Drug-Induced Peripheral Neuropathy: A Narrative Review.
Peripheral neuropathy is a painful condition deriving from many and varied etiologies. Certain medications have been implicated in the iatrogenic development of Drug Induced Peripheral Neuropathy (DIPN) and include chemotherapeutic agents, antimicrobials, cardiovascular drugs, psychotropic, anticonvulsants, among others. This review synthesizes current clinical concepts regarding the mechanism, common inciting medications, and treatment options for drug-induced peripheral neuropathy. The authors undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question and inclusion/exclusion criteria. The most relevant and up to date research was included. Drug-induced peripheral neuropathy is a common and painful condition caused by many different and frequently prescribed medications. Most often, DIPN is seen in chemotherapeutic agents, antimicrobials, cardiovascular drugs, psychotropic, and anticonvulsant drugs. Certain drugs exhibit more consistent neuropathic side effects, such as the chemotherapeutic compounds, but others are more commonly prescribed by a larger proportion of providers, such as the statins. DIPN is more likely to occur in patients with concomitant risk factors such as preexisting neuropathy, diabetes, and associated genetically predisposing diseases. DIPN is often difficult to treat, however medications including duloxetine, and gabapentin are shown to reduce neuropathic pain. Advanced techniques of neuromodulation offer promise though further randomized and controlled studies are needed to confirm efficacy. Awareness of the drugs covered in this review and their potential for adverse neuropathic effect is important for providers caring for patients who report new onset symptoms of pain, paresthesia, or weakness. Prevention of DIPN is especially important because treatment often proves challenging. While many pharmacologic therapies have demonstrated analgesic potential in the pain caused by DIPN, many patients remain refractive to treatment. More studies are needed to elucidate the effectiveness of interventional, neuromodulating therapies.


X-ray-Based Spectroscopic Techniques for Characterization of Polymer Nanocomposite Materials at a Molecular Level.
This review provides detailed fundamental principles of X-ray-based characterization methods, i.e., X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, and near-edge X-ray absorption fine structure, and the development of different techniques based on the principles to gain deeper understandings of chemical structures in polymeric materials. Qualitative and quantitative analyses enable obtaining chemical compositions including the relative and absolute concentrations of specific elements and chemical bonds near the surface of or deep inside the material of interest. More importantly, these techniques help us to access the interface of a polymer and a solid material at a molecular level in a polymer nanocomposite. The collective interpretation of all this information leads us to a better understanding of why specific material properties can be modulated in composite geometry. Finally, we will highlight the impacts of the use of these spectroscopic methods in recent advances in polymer nanocomposite materials for various nano- and bio-applications.


Relapsed diffuse large B-cell lymphoma present different genomic profiles between early and late relapses.
Despite major advances in first-line treatment, a significant proportion of patients with diffuse large B-cell lymphoma (DLBCL) will experience treatment failure. Prognosis is particularly poor for relapses occurring less than one year after the end of first-line treatment (early relapses/ER) compared to those occurring more than one year after (late relapses/LR). To better understand genomic alterations underlying the delay of relapse, we identified copy number variations (CNVs) on 39 tumor samples from a homogeneous series of patients included in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) prospective study. To identify CNVs associated with ER or LR, we devised an original method based on Significance Analysis of Microarrays, a permutation-based method which allows control of false positives due to multiple testing. Deletions of CDKN2A/B (28%) and IBTK (23%) were frequent events in relapsed DLBCLs. We identified 56 protein-coding genes and 25 long non-coding RNAs with significantly differential CNVs distribution between ER and LR DLBCLs, with a false discovery rate < 0.05. In ER DLBCLs, CNVs were related to transcription regulation, cell cycle and apoptosis, with duplications of histone H1T (31%), deletions of DIABLO (26%), PTMS (21%) and CK2B (15%). In LR DLBCLs, CNVs were related to immune response, with deletions of B2M (20%) and CD58 (10%), cell proliferation regulation, with duplications of HES1 (25%) and DVL3 (20%), and transcription regulation, with MTERF4 deletions (20%). This study provides new insights into the genetic aberrations in relapsed DLBCLs and suggest pathway-targeted therapies in ER and LR DLBCLs.


Improved diagnosis of neural tube defects: measurement of concanavalin A-reactive variants of AFP in amniotic fluid.
The proportion of alphafetoprotein (AFP) not reacting with Concanavalin A(Con A) was determined by crossed line affinity immunoelectrophoresis (CLAIE) in amniotic fluid obtained from 16 pregnancies with open neural tube defects and other fetal abnormalities, and 25 pregnancies with normal outcome. The percentage of Con A non-reactive AFP was significantly lower in the presence of open neural tube defects (less than 3.9%, n = 13) compared with that in normal pregnancy (range 6.4-25.2%, n = 25). In this retrospective analysis, 2 pregnancies affected by open neural tube defect escaped diagnosis on the basis of an ambiguous total AFP estimation (+2SD less than x less than +5SD) in the amniotic fluid. These observations suggest that the elimination of false diagnose based on total AFP levels may be possible, if supplementary analysis by CLAIE is performed.


Loxoribine induces chronic lymphocytic leukemia B cells to traverse the cell cycle.
Leukemic B cells from a majority of patients with chronic lymphocytic leukemia (CLL) enter the cell cycle upon stimulation in vitro with loxoribine, a potent 7,8-disubstituted guanine ribonucleoside immunostimulant. In the absence of added costimulants, a proportion of these cells become activated and undergo DNA synthesis and mitosis accompanied by a marked increase in expression of an array of cell surface activation antigens. The resultant activated B-CLL cells exhibit greatly enhanced sensitivity to cycle-active cytotoxic drugs. This approach may be of potential value in the therapy of CLL.


Epigenetics and complex disease: from etiology to new therapeutics.
Epigenetics is a new development in complex non-Mendelian disease, which may not only uncover etiologic and pathogenic mechanisms but may also provide the basis for the development of medications that would target the primary epigenetic causes of such diseases. Such epigenetic drugs would be novel, potentially possessing substantially higher therapeutic potential and a much lower rate of adverse effects in comparison to current symptomatic treatments. A collection of epigenetic drugs already exist at various stages of development and, although their effectiveness has yet to be maximized, they show great promise in the treatment of cancer, psychiatric disorders, and other complex diseases. Here we present a review of the epigenetic theory of complex disease and an evaluation of current epigenetic therapies, as well as predictions of the future directions in this expanding field.


Sustained hematologic and central nervous system remission with single-agent denileukin diftitox in refractory adult T-cell leukemia/lymphoma.
Human T-lymphotrophic virus-1-associated adult T-cell leukemia/lymphoma (ATLL) is a rare and often fatal disease. Initial treatment often includes zidovudine/interferon (IFN)-based therapy, although disease remission is typically not complete or durable. This study reports on a 55-year-old man with relapsed/refractory leukemic-phase ATLL including significant central nervous system (CNS) disease with resistance to previous zidovudine/IFN and arsenic trioxide/IFN treatment. The patient experienced a rapid hematologic and CNS clinical response with single-agent denileukin diftitox therapy (18 microg/kg per day for 5 days). He tolerated 8 cycles of denileukin diftitox therapy well and experienced a sustained complete hematologic and CNS remission. The patient subsequently underwent matched sibling reduced-intensity allogeneic transplantation and remains disease free. Further study examining denileukin diftitox in patients with relapsed/refractory ATLL is warranted.


Between heaven and Earth: the exploration of Titan.
The atmosphere of Titan represents a bridge between the early solar nebula and atmospheres like ours. The low abundances of primordial noble gases in Titan's atmosphere relative to N2 suggest that the icy planetesimals that formed the satellite must have originated at temperatures higher than 75-100 K. Under these conditions, N2 would also be very poorly trapped and thus Titan's nitrogen, like ours, must have arrived as nitrogen compounds, of which ammonia was likely the major component. This temperature constraint also argues against the trapping of methane. Production of this gas on the satellite after formation appears reasonable based on terrestrial examples of serpentinization, disproportionation and reduction of carbon. These processes require rocks, water, suitable catalysts and the variety of primordial carbon compounds that were plausibly trapped in Titan's ices. Application of this same general scenario to Ganymede, Callisto, KBOs and conditions on the very early Earth seems promising.


Position of the Internal Aperture of Vestibular Aqueduct in Patients With Enlarged Vestibular Aqueduct.
To investigate the position of the internal aperture of vestibular aqueduct and its relationship to hearing level in patients with enlarged vestibular aqueduct (EVA). The size of the common crus and the position of the internal aperture of vestibular aqueduct were compared among control subjects, EVA patients with and without other inner ear malformations. Auditory steady-state response thresholds were compared between EVA patients with different positions of internal apertures. The common crus in EVA patients was shorter than in control subjects (p < 0.05). The internal aperture of the vestibular aqueduct opened solely into the common crus in control subjects, simultaneously into the common crus and vestibule in almost 45% of EVA patients, solely into the common crus, and the vestibule in almost 30 and 25% of EVA patients, respectively. Auditory steady-state response thresholds at 2000 and 4000 Hz were higher in EVA patients whose internal apertures of vestibular aqueducts opened simultaneously into the common crus and vestibule than in those whose internal apertures opened solely into the common crus. The common crus is shorter in EVA patients than in control subjects. The internal aperture of the vestibular aqueduct opens solely into the common crus in control subjects. It opens simultaneously into the common crus and vestibule in almost half of the EVA patients. The EVA patients whose internal apertures of vestibular aqueducts open solely into the common crus may have better hearing than those whose internal apertures open simultaneously into the common crus and vestibule.


Alpha-Synuclein conformation affects its tyrosine-dependent oxidative aggregation.
Oxidative stress and aggregation of the protein alpha-synuclein are thought to be key factors in Parkinson's disease. Previous work shows that cytochrome c with H(2)O(2) causes tyrosine-dependent in vitro peroxidative aggregation of proteins, including alpha-synuclein. Here, we examine the role of each of alpha-synuclein's four tyrosine residues and how the protein's conformation affects covalent oxidative aggregation. When alpha-synuclein adopts a collapsed conformation, tyrosine 39 is essential for wild-type-like covalent aggregation. This lone N-terminal tyrosine, however, is not required for wild-type-like covalent aggregation in the presence of a denaturant or when alpha-synuclein is present in noncovalent fibrils. We also show that preformed oxidative aggregates are not incorporated into noncovalent fibrils. These data provide insight into how dityrosine may be formed in Lewy bodies seen in Parkinson's disease.


Treatment outcomes in schizophrenia: qualitative study of the views of family carers.
Schizophrenia is a complex, heterogeneous disorder, with highly variable treatment outcomes, and relatively little is known about what is important to patients. The aim of the study was to understand treatment outcomes informal carers perceive to be important to people with schizophrenia. Qualitative interview study with 34 individuals and 8 couples who care for a person with schizophrenia/schizoaffective disorder. Interviews were transcribed verbatim and analysed by a thematic framework based approach. Carers described well-recognised outcomes of importance, alongside more novel outcomes relating to: Safety (of the patient/others); insight (e.g. into non-reality of psychotic phenomena); respite from fear, distress or pain; socially acceptable behaviour; getting out of the house; attainment of life milestones; changes in personality and/or temperament; reduction of vulnerability to stress; and several aspects of physical health. These findings have the potential to inform the development of patient- or carer- focused outcome measures that take into account the full range of domains that carers feel are important for patients.


A Total Radiation Dose of 70 Gy Is Required After Macroscopically Incomplete Resection of Squamous Cell Carcinoma of the Head and Neck.
To contribute to the definition of the optimal total radiation dose and to determine the role of concurrent chemotherapy after macroscopically incomplete resection of squamous cell carcinoma of the head and neck (SCCHN). Twenty-six patients treated with postoperative radio(chemo)therapy following macroscopically incomplete resection were evaluated. Total radiation dose (70 Gy vs. 59.4-66 Gy), concurrent chemotherapy (yes vs. no) plus six factors were investigated for locoregional control (LRC) and overall survival (OS). On analyses of LRC, 70 Gy was significantly superior to 59.4-66.0 Gy. Two-year LCR rates were 94% and 25%, respectively (p<0.001). Concurrent chemotherapy significantly improved 2-year LRC (90% vs. 0%, p<0.001). Both 70 Gy (92% vs. 11%, p<0.001) and concurrent chemotherapy (80% vs.0%, p<0.001) also resulted in better OS. A total radiation dose of 70 Gy was significantly superior to lower doses regarding both LCR and OS. Concurrent chemotherapy is also very important to achieve optimal outcomes.


Anatomical Modeling of Brain Vasculature in Two-Photon Microscopy by Generalizable Deep Learning.
Objective and Impact Statement. Segmentation of blood vessels from two-photon microscopy (2PM) angiograms of brains has important applications in hemodynamic analysis and disease diagnosis. Here, we develop a generalizable deep learning technique for accurate 2PM vascular segmentation of sizable regions in mouse brains acquired from multiple 2PM setups. The technique is computationally efficient, thus ideal for large-scale neurovascular analysis. Introduction. Vascular segmentation from 2PM angiograms is an important first step in hemodynamic modeling of brain vasculature. Existing segmentation methods based on deep learning either lack the ability to generalize to data from different imaging systems or are computationally infeasible for large-scale angiograms. In this work, we overcome both these limitations by a method that is generalizable to various imaging systems and is able to segment large-scale angiograms. Methods. We employ a computationally efficient deep learning framework with a loss function that incorporates a balanced binary-cross-entropy loss and total variation regularization on the network's output. Its effectiveness is demonstrated on experimentally acquired in vivo angiograms from mouse brains of dimensions up to 808×808×702 μm. Results. To demonstrate the superior generalizability of our framework, we train on data from only one 2PM microscope and demonstrate high-quality segmentation on data from a different microscope without any network tuning. Overall, our method demonstrates 10× faster computation in terms of voxels-segmented-per-second and 3× larger depth compared to the state-of-the-art. Conclusion. Our work provides a generalizable and computationally efficient anatomical modeling framework for brain vasculature, which consists of deep learning-based vascular segmentation followed by graphing. It paves the way for future modeling and analysis of hemodynamic response at much greater scales that were inaccessible before.


Social affective context reveals altered network dynamics in schizophrenia patients.
Impairments in social cognition and interactions are core psychopathologies in schizophrenia, often manifesting as an inability to appropriately relate to the intentions and feelings of others. Neuroimaging has helped to demarcate the dynamics of two distinct functional connectivity circuits underlying the social-affective processes related to mentalization (known as Theory of Mind, ToM) and somatic-affiliation (known as Embodied Simulation, ES). While evidence points to abnormal activation patterns within these networks among those suffering from schizophrenia, it is yet unclear however, if these patients exhibit this abnormal functional connectivity in the context of social-affective experiences. The current fMRI study, investigated functional connectivity dynamics within ToM and ES networks as subjects experienced evolving cinematic portrayals of fear. During scanning, schizophrenia patients and healthy controls passively watched a cinematic scene in which a mother and her son face various threatening events. Participants then provided a continuous and retrospective report of their fear intensity during a second viewing outside the scanner. Using network cohesion index (NCI) analysis, we examined modulations of ES-related and ToM-related functional connectivity dynamics and their relation to symptom severity and the continuous emotional ratings of the induced cinematic fear. Compared to patients, healthy controls showed higher ES-NCI and marginally lower ToM-NCI during emotional peaks. Cross-correlation analysis revealed an intriguing dynamic between NCI and the inter-group difference of reported fear. Schizophrenia patients rated their fear as lower relative to healthy controls, shortly after exhibiting lower ES connectivity. This increased difference in rating was also followed by higher ToM connectivity among schizophrenia patients. The clinical relevance of these findings is further highlighted by the following two results: (a) ToM-NCI was found to have a strong correlation with the severity of general symptoms during one of the two main emotional peaks (Spearman R = 0.77); and (b) k-mean clustering demonstrated that the networks' NCI dynamic during the social-affective context reliably differentiated between patients and controls. Together, these findings point to a possible neural marker for abnormal social-affective processing in schizophrenia, manifested as the disturbed balance between two functional networks involved in social-affective affiliation. This in turn suggests that exaggerated mentalization over somatic-affiliative processing, in response to another's' distress may underlie social-affective deficits in schizophrenia.


Comparison of recirculation percentage of the palindrome catheter and standard hemodialysis catheters in a swine model.
The purpose of this study was to evaluate in vivo recirculation of a new bi-directional dialysis catheter with a symmetric tip design and compare it to currently marketed staggered and split tip catheters. Twelve catheters were placed in three 70-kg male swine. The catheters were connected to a roller type peristaltic pump. Blood flow and recirculation rates were measured with ultrasound (US) dilution. Recirculation was measured in blood flow rates of 300 mL/min, 400 mL/min, and 500 mL/min. The dialysis lines were then reversed and recirculation was measured in flow rate of 400 mL/min. Measurements were conducted with the catheter tip in the right atrium (RA) and repeated with the catheter tip in the superior vena cava (SVC). Recirculation rates measured with the Palindrome catheter tip (Tyco Healthcare Group LP, Mansfield, MA) in the SVC and in the RA were 0%. When the dialysis lines were reversed, the Palindrome catheter average recirculation was 0% with the tip in the SVC and 1% (0%-3%) with the tip in the RA. The average recirculation rates measured with the split tip catheter were 1% (0%-10%) in the SVC and 0% when the catheter tip was in the RA. When the dialysis lines were reversed split tip catheter recirculation was 11% (9%-16%) with the tip in the SVC and 13% (7%-18%) with the tip in the RA. With the staggered tip catheter, 1% (0%-5%) recirculation was measured. When the dialysis lines were reversed, the average recirculation in the staggered tip catheter measured 23% (18%-30%). Recirculation rate with reversal of dialysis lines was significantly lower with the Palindrome catheter when compared to the split tip and staggered tip designs (P < .05). Preliminary results in vivo indicate that the Palindrome catheter demonstrates minimal recirculation with reversal of the dialysis lines compared to currently marketed split tip and staggered tip catheters.


Identification of interferon-gamma as the lymphokine that mediates leukotriene B4-induced immunoregulation.
Leukotriene B4 (LTB4) has been shown to modulate lymphocyte responses in both a positive and a negative way, depending on the particular cell subsets it interacts with. Recent evidence also indicates that LTB4 can directly affect the production of cytokines such as interleukin 1 (IL 1) or interleukin 2 (IL 2) and interferon-gamma (IFN-gamma). In this report, we present evidence that human T cells pulsed with LTB4 modulate IL 1 production by human monocytes by secreting IFN-gamma. In fact, we found that LTB4-pulsed T cells were capable of inducing a suppression of lymphocyte proliferation if allowed to interact with monocytes, but that this suppression was reversed to an enhancing effect when monocytes were treated with the cyclooxygenase inhibitor indomethacin. Furthermore, LTB4-pulsed T cells released a soluble factor that would mediate both effects. This factor was found to be IFN-gamma, because affinity-purified IFN-gamma could reproduce the effects, and a rabbit polyclonal anti-serum to human IFN-gamma could block the activities of supernatants from LTB4-pulsed T cells. LTB4 was also shown to enhance IFN-gamma production by T4+ T cells and to inhibit IFN-gamma production by T8+ T cells. These results suggest that LTB4 may regulate immune cell functions by inducing IFN-gamma production by T4+ cells.


Lessons from initial experience with the in situ saphenous vein graft.
A policy of preference for the in situ saphenous vein was adopted for all patients requiring bypass grafting below the knee. In an initial series of 25 operations, technical complications occurred in eight cases (32%), including venographic extravasation, vein injury during valve lysis, and early graft occlusions due to incomplete valve lysis and routing under tension past the hamstring tendons. Early loss of tibial outflow vessels occurred twice, with retrieval of embolic debris possibly shed from the graft. In spite of these events, at an average follow-up of ten months, 21 grafts were open (84% patency). Two occlusions occurred in patients who suffered operative complications, and another graft was lost after rethrombosis of a donor axillobifemoral prosthesis. Acceptable patency in spite of technical mishaps early in my experience encourages continued efforts to master the in situ method.


Short- and Longterm Glycemic Control of Streptozotocin-Induced Diabetic Rats Using Different Insulin Preparations.
The chemical induction of diabetes with STZ has gained popularity because of the relative ease of rendering normal animals diabetic. Insulin substitution is required in STZ-rats in long-term studies to avoid ketoacidosis and consequently loss of animals. Aim of the present studies was to test different insulin preparations and different ways of administration in their ability to reduce blood glucose in STZ-induced diabetic rats. Single dosing of the long-acting insulin analogue glargine was able to dose-dependently reduce blood glucose over 4 h towards normoglycemia in STZ-treated rats. However, this effect was not sustained until 8 h post injection. A more sustained glucose-lowering effect was achieved using insulin-releasing implants. In STZ-rats, 1 insulin implant moderately lowered blood glucose levels 10 days after implantation, while 2 implants induced normoglycemia over the whole day. According to the glucose-lowering effect 1 as well as 2 insulin implants significantly reduced HbA1c measured after 26 days of implantation. In line with the improved glucose homeostasis due to the implants, urinary glucose excretion was also blunted in STZ-treated rats with 2 implants. Since diabetic nephropathy is one of the complications of longterm diabetes, renal function was characterized in the STZ-rat model. Increases in creatinine clearance and urinary albumin excretion resemble early signs of diabetic nephropathy. These functional abnormalities of the kidney could clearly be corrected with insulin-releasing implants 27 days after implantation. The data show that diabetic STZ-rats respond to exogenous insulin with regard to glucose levels as well as kidney parameters and a suitable dose of insulin implants for glucose control was established. This animal model together with the insulin dosing regimen is suitable to address diabetes-induced early diabetic nephropathy and also to study combination therapies with insulin for the treatment of type 1 diabetes.


Efficiency enhancement in a single bandgap silicon solar cell considering hot-carrier extraction using selective energy contacts.
One of the most important and challenging loss factors of photovoltaics is the heat production of energetic carriers excited by high energy incident photons. The present work shows that if carriers are extracted at their high energies before cooling down due to scattering, the conversion efficiency can be noticeably enhanced. To increase the efficiency of a single-band gap solar cell in this work, selective energy contacts are introduced to a p-i-n structure to extract hot carriers. A selective energy contact solar cell is made up of many collecting contacts with particular energy differences from the conduction band of the cell. In other words, each contact could extract carriers with a special range of energies. The concept of selective energy contact solar cells is to collect high energy carriers, i.e. electrons in this case, within a range of energies onto external electrodes before they cool down. The comparison between conventional solar cells and selective energy contact solar cells shows a significant enhancement in electron collection and efficiency. Based on simulation results, it is observed that the efficiency of the selective energy contact solar cell has been enhanced substantially exceeding almost twice as much as a conventional solar cell's and reaching a significant 34% efficiency.


Hypertension and diabetes. Clinical problems.
The choice of an appropriate antihypertensive agent and the hazards of postural hypotension are common problems faced in the treatment of diabetic hypertensive patients. The results of 3 studies addressing these problems are described in this report. In the first study, indoramin, an alpha-blocking agent, was administered to patients with non-insulin-dependent diabetes and mild to moderate hypertension. Blood pressure control was achieved in 57% of patients with mild, and in none with moderate hypertension. The blood glucose and insulin responses to an oral 50g glucose loading, as well as the blood concentrations of HbA1 did not change during therapy. Seven patients were excluded because of side effects. In 4 of them postural hypotension was observed. In the second study, the effects of angiotensin-converting enzyme (ACE) inhibitors, administered to patients with non-insulin-dependent diabetes and mild to moderate hypertension, were evaluated. Blood pressure control was achieved in 78% of the patients on captopril (n = 14) and in 74% of patients on enalapril therapy (n = 23). Symptomatic postural hypotension (n = 2) and hyperkalaemia (n = 2) were observed with both drugs. Significant reductions in 24-hour urinary protein or albumin excretion were detected in 12 patients on enalapril therapy. No changes in 2-hour postprandial blood glucose and HbA1 levels were observed during therapy with ACE inhibitors. In the third study, dopaminergic antagonist agents were evaluated in diabetic patients with orthostatic hypotension. In 7 patients metoclopramide (20mg intravenously) reduced the fall in mean arterial pressure induced by upright tilt.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunohistochemical localization of neuron-specific enolase in the human hypophysis and pituitary adenomas.
Neuron-specific enolase (NSE) was localized, using the immunoperoxidase technique, in the cytoplasm of the five adenohypophyseal hormone-secreting cell types, and in nerve fibers of the pars nervosa of the human pituitary. Crooke's hyaline material was negative. Neuron-specific enolase was found in all pituitary adenoma types; there was no correlation between degree of granularity or differentiation of tumor cells and intensity of NSE immunopositivity. One hypothalamic hamartoma was positive for NSE; a craniopharyngioma and a neurohypophyseal granular cell tumor were not. Neuron-specific enolase was present in peptide hormone-producing endocrine cells outside the pituitary and in their tumors; the majority of other tumors were negative for NSE, although one breast carcinoma, one ovarian cystadenocarcinoma, and one lymphoma were positive for NSE. In control studies, absorption of NSE antisera with growth hormone abolished immunoreactivity; there was no immunologic cross-reaction demonstrable by radioimmunoassay.


MicroRNA-124 acts as a tumor-suppressive miRNA by inhibiting the expression of Snail2 in osteosarcoma.
The aim of the present study was to investigate the clinical significance of hsa-microRNA-124-3p (miR-124) in osteosarcoma (OS), and examine its role in cell growth and invasion. Using a microRNA chip array, the expression of miR-124 was detected in samples of surgically resected OS and matched against the levels of expression in tumor-adjacent normal tissues. The levels of miR-124 were upregulated in the OS cells through the transfection of miR-124 mimics. Cell proliferation and Transwell assays were performed to determine cell proliferation and invasion; Reverse transcription-quantitative polymerase chain reaction, western blot and luciferase assays were then used to detect the expression of the target gene snail family zinc finger 2 (Snail2). The expression of miR-124 was significantly lower in the OS tissues, compared with that in the tumor-adjacent normal tissues; and the expression of miR-124 in the tumor tissues was significantly associated with tumor size. miR-124 directly repressed the expression of Snail2, and resulted in a significant inhibition of cell proliferation and invasion. In a mouse model, the overexpression of miR-124 significantly inhibited U2OS cell proliferation and invasion. Taken together, miR-124 was associated with the adverse clinical and pathological features observed in OS. It acted as a tumor suppressor to regulate the proliferation and invasion of OS cells by targeting Snail2, suggesting that miR-124 may be key in the progression of OS.


The effects of sialic acid on the gene expression of fibrillar collagens: different changes in normal and fibrotic scar derived fibroblasts.
To investigate the effect of free sialic acid on collagen gene expression in fibroblasts. Cell culture study. University hospital, Finland. CELL LINES: Human granulation tissue fibroblasts, human hypertrophic scar fibroblasts and human keloid fibroblasts. Treatment of cell cultures with 3 microM, 30 microM and 300 microM N-acetyl-neuraminic acid. The measurement of steady state level of mRNA for type I and type III collagen. Fibroblast lines react dissimilarly under the influence of sialic acid. Granulation tissue fibroblasts showed decrease in the gene expression of type I and III collagen, while keloid fibroblasts contrastingly showed an increase. Hypertrophic scar derived fibroblasts showed no change. Sialic acids may decrease collagen gene expression in granulation tissue and that disturbed wound healing in diabetics and smokers may in part be due to direct effect of sialic acids on fibroblasts. Sialic acids may in part induce keloid formation.


Structural organization and genomic sequence of mouse syndecan-1 gene.
Syndecan-1 is an integral membrane proteoglycan, which binds several extracellular matrix components and growth factors. Its expression follows morphogenetic rather than histological patterns during embryonic development and is regulated by epithelial-mesenchymal interactions during organogenesis. Malignant transformation has been shown to suppress syndecan-1 expression. In order to understand better the regulation of syndecan-1 expression, we have determined the structural organization of mouse syndecan-1 gene. Several genomic clones were isolated, covering the entire 23-kilobase (kb) syndecan-1 gene. All five exons, four introns, and the 5'- and 3'-flanking regions were sequenced. The first intron was very long (17,582 base pairs (bp)) if compared with the others that were only a few hundred nucleotides in length. The first exon contained only the signal sequence and exons II-IV all the glycosaminoglycan binding sites. The fifth exon resided both transmembrane and cytoplasmic domains, which are known to be conserved among the members of the syndecan family. This genomic structure explains why these members could have heterologous extracellular domains and homologous transmembrane and cytoplasmic domains. Syndecan-1 gene was shown by primer extension analysis to have three transcription initiation sites which were confirmed by polymerase chain reaction. These initiation sites were found to locate -217, -266, and -591 bp from described cDNA (Saunders, S., Jalkanen, M., O'Farrell, S., and Bernfield, M. (1989) J. Cell Biol. 108, 1547-1556). Within the 5'-end of the gene a 2000-bp-long CpG nucleotide-rich sequence resembling a CpG island was found, which started from the transcription initiation sites and ended in the first intron. At the 3'-end of the gene an other polyadenylation signal sequence was revealed 638 bp downstream from the first one. The two mRNAs (2.6 kb and 3.4 kb) were shown to be produced by alternative polyadenylation.


Outbreak of JK diphtheroid infections associated with environmental contamination.
The group JK diphtheroid organism is a multiply resistant opportunistic pathogen which infects immunocompromised patients sporadically. We describe the first reported outbreak of JK diphtheroid infections, in which four cases of bacteremia and one Hickman catheter site infection occurred during 4 weeks on a hematology ward. On this ward, JK diphtheroid was recovered from 17 of 39 patients, 10 of 17 30-ft3 (0.840-m3) air samples, surfaces in 9 of 13 patient rooms, and hands of 4 of 22 personnel. Previously identified risk factors for JK diphtheroid sepsis (male gender, broad-spectrum antibiotic therapy, granulocytopenia, and prolonged hospital stay) were present in infected patients but did not distinguish them from patients who were only colonized. Emphasis on aseptic practices was associated with termination of the outbreak and negative hand cultures from personnel, despite continued patient colonization and environmental contamination.


Substitution Kinetics, Albumin and Transferrin Affinities, and Hypoxia All Affect the Biological Activities of Anticancer Vanadium(V) Complexes.
Limited stability of most transition-metal complexes in biological media has hampered their medicinal applications but also created a potential for novel cancer treatments, such as intratumoral injections of cytotoxic but short-lived anticancer drugs. Two related V(V) complexes, [VO(Hshed)(dtb)] (1) and [VO(Hshed)(cat)] (2), where H2shed = N-(salicylideneaminato)-N'-(2-hydroxyethyl)-1,2-ethanediamine, H2dtb = 3,5-di-tert-butylcatechol, and H2cat = 1,2-catechol, decomposed within minutes in cell culture medium at 310 K (t1/2 = 43 and 9 s for 1 and 2, respectively). Despite this, both complexes showed high antiproliferative activities in triple-negative human breast cancer (MDA-MB-231) cells, but the mechanisms of their activities were radically different. Complex 1 formed noncovalent adducts with human serum albumin, rapidly entered cells via passive diffusion, and was nearly as active in a short-term treatment (IC50 = 1.9 ± 0.2 μM at 30 min) compared with a long-term treatment (IC50 = 1.3 ± 0.2 μM at 72 h). The activity of 1 decreased about 20-fold after its decomposition in cell culture medium for 30 min at 310 K. Complex 2 showed similar activities (IC50 ≈ 12 μM at 72 h) in both fresh and decomposed solutions and was inactive in a short-term treatment. The activity of 2 was mainly due to the reactions among V(V) decomposition products, free catechol, and O2 in cell culture medium. As a result, the activity of 1 was less sensitive than that of 2 to the effects of hypoxic conditions that are characteristic of solid tumors and to the presence of apo-transferrin that acts as a scavenger of V(V/IV) decomposition products in blood serum. In summary, complex 1, but not 2, is a suitable candidate for further development as an anticancer drug delivered via intratumoral injections. These results demonstrate the importance of fine-tuning the ligand properties for the optimization of biological activities of metal complexes.


[Diagnosis and treatment of atlanto-occipital ruptures].
Atlantooccipital rupture is a rare ligamentous injury, which is usually accompanied by multiple trauma. Literature and personal communications report of 30 patients with such an injury. Long term survival is known in 18 cases, but there were severe neurological deficits in two cases. Reports of five of our own patients are presented. Death occurred after a few hours in three cases. One patient survived for four weeks, and one girl fully recovered after timely atlantooccipital fusion. In seven of 18 cases who have survived for a long time, the diagnosis was made only at a late stage. This underscores the necessity of including the occipitocervical transition in the diagnosis of the cervical spine. This applies in particular to unconscious accident casualties. Standard X-rays of the upper cervical spine (supplemented if necessary by cautious radiographic control under mild head extension) verify the diagnosis. In treatment, an early fusion of the cervicooccipital transition is to be given preference. Only in this way can stable healing and thus the most important precondition for neurological restitution be fulfilled.


Squalene-Adenosine Nanoparticles: Ligands of Adenosine Receptors or Adenosine Prodrug?
Adenosine receptors (ARs) represent key drug targets in many human pathologies, including cardiovascular, neurologic, and inflammatory diseases. To overcome the very rapid metabolization of adenosine, metabolically stable AR agonists and antagonists were developed. However, few of these molecules have reached the market due to efficacy and safety issues. Conjugation of adenosine to squalene to form squalene-adenosine (SQAd) nanoparticles (NPs) dramatically improved the pharmacological efficacy of adenosine, especially for neuroprotection in stroke and spinal cord injury. However, the mechanism by which SQAd NPs displayed therapeutic activity remained totally unknown. In the present study, two hypotheses were discussed: 1) SQAd bioconjugates, which constitute the NP building blocks, act directly as AR ligands; or 2) adenosine, once released from intracellularly processed SQAd NPs, interacts with these receptors. The first hypothesis was rejected, using radioligand displacement assays, as no binding to human ARs was detected, up to 100 µM SQAd, in the presence of plasma. Hence, the second hypothesis was examined. SQAd NPs uptake by HepG2 cells, which was followed using radioactive and fluorescence tagging, was found to be independent of equilibrative nucleoside transporters but rather mediated by low-density lipoprotein receptors. Interestingly, it was observed that after cell internalization, SQAd NPs operated as an intracellular reservoir of adenosine, followed by a sustained release of the nucleoside in the extracellular medium. This resulted in a final paracrine-like activation of the AR pathway, evidenced by fluctuations of the second messenger cAMP. This deeper understanding of the SQAd NPs mechanism of action provides a strong rational for extending the pharmaceutical use of this nanoformulation.


Pancoast syndrome due to pulmonary metastasis of sarcomatoid hepatocellular carcinoma.
Hepatocellular carcinoma is the most common primary liver malignancy, and sarcomatoid hepatocellular carcinoma is a rare malignancy containing both carcinomatous and sarcomatous components. We report a 64-year-old male patient treated with open right trisectionectomy for a 16cm right hemiliver tumour. The diagnosis of sarcomatoid hepatocellular carcinoma was confirmed on histology. Five months after hepatic resection, patient had symptoms suggestive of Horner's syndrome along with left sided shoulder pain, hand weakness, reduced power of the intrinsic hand muscles and reduced pain perception over the C8/T1 dermatome. Magnetic Resonance Imaging (MRI) showed a mass at the left lung apex/superior sulcus involving the left C8, T1 nerve roots, scalene muscles, and brachial plexus. The mass closely abutted the left first rib and partially encased the left subclavian artery. The patient was managed with palliative chemoradiotherapy for Pancoast syndrome. Hepatocellular carcinoma pulmonary metastasis causing Pancoast syndrome is a rare occurrence with only four prior reports, and to the best of our knowledge, pulmonary metastasis from sarcomatoid hepatocellular carcinoma causing Pancoast syndrome is unreported. In this report, we will discuss the clinicopathological characteristics of this case which may provide insight into diagnosis and management of other sarcomatoid hepatocellular carcinoma patients.


Quantifying Age Heaping and Age Misreporting in a Multicentric Survey.
Demographic indices known as the age-heaping indexes were used to explore the patterns of age misreporting in a multicentric survey. The data of 3252 individuals were analyzed, and measurement of errors in age for the sampled data has been evaluated by Whipple's Index (WI), Myer's Blended Index, and United Nations Age-Sex Accuracy Score which comprises Sex Ratio Score, Male Age Ratio Score (ARS), and Female ARS. Out of total 3252 participants, 828 (25.5%) were female. The mean statistical division age of our population was 34 (8.5) years and ranged from 15 to 65 years. The percentage of female ages ending with digits 0 or 5 is 23.55% and percentage of male ages ending with digits 0 or 5 is 23.28%. The calculated WI was 117.75 and 116.34 for males and females, respectively. The calculated Myer's Index for females and males is 10.53 and 25, respectively. The study provides evidence that probably age-heaping bias is less of problem in the conducted study.


Modelling blood flow in patients with heart valve disease using deep learning: A computationally efficient method to expand diagnostic capabilities in clinical routine.
The computational modelling of blood flow is known to provide vital hemodynamic parameters for diagnosis and treatment-support for patients with valvular heart disease. However, most diagnosis/treatment-support solutions based on flow modelling proposed utilize time- and resource-intensive computational fluid dynamics (CFD) and are therefore difficult to implement into clinical practice. In contrast, deep learning (DL) algorithms provide results quickly with little need for computational power. Thus, modelling blood flow with DL instead of CFD may substantially enhances the usability of flow modelling-based diagnosis/treatment support in clinical routine. In this study, we propose a DL-based approach to compute pressure and wall-shear-stress (WSS) in the aorta and aortic valve of patients with aortic stenosis (AS). A total of 103 individual surface models of the aorta and aortic valve were constructed from computed tomography data of AS patients. Based on these surface models, a total of 267 patient-specific, steady-state CFD simulations of aortic flow under various flow rates were performed. Using this simulation data, an artificial neural network (ANN) was trained to compute spatially resolved pressure and WSS using a centerline-based representation. An unseen test subset of 23 cases was used to compare both methods. ANN and CFD-based computations agreed well with a median relative difference between both methods of 6.0% for pressure and 4.9% for wall-shear-stress. Demonstrating the ability of DL to compute clinically relevant hemodynamic parameters for AS patients, this work presents a possible solution to facilitate the introduction of modelling-based treatment support into clinical practice.


Oral terbinafine (Lamisil) in the treatment of fungal infections of the skin and nails.
The efficacy and safety of antifungal drugs depend upon their mode of action, the minimal inhibitory concentration (MIC) and its relationship to the minimal fungicidal concentration (MFC), the spectrum of activity and drug kinetics at the involved site. Terbinafine acts at the fungal cell wall. Its MIC against dermatophytes is the lowest of all currently available systemic antifungal agents. It is the only one with an MIC:MFC ratio of 1:1 so that terbinafine should be effective over very short treatment durations in dermatophyte infections of the scalp, palms and soles, and nail, providing that drug penetration is adequate, as it appears to be. Therapeutic levels persist for a considerable period after the cessation of treatment, also favouring short-duration therapy. Terbinafine is effective against all varieties of dermatophyte. Terbinafine given over 4 weeks or less is effective against Trichophyton of the scalp in children and adults. Its efficacy in zoophilic ectrothrix infection is anecdotal, but it is likely on theoretical grounds. Terbinafine is also effective against pityriasis versicolor and vaginal candidosis, but only topically. As of March 1996, around 3,000,000 patients have been treated worldwide with terbinafine, mostly for 12 weeks for toe-nail onychomycosis. Gastro-intestinal disturbance and minor skin rashes are seen in 5 and 2% of patients, respectively.


Infant Formula Supplemented With Milk Fat Globule Membrane, Long-Chain Polyunsaturated Fatty Acids, and Synbiotics Is Associated With Neurocognitive Function and Brain Structure of Healthy Children Aged 6 Years: The COGNIS Study.
Adequate nutrient intake during the first few months of life plays a critical role on brain structure and function development. To analyze the long-term effects of an experimental infant formula (EF) on neurocognitive function and brain structure in healthy children aged 6 years compared to those fed with a standard infant formula or breastfed. The current study involved 108 healthy children aged 6 years and participating in the COGNIS Study. At 0-2 months, infants were randomized to receive up to 18 months of life a standard infant formula (SF) or EF enriched with milk fat globule membrane (MFGM), long-chain polyunsaturated fatty acids (LC-PUFAs) and synbiotics. Furthermore, a reference group of breastfed (BF) infants were also recruited. Children were assessed using neurocognitive tests and structural Magnetic Resonance Imaging (MRI) at 6 years old. Experimental infant formula (EF) children showed greater volumes in the left orbital cortex, higher vocabulary scores and IQ, and better performance in an attention task than BF children. EF children also presented greater volumes in parietal regions than SF kids. Additionally, greater cortical thickness in the insular, parietal, and temporal areas were found in children from the EF group than those fed with SF or BF groups. Further correlation analyses suggest that higher volumes and cortical thickness of different parietal and frontal regions are associated with better cognitive development in terms of language (verbal comprehension) and executive function (working memory). Finally, arachidonic acid (ARA), adrenic acid (AdA), docosahexaenoic acid (DHA) levels in cheek cell glycerophospholipids, ARA/DHA ratio, and protein, fatty acid, and mineral intake during the first 18 months of life seem to be associated with changes in the brain structures at 6 years old. Supplemented infant formula with MFGM components, LC-PUFAs, and synbiotics seems to be associated to long-term effects on neurocognitive development and brain structure in children at 6 years old. https://www.clinicaltrials.gov/, identifier: NCT02094547.


Follow up of test results after hours.
This article examines a recent Coronial inquest in which the Coroner made recommendations to general practitioners regarding the process of notification by pathology practices of abnormal and life threatening results and how GPs respond to such notifications. An addendum to the Standards for general practices provides guidance for GPs and their staff on the systems to manage the follow up of test results outside normal general practice opening hours.


Frontoparietal anodal tDCS reduces ketamine-induced oscillopathies.
During the prodromal phase of schizophrenia with its complex and insidious clinical picture, electroencephalographic recordings detect widespread oscillation disturbances (or oscillopathies) during the wake-sleep cycle. Neural oscillations are electrobiomarkers of the connectivity state within systems. A single-systemic administration of ketamine, a non-competitive NMDA glutamate receptor antagonist, transiently reproduces the oscillopathies with a clinical picture reminiscent of the psychosis prodrome. This acute pharmacological model may help the research and development of innovative treatments against psychotic transition. Transcranial electrical stimulation is recognized as an appropriate non-invasive therapeutic modality since it can increase cognitive performance and modulate neural oscillations with little or no side effects. Therefore, our objective was to set up, in the sedated adult rat, a stimulation method that is able to normalize ketamine-induced increase in gamma-frequency (30-80 Hz) oscillations and decrease in sigma-frequency (10-17 Hz) oscillations. Unilateral and bipolar frontoparietal (FP), transcranial anodal stimulation by direct current (<+1 mA) was applied in ketamine-treated rats. A concomitant bilateral electroencephalographic recording of the parietal cortex measured the stimulation effects on its spontaneously occurring oscillations. A 5 min FP anodal tDCS immediately and quickly reduced, significantly with an intensity-effect relationship, the ketamine-induced gamma hyperactivity, and sigma hypoactivity at least in the bilateral parietal cortex. A duration effect was also recorded. The tDCS also tended to diminish the ketamine-induced delta hypoactivity. These preliminary neurophysiological findings are promising for developing a therapeutic proof-of-concept against neuropsychiatric disorders.


IgG4-related hepatic inflammatory pseudotumour: could MRI suggest the correct diagnosis?
We report a case of a 62-year-old woman, HIV positive, with a 3-week history of jaundice and elevated cholestatic enzymes. Imaging studies displayed intrahepatic biliary dilatation and a central liver lesion. Pathology described lesions of active cholangitis, lymphoplasmacytic infiltration and fibrosis, suggesting a hepatic inflammatory pseudotumour (IPT) IgG4 related. IgG4-related lymphoplasmacytic form of IPT belongs to IgG4-related diseases. We discuss the importance to include IgG4-related hepatic IPT as part of the differential diagnosis of any liver lesion, highlighting potential imaging clues that may help in establishing the correct diagnosis.


Intentionally induced intestinal barrier dysfunction causes inflammation, affects metabolism, and reduces productivity in lactating Holstein cows.
Study objectives were to evaluate the effects of intentionally reduced intestinal barrier function on productivity, metabolism, and inflammatory indices in otherwise healthy dairy cows. Fourteen lactating Holstein cows (parity 2.6 ± 0.3; 117 ± 18 d in milk) were enrolled in 2 experimental periods. Period 1 (5 d) served as the baseline for period 2 (7 d), during which cows received 1 of 2 i.v. treatments twice per day: sterile saline or a gamma-secretase inhibitor (GSI; 1.5 mg/kg of body weight). Gamma-secretase inhibitors reduce intestinal barrier function by inhibiting crypt cell differentiation into absorptive enterocytes. During period 2, control cows receiving sterile saline were pair-fed (PF) to the GSI-treated cows, and all cows were killed at the end of period 2. Administering GSI increased goblet cell area 218, 70, and 28% in jejunum, ileum, and colon, respectively. In the jejunum, GSI-treated cows had increased crypt depth and reduced villus height, villus height-to-crypt depth ratio, cell proliferation, and mucosal surface area. Plasma lipopolysaccharide binding protein increased with time, and tended to be increased 42% in GSI-treated cows relative to PF controls on d 5 to 7. Circulating haptoglobin and serum amyloid A concentrations increased (585- and 4.4-fold, respectively) similarly in both treatments. Administering GSI progressively reduced dry matter intake (66%) and, by design, the pattern and magnitude of decreased nutrient intake was similar in PF controls. A similar progressive decrease (42%) in milk yield occurred in both treatments, but we observed no treatment effects on milk components. Cows treated with GSI tended to have increased plasma insulin (68%) and decreased circulating nonesterified fatty acids (29%) compared with PF cows. For both treatments, plasma glucose decreased with time while β-hydroxybutyrate progressively increased. Liver triglycerides increased 221% from period 1 to sacrifice in both treatments. No differences were detected in liver weight, liver moisture, or body weight change. Intentionally compromising intestinal barrier function caused inflammation, altered metabolism, and markedly reduced feed intake and milk yield. Further, we demonstrated that progressive feed reduction appeared to cause leaky gut and inflammation.


[Novel reagent for labeling of biomolecules--activated derivative of pyrene dichromophore with excimeric fluorescence].
N-[2-(1-pyrenyl)ethyl]-1-pyrenylacetamide, bis[2-(1-pyrenyl)ethyl]amine, and N,N-bis[2-(1-pyrenyl)ethyl]succinamide were synthesized from 1-pyrenylacetic acid. These compounds contain adjacent pyrene residues and display excimer fluorescence. The latter compound, as a pentafluorophenyl ester, was used to prepare fluorescently labeled oligodeoxyribonucleotide (5)CAGGAAACAGCTATGAC. For N,N-bis[2-(1-pyrenyl)ethyl]succinamide, the excimer-to-monomer fluorescence ratio and intensity of fluorescence in water-methanol solutions changed in the presence of single-stranded and double-stranded oligonucleotides, upon attachment to an oligonucleotide, and upon hybridization of the resulting conjugate with the complementary nucleotide sequence.


A comparative analysis of Center for Independent Living staff and board of directors regarding CIL services and consumer participation.
Community living of people with disabilities spans independent living and community engagement. Consumer choice and control of their level of community participation requires community accessibility, resources and supports. Some people with disabilities have difficulties procuring and maintaining these resources. Centers for Independent Living (CIL) are advocacy and service agencies that have been empowering consumers to meet their needs for over 40 years. Despite this history, little is known about the value of CIL services for increasing community participation of people with disabilities. We administered the CIL Participation Service Survey to 420 CIL staff members and 107 CIL board members to examine their opinions about the relative value of different CIL services for increasing community participation of their consumers. Results indicated that both staff and board members have very high regard for the value and quality of CIL services. The Independent Living (IL) philosophy of consumer choice and control was among the most highly rated aspects of CIL service delivery for both staff and board members. Overall, staff and board member responses were very consistent in terms of the top-rated strengths and weaknesses of CIL services for increasing participation among consumers. Differences appeared to reflect the daily staff focus on specific consumer need versus board members' view of larger community issues.


Awareness in Apraxia and Agnosia.
Disconnected awareness in a diagonistic dyspraxic patient and degraded awareness in a visually agnosic patient were investigated. The first case was a male patient with disconnection syndrome including diagonistic dyspraxia. Speech regulation of interruptive actions in his left hand was introduced for the purpose of reorganization of bimanual activity. As a result of the therapy, he became able to restrain his left hand activities, and be independent in activities of daily living. The second case was a male patient with visual agnosia whose dominant complaint was face recognition impairment. Measurable recovery of visual perception was achieved through activities planned to reorganize his visual perception with intact kinesthetic information.


A computationally simpler algorithm for the UMVUE of a normal mean following a group sequential trial.
When using data collected in a group sequential clinical trial, the sample mean is no longer the uniform minimum variance unbiased estimator (UMVUE) of the mean of a normal distribution. Emerson (1993, Computers and Biomedical Research, 26, 68-73) described an algorithm for computing the UMVUE in this setting. This algorithm, although computationally expensive, used only the basic software necessary for deriving group sequential boundaries. In this paper, we present an improved algorithm that results in greatly decreased computation times.


Influence of hospital admission in the pharmacotherapy complexity of HIV+ patients.
To determine the variation in the pharmacotherapy complexity index in HIV+ patients after hospital admission. A retrospective, single-center study with HIV+ patients on antiretroviral treatment (ART) who were admitted to hospital between 2008 and 2015 were conducted. Demographic, analytical, clinical and pharmacotherapy variables were collected, as well as those about the use of healthcare resources. The primary endpoint was the variation in the overall complexity index after a hospital admission, measured through the MRCI tool (University of Colorado). There was also an analysis of the variation in adherence to ART, and of the causes that led to an increase in pharmacotherapy complexity after hospitalization. The study included 146 patients (84.9% male) with 45.3 ± 9.1 years as mean age; 30.8% of these patients had experienced an admission to hospital in the previous year, with a median stay of seven days (IQR: 4-12,5). The mean overall complexity before hospital admission was 14.5 ± 7.2 vs. 16.5 ± 8.0 after admission, with a significant difference (1.97 [CI = 0.85;3.09]). The percentage of patients adherent to ART before admission was 58.3% vs. 41.8% after admission (p = 0.023). The only factor associated to an increase in complexity was having five or more chronic drugs prescribed before admission (OR = 3.146 [1.045-9.471]). The overall pharmacotherapy complexity increased after hospital admission, reducing the adherence to ART. Chronic treatment prescribed before admission was the only factor associated with an increase in complexity after admission.


Evidence for existence of somatostatin-like immunoreactivity with molecular heterogeneity in porcine ovaries.
Measurement of somatostatin (SRIF) by RIA in porcine ovarian tissues after removal of the follicular fluid revealed the existence of immunoreactive (IR) SRIF at concentrations of 2.2 +/- 0.6 ng/g wet weight (mean +/- SD). On gel chromatographic analysis of ovarian extracts one major and two minor components with SRIF-like immunoreactivities have been detected. The major component comprised 59.5 +/- 15.1% of the total IR-SRIF and was coeluted with synthetic tetradecapeptide (SRIF 14). The two other components seemed to have almost the same molecular weights as synthetic octacosapeptide (SRIF 28) (25.1 +/- 10%) and pro-somatostatin (15.4 +/- 5.5%), respectively. It is concluded that SRIF in porcine ovaries is heterogeneous, comprising SRIF 14 as a major component, as well as larger forms of SRIF which probably represent SRIF precursors.


Can autistic children read the mind of an animated triangle?
Are children with an autism spectrum disorder (ASD), but normal-range intelligence, impaired on theory of mind skills measured by responses to abstract animations in the form of a computerized cartoon? Fifty-six cases and closely matched comparisons were tested. We rated verbal responses according to the length of their descriptions, their appropriateness and the children's use of 'mentalizing' terms. Children with ASD used 'mentalizing' language to describe the animations as well as comparisons, although the content of their descriptions was significantly less appropriate. Performance on this task was not well correlated with standardized measures of parent-reported behaviour or the child's interactions with an observer. The implications of our results are discussed in relation to previous studies that have used this methodology.


The use of recombinant human thyrotropin (Thyrogen) in the diagnosis and treatment of thyroid cancer.
The introduction of human recombinant thyrotropin (rhTSH/Thyrogen) into the diagnosis of thyroid cancer has substantially ameliorated the patient's quality of life through the avoidance of debilitating hypothyroidism. With the aim of updating the use of Thyrogen, we report 7 cases which were treated with Thyrogen for diagnostic or therapeutic purposes. All 7 patients were thyroidectomised and radioiodine ablated and all had detectable [> 1 ng/ml] basal serum thyroglobulin (b-Tg) levels. Thyrogen stimulation resulted in a rise of Tg (s-Tg) in all patients. Five patients had negative whole body scanning (WBS) and no clinical or radiological signs of disease. Two patients with a b-Tg value of 5 ng/ml and 11 ng/ml, respectively showed a s-Tg of 17 ng/ml and 84 ng/ml, respectively, whereas WBS was negative. Both of these patients received 100 mCi (3700 MBq) 131I. Owo patients had a positive Tg and positive WBS with skull, lung and hepatic metastases and received 150 131I after preparation with Thyrogen. Six months later one of these patients was free of disease and the other will be evaluated during the coming months. In conclusion, Thyrogen emerges as a reliable and safe agent for the diagnosis of thyroid cancer. Furthermore, it appears that Thyrogen could be used in the treatment of metastases as an alternative to thyroid hormone withdrawal.


Not your mother's view: the dynamics of toddler visual experience.
Human toddlers learn about objects through second-by-second, minute-by-minute sensory-motor interactions. In an effort to understand how toddlers' bodily actions structure the visual learning environment, mini-video cameras were placed low on the foreheads of toddlers, and for comparison also on the foreheads of their parents, as they jointly played with toys. Analyses of the head camera views indicate visual experiences with profoundly different dynamic structures. The toddler view often consists of a single dominating object that is close to the sensors and thus that blocks the view of other objects such that individual objects go in and out of view. The adult view, in contrast, is broad and stable, with all potential targets continually in view. These differences may arise for several developmentally relevant reasons, including the small visuo-motor workspace of the toddler (short arms) and the engagement of the whole body when actively handling objects.


Responses of plants and invertebrate trophic groups to contrasting herbicide regimes in the Farm Scale Evaluations of genetically modified herbicide-tolerant crops.
Effects of genetically modified herbicide-tolerant (GMHT) and conventional crop management on invertebrate trophic groups (herbivores, detritivores, pollinators, predators and parasitoids) were compared in beet, maize and spring oilseed rape sites throughout the UK. These trophic groups were influenced by season, crop species and GMHT management. Many groups increased twofold to fivefold in abundance between early and late summer, and differed up to 10-fold between crop species. GMHT management superimposed relatively small (less than twofold), but consistent, shifts in plant and insect abundance, the extent and direction of these effects being dependent on the relative efficacies of comparable conventional herbicide regimes. In general, the biomass of weeds was reduced under GMHT management in beet and spring oilseed rape and increased in maize compared with conventional treatments. This change in resource availability had knock-on effects on higher trophic levels except in spring oilseed rape where herbivore resource was greatest. Herbivores, pollinators and natural enemies changed in abundance in the same directions as their resources, and detritivores increased in abundance under GMHT management across all crops. The result of the later herbicide application in GMHT treatments was a shift in resource from the herbivore food web to the detritivore food web. The Farm Scale Evaluations have demonstrated over 3 years and throughout the UK that herbivores, detritivores and many of their predators and parasitoids in arable systems are sensitive to the changes in weed communities that result from the introduction of new herbicide regimes.


Role of Ultrasonography in the Evaluation of Normal Developmental Pattern of Fetal Cerebral Sulci Between 18 and 32 Weeks of Gestational Age.
Background Brain development is a crucial process of intrauterine life and can be readily visualized on ultrasonography. This study aims to visualize developmental patterns of various fetal cerebral sulci using ultrasonography between 18 and 32 weeks of gestation. Sulci are best visualized on images that are taken perpendicular to their expected course of development. Initially, they appear as small dot/dimple on the brain surface and later develop into a V-shaped indentation and finally deepen to form notch and echogenic line into the brain forming a Y-shaped configuration. Material and methods This was a cross-sectional observational study conducted on 241 antenatal mothers with a singleton pregnancy between 18 and 32 weeks of gestational age. Demographic and clinical data were obtained. Ultrasonography was performed using PHILIPS EPIQ 5, a curvilinear probe of frequency 2-5MHz. Sulci/fissures that are reported to appear early on anatomical studies were evaluated, specifically the parieto-occipital fissure, calcarine fissure, cingulate sulci, insula/Sylvian fissure, and convexity sulci. Comparison of the categorical outcomes was performed between study groups using the chi-square test. A p-value of <0.05 was considered statistically significant. Results The study included 241 participants. The mean age of antenatal mothers was 24.09 ± 4.13 years, and the mean fetal gestational age was 24.99 ± 4.13 weeks. Parieto-occipital fissure was the first fissure to develop and was present as a V-shaped indentation at 18 weeks and as a Y-shaped configuration by 21-22 weeks. Calcarine fissure was the next fissure to appear; it appeared as a dot by 18 weeks and developed into a V-shaped indentation by 20 weeks and as a Y-shaped configuration by 23 weeks. All fissures except cingulate sulci had appeared by 20 weeks, and calcarine sulci appeared later in the gestation by 21 weeks. Sylvian fissure initially appeared as a smooth surface and later underwent operculization to form obtuse and acute angulations with the adjacent temporal lobe by 20 and 24 weeks, respectively. Convexity sulci appeared later in gestation, beyond 25-26 weeks. Conclusions Ultrasonography, which is the commonest modality used in antenatal assessment of the fetus, can also be used to identify, familiarize, and provide a standard reference to assess normality of fetal sulcations. Neuronal migration disorders result in a wide spectrum of malformations of cortical development whose clinical manifestations include severe psychomotor retardation, developmental delays, motor deficits, seizures, and failure to thrive. Knowledge of normal development patterns of fetal cerebral sulci helps in early suspicion and detection of these cortical malformations, when present.


Prevalence of bronchial asthma and association with environmental tobacco smoke exposure in adolescent school children in Chandigarh, north India.
Prevalence of asthma and its association with environmental tobacco smoke (ETS) exposure were examined among adolescent schoolchildren in Chandigarh, India. Using a previously standardized questionnaire, data from 9090 students in the 9- to 20-year age range were analyzed. There were 4367 (48%) boys, in whom the observed prevalence of asthma was 2.6%. Among 4723 (52%) girls, asthma was present in 90 (1.9%) students. Presence of one or more respiratory symptoms was reported by 31% students. More students with asthma had either parents or other family members smoking at home as compared to nonasthmatics (41% vs. 28%, p<0.0001). The odds ratio for being asthmatic for patients exposed to ETS compared to those not exposed to ETS was 1.78 (95% confidence interval 1.33-2.31). ETS was also positively associated with prevalence of all the respiratory symptoms, with odds ratios varying between 1.6 and 2.25.


Chronic functional dyspepsia: short- and medium-term outcome of a therapeutic trial with cisapride.
In an open, multicenter trial, 329 patients (who attended gastroenterology practices or outpatient gastroenterology departments of hospitals) with a mean age of 47.3 years, received 5 mg of cisapride three times a day (TID) for at least 2 weeks for the treatment of persistent, recurring symptoms of functional dyspepsia. The patients' symptoms required investigation or were unresponsive to previous drug treatment. When necessary, the dose of cisapride was increased to 10 mg TID, in most patients after 1 week of treatment, and the duration of therapy was extended to 4 weeks. At the end of cisapride treatment, the most frequently reported symptoms of functional dyspepsia were significantly improved. At the onset of the trial, 72.3% of patients complained of a moderate-to-severe feeling of fullness; this decreased to 19.7% after 2 weeks of treatment and to 15.3% after 4 weeks. The symptoms of bloating, a feeling of heaviness in the stomach, and postprandial epigastric discomfort showed similar improvement. Overall, 43.6% of patients were symptom-free or almost symptom-free after 1 week of cisapride treatment, 69.6% after 2 weeks, and 71.5% after 4 weeks. Only 11% of patients needed the increased dose of cisapride. Six weeks after completion of the trial, 74 patients (22.5%) had recurrent symptoms of functional dyspepsia. Adverse experiences were noted in 74 patients (22.5%), most commonly loose stools (7.6% of all patients), fatigue (4.9%), and headaches (4.0%). In most cases, these adverse experiences were mild and transient in nature and led to premature discontinuation of treatment in 11 patients (3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)


Late Miocene decoupling of oceanic warmth and atmospheric carbon dioxide forcing.
Deep-time palaeoclimate studies are vitally important for developing a complete understanding of climate responses to changes in the atmospheric carbon dioxide concentration (that is, the atmospheric partial pressure of CO(2), p(co(2))). Although past studies have explored these responses during portions of the Cenozoic era (the most recent 65.5 million years (Myr) of Earth history), comparatively little is known about the climate of the late Miocene (∼12-5 Myr ago), an interval with p(co(2)) values of only 200-350 parts per million by volume but nearly ice-free conditions in the Northern Hemisphere and warmer-than-modern temperatures on the continents. Here we present quantitative geochemical sea surface temperature estimates from the Miocene mid-latitude North Pacific Ocean, and show that oceanic warmth persisted throughout the interval of low p(co(2)) ∼12-5 Myr ago. We also present new stable isotope measurements from the western equatorial Pacific that, in conjunction with previously published data, reveal a long-term trend of thermocline shoaling in the equatorial Pacific since ∼13 Myr ago. We propose that a relatively deep global thermocline, reductions in low-latitude gradients in sea surface temperature, and cloud and water vapour feedbacks may help to explain the warmth of the late Miocene. Additional shoaling of the thermocline after 5 Myr ago probably explains the stronger coupling between p(co(2)), sea surface temperatures and climate that is characteristic of the more recent Pliocene and Pleistocene epochs.


Nephrostomy Tube Misplaced into the Right Atrium: An Extremely Rare Case and Review of the Literature.
Although percutaneous nephrolithotomy is generally safe, it has various complications. We present an extremely rare case in which the nephrostomy tube pierced renal parenchyma, proceeded through the right renal vein and inferior vena cava, finally reaching the right atrium. Such a tube misplaced to atrium level was firstly reported, which was safely withdrawn using a 2-step process under fluoroscopic monitoring. We also recommend the tube be marked with different color lines to maintain awareness of the tube length that has passed the peel-away sheath. Such information might help to avoid such complication.


The role of technology in critical care nursing.
This paper is a report of a study to identify the meaning for critical care nurses of technology related to weaning from mechanical ventilation and to explore how that technology was used in practice. The literature concerned with the development of critical care (intensive care and high dependency units) focuses mainly on innovative medical technology. Although this use of technology in critical care is portrayed as new, it actually represents a transfer of technology from operating theatres. An ethnographic study was conducted and data were collected on one critical care unit in a large teaching hospital over a 6-month period in 2004. The methods included participant observation, interviews and the collection of field notes. The overall theme 'The nursing-technology relation' was identified. This comprised three sub-themes: definition of technology, technology transferred and technology transformed. Novice nurses took a task-focussed approach to weaning, treating it as a 'medical' technology transferred to them from doctors. Expert nurses used technology differently and saw its potential to become a 'nursing technology'. Nurses need to examine how they can adapt and to 'reconfigure' technology so that it can be transformed into a nursing technology. Those technologies that do not fit with nursing may have no place there. Rather than simply extending and expanding their roles through technology transfer, nurses should transform those technologies that preserve the essence of nursing and can contribute to a positive outcome for patients.


Towards the recovery of a sense of self: An interpretative phenomenological analysis of patients' experience of body-oriented psychotherapy for schizophrenia.
Increasing evidence supports the efficacy of body-oriented psychotherapy (BPT) for schizophrenia. Yet, so far no research has investigated outcome in relation to therapy process: Why and how BPT is effective. In this study, we qualitatively explore participants' experience of a manualized BPT for schizophrenia to shed light on the process of therapeutic change. We conducted in-depth interviews with 6 participants who completed a 10-week BPT group intervention. Interviews explored participants' experience of change and helpful aspects of therapy and were analysed using interpretative phenomenological analysis. We identified six master themes across the interviews: (i) Being a whole: body-mind connection; (ii) Being agentic and being able; (iii) Being unique and worthy: Being accepted for who one is; (iv) Changing interactions: Engaging in authentic interpersonal contact; (v) Being part of a group: Feeling integrated; and (vi) Hope and investing in the future. We discuss the clinical implications for each theme and bring the findings together by describing therapeutic change in schizophrenia as a recovery of sense of self at different but interlocked levels. Moreover, we put forward recommendations for both specific and common factors for schizophrenia therapy. Clinical or methodological significance of this article: The clinical significance of this study is twofold. On the one hand, the findings of this analysis might inform the theory and practice of BPT and might directly feedback into a further development of the manual guidelines. On the other hand, common helpful factors have been identified thatmight also be relevant for the more general clinical practice concerning patients with schizophrenia. Here, we summarize our key messages for the clinical practitioner emerging from the findings: The inclusion of bodily aspects and a focus on pre-reflective experience in psychotherapy can help persons with schizophrenia recover the sense of being a body-mind unity. Empowering persons with schizophrenia, instead of instructing them, seems to foster a sense of agency and self-confidence, which are crucial to the recovery process. A twofold therapeutic stance characterized by openness towards the other and authenticity was experienced by patients as facilitating the rapport building. This might help persons with schizophrenia engage in the relation. Social inclusion might enhance therapeutic change and recovery in schizophrenia. Group therapy might be helpful for fostering a feeling of social belonging, but the inclusion in the wider social and community context remains a critical issue. The experience of joyful moments in psychotherapy might positively contribute to therapeutic change in that it fosters a sense of hope for the future. Overall our paper contributes to the literature aiming at expanding the range of therapeutic modalities, focussing on the creation and use of mixed models of therapy within and beyond talking practices.


Pregnancy outcome among women universally screened for gestational diabetes mellitus with a lime-flavoured drink.
We performed a prospective study involving 400 consecutive pregnant patients to determine whether the administration of a lime-flavoured glucose drink followed by a blood test 1 h later was a better method of screening for gestational diabetes (GDM) than the use of selective screening based on risk factors (maternal age over 30 years, East Indian ancestry and obesity). Complete data were available for 388 women, 76 were screen positive (1 h blood glucose ≥ 140 mg/dl) and GDM was diagnosed in 42 (using a 75 g oral glucose tolerance test) giving a positive predictive value of 55%. Selective screening applied to the same population would have identified only 34 cases, eight fewer with GDM. In this population, the use of the lime-flavoured glucose drink detected approximately 25% more cases of GDM than selective screening based on risk factors. Caesarean sections were performed in 18 (42.8%) of women with gestational diabetes. None of the four perinatal deaths was observed among the women with gestational diabetes.


Improved Thermal Stability and Film Uniformity of Halide Perovskite by Confinement Effect brought by Polymer Chains of Polyvinyl Pyrrolidone.
Polyvinyl pyrrolidone (PVP) is doped to PbI2 and organic salt during two-step growth of halideperovskite. It is observed that PVP molecules can interact with both PbI2 and organic salt, reduce the aggregation and crystallization of the two, and then slow down the coarsening rate of perovskite. As doping concentration increases from 0 to 1 mM in organic salt, average crystallite size of perovskite decreases monotonously from 90 to 34 nm; Surface fluctuation reduces from 259.9 to 179.8 nm at first, and then increases; Similarly, surface roughness decreases from 45.55 to 26.64 nm at first, and then rises. Accordingly, a kind of "confinement effect" is resolved to crystallite growth and surface fluctuation/roughness, which helps to build compact and uniform perovskite film. Density of trap states (t-DOS) is cut down by ≈60% at moderate doping (0.2 mM). Due to the "confinement effect", power conversion efficiency of perovskite solar cells is improved from 19.46 (±2.80) % to 21.50 (±0.99) %, and further improved to 24.11% after surface modification. Meanwhile, "confinement effect" strengthens crystallite/grain boundaries and improves thermal stability of both film and device. T80 of device increases to 120 h, compared to 50 h for reference ones.


Modeling subdiffusive light scattering by incorporating the tissue phase function and detector numerical aperture.
To detect small-scale changes in tissue with optical techniques, small sampling volumes and, therefore, short source–detector separations are required. In this case, reflectance measurements are not adequately described by the diffusion approximation. Previous studies related subdiffusive reflectance to ? or ? , which parameterize the phase function. Recently, it was demonstrated that ? predicts subdiffusive reflectance better than ? , and that ? becomes less predictive for lower numerical apertures (NAs). We derive and evaluate the parameter R p NA , which incorporates the NA of the detector and the integral of the phase function over the NA in the backward and forward directions. Monte Carlo simulations are performed for overlapping source/detector geometries for a range of phase functions, reduced scattering coefficients, NAs, and source/detector diameters. R p NA improves prediction of the measured reflectance compared to ? and ? . It is, therefore, expected that R p NA will improve derivation of optical properties from subdiffusive measurements.


Co-administration of Radix curcumae alters the tissue distribution of danshensu in Radix salviae miltiorrhiae in rabbits.
The tissue distribution profile of danshensu, one of the bioactive components in Radix salviae miltiorrhiae, was investigated after oral administration of Radix salviae miltiorrhiae coupled with Radix curcumae in rabbits. Eighteen rabbits were evenly divided into 3 groups. Rabbits of the groups were orally administrated with carboxymethyl cellulose, Radix salviae miltiorrhiae (10.0 g/kg) and Radix salviae miltiorrhiae (10.0 g/kg) coupled with Radix curcumae (5.0 g/kg), respectively. High performance liquid chromatography-electrospray ionic trap mass spectrometry (HPLC-ESI-MS(n)) was used for the determination of danshensu in the tissues including heart, liver, kidney and brain. The statistical results demonstrated that the characteristic profiles of danshensu were c(kidney) > c(heart) > c(liver) > c(brain) and c(kidney) > c(brain) > c(liver) > c(heart) after administration of Radix salviae miltiorrhiae and Radix salviae miltiorrhiae coupled with Radix curcumae, respectively, indicating that Radix curcumae could obviously increase the concentration of danshensu in brain. This result would provide substantial foundation for the harmonizing effect of shi herb in a Chinese compound prescription.


Gemcitabine and oxaliplatinum: an effective regimen in patients with refractory and relapsing Hodgkin lymphoma.
Most Hodgkin lymphomas (HL) can be cured with current strategies. However, one-third of the cases do not respond or relapse and need salvage regimens. We report the results of a retrospective study using the gemcitabine and oxaliplatinum (GemOx) regimen. Patients who relapsed or failed to achieve complete response were eligible and received GemOx salvage therapy. To avoid selection bias and thus to overcome the retrospective nature of the study, all treated patients were included from the pharmacy database. Between 2003-2013, 24 HL patients - relapsing (number [n]=12) or refractory (n=12) - were included, receiving a total of 26 induction treatments with GemOx. Mean previous regimens were 2.38 (42% relapsing after autologous transplantation). Median follow-up was 37 months, and 71% responded (38% of patients achieved complete response). The factors related to better progression-free survival were: B symptoms; response to GemOx; and consolidation with stem cell transplantation. Grades 1 and 2 neurological toxicity was present in 17% of patients. Hematological toxicity was common, with grades 3 and 4 neutropenia (25%) and thrombocytopenia (34%) observed. Progression-free survival was better in patients consolidated with stem cell transplantation. The peripheral blood stem cell collection after GemOx was successful for all candidates. 1) The GemOx regimen is effective in relapsed or refractory HL with manageable toxicity. 2) No mobilization failures were observed. 3) Consolidation after response is needed. 4) Its efficacy and favorable toxicity profile might make multiple administrations possible in several recurrences in HL.


Fundus autofluorescence in patients with pseudoxanthoma elasticum.
To characterize changes in fundus autofluorescence in patients with pseudoxanthoma elasticum (PXE). Fundus autofluorescence intrinsically derives from lipofuscin, and the degree of autofluorescence is thought to indicate the degree of retinal pigment epithelium (RPE) metabolic activity. Twelve eyes of 6 patients (2 men, 4 women) with PXE were studied with a confocal scanning laser ophthalmoscope. Patient age ranged from 42 to 62 years. The autofluorescence of abnormal retinal areas was compared digitally with that of neighboring, presumed healthy control areas. When the average gray level of a fundus region was 2 SDs above or below the average gray level of a control area, autofluorescence of the fundus region was considered abnormal. In all 12 eyes, some segments of the angioid streaks showed decreased fundus autofluorescence, and other segments of the streaks showed normal autofluorescence. Areas of peripapillary chorioretinal atrophy seen in 2 eyes and of disciform scarring seen in 3 eyes showed decreased autofluorescence. Solitary or multiple drusen-like spots showed increased autofluorescence in all 12 eyes. Atrophic and degenerative RPE regions showed decreased fundus autofluorescence in areas of chorioretinal atrophy and in some segments of the angioid streaks. Some drusen-like spots showed increased autofluorescence. The characteristic changes in autofluorescence that we observed in PXE patients suggest that the content of the drusen-like substance differs from that of senile drusen and that the drusen-like lesions are similar to the sub-RPE deposits seen in macular dystrophy.


Suturing of the nasal septum after septoplasty, is it an effective alternative to nasal packing?
To discuss and compare the results of suturing the nasal septum after septoplasty with the results of nasal packing. A prospective study, which was performed at Prince Hashem Military Hospital in Zarqa, Jordan and Prince Rashed Military Hospital in Irbid, Jordan between September 2005 and August 2006 included 169 consecutive patients that underwent septoplasty. The patients were randomly divided into 2 groups. After completion of surgery, the nasal septum was sutured in the first group while nasal packing was performed in the second group. Thirteen patients (15.3%) in the first group and 11 patients (13%) in the second group had minor oozing in the first 24 hours, 4 patients (4.8%) had bleeding after removal of the pack in the second group. Four patients (4.8%) developed septal hematoma in the second group. Two patients (2.4%) had septal perforation in the second group. One patient (1.1%) in the first group, and 5 patients (5.9%) in the second group had postoperative adhesions. Five patients (5.9%) were found to have remnant deviated nasal septum in each group. The operating time was 4 minutes longer in the first group. Septal suturing after septoplasty offers the following advantages: elimination of discomfort for the patients, minimal complications, the outcome is almost the same as with nasal packing, and finally the hospital stay is less than with nasal packing. Therefore, suturing of the nasal septum after septoplasty should be a preferred alternative to nasal packing.


Evaluation of machine learning models on protein level inference from prioritized RNA features.
The parallel measurement of transcriptome and proteome revealed unmatched profiles. Since proteomic analysis is more expensive and challenging than transcriptomic analysis, the question of how to use messenger RNA (mRNA) expression data to predict protein level is extremely important. Here, we comprehensively evaluated 13 machine learning models on inferring protein expression levels using RNA expression profile. A total of 20 proteogenomic datasets from three mainstream proteomic platforms with >2500 samples of 13 human tissues were collected for model evaluation. Our results highlighted that the appropriate feature selection methods combined with classical machine learning models could achieve excellent predictive performance. The voting ensemble model outperformed other candidate models across datasets. Adding the mRNA proxy model to the regression model further improved the prediction performance. The dataset and gene characteristics could affect the prediction performance. Finally, we applied the model to the brain transcriptome of cerebral cortex regions to infer the protein profile for better understanding the functional characteristics of the brain regions. This benchmarking work not only provides useful hints on the inherent correlation between transcriptome and proteome, but also has practical value of the transcriptome-based prediction of protein expression levels.


Preliminary Tc Calculations for Iron-Based Superconductivity in NaFeAs, LiFeAs, FeSe and Nanostructured FeSe/SrTiO3 Superconductors.
Many theoretical models of iron-based superconductors (IBSC) have been proposed, but the superconducting transition temperature (Tc) calculations based on these models are usually missing. We have chosen two models of iron-based superconductors from the literature and computed the Tc values accordingly; recently two models have been announced which suggest that the superconducting electron concentration involved in the pairing mechanism of iron-based superconductors may have been underestimated and that the antiferromagnetism and the induced xy potential may even have a dramatic amplification effect on electron-phonon coupling. We use bulk FeSe, LiFeAs and NaFeAs data to calculate the Tc based on these models and test if the combined model can predict the superconducting transition temperature (Tc) of the nanostructured FeSe monolayer well. To substantiate the recently announced xy potential in the literature, we create a two-channel model to separately superimpose the dynamics of the electron in the upper and lower tetrahedral plane. The results of our two-channel model support the literature data. While scientists are still searching for a universal DFT functional that can describe the pairing mechanism of all iron-based superconductors, we base our model on the ARPES data to propose an empirical combination of a DFT functional for revising the electron-phonon scattering matrix in the superconducting state, which ensures that all electrons involved in iron-based superconductivity are included in the computation. Our computational model takes into account this amplifying effect of antiferromagnetism and the correction of the electron-phonon scattering matrix, together with the abnormal soft out-of-plane lattice vibration of the layered structure. This allows us to calculate theoretical Tc values of LiFeAs, NaFeAs and FeSe as a function of pressure that correspond reasonably well to the experimental values. More importantly, by taking into account the interfacial effect between an FeSe monolayer and its SrTiO3 substrate as an additional gain factor, our calculated Tc value is up to 91 K and provides evidence that the strong Tc enhancement recently observed in such monolayers with Tc reaching 100 K may be contributed from the electrons within the ARPES range.


Diabetes in the elderly. A unique set of management challenges.
The overall goals in regard to management of diabetes in the elderly are twofold. First, blood glucose control should be kept as near normal as possible (certainly always less than 200 mg/dl) without inordinately increasing risks related to therapy; this will decrease the risk of acute complications and hopefully of long-term ones as well. Second, overall functional status should be maintained or improved. Although a number of factors peculiar to old age complicate the management of diabetes, with careful planning these goals should be attainable.


Dynamic and balanced regulation of the thrABC operon gene for efficient synthesis of L-threonine.
L-threonine is an essential amino acid used widely in food, cosmetics, animal feed and medicine. The thrABC operon plays an important role in regulating the biosynthesis of L-theronine. In this work, we systematically analyzed the effects of separating thrAB and thrC in different proportions on strain growth and L-threonine production in Escherichia coli firstly. The results showed that higher expression of thrC than thrAB enhanced cell growth and L-threonine production; however, L-threonine production decreased when the thrC proportion was too high. The highest L-threonine production was achieved when the expression intensity ratio of thrAB to thrC was 3:5. Secondly, a stationary phase promoter was also used to dynamically regulate the expression of engineered thrABC. This strategy improved cell growth and shortened the fermentation period from 36 h to 24 h. Finally, the acetate metabolic overflow was reduced by deleting the ptsG gene, leading to a further increase in L-threonine production. With these efforts, the final strain P 2.1 -2901ΔptsG reached 40.06 g/L at 60 h fermentation, which was 96.85% higher than the initial control strain TH and the highest reported titer in shake flasks. The maximum L-threonine yield and productivity was obtained in reported fed-batch fermentation, and L-threonine production is close to the highest titer (127.30 g/L). In this work, the expression ratio of genes in the thrABC operon in E. coli was studied systematically, which provided a new approach to improve L-threonine production and its downstream products.


The impact of fever as a testing indication on the detection rate of deep vein thrombosis in neurocritically ill patients.
Deep vein thrombosis (DVT) is considered a possible source of non-infectious, non-central fever in the intensive care unit (ICU). In the neurocritically ill, it is unknown whether lower extremity venous Doppler ultrasonography (LEVDUS) for DVT in the setting of fever leads to a higher detection rate than the baseline detection rate of DVT in this population. The aim of this study was to compare the DVT detection rate of LEVDUS performed for the indication of fever to LEVDUS performed for other indications in a neurosciences ICU. Requisition forms for all LEVDUS performed in a referral neurosciences ICU were reviewed and separated into those with "fever" as the stated reason for request and those with other stated reasons. The DVT detection rate was compared between these two categories of indications. Five hundred eleven LEVDUS were analyzed, of which 422 had been ordered for indications other than fever. Sixteen of these tests were positive, a detection rate of 3.8%. The remaining 89 LEVDUS had "fever" as the ordering indication. Six of these tests were positive for DVT, a detection rate of 6.7%. The likelihood of positivity of a test obtained as part of fever evaluation relative to one obtained for non-fever indications was not significantly different (OR, 1.83; 95% CI, 0.570-5.11; P = 0.246). LEVDUS triggered by fever detected DVT at a numerically, but not statistically significantly higher rate than did LEVDUS performed for other indications in a neurocritically ill population. More rigorous investigation of this question is needed.


Cyclooxygenase-2 and inducible nitric oxide synthase expression in thyroid neoplasms and their clinicopathological correlation.
To evaluate the expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in thyroid neoplasms in a Korean population, we studied a total of 154 cases: papillary carcinoma of classical type (PTC), 86; follicular adenoma (FA), 21; follicular carcinoma (FC), 35; medullary carcinoma (MC), 3; undifferentiated carcinoma (UC), 5; and Hurthle cell neoplasm (HN), 4. Using immunohistochemical staining, COX-2 expression was detected in 62 (72.1%) PTC specimens, 5 (23.8%) FA specimens, 10 (28.6%) FC specimens, 0 (0.0%) MC specimens, 1 (20.0%) UC specimen, and 3 (75%) HN specimens. iNOS expression was detected in 66 (76.7%) PTC specimens, 4 (19.0%) FA specimens, 13 (37.1%) FC specimens, 0 (0.0%) MC specimens, 3 (60.0%) UC specimens, and 4 (100%) HN specimens. The results showed that COX-2 and iNOS were frequently expressed in the PTC and HN specimens, and iNOS was more frequently overexpressed in the FC specimens than in the FA specimens. In PTC, COX-2 and iNOS were significantly overexpressed in patients over 45 yr of age (p=0.029, p=0.041), and iNOS expression was increased in patients with a large primary tumor (p=0.028). These results suggest that the upregulation of COX-2 and iNOS may contribute to the tumor progression of thyroid gland, particularly in PTC and HN, and iNOS may play an adjuvant role during the tumor progression of FC.