppresses B Cell Survival, Proliferation, and Differentiation.
The class I phosphoinoside-3-kinases (PI3Ks) are important enzymes that relay signals from cell surface receptors to downstream mediators driving cellular functions. Elevated PI3K signaling is found in B cell malignancies and lymphocytes of patients with autoimmune disease. The p110δ catalytic isoform of PI3K is a rational target since it is critical for B lymphocyte development, survival, activation, and differentiation. In addition, activating mutations in PIK3CD encoding p110δ cause a human immunodeficiency known as activated PI3K delta syndrome. Currently, idelalisib is the only selective p110δ inhibitor that has been FDA approved to treat certain B cell malignancies. p110δ inhibitors can suppress autoantibody production in mouse models, but limited clinical trials in human autoimmunity have been performed with PI3K inhibitors to date. Thus, there is a need for additional tools to understand the effect of pharmacological inhibition of PI3K isoforms in lymphocytes. In this study, we tested the effects of a potent and selective p110δ inhibitor, IPI-3063, in assays of B cell function. We found that IPI-3063 potently reduced mouse B cell proliferation, survival, and plasmablast differentiation while increasing antibody class switching to IgG1, almost to the same degree as a pan-PI3K inhibitor. Similarly, IPI-3063 potently inhibited human B cell proliferation in vitro. The p110γ isoform has partially overlapping roles with p110δ in B cell development, but little is known about its role in B cell function. We found that the p110γ inhibitor AS-252424 had no significant impact on B cell responses. A novel dual p110δ/γ inhibitor, IPI-443, had comparable effects to p110δ inhibition alone. These findings show that p110δ is the dominant isoform mediating B cell responses and establish that IPI-3063 is a highly potent molecule useful for studying p110δ function in immune cells.


Synthesis, structure and electrochemistry of ferrocene-peptide macrocycles.
Redox active cyclopeptides Fc[CSA]2 (5), Fc[Gly-CSA]2 (6), Fc[Ala-CSA]2 (7), Fc[Val-CSA](2) and Fc[Leu-CSA]2 (9) (CSA = cysteamine) which are formed by the reaction of ferrocenedicarboxylic acid with peptide cystamines at high dilutions. These systems exhibit H-bonding involving the amide NH in solution as shown by their temperature dependent NMR spectra. With the exception of 5, the ferrocene macrocycles display intramolecular N...O cross-ring H-bonding in the solid state involving the amino acids proximal to the ferrocene.


Idiopathic infantile arterial calcification: a rare cause of sudden unexpected death in childhood.
Unexpected child death investigation is a difficult area of forensic practice in view of the wide range of possible genetic, congenital, and acquired natural and nonnatural causes. Idiopathic infantile arterial calcification (IIAC) is a rare autosomic recessive disease usually diagnosed postmortem. Inactivating mutations of the ENPP1 gene were described in 80% of the cases with IIAC. We report a case of a 5-year-old girl submitted to a forensic autopsy due to sudden death and possible medical negligence/parents child abuse. Major alterations found (intimal proliferation and deposition of calcium hydroxyapatite around the internal elastic lamina and media of arteries; acute myocardial infarct, stenotic and calcified coronary artery; perivascular and interstitial myocardial fibrosis; and subendocardial fibroelastosis) were diagnostic of IIAC. We reviewed IIAC cases published in the English literature and highlight the importance of adequate autopsy evaluation in cases of sudden child death.


Determination of deoxynivalenol in cereals and cereal products by immunoaffinity column cleanup with liquid chromatography: interlaboratory study.
An interlaboratory study was performed on behalf of the UK Food Standards Agency to evaluate the effectiveness of an immunoaffinity column cleanup liquid chromatographic (LC) method for the determination of deoxynivalenol in a variety of cereals and cereal products at proposed European regulatory limits. The test portion was extracted with water. The sample extract was filtered a applied to an immunoaffinity column. After being washed with water, the deoxynivalenol was eluted with acetonitrile or methanol. Deoxynivalenol was quantitated by reversed-phase LC with UV determination. Samples of artificially contaminated wheat-flour, rice flour, oat flour, polenta, and wheat based breakfast cereal, naturally contaminated wheat flour, and blank (very low level) samples of each matrix were sent to 13 collaborators in 7 European countries. Participants were asked to spike test portions of all samples at a range of deoxynivalenol concentrations equivalent to 200-2000 ng/g deoxynivalenol. Average recoveries ranged from 78 to 87%. Based on results for 6 artificially contaminated samples (blind duplicates), the relative standard deviation for repeatability (RSDr) ranged from 3.1 to 14.1%, and the relative standard deviation for reproducibility (RSDR) ranged from 11.5 to 26.3%. The method showed acceptable within-laboratory and between-laboratory precision for all 5 matrixes, as evidenced by HorRat values < 1.3.


The modulation in subunits e and g amounts of yeast ATP synthase modifies mitochondrial cristae morphology.
Subunits e and g of Saccharomyces cerevisiae ATP synthase are required to maintain ATP synthase dimeric forms. Mutants devoid of these subunits display anomalous mitochondrial morphologies. An expression system regulated by doxycycline was used to modulate the expression of the genes encoding the subunits e and g. A decrease in the amount of subunit e induces a decrease in the amount of subunit g, but a decrease in the amount of subunit g does not affect subunit e. The loss of subunit e or g leads to the loss of supramolecular structures of ATP synthase, which is fully reversible upon removal of doxycycline. In the absence of doxycycline, mitochondria present poorly defined cristae. In the presence of doxycycline, onion-like structures are formed after five generations. When doxycycline is removed after five generations, cristae are mainly observed. The data demonstrate that the inner structure of mitochondria depends upon the ability of ATP synthase to make supramolecular structures.


A DFT study of the possible role of vinylidene and carbene intermediates in the mechanism of the enzyme acetylene hydratase.
The mode of action of the tungstoprotein, acetylene hydratase, is unresolved at present.We have carried out density functional theory (DFT) calculations to investigate two proposed mechanisms, and also propose a new mechanism based on our calculations. We find that the previously proposed single step mechanisms which involve the attack of a water molecule, catalysed by Asp13, have barriers greater than 40 kcal mol(-1). We propose a new mechanism which involves two tungsten complexes, a vinylidene and a carbene, as stable intermediates. We calculate the potential energy surfaces for their formation, and for the decomposition of the carbene complex to yield acetaldehyde. All the barriers along the pathway are less than 30 kcal mol(-1), except for the barrier to carbene formation which is 34 kcal mol(-1).


Sex Differences in Associations of Cognitive Function with Perceptions of Pain in Older Adults.
Sex differences in pain have been shown to exist in older adults with normal cognition and people with Alzheimer's disease. It is unknown if sex differences in pain in older adults exist in a range of communicative older adults with varying cognitive ability from no impairment to moderately severe cognitive impairment. This study proposes to compare the association between psychophysical responses to experimental thermal pain between males and females to determine if sex differences in pain exist across the cognitive spectrum. We conducted a secondary analysis of data from an age- and sex-matched between-groups cross-sectional study examining the psychophysical response to contact heat in people with and without dementia. Median age of males (n = 38) and females (n = 38) was 73 (range: 68-87) with similar distributions of Mini-Mental State Examination (MMSE) scores (range: 11-30). Findings revealed inverse statistically significant associations with the threshold temperature of warmth (females: r = -0.41, p = 0.010; males: r = -0.33, p = 0.044). There was an apparent divergent pattern of MMSE associations with unpleasantness ratings between the groups. At the moderate pain threshold, that difference became statistically significant (p = 0.033). Females demonstrated a positive association of MMSE with unpleasantness (r = 0.30, p = 0.072), while males demonstrated an inverse association at that respective threshold (r = -0.20, p = 0.221). Between-group findings suggest that patterns of responses to thermal stimulus intensity may differ between males and females with worsening cognition with females reporting significantly less unpleasantness with the percept of moderate pain and males reporting significantly higher unpleasantness with moderate pain perception.


RICH-1 has a BIN/Amphiphysin/Rvsp domain responsible for binding to membrane lipids and tubulation of liposomes.
RhoGAP interacting with CIP4 homologs-1 (RICH-1) was previously found in a yeast two-hybrid screen for proteins interacting with the SH3 domain of the Cdc42-interacting protein 4 (CIP4). RICH-1 was shown to be a RhoGAP for Cdc42 and Rac. In this study, we show that the BIN/Amphiphysin/Rvsp (BAR) domain in RICH-1 confers binding to membrane lipids, and has the potential to deform spherical liposomes into tubes. In accordance with previous findings for the BAR domains in endophilin and amphiphysin, RICH-1-induced tubes appeared striated. We propose that these striated structures are formed by oligomerization of RICH-1 through a putative coiled-coil region within the BAR domain. In support of this notion, we show that RICH-1 forms oligomers in the presence of the chemical cross-linker BS3. These results point to an involvement of RICH-1 in membrane deformation events.


Slow motion increases perceived intent.
To determine the appropriate punishment for a harmful action, people must often make inferences about the transgressor's intent. In courtrooms and popular media, such inferences increasingly rely on video evidence, which is often played in "slow motion." Four experiments (n = 1,610) involving real surveillance footage from a murder or broadcast replays of violent contact in professional football demonstrate that viewing an action in slow motion, compared with regular speed, can cause viewers to perceive an action as more intentional. This slow motion intentionality bias occurred, in part, because slow motion video caused participants to feel like the actor had more time to act, even when they knew how much clock time had actually elapsed. Four additional experiments (n = 2,737) reveal that allowing viewers to see both regular speed and slow motion replay mitigates the bias, but does not eliminate it. We conclude that an empirical understanding of the effect of slow motion on mental state attribution should inform the life-or-death decisions that are currently based on tacit assumptions about the objectivity of human perception.


The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus.
Cyclo(l-Ala-l-Pro) inhibits aflatoxin production in aflatoxigenic fungi without affecting fungal growth. The mode of action of cyclo(l-Ala-l-Pro) in inhibiting aflatoxin production of Aspergillus flavus was investigated. A glutathione S-transferase (GST) of the fungus, designated AfGST, was identified as a binding protein of cyclo(l-Ala-l-Pro) in an experiment performed using cyclo(l-Ala-l-Pro)-immobilized Sepharose beads. Cyclo(l-Ala-l-Pro) specifically bound to recombinant AfGST and inhibited its GST activity. Ethacrynic acid, a known GST inhibitor, inhibited the GST activity of recombinant AfGST and aflatoxin production of the fungus. Ethacrynic acid reduced the expression level of AflR, a key regulatory protein for aflatoxin production, similar to cyclo(l-Ala-l-Pro). These results suggest that cyclo(l-Ala-l-Pro) inhibits aflatoxin production by affecting GST function in A. flavus, and that AfGST inhibitors are possible candidates as selective aflatoxin production inhibitors.


Bilateral adrenal hemorrhage in the background of Escherichia coli sepsis: a case report.
Sepsis is a syndrome of life-threatening organ dysfunction caused by a dysregulated host response to infection. It can have devastating consequences, including bilateral adrenal hemorrhage, particularly in patients at high thrombotic risk, such as those with antiphospholipid syndrome and those on long-term anticoagulation. A 49-year-old white woman re-presented to hospital with a history suggestive of sepsis. She had a medical background of primary antiphospholipid syndrome on lifelong warfarin. Ten days prior to this presentation, she had been hospitalized following Escherichia coli bacteremia, commenced on intravenous antibiotics, and discharged 2 days later with a prescribed 5-day course of oral amoxicillin. On readmission, she had ongoing fever, myalgia, malaise, and hypotension. Investigations revealed anemia with thrombocytopenia, hyponatremia, and acute-on-chronic kidney injury. Despite treatment for urosepsis, she became tachypneic, clammy, light-headed, drowsy, and hypothermic. Computed tomography revealed bilateral adrenal hemorrhage, and biochemical examination confirmed hypoadrenalism. Following discharge, she had persistent renal and hepatic injury lasting 3 months. Early identification, intensive monitoring, and aggressive support may reduce the acquired thrombotic risk and avoid potentially life-threatening outcomes of sepsis.


Psychiatric aspects of complex partial seizures: case report.
A patient is described who had a personal and family history of rage attacks, mood disturbance, and epileptiform EEGs. The patient achieved a return to emotional stability with the introduction of anticonvulsant drug therapy. Symptoms relapsed and then remitted as anticonvulsants were stopped and then reinstituted.


Voluntary head stabilization in space during oscillatory trunk movements in the frontal plane performed in weightlessness.
The ability voluntarily to stabilize the head in space during lateral rhythmic oscillations (0.59+/-0.09 Hz) of the trunk has been investigated during microgravity (microG) and normal gravity (nG) conditions (parabolic flights). Five healthy young subjects, who gave informed consent, were examined. The movements were performed with eyes open or eyes closed, during phases of either microG or nG. The main result was that head orientation with respect to vertical may be stabilized about the roll axis under microG with, as well as without vision, despite the reduction in vestibular afferent and muscle proprioceptive inputs. Moreover, the absence of head stabilization about the yaw axis confirms that the degrees of freedom of the neck can be independently controlled, as was previously reported. These results seem to indicate that voluntary head stabilization does not depend crucially upon static vestibular afferents. Head stabilization in space may in fact be organized on the basis of either dynamic vestibular afferents or a short-term memorized postural body schema.


Divergent wiring of repressive and active chromatin interactions between mouse embryonic and trophoblast lineages.
The establishment of the embryonic and trophoblast lineages is a developmental decision underpinned by dramatic differences in the epigenetic landscape of the two compartments. However, it remains unknown how epigenetic information and transcription factor networks map to the 3D arrangement of the genome, which in turn may mediate transcriptional divergence between the two cell lineages. Here, we perform promoter capture Hi-C experiments in mouse trophoblast (TSC) and embryonic (ESC) stem cells to understand how chromatin conformation relates to cell-specific transcriptional programmes. We find that key TSC genes that are kept repressed in ESCs exhibit interactions between H3K27me3-marked regions in ESCs that depend on Polycomb repressive complex 1. Interactions that are prominent in TSCs are enriched for enhancer-gene contacts involving key TSC transcription factors, as well as TET1, which helps to maintain the expression of TSC-relevant genes. Our work shows that the first developmental cell fate decision results in distinct chromatin conformation patterns establishing lineage-specific contexts involving both repressive and active interactions.


Magnetism in gold nanoparticles.
Gold nanoparticles currently elicit an intense and very broad research activity because of their peculiar properties. Be it in catalysis, optics, electronics, sensing or theranostics, new applications are found daily for these materials. Approximately a decade ago a report was published with magnetometry data showing that gold nanoparticles, most surprisingly, could also be magnetic, with features that the usual rules of magnetism were unable to explain. Many ensuing experimental papers confirmed this observation, although the reported magnetic behaviours showed a great variability, for unclear reasons. In this review, most of the experimental facts pertaining to "magnetic gold" are summarized. The various theories put forth for explaining this unexpected magnetism are presented and discussed. We show that despite much effort, a satisfying explanation is still lacking and that the field of hypotheses should perhaps be widened.


Cyclic di-GMP riboswitch-regulated type IV pili contribute to aggregation of Clostridium difficile.
Clostridium difficile is an anaerobic Gram-positive bacterium that causes intestinal infections with symptoms ranging from mild diarrhea to fulminant colitis. Cyclic diguanosine monophosphate (c-di-GMP) is a bacterial second messenger that typically regulates the switch from motile, free-living to sessile and multicellular behaviors in Gram-negative bacteria. Increased intracellular c-di-GMP concentration in C. difficile was recently shown to reduce flagellar motility and to increase cell aggregation. In this work, we investigated the role of the primary type IV pilus (T4P) locus in c-di-GMP-dependent cell aggregation. Inactivation of two T4P genes, pilA1 (CD3513) and pilB1 (CD3512), abolished pilus formation and significantly reduced cell aggregation under high c-di-GMP conditions. pilA1 is preceded by a putative c-di-GMP riboswitch, predicted to be transcriptionally active upon c-di-GMP binding. Consistent with our prediction, high intracellular c-di-GMP concentration increased transcript levels of T4P genes. In addition, single-round in vitro transcription assays confirmed that transcription downstream of the predicted transcription terminator was dose dependent and specific to c-di-GMP binding to the riboswitch aptamer. These results support a model in which T4P gene transcription is upregulated by c-di-GMP as a result of its binding to an upstream transcriptionally activating riboswitch, promoting cell aggregation in C. difficile.


Distinct N and C Cross-Feeding Networks in a Synthetic Mouse Gut Consortium.
The complex interactions between the gut microbiome and host or pathogen colonization resistance cannot be understood solely from community composition. Missing are causal relationships, such as metabolic interactions among species, to better understand what shapes the microbiome. Here, we focused on metabolic niches generated and occupied by the Oligo-Mouse-Microbiota (OMM) consortium, a synthetic community composed of 12 members that is increasingly used as a model for the mouse gut microbiome. Combining monocultures and spent medium experiments with untargeted metabolomics revealed broad metabolic diversity in the consortium, constituting a dense cross-feeding network with more than 100 pairwise interactions. Quantitative analysis of the cross-feeding network revealed distinct C and N food webs, highlighting the two Bacteroidetes members Bacteroides caecimuris and Muribaculum intestinale as primary suppliers of carbon and a more diverse group as nitrogen providers. Cross-fed metabolites were mainly carboxylic acids, amino acids, and the so far not reported nucleobases. In particular, the dicarboxylic acids malate and fumarate provided a strong physiological benefit to consumers, presumably used in anaerobic respiration. Isotopic tracer experiments validated the fate of a subset of cross-fed metabolites, such as the conversion of the most abundant cross-fed compound succinate to butyrate. Thus, we show that this consortium is tailored to produce the anti-inflammatory metabolite butyrate. Overall, we provide evidence for metabolic niches generated and occupied by OMM members that lays a metabolic foundation to facilitate an understanding of the more complex in vivo behavior of this consortium in the mouse gut. IMPORTANCE This article maps out the cross-feeding network among 10 members of a synthetic consortium that is increasingly used as the model mouse gut microbiota. Combining metabolomics with in vitro cultivations, two dense networks of carbon and nitrogen exchange are described. The vast majority of the ∼100 interactions are synergistic in nature, in several cases providing distinct physiological benefits to the recipient species. These networks lay the groundwork toward understanding gut community dynamics and host-gut microbe interactions.


Insights into the complexation of N-Allyl-4-(4-(N-phenylureido)benzylamino)-1,8-naphthalimide with various anions.
A new urea functionalised 4-amino-1,8-naphthalimide based fluorescent anion sensor was synthesised in 64% yield over three steps. Fluorescence and 1H NMR titrations showed that the sensor complexes strongly with acetate and dihydrogen phosphate and to a lesser extent bromide. The corresponding binding stoichiometries were examined using 1H NMR titrations. Results show that the sensor molecule initially forms 1:1 complexes through hydrogen bonding to the urea moiety, followed by secondary complexation to form higher order host:guest stoichiometries. Specifically, oxyanions complex to the sensor via hydrogen bonding through synergistic aryl C-H and N-H anion interactions in a 1:2 sensor:oxyanion arrangement. Furthermore, 2:1 sensor:oxyanion complexes are formed through an oxyanion linkage between two urea functionalities on different host molecules. This contrasts the majority of previous reports for similar hosts, which indicate 1:1 binding stoichiometry.


A modified technique for mitral valve replacement.
Between 1976 and 1983 254 mitral valve prostheses (243 Björk-Shiley and 14 bioprostheses) were implanted in 252 patients using a modified technique. The age of patients varied from 26-72 years (mean 56 +/- 18 years). This technique allows an equidistant placement of sutures and accurate stitching of mitral valve annulus to the prosthetic valve ring. Follow-up averaged 67 +/- 21.6 months (3-7 years). Linearized aseptic dehiscence was 0.17 per 100 patient years. This technique was especially useful in patients with small left atrium and minimised the risk of a major prosthetic detachment.


Clinical Course and Outcomes of Late Kidney Allograft Dysfunction.
Background. This study is provided to increase the efficiency of the treatment of kidney transplant recipients by predicting the development of the late allotransplant dysfunction. Methods. 330 patients who have lived for more than one year with functioning kidney allograft were evaluated. To predict the subsequent duration of the well-functioning of allotransplant the prognostic significance of 15 baseline clinical and sociodemographic characteristics on the results of the survey one year after transplantation was investigated. The result was considered to be positive in constructing the regression prognostication model if recipient lived more than 3 years from the time of transplantation. Results. It was established that more late start of renal allograft dysfunction after transplantation correlates with the more time it takes till complete loss of allograft function. Creatinine and hemoglobin blood concentration and the level of proteinuria one year after transplantation within created mathematical model allow predicting the loss of kidney transplant function three years after the transplantation. Patients with kidney transplant dysfunction are advised to renew the program hemodialysis upon reaching plasma creatinine concentration 0.5-0.7 mmol/L. Conclusion. Values of creatinine, hemoglobin, and proteinuria one year after transplantation can be used for subsequent prognostication of kidney transplant function.


Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes.
Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.


Etoposide 1.0 g/m2 or 1.5 g/m2 combined with granulocyte colony-stimulating factor for mobilization of peripheral blood stem cells in patients with malignancy: efficacy and toxicity.
The purpose of this study was to observe the efficacy and toxicity of etoposide at two dose levels for peripheral blood stem cell (PBSC) mobilization and disease debulking in patients with malignancy. Simultaneously, factors affecting the yield of CD34+ cells were explored. Thirty-eight patients received etoposide 1.0 g/m2 (group A) or 1.5 g/m2 (group B) followed by granulocyte colony-stimulating factor (G-CSF) 300 microg/day for PBSC mobilization in a non-randomized manner. Each group had 19 patients. The median number of CD34+ cells collected was 17.33 x 10(6)/kg (range 4.85-89.00 x 10(6)/kg) in group A and 26.54 x 10(6)/kg (range 1.85-108.00 x 10(6)/kg) in group B. Altogether, 34/38 (89.5%) patients obtained the target total collection of at least 4 x 10(6) CD34+ cells/kg by a single leukapheresis. Vomiting was the most common grade 3/4 non-hematologic toxicity. For 19 evaluable patients, partial response was achieved in four (21.1%), stable disease in 11 (57.8%) and progressive disease in four (21.1%) patients. All parameters between the two groups did not reach a significant level. With multivariate analysis, the most predictive factor for CD34+ yield of the first leukapheresis was the percentage of CD34+ CD38(-) cells in peripheral blood. These results indicate that etoposide combined with G-CSF is an effective and tolerable regimen for PBSC mobilization, given at a dose of either 1.0 g/m2 or 1.5 g/m2.


Evidence for direct control of an in vitro plaque-forming cell response by quantitative properties of intact, fluid, haptenated liposomes: a potential model system for antigen presentation by macrophages.
Stimulation of the primary in vitro plaque-forming cell (PFC)2 response to fluid, haptenated liposomes by spleen cells depleted of a Sephadex-adherent population has been made possible by the addition of an uncharacterized cell-derived soluble factor(s). In its absence, PFC responses by such cells are greatly reduced or absent. The factor(s) is present in the supernatant from Concanavalin A-stimulated spleen cells. This phenomenon has permitted a comparison of the behavior of cultures with and without adherent cells, with a view to determining the relative likelihood of liposomes or adherent cells functioning as antigen presenters in this system. Two modes of control by quantitative properties of liposomes have been studied. PFC stimulation is controlled, in a biphasic manner, by varying either liposomal epitope density at constant liposome concentration or liposome concentration at fixed epitope density. Overall hapten concentration in the cultures is only of significance as a consequence of epitope density and liposome concentration; it does not, itself, control the response. Whole spleen cell cultures and cultures depleted of Sephadex-adherent cells but supplemented with soluble factor(s) exhibit the same biphasic response profiles when these quantitative properties of liposomes are varied. The results argue against the role of Sephadex-adherent cells as antigen presenters in whole spleen cell cultures. A model in which antigen presentation is accomplished by intact liposomes, in both whole spleen and adherent cell-depleted cultures, is consistent with the data.


Role of DAX-1 (NR0B1) and steroidogenic factor-1 (NR5A1) in human adrenal function.
The nuclear receptor transcription factors DAX-1 (NR0B1) and SF-1 (NR5A1) regulate many aspects of adrenal and reproductive development and function. Disruption of the genes encoding these factors can be associated with pediatric adrenal disease. DAX-1 mutations are classically associated with X-linked adrenal hypoplasia congenita, hypogonadotropic hypogonadism and impaired spermatogenesis. However, other phenotypes are also being reported, such as isolated mineralocorticoid insufficiency, premature sexual development, primary adrenal insufficiency in a 46, XX patient and late-onset X-linked adrenal hypoplasia congenita and/or hypogonadotropic hypogonadism. SF-1 mutations have also been associated with primary adrenal insufficiency, together with 46, XY disorders of sex development. However it is emerging that SF-1 changes are a relatively rare cause of primary adrenal failure in humans, and most individuals with SF-1 mutations have a spectrum of 46, XY disorders of sex development phenotypes. These conditions range from 46, XY females with streak gonads and müllerian structures, through children with ambiguous genitalia and inguinal testes, to severe penoscrotal hypospadias with undescended testes. Therefore, the human gonad appears to be more sensitive than the adrenal gland to loss of SF-1 function. This review will focus on the expanding range of phenotypes associated with DAX-1 and SF-1 mutations.


An academic centre for gene therapy research with clinical grade manufacturing capability.
Huddinge University Hospital is a major teaching hospital affiliated with the Karolinska Institute in Southern Stockholm. For the past few years several groups have been working there in different areas of gene therapy relating to cancer, genetic and infectious diseases. However, a facility to produce clinical grade material under good manufacturing practice was lacking. To this end, Huddinge University Hospital has taken the initiative to open a Gene Therapy Research Center in 1996. This facility, which is unique of its kind in Scandinavia, is located in the Novum Research Park, Huddinge, and is a part of the existing Clinical Research Center. The newly built centre will allow clinicians and researchers to develop and produce vectors (viral and nonviral) for clinical trials and do basic research to understand the mechanisms of diseases. Although the centre will primarily serve the academic institutions it will also extend its facilities to other investigators in this field. The production unit is run in collaboration with the Faculty of Medicine, University of Lund. On-going projects include production of plasmid vectors for prevention of postangioplasty restenosis, DNA vaccine for HIV-1, cationic liposome DNA complexes for cystic fibrosis and retroviral vectors for HIV-1.


Phosphorylation of protein kinase A (PKA) regulatory subunit RIα by protein kinase G (PKG) primes PKA for catalytic activity in cells.
cAMP-dependent protein kinase (PKAc) is a pivotal signaling protein in eukaryotic cells. PKAc has two well-characterized regulatory subunit proteins, RI and RII (each having α and β isoforms), which keep the PKAc catalytic subunit in a catalytically inactive state until activation by cAMP. Previous reports showed that the RIα regulatory subunit is phosphorylated by cGMP-dependent protein kinase (PKG) in vitro, whereupon phosphorylated RIα no longer inhibits PKAc at normal (1:1) stoichiometric ratios. However, the significance of this phosphorylation as a mechanism for activating type I PKA holoenzymes has not been fully explored, especially in cellular systems. In this study, we further examined the potential of RIα phosphorylation to regulate physiologically relevant "desensitization" of PKAc activity. First, the serine 101 site of RIα was validated as a target of PKGIα phosphorylation both in vitro and in cells. Analysis of a phosphomimetic substitution in RIα (S101E) showed that modification of this site increases PKAc activity in vitro and in cells, even without cAMP stimulation. Numerous techniques were used to show that although Ser101 variants of RIα can bind PKAc, the modified linker region of the S101E mutant has a significantly reduced affinity for the PKAc active site. These findings suggest that RIα phosphorylation may be a novel mechanism to circumvent the requirement of cAMP stimulus to activate type I PKA in cells. We have thus proposed a model to explain how PKG phosphorylation of RIα creates a "sensitized intermediate" state that is in effect primed to trigger PKAc activity.


Determining first admissions in a hospital discharge file via record linkage.
The aim of this study was to identify first admissions in a public hospital discharge file with the greatest possible accuracy. Computerised data linkage was used to link injury events. This involved the use of "internal" data linkage (unduplication) which, in data linkage terms, is equivalent to matching two identical files. Admission status indicators obtained from deterministic and probabilistic linkages were compared with those obtained from a manual review. Small absolute reductions in error were obtained using a probabilistic linkage over a deterministic linkage. However, these reflected large relative reductions in error. A validity check confirmed initial results and discounted against possible bias due to the subjective nature of the probabilistic linking procedure.


Platelet-rich fibrin prepared from stored whole-blood samples.
In regenerative therapy, self-clotted platelet concentrates, such as platelet-rich fibrin (PRF), are generally prepared on-site and are immediately used for treatment. If blood samples or prepared clots can be preserved for several days, their clinical applicability will expand. Here, we prepared PRF from stored whole-blood samples and examined their characteristics. Blood samples were collected from non-smoking, healthy male donors (aged 27-67 years, N = 6), and PRF clots were prepared immediately or after storage for 1-2 days. Fibrin fiber was examined by scanning electron microscopy. Bioactivity was evaluated by means of a bioassay system involving human periosteal cells, whereas PDGF-BB concentrations were determined by an enzyme-linked immunosorbent assay. Addition of optimal amounts of a 10% CaCl2 solution restored the coagulative ability of whole-blood samples that contained an anticoagulant (acid citrate dextrose) and were stored for up to 2 days at ambient temperature. In PRF clots prepared from the stored whole-blood samples, the thickness and cross-links of fibrin fibers were almost identical to those of freshly prepared PRF clots. PDGF-BB concentrations in the PRF extract were significantly lower in stored whole-blood samples than in fresh samples; however, both extracts had similar stimulatory effects on periosteal-cell proliferation. Quality of PRF clots prepared from stored whole-blood samples is not reduced significantly and can be ensured for use in regenerative therapy. Therefore, the proposed method enables a more flexible treatment schedule and choice of a more suitable platelet concentrate immediately before treatment, not after blood collection.


Locating Forest Management Units Using Remote Sensing and Geostatistical Tools in North-Central Washington, USA.
In this study, we share an approach to locate and map forest management units with high accuracy and with relatively rapid turnaround. Our study area consists of private, state, and federal land holdings that cover four counties in North-Central Washington, USA (Kittitas, Okanogan, Chelan and Douglas). This area has a rich history of landscape change caused by frequent wildfires, insect attacks, disease outbreaks, and forest management practices, which is only partially documented across ownerships in an inconsistent fashion. To consistently quantify forest management activities for the entire study area, we leveraged Sentinel-2 satellite imagery, LANDFIRE existing vegetation types and disturbances, monitoring trends in burn severity fire perimeters, and Landsat 8 Burned Area products. Within our methodology, Sentinel-2 images were collected and transformed to orthogonal land cover change difference and ratio metrics using principal component analyses. In addition, the Normalized Difference Vegetation Index and the Relativized Burn Ratio index were estimated. These variables were used as predictors in Random Forests machine learning classification models. Known locations of forest treatment units were used to create samples to train the Random Forests models to estimate where changes in forest structure occurred between the years of 2016 and 2019. We visually inspected each derived polygon to manually assign one treatment class, either clearcut or thinning. Landsat 8 Burned Area products were used to derive prescribed fire units for the same period. The bulk of analyses were performed using the RMRS Raster Utility toolbar that facilitated spatial, statistical, and machine learning tools, while significantly reducing the required processing time and storage space associated with analyzing these large datasets. The results were combined with existing LANDFIRE vegetation disturbance and forest treatment data to create a 21-year dataset (1999-2019) for the study area.


An expected increase in the efficiency of antiproton cancer therapy with the use of gold nanoparticles.
The use of gold nanoparticles in antiproton cancer therapy is proposed. The energy transferred to gold by particles bombarding a tumor and arising in it is considered as one of the parameters determining the biological effect of gold in proton and antiproton cancer therapies. An example corresponding to the assumption about the importance of this parameter is analyzed. It is shown that the energy transferred to gold by products of annihilation of stopped antiprotons in soft biological tissues can exceed that transferred by antiprotons before their annihilation.


Inclusion of underserved racial and ethnic groups in cancer intervention research using new media: a systematic literature review.
An increasing number of behavioral and psychosocial cancer interventions incorporate new media elements that are digital, networked, and interactive. However, it is unclear to what extent new media is being leveraged to benefit underserved racial and ethnic groups who disproportionately bear the burden of cancer. This inquiry is timely in light of growing evidence that these groups are receptive to new media. A systematic literature review was conducted to assess the inclusion of these groups in research on cancer-related new media interventions and use of new media to reduce racial and ethnic cancer disparities. A systematic search of three databases was conducted for articles published between January 2000 and March 2012 that presented studies of user experience with a behavioral or psychosocial cancer-related intervention with at least one new media component. Thirty-six articles were included in the final review. In about one-quarter of the studies, less than 20% of participants were African American, Latino, Asian American, or American Indian. In less than 10% of the studies, 80% or more of the samples were members of the aforementioned groups. Almost one-third of the studies reviewed were categorized as disparity focused but limited data were available on racial and ethnic differences in responses to new media interventions. Findings suggest that the promise and potential of new media cancer interventions are largely unrealized among the underserved. Additional research is needed to investigate a wide range of issues related to the development and delivery of such interventions in diverse racial and ethnic groups.


Disruption of the polyhydroxyalkanoate synthase gene in Aeromonas hydrophila reduces its survival ability under stress conditions.
Aeromonas hydrophila 4AK4 produces PHBHHx copolyesters consisting of 3-hydroxybutyrate and 3-hydroxyhexanoate. In this paper, the physiological functions of PHBHHx on the bacterial survival ability were systematically studied using a PHBHHx synthase PhaC-disrupted mutant termed A. hydrophila CQ4 and its wild type A. hydrophila 4AK4. It was found that PHBHHx synthesis in A. hydrophila 4AK4 provided improved resistance against environmental stress factors including heat and cold treatments, hydrogen peroxide, UV irradiation, ethanol and high osmotic pressure compared with its PHBHHx synthase negative mutant A. hydrophila CQ4. The above resistant abilities were further confirmed by the different expression levels of sigma factor sigma(S) encoded by rpoS via real-time PCR study. The results suggested that rpoS played an important role in the enhanced resistance of host strain to stresses conferred by PHBHHx.


Detecting peripersonal space: The promising role of ultrasonics.
The approach of an external stimulus to the peripersonal space (PPS) modifies some physiological measures, including the cerebral blood flow (CBF) in the supplementary motor area and premotor cortex. CBF measurement may be useful to assess brain activations when producing specific motor responses, likely mediated by cortical and subcortical neural circuits. This study investigated PPS in 15 healthy humans by characterizing the hemodynamic responses (pulsatility index, PI; and heart rate, HR) related to different directions of movements of individual's hand toward and backward his/her own face, so to perturb PPS). We observed that the CBF and HR were enhanced more when the stimulated hand was inside the PPS of the face in the passive and active condition than when the hand was outside the PPS and during motor imagery task. These results suggest that the modulation of PPS-related brain responses depends on specific sensory-motor integration processes related to the location and the final position of a target in the PPS. We may thus propose TCD as a rapid and easy approach to get information concerning brain responses related to stimuli approaching the PPS. Understanding the modulations of brain activations during tasks targeting PPS can help to understand the results of psychophysical and behavioral trials and to plan patient-tailored cognitive rehabilitative training.


Elevated tumor marker CA 19-9 in the differential diagnosis of pancreatic mass lesions.
Inflammatory and neoplastic tumors of the pancreas still remain a diagnostic dilemma for a surgeon mainly due to subtle differences between these two sorts of tumors. The aim of the study was to assess the utility of the serum marker, CA 19-9, in the differential diagnosis of pancreatic tumors. 150 patients with heterogenic pancreatic lesion were diagnosed and treated at 2nd Department of General Surgery, Medical University of Lublin between June 1998 and Dec. 2003. Their age ranged between 26 and 78 years. Based upon cytology and histology, patients were assigned to malignant or benign group. The serum from all the patients was assayed for the CA 19-9 test and sensitivity and specificity of the CA 19-9 test was determined. Finally pancreatic cancer was diagnosed in 98 patients, benign pancreatic lesion in 52 patients. Based upon the serum level of the CA 19-9 true positive results were found in 82 patients, true negative results in 47 patients, false negative results in 16 patients and false positive results in 5 patients. Sensitivity of the CA 19-9 assay was 83.7% and specificity was 90.4%. An elevated serum level of the CA 19-9 in the presence of pancreatic lesions usually suggests malignant nature of the lesion. A high CA 19-9 level is typical of advanced inoperable pancreatic cancer. Taking into account a limited sensitivity and specificity of the CA 19-9 assay, its results should be interpreted in consistency with an analysis of imaging examinations such as US and CT.


White emission via electroplex emission from two blue materials.
Influences of electric fields on the emission from organic light-emitting diodes (OLEDs) based on poly (N-vinylcarbazole) (PVK); 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline (BCP); and tris (8-hydroxyquinoline) aluminum (Alq3) were studied. There are three emission peaks at 420 nm, 520 nm, and 620 nm of the device ITO/PEDOT: PSS/PVK/BCP/LiF/Al under different driving voltages. The emissions at 420 nm and 520 nm should be from the exciton emission of PVK and Alq3, respectively. The last emission at 620 nm could be attributed to electroplex emission at the interface between the PVK and BCP layers. A high intensity white emission via electroplex formation was obtained with Commission International d'Eclairage (CIE) coordinates (0.33, 0.34) at 15 V, which is very close to the equienergy white point (0.33, 0.33).


CELL POPULATION KINETICS OF AN OSTEOGENIC TISSUE. II.
A study of the cell kinetics on the actively growing periosteal surface of the femur of rabbits aged 2 weeks has been continued. A single injection of tritiated thymidine was given and the rabbits killed from 1 hour to 4 days after injection. The grain count spectra of the different cell types, pre-osteoblast, osteoblast, and osteocyte, have been compared at different times after injection. The results showed evidence for the uptake of thymidine in nuclei which is not associated with cell division. A small percentage of osteoblasts was initially labeled at 1 hour and there was evidence that the majority of these had not divided by 3 or 4 days after injection. Some thymidine-labeled cells had also become osteocytes without division. Furthermore, it appeared that a considerable fraction of the initially labeled pre-osteoblasts did not divide. The S period for the pre-osteoblasts and osteoblasts was measured using a double-labeled thymidine technique.


Induction of cytochrome P450 1A and 2B by alpha- and beta-ionone in Sprague Dawley rats.
Beta-lonone has been reported to induce the cytochrome P450 (P450) 281 in rats. In this study, the effects of beta-ionone and an isomer, alpha-ionone, on liver P450 1A and 2B expression in Sprague Dawley rats were investigated. Subcutaneous administration of alpha- and beta-ionone 72 and 48 hr prior to sacrificing the animals induced the liver microsomal P450 1A and 2B proteins. P450 2B1 induction was associated with the accumulation of its corresponding mRNA. Induction by beta-ionone was much higher than that by a-ionone in both the mRNA and protein levels. When the route of administration was compared, P450 2B was induced more strongly after oral administration compared to that after subcutaneous injection. A single oral dose of 100, 300 and 600 mg/kg of alpha- and beta-ionone for 24 h induced P450 2B1-selective pentoxyresorufin O-depentylase activity comparably in a dose-dependent manner. In addition, alpha- and beta-ionone induced the P450 1A and 2B proteins. These results suggest that alpha- and beta-ionone might be potent P450 281 inducers in rats, and that both ionones may be useful for examining the role of metabolic activation in chemical-induced toxicity where metabolic activation is required.


The effects of age on spatial frequency perception in human subjects.
Visual performance was measured in sixty-six subjects aged from 5 to 94 years. The curve of contrast sensitivity against spatial frequency was obtained for each subject. This curve had a peak contrast sensitivity in the 2-6 c/deg (cycles/degree) range with the fall-offs to either side of the peak described, on a double logarithmic plot, by straight lines. With advancing age, the position of the peak sensitivity remained unchanged but there was an overall decrease in contrast sensitivity. The highest spatial frequency which could be perceived remained constant up to 50 years, thereafter it fell with increasing age. The slope of the low frequency straight line remained unchanged while that of the high frequency straight line fell with increasing age, i.e. the loss of contrast sensitivity was greater for middle range spatial frequencies than for higher spatial frequencies. The possible site of these changes, i.e. the optics of the eye, the retina/brain or higher decision making centres, is discussed.


Side-to-Side Anastomosis Training Model Using Rat Common Carotid Arteries.
The side-to-side anastomosis is one of the difficult bypass configurations that may be used in various complex cerebral vascular and neoplastic cases. Few pure arterial models exist for practicing this bypass subtype. To provide an optimized side-to-side anastomosis training model using rat common carotid arteries (CCA). Bilateral CCAs were exposed in the neck of 10 anesthetized Sprague-Dawley rats. The arteries were juxtaposed in parallel, using temporary aneurysm clips applied proximally and distally. CCA caliber and the length of CCA juxtaposition were measured. Side-to-side anastomosis was completed and ischemia time was recorded. Unintended complications were recorded for further analysis. Anastomosis was completed successfully in all animals. The CCAs were approximated in all animals without any difficulty or undue tension. In 2 rats, death occurred prior to completion of anastomosis, which was attributed to injury to the external jugular vein during vessel exposure. Mean ischemia time was 35 min with an average of 22 sutures done to complete the anastomosis. The average CCA caliber was 1.1 ± 0.2 mm and the arteries could be juxtaposed for an average length of 10.2 ± 1.5 mm. Full exposure of the cervical segment of the CCAs enables tension-free approximation of adequate length of the vessel for a side-to-side anastomosis. Avoiding complications during exposure helps in prevention of animal death during the ischemia period.


Measuring the structure of visual fields in nursing units.
The purpose of this study was to develop quantitative measures of the structure of visual fields in nursing units. The structure of visual fields in nursing units-especially visibility toward patient beds-is believed to have a direct influence on the routine use of space by medical staff and patient outcomes within units. Although previous studies are suggestive, none has developed rigorous measures of the visibility within nursing units. To compare the degree of visibility toward patient beds among different nursing units, the targeted visibility index (TVI) was introduced. The TVI measures the degree to which an observer can see all targets in a nursing unit. It provided a comparative spatial quality evaluation of various nursing unit configurations with differing numbers of patient beds. It was developed and programmed on the ArcGIS version 9.2 platform (ESRI Inc., Redlands, CA) with component object model-based ArcObjects and Visual Basic for Application language (Microsoft). The assessment of three nursing unit designs by TVI aligned exactly with empirical evaluations conducted in previous studies. This study provided an opportunity and supplied relevant measures for healthcare facility designers to specify the visual structures of important behavioral effects. It is anticipated that the TVI will contribute to the understanding of healthcare design and the resulting outcomes.


Plasminogen activator inhibitor-1 is associated with the metabolism and development of advanced colonic polyps.
Implications of plasminogen activator inhibitor-1 (PAI-1) in colonic polyps remain elusive. A prospective study was conducted with 188 consecutive subjects who underwent colonoscopy at a tertiary referral center. Biochemical parameters, serum PAI-1 levels, PAI-1 single-nucleotide polymorphisms (rs-1799889), and colonic polyp profiles were analyzed at baseline and 24 and 48 weeks postpolypectomy. Of 188 patients (mean age: 56.8 years), 78.7% had adenomas; the median polyp number and size were 2 and 1.2cm, respectively. Multivariate analyses revealed the following baseline associations: PAI-1 levels (95% confidence interval [CI] for estimated β: 0.012-0.223) and polyp pathology (0.294-0.63) with polyp size; polyp size (0.085-0.498) and platelet count (0.013-0.027) with PAI-1 levels. At 24 weeks postpolypectomy, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and platelet count were independently associated with PAI-1 levels. Among patients with colonic adenomas, baseline PAI-1 levels (95% CI odds ratio: 1.06-1.686; cut-off value: >10.65 ng/mL, area under curve: 0.662, P = 0.032) and the PAI-1-rs-17998894G/4G genotype (0.036-0.912) were associated with high-grade dysplasia. Compared with baseline levels, repeated measures analysis of variance showed that PAI-1 levels increased, with concurrent increased HOMA-IR indexes, but decreased alanine transaminase levels and polyp size in follow-up colonoscopies at 24 weeks postpolypectomy. PAI-1 returned to baseline levels, and HOMA-IRs and triglyceride/high-density lipoprotein-cholesterol ratios decreased at 48 weeks postpolypectomy. Taken together, serum PAI-1 levels were positively associated with colonic polyp size and high-grade dysplasia, which was modulated by the PAI-1-rs-17998894G/4G genotype. The beneficial postpolypectomy inflammatory and metabolic alterations might be transiently counter regulated by elevated PAI-1 levels, with a link to HOMA-IR.


Calibration of sound power sources: Current status and new developments.
Reference sound sources used in sound power measurements are currently calibrated according to well-documented techniques. Low frequency limitations and solely broadband analysis restrict the applicability of these methods. The concept of traceability is introduced to overcome these deficiencies. This study presents the calibration of reference sound sources through a measurement chain, which is based on the substitution method. The applicability of the substitution method extends to sound intensity measurements and narrowband frequency analysis. A specially designed apparatus allows the detection of the sound field over a fully scanned hemisphere. The results of the apparatus are comparable to the results of the existing methods. The substitution method reduces the required corrections, which are presented. The sound power levels are supplemented by a transparent uncertainty budget, which allows the estimation of each uncertainty component individually. The comparison between the methods is also given in terms of a confidence interval.


Comprehensive gene and microRNA expression profiling on cardiovascular system in zebrafish co-exposured of SiNPs and MeHg.
Air pollution has been shown to increase cardiovascular diseases. However, little attention has been paid to the combined effects of PM and air pollutants on the cardiovascular system. To explore this, a high-throughput sequencing technology was used to determine combined effects of silica nanoparticles (SiNPs) and MeHg in zebrafish. Our study demonstrated that SiNPs and MeHg co-exposure could cause significant changes in mRNA and miRNA expression patterns in zebrafish. The differentially expressed (DE) genes in profiles 17 and 26 of STC analysis suggest that SiNPs and MeHg co-exposure had more proinflammatory and cardiovascular toxicity in zebrafish than single exposure. Major gene functions associated with cardiovascular system in the co-exposed zebrafish were discerned from the dynamic-gene-network, including stxbp1a, celf4, ahr1b and bai2. In addition, the prominently expressed pathway of cardiac muscle contraction was targeted by 3 DE miRNAs identified by the miRNA-pathway-network (dre-miR-7147, dre-miR-26a and dre-miR-375), which included 23 DE genes. This study presents a global view of the combined SiNPs and MeHg toxicity on the dynamic expression of both mRNAs and miRNAs in zebrafish, and could serve as fundamental research clues for future studies, especially on cardiovascular system toxicity.


Is there a difference between aortic and brachial vein blood lipoprotein and total cholesterol levels?
Atherosclerosis is a disease of the arteries that is not practically observed in veins. There are a lot of proposed mechanisms underlying this phenomenon. We aimed to compare the lipoprotein and total cholesterol levels in aortic and venous blood samples. A total of 125 patients ≥18 years of age were included in the study. After overnight fasting, we drew blood from the proximal ascending aorta and brachial vein. Serum lipid profiles were compared between these samples. Out of 125 patients, 45 (36%) were females, and 80 (64%) were males. The mean age of the patients was 62 years (24-85 years). Notably, 39 (31%) patients were using statin treatment. Coronary angiography showed that 103 (82%) patients had coronary artery disease. Mean arterial total cholesterol (low-density lipoprotein), high-density lipoprotein, and triglyceride levels were significantly lower than mean venous total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels (187.3±45.3 mg/dL vs. 204.5±52.6 mg/dL, p<0.001; 116.7±41.5 mg/dL vs. 128±45 mg/dL, p<0.001; 40.8±12.9 mg/dL vs. 45.3±13.3 mg/dL, p<0.001; and 142.8±81.5 vs. 161.5±100.3 mg/dL, p<0.001, respectively). Aortic lipoprotein and total cholesterol levels are significantly lower than venous lipoprotein and total cholesterol levels in patients presenting to the hospital for coronary angiography.


Early Zinc Supplementation and Enhanced Growth of the Low-Birth Weight Neonate.
Nutritional deficits are almost universal in Low-Birth Weight babies. Zinc is essential for normal infant growth and its supplementation assists growth probably through insulin-like growth factor-1. This double-blind randomized-controlled trial aimed at evaluating the role of zinc in catch-up growth of low-birth-weight infants and investigating its proposed mediator. The study was conducted in Ain Shams University Maternity Hospital. Two hundred low-birth-weight neonates were simply randomized to either oral zinc therapy or placebo. Anthropometric measurements were recorded at birth, 3, 6, and 12 months; including weight, recumbent length, head, waist, chest, and mid-upper arm circumferences, and triceps and sub-scapular skin fold thickness. We found that initial and 3-months measurements, except weight, were comparable in the 2 groups. All measurements at 6- and 12-months, except sub-scapular skin-fold-thickness, were significantly higher in zinc group than placebo. Catch-up growth, at 12-months, was significant in zinc group and was significantly higher in appropriate-for-gestational-age vs. small-for-gestational-age, in preterm vs. term, and in male vs. female infants. The median 6-months insulin-like growth factor-1 levels were significantly higher in zinc group. We conclude that early start of oral zinc supplementation in low-birth-weight neonates assists catch-up growth, probably through rise of insulin-like growth factor-1.


Parental responses to their developmentally delayed children and the South Glamorgan Home Advisory Service.
This study was undertaken to investigate how parents who have a child with some degree of handicap describe their child's behaviour and their own feelings and adjustment to having such a child. Their response was compared with that of parents of age-matched children without any known development difficulties. The parents and children were grouped according to the manifested handicap of the child (Down's syndrome, developmental quotient (DQ) greater than 65, DQ less tha 65 with/without limb dysfunction and normal controls). The children's ages ranged from 4 to 126 months and they all had received the South Glamorgan Home Advisory Service (HAS) at some time. Sixty-one families completed attitude and behaviour rating scales and parents were asked to express their preferences for prescribed services. The attitude and rating scales were also completed by twenty-five control families with normal children. A consistent trend was revealed towards increasingly favourable attitudes and feelings from past to future, and the DQ less than 65, with/without limb dysfunction, group was found to require further investigation in terms of provision of appropriate services. A distinct preference was shown for the South Glamorgan Home Advisory Service.


Digitizing tuberculosis treatment monitoring in Wuhan city, China, 2020-2021: Impact on medication adherence.
Digital technologies can improve adherence to tuberculosis (TB) treatment. We studied the impact of digitizing TB treatment monitoring on adherence among TB patients in Wuhan, China, during 2020-2021. We compared an electronic system introduced to monitor TB medication adherence (e-Patient Service System; e-PSS) with the p paper-based standard of care (TB Control Information System; TCIS) in terms of prescribed TB treatment doses taken by patients and patient outcome after six months of follow up. We designed a cross sectional study using retrospective data for all drug susceptible pulmonary TB patients recorded on both systems. The main indicators were: compliant first follow up visit (within 3 days of start of treatment); medication adherence (80% or more of monthly doses taken); and end of treatment success ratio. A total of 1,576 TB patients were recorded in TCIS in July September, 2020 and 1,145 TB cases were included in e-PSS in January March, 2021. The distribution of patient demographic and clinical features was similar between the two groups. A larger proportion from the e-PSS group visited the community doctor in the first three days compared with the TCIS group (48.91 versus 29. 76 % respectively). Medication adherence was also higher in the e-PSS group during the 6 months of treatment than in the TCIS group (84. 28 versus 80.3 3 % respectively). Treatment success was 92.52% in the e-PSS group and 92.07% in the TCIS group. Multivariate logistic regress ion analysis demonstrated that adjusted odds ratios for compliant first follow up visit, medication adherence and favorable treatment outcome in the e-PSS versus TCIS groups were 2.94 (95% 2.47 3.50), 1.33 (95% 1.08 1.63), and 1. 12 (95% CL: 0.79 1.57) respectively. This study revealed improvements in TB care following an intervention to monitor treatment digitally in patients in Wuhan, China.


Rapid Catalytic Reduction of 4-Nitrophenol and Clock Reaction of Methylene Blue using Copper Nanowires.
Copper nanowires (CuNWs) with a high aspect ratio of ~2600 have been successfully synthesized by using a facile hydrothermal method. The reductions of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) and methylene blue (MB) to leucomethylene blue (LMB) by using sodium borohydride (NaBH4) were used as models to test the catalytic activity of CuNWs. We showed that by increasing the CuNWs content, the rate of reduction increased as well. The CuNWs showed an excellent catalytic performance where 99% reduction of 4-NP to 4-AP occurred in just 60 s by using only 0.1 pg of CuNWs after treatment with glacial acetic acid (GAA). The rate constant (kapp) and activity factor (K) of this study is 18 and ~1010 fold in comparison to previous study done with no GAA treatment applied, respectively. The CuNWs showed an outstanding catalytic activity for at least ten consecutive reusability tests with a consistent result in 4-NP reduction. In clock reaction of MB, approximately 99% of reduction of MB into LMB was achieved in ~5 s by using 2 μg CuNWs. Moreover, the addition of NaOH can improve the rate and degree of recolorization of LMB to MB.


The birds, the bees, and the virtual flowers: can pollinator behavior drive ecological speciation in flowering plants?
Biologists have long assumed that pollinator behavior is an important force in angiosperm speciation, yet there is surprisingly little direct evidence that floral preferences in pollinators can drive floral divergence and the evolution of reproductive (ethological) isolation between incipient plant species. In this study, we expose computer-generated plant populations with a wide variation in flower color to selection by live and virtual hummingbirds and bumblebees and track evolutionary changes in flower color over multiple generations. Flower color, which was derived from the known genetic architecture and phenotypic variance of naturally occurring plant species pollinated by both groups, evolved in simulations through a genetic algorithm in which pollinator preference determined changes in flower color between generations. The observed preferences of live hummingbirds and bumblebees were strong enough to cause adaptive divergence in flower color between plant populations but did not lead to ethological isolation. However, stronger preferences assigned to virtual pollinators in sympatric and allopatric scenarios rapidly produced ethological isolation. Pollinators can thus drive ecological speciation in flowering plants, but more rigorous and comprehensive behavioral studies are required to specify conditions that produce sufficient preference levels in pollinators.


Regulation by the antioxidants ascorbate, cysteine, and dapsone of the increased extracellular and intracellular generation of reactive oxidants by activated phagocytes from cigarette smokers.
The bimodal pattern of N-formyl-methionyl-leucyl-phenylalanine (FMLP)-activated luminol-enhanced chemiluminescence with distinct early (occurring within 1 min) extracellular and late intracellular oxidative responses was compared in polymorphonuclear leukocytes (PMNL) from asymptomatic cigarette smokers and nonsmoking control subjects. Relative to control PMNL, the PMNL from smokers were hyperreactive to FMLP stimulation with increased generation of both extracellular (p less than 0.025) and intracellular (p less than 0.025) reactive oxidants. Smokers' PMNL also showed increased PMNL-activated superoxide generation and increased apparent receptors for FMLP. The water-soluble antioxidants ascorbate and cysteine (2.5 X 10(-5) M to 2.5 X 10(-4) M) selectively neutralized the extracellular activity of PMNL-derived reactive oxidants. The lipid-soluble antioxidant dapsone (1.25 to 30 micrograms/ml), on the other hand, inhibited both the extracellular and intracellular FMLP-activated chemiluminescence responses in PMNL from smokers and nonsmoking control subjects. Regulation of the increased extracellular and intracellular membrane-associated oxidative responses in PMNL from cigarette smokers is probably an important function of water-soluble and lipid-soluble antioxidants in vivo.


[Prion-like Propagation Model of Tau].
Abnormal proteins such as tau or α-synuclein that accumulate in brains with dementia have been shown to propagate like prion proteins. However, the expression patterns of tau in the mouse brain are different from those in humans, and the pathogenesis in the animal model of abnormal tau propagation remains incompletely understood. To overcome this problem, a novel mouse showing tau expression patterns similar to those of humans was developed using genome editing techniques. We inoculated the brain of this mouse with a sarkosyl-insoluble fraction containing abnormal tau derived from tauopathy patients and examined the accumulation of tau pathologies. We also performed a detailed analysis of the relationship between the inoculation site and the sites where tau accumulates abnormally by histochemical and neuronal circuitry and elucidated the propagation mechanism of the abnormally accumulated protein. This research is expected to lead to the development of novel drugs for the treatment of dementia using the innovative approach of "inhibition of abnormal protein propagation".


A segregated model of recombinant multicopy plasmid propagation.
A segregated model of multicopy plasmid propagation has been formulated which incorporates plasmid replication and partition functions, as well as the effect of plasmid presence on host growth rate. Growth of plasmid-free cells in selective medium is explicitly analyzed. The model parameters can be determined from experimentally measurable quantities. Propagation of a recombinant multicopy plasmid in the yeast Saccharomyces cerevisiae is analyzed using this model.


Patients' experiences of emergency admission: how relevant is the British government's Patients Charter?
This paper evaluates the British government's Patients Charter from the perspective of patients admitted via accident and emergency departments. It uses qualitative data obtained about issues of concern to these patients to judge whether the standards set out in the Charter are appropriate to their priorities and, conversely, if there are issues of importance to these patients which the Charter overlooks. Semi-structured interviews were conducted with 83 patients admitted to two London hospitals. It is concluded that the rights and standards outlined in the Patients Charter are generally appropriate to these patients' experiences, although some are defined too narrowly. The study identified a number of issues of importance to patients which are not mentioned in the Patients Charter: pain relief, giving information, receiving information, reception staff, examinations and investigations, physical environment, and other people in casualty. The patient wants rather more than recent British government documents suggest.


Differences in nuclear retention characteristics of agonist-activated glucocorticoid receptor may determine specific responses.
We studied the glucocorticoid response to the synthetic steroid pregna-1,4-diene-11beta-ol-3,20-dione (DeltaHOP) in several cell types and correlated its biological effect with the ability of the glucocorticoid receptor (GR) to be retained in the nuclear compartment. We observed that the DeltaHOP-transformed GR was diffusely distributed in the nucleus compared to the discrete structures observed for the dexamethasone (DEX)-transformed GR. Despite the fact that the receptor was entirely nuclear upon binding of each steroid and exhibited identical nuclear export rates, a greater amount of DeltaHOP-transformed GR was recovered in the cytoplasmic fraction after hypotonic cell lysis. Furthermore, accelerated nuclear export of GR was evidenced in digitonin-permeabilized cells treated with ATP and molybdate. Inasmuch as limited trypsinization of DEX-GR and DeltaHOP-GR complexes yielded different proteolytic products, we conclude that GR undergoes a differential conformational change upon binding of each ligand. We propose that these conformational differences may consequently lead to changes of stability in the interaction of the GR with chromatin. Therefore, the dynamic exchange of liganded GR with chromatin is likely to have significant consequences for the observed pleiotropic physiological responses triggered by glucocorticoid ligands, not only in different tissues but also in the same cell type.


The role of taste in food selection by African apes: implications for niche separation and overlap in tropical forests.
Ripe fruit eating shapes the behavior of most of the apes. Gorillas (Gorilla gorilla) and chimpanzees (Pan troglodytes) are very different sizes and, consequently, have been traditionally viewed as ecologically distinct, but few studies have explored the behavioral and physiological foundations of their diets. Debate continues on the extent that large-bodied gorillas may be less selective and more opportunistic fruit eaters than chimpanzees. Taste responses have been predicted to relate to body size and digestive strategies. This study employs laboratory research on taste perception and discrimination among captive zoo-housed chimpanzees and relates it to previous work on gorillas to better characterize diets and niche separation among these apes. During the captive trials, differences were recorded in consumption patterns of water and varying concentrations of dilute aqueous fructose (sweet) and tannic acid solutions (astringent), compounds commonly found in wild foods. The chimpanzees exhibited similar preference thresholds for fructose (50 mM) to other primates studied. They exhibited slightly lower inhibition thresholds for tannic acid solutions than gorillas, but higher than smaller primates studied to date. These preliminary findings suggest that tannin tolerance may well be mediated by body size, though possible species differences in salivary proteins or other sensory differences remain to be explored. This research furthers our efforts to understand the roles of body size and physiological adaptations in shaping diet and niche separation of chimpanzees and gorillas.


[The double approach in recent cervical injury. Indications apropos of 15 cases and a review of the literature].
The authors presented 15 cases of recent spinal cervical injuries treated with double approach procedure. Neurological disorders were variable but instability was severe in all cases. In 11 cases with severe neurological disorders the anterior procedure was made immediately, in 4 cases secondary with one or two sequences. In all cases was made discectomy and arthrodesis or removal vertebral body and arthrodesis associated with a posterior stabilization using generally bilateral plates of Roy-Camille. The functional spinal results were excellent with immediate or early mobilisation. In 4 cases with incomplete quadriplegia was observed favorable recovery. In 9 cases with complete quadriplegia two excellent recovery are obtained.


High-throughput in vivo screening for bone anabolic compounds with zebrafish.
Osteoporosis and diseases of bone loss are a major public health problem for the present and the future since longevity and prevalence of the disease are increasing in all parts of the world. The bisphosphonates, widely used in the treatment of osteoporosis, act by inhibiting bone resorption. However, there are few agents that promote or increase bone formation in patients who have suffered substantial bone loss. To facilitate the identification of novel anabolic therapies, the authors have developed a rapid, high-throughput in vivo screen using larval zebrafish (Danio rerio) in which they are able to identify agents with anabolic effects in the skeleton within a 6-day time period. Vitamin D3 analogs and intermittent parathyroid hormone (PTH) result in dose-dependent increases in the formation of mineralized bone, whereas continuous exposure to PTH results in net bone loss. Because this model is fast, economical, and genetically tractable, it provides a powerful adjunct to mammalian models for the identification of new anabolic bone agents and offers the potential for genetic elucidation of pathways important in osteoblastic activity.


Home hospitalization in the spectrum of community geriatric care.
The Home Hospitalization Programme was initiated in Jerusalem in 1991 to provide intensive medical care at home in order to prevent or shorten hospitalizations. The programme was based upon regular home visits by physicians, and nursing assessment to determine the need for regular nursing care. Primary-care physicians and nurses were renumerated by a global monthly fee, and were on 24-h call in addition to their periodic visits. Patients were recruited by senior geriatric physicians from acute hospital wards, as well as from the community, at the family doctor's request. Ancillary services available to the home hospitalization team included laboratory and electrocardiographic testing, specialty consultations, physical occupational or speech therapy, social work and home help up to 3 h daily. Monthly visits by a senior physician provided oversight and further consultation. Home hospitalization grew out of the continuing care division of the Clalit Sick Fund, a health maintenance organization providing umbrella medical insurance and ambulatory care. The programme grew synergistically with the other facilities of continuing care to encompass a network of comprehensive services to acute, subacute and chronic patients both at home and in institutional settings. In 4 years this network succeeded in establishing the focus of subacute intensive care in the community, achieving high levels of patient and family satisfaction, as well as striking economic advantages. In its first 2 years of operation home hospitalization saved S4 million due to reduced hospital utilization, and preliminary data for the subsequent 2 years indicated that this trend continued. Home hospitalization became the hub of a far-reaching system of supportive, intensive and humane care in the community.


Severe Asherman's syndrome complicated with placenta increta conceived by intracytoplasmic sperm injection following hysteroscopic surgery.
Although severe Asherman's syndrome is a disease that may cause infertility, pregnancy and childbirth are possible by performing hysteroscopic surgery. However, the obstetrical outcome is not always satisfactory. We report a case where severe Asherman's syndrome occurred following a cesarean section. Hysteroscopic surgery was performed due to secondary infertility, and pregnancy was achieved through a subsequent intracytoplasmic sperm injection. At 23 weeks of gestation, the patient was hospitalized due to the threat of premature labor, and a cesarean section was performed at 29 weeks of gestation after pregnancy-induced hypertension occurred. It was determined to be abnormal adherent placentation such as placenta increta through intraoperative findings, and a cesarean hysterectomy was performed. The pathological diagnosis of the uterus was placenta increta. Due to the risk of complications from placenta increta in pregnancies following hysteroscopic surgery in patients with severe Asherman's syndrome, it is important to realize the high risk involved in such cases during the pregnancy course, and careful perinatal management should be required.


Insulin growth factor-I and epidermal growth factor receptors recruit distinct upstream signaling molecules to enhance AKT activation in mammary epithelial cells.
IGF-I and epidermal growth factor (EGF) stimulate both normal mammary epithelial cell (MEC) growth and tumorigenesis. Whereas both growth factors increase DNA synthesis in MECs, how they evoke a greater response in combination when they activate similar signaling pathways remains unknown. In the present study, we investigated the signaling pathways by which these mitogens act in concert to increase DNA synthesis. Only EGF activated the MAPK pathway, and no further increase in MAPK activation was observed when both mitogens were added together. Both growth factors activated the phosphatidylinositol-3 kinase pathway, and simultaneous treatment enhanced phosphorylation of both AKT and its downstream target, p70S6K. The enhanced activation of AKT was observed at multiple time points (5 and 15 min) and growth factor concentrations (2.5-100 ng/ml). IGF-I activated AKT via insulin receptor substrate-1 and p85, the regulatory subunit of phosphatidylinositol-3 kinase. Treatment with EGF had no effect on insulin receptor substrate-1; however, it activated the EGF receptor, SHC, and c-Src. EGF treatment caused the association of SHC with Grb2 and Gab2 with phospho-SHC, phospho-Gab1, Grb2, and p85. Interestingly, inhibition of Src activation blocked the ability of EGF, but not IGF-I, to activate AKT. This corresponded with a decrease in phosphorylation of the EGF receptor and its association with phospho-SHC as well as downstream signaling. Unexpectedly, inhibition of Src increased basal MAPK activation. This is the first study to show that EGF and IGF-I use separate upstream components within a given MEC line to enhance AKT phosphorylation, contributing to increased DNA synthesis.


A Modified Dual-plane Technique Using the Serratus Anterior Fascia in Primary Breast Augmentation.
Breast augmentations are commonly performed aesthetic surgical procedures. As the breast is a changeable structure, the ideal location of an implant would be a plane that can adjust to the dynamic changes of the breast. We present a modified dual-plane technique for breast augmentation using the fascia for thin patients. Between June 2014 and June 2015, 27 patients with small breasts underwent breast augmentation using the modified dual-plane technique. The average age was 29.4 years (range, 20-41 y). The mean body mass index was 18.9 kg/m2 (range, 17.6-20.4 kg/m2). The mean size of the implant was 288.9 ml (range, 255-360 ml) on the right side and 281.6 ml (range, 255-360 ml) on the left side. All the patients returned to daily-life activities within 1 week. There have been no complications during minimum follow-up periods of 18 months. The mean follow-up was 25.6 months (range, 18-36 mo). Visible, palpable implants and rippling after breast augmentation with implants are relatively common problems. Our modified dual-plane technique with the serratus anterior fascia can reduce visible rippling and yields a natural-looking breast, especially in thin patients.


Polarizable Embedding without Artificial Boundary Polarization.
We present a fully self-consistent polarizable embedding (PE) model that does not suffer from unphysical boundary polarization. This is achieved through the use of the minimum-image convention (MIC) in the induced electrostatics. It is a simple yet effective approach that includes a more physically accurate description of the polarization throughout the molecular system. Using PE with MIC (PE-MIC), we shed new light on the limitations of commonly employed cutoff models, such as the droplet model, when used in PE calculations. Specifically, we investigate the effects of the unphysical polarization at the outer boundary by comparing induced dipoles and the associated electrostatic potentials, as well as some optical properties of solute-solvent and biomolecular systems. We show that the magnitude of the inaccuracies caused by the unphysical polarization depends on multiple parameters: the nature of the quantum subsystem and of the environment, the cutoff model and distance, and the calculated property.


Follow up of lung transplant recipients using an electronic nose.
Lung transplantation is the only available treatment for some end-stage lung diseases. However, patients following lung transplantation need tight control to prevent serious complications, but mainly invasive techniques are available. An electronic nose is a non-invasive way to measure exhaled volatiles. In this study we investigated the potential of electronic nose measurements in lung transplant patients and compared the 'breathprint' with clinical parameters. Sixteen patients with lung transplant and 33 healthy subjects participated in the study. Exhaled breath was collected; laboratory tests and lung function measurements were carried out. Breath samples were processed by an electronic nose, analysed using principal component analysis and compared to blood (CRP, tacrolimus) and lung function parameters. Significant differences were found in exhaled breath volatile compound pattern between healthy subjects and lung transplant recipients. The plasma level of tacrolimus showed significant relationship with 'breathprint' in lung transplanted patients. Patients living with transplanted lungs can be discriminated from healthy subjects by exhaled breath volatile organic compounds' profile. Treatment after lung transplantation needs to be taken into consideration when using an electronic nose as medication may have profound influence on breathprints.


Multiple Mycobacterium tuberculosis infections in an HIV-infected patient.
Mycobacterial colonies of two different morphologies were isolated from one sputum sample of a HIV-positive patient. One morphological type was resistant to streptomycin (STR) and susceptible to isoniazid (INH), while the other isolate with different colony morphology was resistant to both of these anti-TB drugs. A mycobacterial isolate of one pus from a lymph node sample was resistant to these two anti-TB drugs, while the other isolate from another pus sample was resistant to STR but susceptible INH. IS6110 RFLP based finger printing revealed that the HIV-positive patient was infected with different strains of Mycobacterium tuberculosis. A subculture of isolates on solid medium is useful to examine mixed infection.