Gene rearrangement and truncated mRNA in cell lines with 11q23 translocation.
We have previously demonstrated that the breakpoints of t(11;19)(q23;p13) leukemias are within 360 kb of the CD3 gene. One of the phage clones, 6n, which was isolated from the yeast artificial chromosome clone yB22B2 containing CD3, was found to be within 60 kb of t(11;19) breakpoints. In this study, gene walking was conducted and two phage clones (lambda Hp8-3 and lambda Hp23-13) were isolated from a human placenta genomic library. Southern blot analysis with a genomic probe from lambda Hp8-3 detected gene rearrangements in t(4;11) and t(11;19) cell lines with BamHI digestion. Subsequently, using reiterated sequence-free probes from both ends of 6n that detected transcriptional units in various hematopoietic cells, we isolated cDNA clones. These cDNA clones were classified into two groups (designated MLL-a and MLL-b), which do not hybridize to each other. Northern blot analysis with MLL-a cDNA detected 15-, 14- and 12-kb mRNAs, while MLL-b detected the additional 9.7- and 5-kb mRNAs in peripheral blood lymphocytes. MLL-b cDNA detected a truncated form of 12.5-kb mRNA in t(4;11) cell lines and a truncated form of 10-kb or 9.2-kb mRNA in t(11;19) cell lines. MLL-a did not demonstrate a truncated form of mRNA, but the stronger 14-kb signal was noted in t(4;11) cells, while this signal was very weak in t(11;19) cells. By Southern blot analysis, MLL-b cDNA detected gene rearrangement in cell lines with t(4;11) and t(11;19), whereas MLL-a did not. Furthermore, chimeric cDNA clones were isolated from cDNA libraries of t(4;11) and t(11;19) cell lines with a MLL-b cDNA probe. These results indicate that the MLL-b cDNA is derived from the common target gene involved in 11q23 translocation with 4q21 or 19p13.


Terbinafine-loaded wound dressing for chronic superficial fungal infections.
In spite of developing new drugs and modern formulations, the treatments of chronic fungal infections are still challenging. Fibrous wound dressings are new suggestions for the treatment of chronic superficial infections. In the present study, we formulated an antifungal agent, terbinafine hydrochloride (TFH), which is a hydrophobic drug, in wound dressings prepared by electrospun polycaprolactone, polycaprolactone/gelatin (50:50 w/w) and gelatin. To obtain more water-stable meshes, the preparations were treated by glutaraldehyde and their properties were determined before and after treatment. The morphology of fibrous meshes was observed by scanning electron microscopy. Drug loading efficiency and release rate were measured by high performance liquid chromatography (HPLC) and the release rate was monitored for 144h. Antifungal tests were performed on Trichophyton mentagrophytes, Aspergillus fumigatus and Candida albicans cultured on Muller-Hinton agar. The toxicity of the meshes was measured after 24h and 14days by MTT assay. Terbinafine loading of polycaprolactone/gelatin (50:50) was 100% and it released the highest amount of TFH too. In antifungal tests, all samples were able to hinderT. mentagrophytes and A. fumigatus but not C. albicans growth among them, polycaprolactone fibers made the largest inhibition zone. In MTT assay, none of prepared samples showed toxicity against L929 cells. Teken together, the prepared TFH-loaded PCL/gelatin electrospun meshes were able to release TFH slowly and in a steady state in time. With respect to no obvious cytotoxicity in MTT assay and stong antifungal activity toward T. mentagrophytesin vitro, these TFH-based meshes could be considered as potential candidates in clinical application as wound dressing for treatment of chronic dermatophytosis.


Hemispheres as independent resource systems: limited-capacity processing and cerebral specialization.
In this article, we develop as framework for understanding how cerebral specialization of function contributes to the flexibility of human information processing. We propose that the left and right hemispheres together form a system of two mutually inaccessible and finite pools of resources. Further, we propose that these two types of resources cannot be made available in different amounts at any given time. This framework is essentially a special case of a multiple-resources model of limited-capacity information processing. It accounts for a broad range of data from experiments involving perceptual and cognitive information processing, control of motor performance, and changes in electrical activity of the brain. It also provides insights into why the cerebral specialization literature has been plagued with problems that have made theorizing so difficult. In addition, the theory provides insights into mechanisms that might be responsible for patterns of task interference that are not easily handled by an information-processing model in which processes compete for supplies from a single pool of undifferentiated resources. Thus, the framework we are proposing has important theoretical and methodological implications for researchers in both divided attention and cerebral specialization.


Chemotherapy in canine acute megakaryoblastic leukemia: a case report and review of the literature.
Acute myeloid leukemia (AML) in dogs is a rare disease with poor prognosis. In most subjects, palliative treatment or euthanasia is performed. A 3.5-year-old male castrated labrador with AML-M7, which was treated with induction polychemotherapy (8 cycles) using vincristine (0.5 mg/m(2)/cycle), daunorubicin (20 mg/m(2)/cycle), cytosine arabinoside (ARA-C, 100 mg/m(2)/cycle) and prednisolone (1 mg/kg/day) is reported. Treatment was well tolerated and complete remission was achieved. Postinduction chemotherapy consisted of ARA-C, daunorubicin and prednisolone. After 3, 5 and 18 months, the subject relapsed. Each relapse was treated with ARA-C (up to 1,000 mg/m(2)) and etoposide or daunorubicin. Again, no severe side-effects occurred and the disease was controlled, with 37 chemotherapy-cycles (ARA-C, 3 x 1,000 mg/m(2)/cycle), for 24 months. Based on a literature-search, this is the first report documenting a long-term response of canine AML, probably resulting from the high-dose ARA-C. Clinical trials using high-dose ARA-C are now required to confirm antileukemic efficacy in canine leukemias.


A simulation study to compare three self-controlled case series approaches: correction for violation of assumption and evaluation of bias.
The assumption that the occurrence of outcome event must not alter subsequent exposure probability is critical for preserving the validity of the self-controlled case series (SCCS) method. This assumption is violated in scenarios in which the event constitutes a contraindication for exposure. In this simulation study, we compared the performance of the standard SCCS approach and two alternative approaches when the event-independent exposure assumption was violated. Using the 2009 H1N1 and seasonal influenza vaccines and Guillain-Barré syndrome as a model, we simulated a scenario in which an individual may encounter multiple unordered exposures and each exposure may be contraindicated by the occurrence of outcome event. The degree of contraindication was varied at 0%, 50%, and 100%. The first alternative approach used only cases occurring after exposure with follow-up time starting from exposure. The second used a pseudo-likelihood method. When the event-independent exposure assumption was satisfied, the standard SCCS approach produced nearly unbiased relative incidence estimates. When this assumption was partially or completely violated, two alternative SCCS approaches could be used. While the post-exposure cases only approach could handle only one exposure, the pseudo-likelihood approach was able to correct bias for both exposures. Violation of the event-independent exposure assumption leads to an overestimation of relative incidence which could be corrected by alternative SCCS approaches. In multiple exposure situations, the pseudo-likelihood approach is optimal; the post-exposure cases only approach is limited in handling a second exposure and may introduce additional bias, thus should be used with caution.


Papillary thyroid cancer recurrence 43 Years following Total Thyroidectomy and radioactive iodine ablation: a case report.
Recurrent papillary thyroid carcinoma (PTC) beyond the first two decades of definitive treatment (i.e. total thyroidectomy and radioactive iodine ablation) is a rare occurrence. We present a case of a 71-year old Caucasian female with a distant history of PTC treated with total thyroidectomy and radioactive iodine ablation who experienced recurrence of her disease 43 years following initial diagnosis and definitive treatment. She presented with palpable left-sided neck mass and subsequently underwent a level II, III, neck dissection and adjuvant iodine ablation. This case presents the latest recurrence in papillary thyroid cancer documented to date in the literature. This case exemplifies the need for the head and neck surgeon, radiation oncologist, general practitioner and radiologist to consider new lateral neck mass as late-presenting recurrence of PTC until proven otherwise regardless of low recurrence rates beyond two decades from treatment and low prognostic risk scores.


Palm Oil Fuel Ash-Based Eco-Friendly Concrete Composite: A Critical Review of the Long-Term Properties.
Rapid global infrastructural developments and advanced material science, amongst other factors, have escalated the demand for concrete. Cement, which is an integral part of concrete, binds the various individual solid materials to form a cohesive mass. Its production to a large extent emits many tons of greenhouse gases, with nearly 10% of global carbon (IV) oxide (CO2) emanating from cement production. This, coupled with an increase in the advocacy for environmental sustainability, has led to the development of various innovative solutions and supplementary cementitious materials. These aims to substantially reduce the overall volume of cement required in concrete and to meet the consistently increasing demand for concrete, which is projected to increase as a result of rapid construction and infrastructural development trends. Palm oil fuel ash (POFA), an industrial byproduct that is a result of the incineration of palm oil wastes due to electrical generation in power plants has unique properties, as it is a very reactive materials with robust pozzolanic tendencies, and which exhibits adequate micro-filling capabilities. In this study, a review on the material sources, affecting factors, and durability characteristics of POFA are carefully appraised. Moreover, in this study, a review of correlated literature with a broad spectrum of insights into the likely utilization of POFA-based eco-friendly concrete composites as a green material for the present construction of modern buildings is presented.


Comparison between submucosal (extra-nodal) and nodal non-Hodgkin's lymphoma (NHL) in the oral and maxillofacial region.
Fifty-two cases of non-Hodgkin's lymphoma (NHL) in the oral and maxillofacial region, comprising 31 submucosal (extra-nodal) and 21 cervical node NHLs, were investigated. The patients' ages ranged from 5 to 86 years, with a bimodal age distribution among young people below 12 years of age (average 8 years) and in those aged 30 years or older (average 60.3 years). The male-to-female gender difference ratio was 1.3:1. Patients presented with swelling as the major symptom. Histologically, diffuse, large cell malignant lymphoma was the most frequent type and 67.9% of lymphomas were of intermediate malignancy as defined by the Working Formulation for Clinical Usage. All submucosal lymphomas showed diffuse proliferation patterns, although follicular proliferation was identified in 5 of the 21 nodal lymphomas. Immunohistochemistry showed that the B-cell type was predominant, especially in nodal lymphomas.


Treatment of spasmodic torticollis with intradural selective rhizotomies.
To determine the effects of ventral cervical and selective spinal accessory nerve rhizotomy on spasmodic torticollis, 58 patients who had undergone surgery between 1979 and 1987 were reviewed retrospectively. At the time of surgery, each nerve rootlet was electrically stimulated to determine its effect on the nuchal musculature prior to sectioning. Forty-nine patients (85%) had a marked improvement in their condition, with 33 (57%) attaining an excellent result and 16 (28%) noting significant improvement. Patients complained of abnormal head posture, nuchal muscle spasms, and pain prior to surgery. Muscle spasms were completely relieved in 42 patients (72%) and markedly reduced in 10 (17%). Of the 47 patients with preoperative pain, 30 (64%) were free of their pain and eight (17%) noted that the pain was reduced in intensity and frequency. Thirty-four patients (59%) reported that their resting head posture was restored to a neutral position. The likelihood that a patient's head posture returned to normal was inversely proportional to the preoperative duration of the spasmodic torticollis. Twenty-six patients (45%) suffered mild transient difficulty with swallowing solid foods in the immediate postoperative period. In most cases these minor difficulties abated in the months following surgery.


Effect of adipocyte beta3-adrenergic receptor activation on the type 2 diabetic MKR mice.
The antiobesity and antidiabetic effects of the beta3-adrenergic agonists were investigated on nonobese type 2 diabetic MKR mice after injection with a beta3-adrenergic agonist, CL-316243. An intact response to acute CL-316243 treatment was observed in MKR mice. Chronic intraperitoneal CL-316243 treatment of MKR mice reduced blood glucose and serum insulin levels. Hyperinsulinemic euglycemic clamps exhibited improvement of the whole body insulin sensitivity and glucose homeostasis concurrently with enhanced insulin action in liver and adipose tissue. Treating MKR mice with CL-316243 significantly lowered serum and hepatic lipid levels, in part due to increased whole body triglyceride clearance and fatty acid oxidation in adipocytes. A significant reduction in total body fat content and epididymal fat weight was observed along with enhanced metabolic rate in both wild-type and MKR mice after treatment. These data demonstrate that beta3-adrenergic activation improves the diabetic state of nonobese diabetic MKR mice by potentiation of free fatty acid oxidation by adipose tissue, suggesting a potential therapeutic role for beta3-adrenergic agonists in nonobese diabetic subjects.


Estrogen increases endothelial nitric oxide synthase via estrogen receptors in rat cerebral blood vessels: effect preserved after concurrent treatment with medroxyprogesterone acetate or progesterone.
In vivo and in vitro rat models of hormone therapy were used to test the following hypotheses: (1) estrogen acts directly on cerebrovascular estrogen receptors to increase endothelial nitric oxide synthase (eNOS); (2) increased protein correlates with higher NOS activity; and (3) effects of estrogen on eNOS are altered by concurrent treatment with either medroxyprogesterone acetate (MPA) or progesterone. Blood vessels were isolated from brains of ovariectomized female rats; some were treated for 1 month with estrogen, estrogen and progesterone, or estrogen and MPA. Isolated cerebral vessels were also treated in vitro with estrogen in the absence and presence of progesterone, MPA, tamoxifen, and the estrogen receptor antagonist ICI 182 780. Levels of eNOS were measured by Western blot, and NOS activity was measured by [14C]arginine-[14C]citrulline conversion. Chronic hormone treatment in vivo resulted in plasma levels of 17beta-estradiol, progesterone, and MPA in the range of values found in humans. Estrogen treatment resulted in higher levels of cerebrovascular NOS activity that paralleled increases in eNOS protein. In vitro estrogen treatment for 18 hours also resulted in a concentration-dependent increase in eNOS protein (EC50 approximately 300 pmol/L) that was completely prevented by estrogen receptor antagonists tamoxifen or ICI 182 780. However, cotreatment with progesterone or MPA, either in vivo or in vitro, did not alter the effect of estrogen on eNOS protein. Estrogen receptor activation in cerebrovascular tissue results in increased eNOS activity and protein levels. The latter effect persists in the presence of either progesterone or MPA. Thus, increased NO production by eNOS may contribute to the neuroprotective effects of estrogen.


Porpholactone Chemistry: Shining New Light on an Old Cofactor.
The emergence of porpholactone chemistry, discovered over 30 years ago, has significantly stimulated the development of biomimetic tetrapyrrole chemistry. It offers an opportunity, through modifications of non-pyrrolic building blocks, to clarify the relationship between chemical structure and excited-state properties, deciphering the structural code for the biological functions of life pigments. With intriguing photophysical properties in the red to near-infrared (NIR) regions, facile modulation of their electronic nature by fine-tuning chemical structures, and coordination ability with diverse metal ions, these novel porphyrinoids have favorable prospects in the fields of optical materials, bioimaging and therapy, and catalysis. In this Minireview, we summarize the brief history of porpholactone chemistry, and focus on the studies carried out in our group, particularly on the regioisomeric effect, NIR lanthanide luminescence, and metal catalysis. We outline the perspectives of these compounds in the construction of porpholactone-related biomedical applications and optical and energy materials, in order to inspire more interest and further advance bioinspired inorganic chemistry and lanthanide chemical biology.


Visual perception of lifted weight.
The weight of a box can be seen by observing another person lifting and carrying it. Evidence is provided in two experiments, the first of which employed videotaped events with the actor and box visible only as 21 bright patches. Observers judged the weight of the box rather linearly with an average slope of .87 and with a pooled standard deviation of 3.8 kg. The second experiment compared visual and haptic perception of box weight in similar events under conditions of live action. Average slopes of 1.00 in the visual mode and 1.20 in the haptic mode were obtained with standard deviations of 3.1 kg and 2.0 kg, respectively. It is concluded that the weight of the box, as a dynamic variable of the event, is well specified in the kinematic pattern and hence in the optic array. Furthermore, the visual system is efficient in picking up such information.


Cervical spinal cord injuries in patients with cervical spondylosis.
Eighty-eight patients over age 40 with traumatic cervical spinal cord injuries were clinically and radiographically evaluated, and comparison was made with 35 spinal cord injury patients under age 36. While most older patients sustained obvious bony and/or ligamentous damage commensurate with their neurologic findings, 25 (28%) of the 88 patients had no demonstrable bony abnormalities and 17 (20%) of the 88 patients had only minimal evidence of bony injury. Of particular interest are the patients with severe cord injuries, yet no bony abnormalities, who seem to form a distinct subgroup of the cervical spinal cord injury patient on the basis of radiographic and clinical features. Of these 25 patients, 24 (96%) had severe cervical spondylosis. Fourteen (56%) of the 25 patients were injured in falls, five (36%) of these 14 being of a seemingly trivial nature. Of the 42 patients with minimal or no demonstrable bony abnormalities, 33 (79%) were evaluated with plain tomography and no occult fractures or other significant pathology was demonstrated. Pantopaque myelography in 27 (64%) of the 42 cases revealed no extruded disk or other surgical lesion in any patient. In large measure, these injuries can be attributed to cervical spondylosis, which narrows the canal and makes the cord more susceptible to compression by the bulging ligamenta flava during hyperextension.


Cyanide-Free Synthesis of Glycosyl Carboxylic Acids and Application for the Synthesis of Scleropentaside A.
We have developed a cyanide-free strategy for the synthesis of glycosyl carboxylic acids, which can provide 1,2-trans or 1,2-cis glycosyl carboxylic acids and is compatible with common protecting groups. The synthetic utility was demonstrated by the synthesis of 12 unreported glycosyl acids and the total synthesis of scleropentaside A.


[Paired filtration dialysis and free radicals].
Extracorporeal dialysis compensating kidney function represents a risk of elevated production of free radicals (FR). Paired filtration dialysis (PFD) is a hemodialysing method used to compensate kidney function. The aim of our work was to study effects of PFD with two types of hemodiafilters on the activity of free radicals. Group of nine regularly dialysed patients was treated with PFD 1) with demodiafilter SG3, composed of polysulphone high-flux hemodiafilter and hemophane low-flux dialysator, 2) with hemodiafilter SG30, composed of identical hemodiafilter as the above on and of a polysulphone low-flux dialysator. Parameters related to FR were examined before, at 30th minute and at the end of procedure. Plasma concentration of substances reacting with thiobarbiturate acid (TBARS) increased at 30th minute when PFD with SG3 was used (3.24 +/- 0.36 versus 3.48 +/- 0.31, p < 0.01) and at the end of the procedure (3.24 +/- 0.36 versus 3.58 +/- 0.48, p < 0.05). Glutathione values in erythrocytes (GSH) decreased at 30th minute of PFD with SG3 (1.85 +/- 0.27 versus 1.68 +/- 0.20, p < 0.05). Plasma antioxidative capacity decreased at 30th minute and at the end of PFD with equal significance when either type of treatment was used (p < 0.001). Glutathione peroxidase (GSHPx) decreased at 30th minute of PFD with SG30 (35.6 +/- 3.8 versus 32.2 +/- 3.1, p < 0.05). Selenium (Se) in blood decreased at 30th minute (44.9 +/- 5.4 versus 40.4 +/- 5.9, p < 0.05) and at the end of PFD with the same membrane (44.9 +/- 5.4 versus 39.4 +/- 5.2, p < 0.05). Elevation of TBARS and decrease of GSH show the presence of oxidative stress during the PFD treatment with hemodiafilter SG3. Changes probably result from the contact of blood with the hemophane membrane. The decrease of GSHPx during PFD with hemodiafilter SG30 is probably caused by the loss of Se. From the point of FR production, hemodiafilter SG30 can be considered as more advantageous, from the point of Se loss and decreased activity of GSHPx, hemodiafilter SG3 has better effects.


Cardioprotective effect of boswellic acids against doxorubicin induced myocardial infarction in rats.
The aim of the present study was to evaluate the cardioprotective activity of boswellic acids in doxorubicin (DOX) induced cardiotoxicity. DOX (2.5mg/kg) was used intraperitoneally in rats to induce cardiotoxicity in six divided doses every alternate day over a period of two weeks. Dexrazoxane (10:1) was used as a standard drug. Boswellic acids (250, 500 and 750 mg/kg) were orally administered to rats for 14 days. After 14 days, rats were sacrificed, and blood was withdrawn through cardiac puncture. The blood lipid profile and cardiac biomarkers including LDH, CK-MB, CPK, SGOT and troponin T were measured. The heart of rats was isolated for histopathological studies. Graphpad Prism was used for statistical analysis. There was a significant increase in the level of cardiac enzymes and complete lipid profile parameters in diseased group as compared to control group. Pre-treatment with boswellic acids decreased level of all the measured parameters and decreased the severity of myocardial damage as supported by histopathological studies. It was concluded that boswellic acids possess cardioprotective potential by lowering cardiac biomarkers and blood lipid profile. Thus, boswellic acids might act as cardioprotective agent against doxorubicin induced cardiotoxicity.


Artifact reduction in EPI with phase-encoded reference scan.
Echo-planar imaging is becoming widely used for various applications. However, because of inherent limitations, images obtained with EPI are often degraded by artifacts arising from the inconsistency between the odd and even echoes in the acquired data. Several correction techniques, including those based on reference measurement, have been previously reported. In this paper, a correction method based on phase-encoded reference measurement is described. This technique is demonstrated with experimental data obtained at 4 Tesla and compared with techniques that use nonphase-encoded reference scan. Results from experimental studies indicate that the present approach reduces the ghost intensity by a factor of 2-3.


Lung microvessel injury from peritoneal abscesses and gram-negative bacteremia.
To analyze the effect of an extrathoracic focus of infection on lung vessel wall structure, we produced peritoneal abscesses in the rat, over a period of 3 to 7 weeks, by implanting capsules containing live gram-negative bacteria (3.0 x 10(7) Escherichia coli and 5.0 x 10(7) Bactercides fragilis) with an adjutant. We document here by arteriography, morphometric analysis, and high resolution microscopy, microvessel cell injury, and wall remodeling. In the sepsis-injured lung, both dilated and thick-walled microvessels are present. The walls of dilated vessels are disrupted by extensive endothelial and precursor smooth muscle cell injury. In thick-walled vessels these cells are hypertrophied, and the precursor smooth muscle cells express filaments, demonstrating a shift toward a contractile phenotype. Infiltrating monocytic cells focally consolidate alveolar regions. In the residual nonconsolidated regions, alveolar-capillary membrane cells are attenuated and the capillaries dilated. Vessel changes after 7 weeks are similar to those after 3 weeks but alveolar-capillary membrane injury is more extensive. These structural changes, including the development of precursor smooth muscle cells, may contribute to the known increase in reactivity of these lung vessels to challenge by vasoactive agents.


Value, purpose and accountability: the language of organizational intentions.
A schemata is proposed which provides a framework that associates value, purpose and accountability, in a manner that contributes to a common language with recognizable meanings in discussion and analysis of organizational intentions. The definition of key terms, their hierarchical relationships, and characteristics of the grammar that tie value, purpose and accountability together to assure meaningful dialogues among administrators and those with whom they discuss organizational work, is suggested.


Synergistic photothermal conversion and photocatalysis in 2D/2D MXene/Bi2S3 hybrids for efficient solar-driven water purification.
Plasmonic hybrids are regarded as promising candidates for water purification due to their structure-dependent photocatalysis and photothermal performance. It remains a challenge to develop materials that possess these two characteristics for efficient water purification. Herein, plasmonic Ti3C2Tx/Bi2S3 two-dimensional (2D)/2D hybrids were prepared for efficient solar-driven water purification via the combination of photothermal conversion and photocatalysis. Benefitting from broad light absorption, large 2D/2D interfaces, and efficient charge transfer, the binary hybrids showed high-efficiency photothermal conversion and photothermal-assisted photocatalytic activity. By depositing these 2D/2D hybrids on a hydrophilic and porous cotton piece, the Ti3C2Tx/Bi2S3 membrane displayed a high water evaporation rate and solar-to-vapor efficiency under one-sun irradiation. The solar-driven evaporation of seawater, heavy metal ion solution, and dye solution jointly indicated that the plasmonic membrane shows great potential for drinkable water generation and industrial wastewater treatment. Most importantly, the synergistic effect of photothermal evaporation and photocatalysis of the Ti3C2Tx/Bi2S3 membrane on water purification was demonstrated. The polluted water can not only be treated by evaporation, but also be degraded via photocatalysis under solar light irradiation. This work provides new insight into designing functional materials for water purification based on the combination of photothermal conversion and photocatalysis.


Machine-Learning Based Determination of Gait Events from Foot-Mounted Inertial Units.
A promising but still scarcely explored strategy for the estimation of gait parameters based on inertial sensors involves the adoption of machine learning techniques. However, existing approaches are reliable only for specific conditions, inertial measurements unit (IMU) placement on the body, protocols, or when combined with additional devices. In this paper, we tested an alternative gait-events estimation approach which is fully data-driven and does not rely on a priori models or assumptions. High-frequency (512 Hz) data from a commercial inertial unit were recorded during 500 steps performed by 40 healthy participants. Sensors' readings were synchronized with a reference ground reaction force system to determine initial/terminal contacts. Then, we extracted a set of features from windowed data labeled according to the reference. Two gray-box approaches were evaluated: (1) classifiers (decision trees) returning the presence of a gait event in each time window and (2) a classifier discriminating between stance and swing phases. Both outputs were submitted to a deterministic algorithm correcting spurious clusters of predictions. The stance vs. swing approach estimated the stride time duration with an average error lower than 20 ms and confidence bounds between ±50 ms. These figures are suitable to detect clinically meaningful differences across different populations.


Ileal Peyer's patch emigrants are predominantly B cells and travel to all lymphoid tissues in sheep.
The ileal Peyer's patch (PP) was selectively labeled with fluorescein isothiocyanate by extracorporeal perfusion in 7-12 week-old lambs and the lymphocyte lineage and fate of the emigrants was determined by fluorescence microscopy and flow cytometry. PP emigrants were found in all tissues examined, accounting for 10%-15% of ileal mesenteric lymph node (MLN). 1%-2% of jejunal MLN, jejunal PP, prescapular lymph node (PLN) and 3%-4% of spleen cells. All ileal PP emigrants enter the ileal MLN on their way to the circulation. Removal of the MLN prior to perfusion enabled emigrants to go directly to the circulation and extravasate in distant tissues faster than in intact animals. The ileal MLN might provide an additional level of regulation for ileal PP emigrants. The perfused ileal PP contained about 25 times more B cells than T cells. The emigrant cells found in different tissues included both T and B cells but came to reflect, although to a lesser degree, the B cell composition of the tissue from which they were derived. One day after perfusion the composition of PP emigrants was similar to that of the tissue within which they were found; the spleen was the exception with a bias towards B cells. By day 3 the ratio of B to T cells in the PP emigrants was 1 for jejunal MLN and PLN. 1.5 for ileal MLN and jejunal PP, and 4-5 for the spleen and blood. It was concluded that the PP-derived T cells were recirculating T cells that were in the ileal PP at the time of perfusion. These cells emigrated rapidly and equilibrated such that they accounted for about 1.5% of the T cell pool in various tissues. Most PP-derived B cells were probably produced in the PP. The greatest contribution (24.4%) that ileal PP emigrants made to the B cell pool of a tissue was with the ileal MLN through which they are obliged to pass. The contribution was lower but still very significant in blood (8.9%), spleen (6.8%), PLN (3.9%), jejunal MLN (3.5%) and jejunal PP (1.8%). There was no evidence that ileal PP emigrants made a greater relative contribution to either T or B cell populations in MLN or jejunal PP than to non-gut-associated sites. The B cells were distributed throughout the immune system, which is in accordance with the proposal that the ileal PP is a site of primary B cell genesis in sheep.


Giant schwannoma of thoracic vertebra: A case report.
It is relatively rare for schwannomas to invade bone, but it is very rare for a large mass to form concurrently in the paravertebral region. Surgical resection is the only effective treatment. Because of the extensive tumor involvement and the many important surrounding structures, the tumor needs to be fully exposed. Most of the tumors are completely removed by posterior combined open-heart surgery to relieve spinal cord compression, restore the stability of the spine and maximize the recovery of nerve and spinal cord function. The main objective of this article is to present a schwannoma that had invaded the T5 and T6 vertebral bodies and formed a large paravertebral mass with simultaneous invasion of the spinal canal and compression of the spinal cord. A 40-year-old female suffered from intermittent chest and back pain for 8 years. Computed tomography and magnetic resonance imaging scans showed a paravertebral tumor of approximately 86 mm × 109 mm × 116 mm, where the adjacent T5 and T6 vertebral bodies were invaded by the tumor, the right intervertebral foramen was enlarged, and the tumor had invaded the spinal canal to compress the thoracic medulla. The preoperative puncture biopsy diagnosed a benign schwannoma. Complete resection of the tumor was achieved by a two-step operation. In the first step, the thoracic surgeon adopted a lateral approach to separate the thoracic tumor from the lung. In the second step, a spine surgeon performed a posterior midline approach to dissect the tumor from the vertebral junction through removal of the tumor from the posterior side and further resection of the entire T5 and T6 vertebral bodies. The large bone defect was reconstructed with titanium mesh, and the posterior root arch was nail-fixed. Due to the large amount of intraoperative bleeding, we performed tumor angioembolization before surgery to reduce and avoid large intraoperative bleeding. The postoperative diagnosis of benign schwannoma was confirmed by histochemical examination. There was no sign of tumor recurrence or spinal instability during the 2-year follow-up. Giant schwannoma is uncommon. In this case, a complete surgical resection of a giant thoracic nerve sheath tumor that invaded part of the vertebral body and compressed the spinal cord was safe and effective.


Vitamin supplementation: unmonitored prescription can be dangerous.
A 75-year-old illiterate woman presented with severe dehydration and altered sensorium. Investigations revealed severe hypercalcaemia with deranged renal function. ECG showed changes of hypercalcaemia and hypokalaemia. Since the patient was aged and had an acute presentation, malignancy was considered as the probable aetiology. Following prompt supportive treatment, she regained consciousness on the second day of admission. Later on, she provided a history of daily intake of vitamin D3 (cholecalciferol) sachet (60 000 IU/sachet) for the last 2 weeks, which had actually been prescribed to be taken once per week. Further investigation revealed very high levels of serum vitamin D. This case has been presented to reiterate the importance of known, but often overlooked facts: ECG can provide an important clue regarding the underlying metabolic encephalopathy; mega-dose supplementation of these seemingly innocuous vitamins should be monitored; and treatment regimes should be properly explained and monitored in elderly people.


Hysteroscopic management of intractable uterine bleeding. A review of 103 cases.
One hundred three patients with intractable uterine bleeding were treated using the continuous flow resectoscope. All patients underwent diagnostic hysteroscopy and endometrial sampling prior to surgery. The patients were divided into three groups. Group I (n = 69) patients had a normal hysteroscopic examination. Group II (n = 26) had intrauterine pathology visible on their diagnostic hysteroscopy. Group III (n = 8) had failed to improve satisfactorily on previous hysteroscopic ablation of the endometrium using the Nd:YAG laser. Group I and III patients underwent hysteroscopic ablation of the endometrium using a 3-mm, ball-end electrode. Group II patients underwent hysteroscopic resection of an intra-uterine lesion utilizing a 7-mm wipe loop electrode. The results in all three groups were analyzed and compared. Seventy patients underwent endometrial preparation with one of five pretreatment regimens: danazol, depoleuprolide, depomedroxyprogesterone acetate and surgery.


Patients' knowledge and opinions of ICDs during life, illness and at the time of death.
Use of an implantable cardioverter defibrillator (ICD) is an established therapy for the prevention of sudden cardiac death. However, at the end of life, these devices can prolong the dying experience, causing physical and psychological trauma. Patients are often unaware of their options regarding ICD management at the end of their life, which highlights the need for health professionals to have these discussions with patients. This study aimed to identify patients' knowledge and opinions about their ICD and the factors influencing their knowledge and opinions. Of the 30 participants in this study, 59% had sufficient knowledge about ICDs. There was no relationship between knowledge and time since implantation (p=0.11). A relationship existed between knowledge and age; those that were older were better informed (p=0.008). The authors conclude that patient education and communication are essential for patients with ICDs to enhance decision-making about ICD management at the end of life.


Effects of High-Definition Transcranial Direct-Current Stimulation on Resting-State Functional Connectivity in Patients With Disorders of Consciousness.
Recently a positive treatment effect on disorders of consciousness (DOCs) with high-definition transcranial direct-current stimulation (HD-tDCS) has been reported; however, the neural modulation mechanisms of this treatment's efficacy need further investigation. To better understand the processing of HD-tDCS interventions, a long-lasting HD-tDCS protocol was applied to 15 unresponsive wakefulness syndrome (UWS) patients and 20 minimally conscious states (MCS) patients in this study. Ten minutes of resting-state electroencephalograms (EEGs) were recorded from the patients, and the coma recovery scale-revised scores (CRS-Rs) were assessed for each patient from four time-points (T0, T1, T2, and T3). Brain networks were constructed by calculating the EEG spectral connectivity using the debiased weighted phase lag index (dwPLI) and then quantified the network information transmission efficiency by graph theory. We found that there was an increasing trend in local and global information processing of beta and gamma bands in resting-state functional brain networks during the 14 days of HD-tDCS modulation for MCS patients. Furthermore, the increased functional connectivity not only occurred in the local brain area surrounding the stimulation position but was also present across more global brain areas. Our results suggest that long-lasting HD-tDCS on the precuneus may facilitate information processing among neural populations in MCS patients.


Increasing Prevalence of Group III Penicillin-Binding Protein 3 Mutations Conferring High-Level Resistance to Beta-Lactams Among Nontypeable Haemophilus influenzae Isolates from Children in Korea.
This study investigated the roles of β-lactamase and penicillin-binding protein 3 (PBP3) alterations in the development of recent antimicrobial resistance in nontypeable Haemophilus influenzae (NTHi) isolated from Korean children. Nasopharyngeal NTHi isolates from children at a tertiary children's hospital were tested for antimicrobial susceptibility using E-test. β-lactamase production was screened by the paper disc test, and polymerase chain reaction amplification of blaTEM and blaROB-1 was performed. The ftsI gene was amplified to identify PBP3 alteration. Of the 53 NTHi isolates, 69.8% were ampicillin nonsusceptible. The nonsusceptibility rates for cefaclor were 81.1%, cefpodoxime 69.8%, and amoxicillin/clavulanate 32.1%. About 60.3% and 32.1% of the isolates were genetically β-lactamase-nonproducing ampicillin-resistant (gBLNAR) and genetically β-lactamase-producing amoxicillin/clavulanate-resistant (gBLPACR) strains, respectively. Group III amino acid substitutions comprised 65.6% of the gBLNAR strains and 70.6% of the gBLPACR strains. MIC50 for amoxicillin/clavulanate, cefaclor, cefuroxime, cefpodoxime, and cefixime were more than 2-80 times higher in the gBLNAR and gBLPACR strains compared with gBLPAR strains. Group III gBLNAR strains had significantly higher ampicillin, amoxicillin/clavulanate, cefpodoxime, and cefixime minimum inhibitory concentrations than group II strains. Group III gBLNAR and gBLPACR NTHi strains are highly prevalent in Korea, raising the alarm about increasing β-lactam resistance in NTHi.


Announcement and proposed criteria for demonstration of joint nursing graduate education program projects--HRSA. Notice.
The Health Resources and Services Administration (HRSA) in coordination with the Health Care Financing Administration (HCFA) announces its intent to implement section 8411(a) of the Technical and Miscellaneous Revenue Act of 1988 (Pub. L. 100-647) authorizing a Demonstration of Joint Nursing Graduate Education Programs. Medicare reimbursement rules are modified to promote graduate clinical training opportunities jointly developed by hospitals and educational institutions. This is a demonstration designed to allow a hospital to be reimbursed for reasonable costs incurred pursuant to a written agreement with an educational institution for certain activities conducted as part of an approved educational program that involves a substantial clinical component (as determined by the Secretary) and leads to a master's or doctoral degree in nursing. For the purpose of these projects, payments for costs incurred will be reimbursed on the same basis as if they were allowable direct costs of a hospital-operated approved educational program (other than an approved graduate medical education program), or as otherwise justified, but only to the extent that such activities are directly related to the operation of the educational program conducted under the written agreement between the hospital and the educational institution. The amount paid under a demonstration project to a hospital for a cost reporting period may not exceed $200,000. Five hospitals are to be selected for participation in this Program and fiscal intermediaries will be authorized to reimburse clinical education costs for reporting periods beginning on or after July 1, 1989, and before July 1, 1994.(ABSTRACT TRUNCATED AT 250 WORDS)


Simultaneous quantification of eleven thiopurine nucleotides by liquid chromatography-tandem mass spectrometry.
The prodrugs azathioprine and 6-mercaptopurine, which are well-established anticancer and immunosuppressive agents, are extensively metabolized by activating and inactivating enzymes. Whereas the 6-thioguanine nucleotides (TGN) are currently being considered as major active metabolites, methylthioinosine nucleotides seem to contribute to the cytotoxic effect as well. Thiopurine-related adverse drug reactions and thiopurine failure are frequent. Thus, therapeutic monitoring of TGN and methylthioinosine derivatives has been suggested to improve thiopurine therapy, however with limited success. To elucidate systematically underlying molecular mechanisms as potential explanation for interindividual variability of thiopurine response, we developed a novel highly specific and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantitation of eleven mono-, di-, and triphosphates of thioguanosine, methylthioinosine, methylthioguanosine, and thioinosine. Using stable isotope-labeled analogues as internal standards obtained by chemical synthesis, an intra- and interassay variability below 8% and an accuracy of 92% to 107% were achieved in spiked quality control samples with known standards. All eleven metabolites could be determined in red blood cells from patients with inflammatory bowel diseases and long-term azathioprine therapy. Thus, our novel method opens a new avenue for the understanding of the thiopurine metabolism by quantitation of all important thiopurine nucleotide metabolites in one run.


An Inexpensive Digital Image Analysis Technique for Liver Fibrosis Quantification in Chronic Hepatitis B Patients.
Quantitative digital imaging analysis to evaluate liver fibrosis is accurate, but its clinical use is limited by its high cost and lack of standardization. We aimed to validate an inexpensive digital imaging analysis technique for fibrosis quantification in chronic hepatitis B patients. In total, 142 chronic hepatitis B patients who underwent liver biopsy and analysis of serum fibrosis markers were included. Images of Sirius red stain sections were captured and processed using Adobe Photoshop CS3 software. The percentage of fibrosis (fibrosis index) was determined by the ratio of the fibrosis area to the total sample area, expressed in pixels, and calculated automatically. A strong correlation between the fibrosis index and the Ishak, Metavir, and Laennec histological staging systems were observed (r = 0.83, 0.86, and 0.84, respectively; < 0.001). The cutoff value associated with cirrhosis was 7.7% with an area under the receiver operating characteristic curve (AUROC) of 0.95 (95% confidence interval [CI], 0.92-0.99, p < 0.001). Furthermore, the fibrosis index yielded a cutoff value of 8.9% (AUROC, 0.74; 95% CI, 0.66-0.86), 12% (AUROC, 0.84; 95% CI, 0.75-0.93), and 14% (AUROC, 0.97; 95% CI, 0.92-1.0) for the diagnosis of cirrhosis 4a, 4b, and 4c, respectively. No serum markers or fibrosis models were correlated with the fibrosis index in Metavir F2-F4. The present digital imaging analysis technique is reproducible and available worldwide, allowing its use in clinical practice, and can be considered as a complementary tool to traditional histological methods.


Observation of Photoelectron Circular Dichroism Using a Nanosecond Laser.
Photoelectron circular dichroism (PECD) is a fascinating phenomenon both from a fundamental science aspect but also due to its emerging role as a highly sensitive analytic tool for chiral recognition in the gas phase. PECD has been studied with single-photon as well as multi-photon ionization. The latter has been investigated in the short pulse limit with femtosecond laser pulses, where ionization can be thought of as an instantaneous process. In this contribution, we demonstrate that multi-photon PECD still can be observed when using an ultra-violet nanosecond pulse to ionize chiral showcase fenchone molecules. Compared to femtosecond ionization, the magnitude of PECD is similar, but the lifetime of intermediate molecular states imprints itself in the photoelectron spectra. Being able to use an industrial nanosecond laser to investigate PECD furthermore reduces the technical requirements to apply PECD in analytical chemistry.


Hearing thresholds and tympanic membrane sequelae in children managed medically or surgically for otitis media with effusion.
To determine the long-term effects of ventilation tube insertion on hearing thresholds and tympanic membrane pathologic abnormalities in children with otitis media with effusion. Prospective cohort study. Tertiary care children's hospital, otorhinolaryngology and audiology service. Patients aged 8 to 16 years who participated in a randomized controlled trial of medical vs surgical (ventilation tube [VT]) treatment for recurrent otitis media with effusion at ages 2.5 to 7 years. Hearing thresholds and tympanic membrane sequelae. One hundred thirteen of 125 children who had participated in the trial underwent blinded audiometric, tympanometric, otomicroscopic, and parental questionnaire evaluation 6 to 10 years following the trial. Thirty of 57 [corrected] medical subjects received ventilation tubes and 18 of 56 [corrected] VT subjects received more than 1 set of tubes. To evaluate sequelae risk associated with ventilation tubes independent of disease severity, we compared 27 medical subjects who never received ventilation tubes and 38 subjects randomized to VT who only received 1 set of tubes. Tympanic membrane pathologic abnormalities were present in 81% of VT subjects and 19% of medical subjects (relative risk, 4.4; 95% confidence interval, 2.2-9.9). Hearing thresholds were 2.1 to 8.1 dB higher in subjects treated with tubes (P = .005). In children who were candidates for ventilation tube insertion randomly assigned to receive medical or VT treatment for otitis media with effusion, elevated hearing thresholds and tympanic membrane pathologic abnormalities were more common in VT subjects 6 to 10 years after insertion.


[Bone fracture and the healing mechanisms. Fracture treatment using electrical stimulation].
In 1953, Iwao Yasuda reported on the piezoelectricity of bone and the electrical stimulation of callus formation. Subsequently, various methods of electrical stimulation have been investigated, and the enhancement of callus formation by electrical stimulation is likely to have broad clinical applications for not only the repair of fractures, but also for nonunion and pseudoarthrosis. Recently, these outcomes have been validated by significant double blind clinical trials, and the electrical currents in bone were investigated at the molecular level. Moreover, the application of impedance measurements obtained upon electrical stimulation as a means to evaluate bone maturation was examined. This paper reports on the current methods of electrical stimulation, the fundamental effects on bone formation, and further clinical applications.


The framework of systemic organization applied to older adults as family caregivers of persons with chronic illness and disability.
The Framework of Systemic Organization by Friedemann, according to which families as open systems strive for congruence, a dynamic state of equilibrium, is presented to offer a way to bridge the gap between grand and mid-range theory, between theory and practice. Theoretical tenets composed of system targets of stability, growth, control, and spirituality and the process dimensions of system maintenance and change, coherence, and individuation are suggested for nursing assessment for older adults, individuals, and families. Simple practice application examples of these tenets are delineated for older adult family caregivers of persons with chronic illness and disability within a family system context. Nurses who practice within the Framework of Systemic Organization can assist elders, as family caregivers, in a meaningful way to adjust to the realities of their situation.


Effects of early-life conditions on adult mortality: a review.
"This paper considers the effects of health conditions in childhood on an individual's mortality risks as an adult. It examines epidemiologic evidence on some of the major mechanisms expected to create a linkage between childhood and adult mortality and reviews demographic and epidemiologic studies for evidence of the hypothesized linkages....Many empirical studies support the notion that childhood conditions play a major role in adult mortality, but only in the case of respiratory tuberculosis has the demographic importance of a specific mechanism been established by cohort studies. One's date and place of birth also appear to be persistently associated with risks of adult death in a wide variety of circumstances. An individual's height, perhaps the single best indicator of nutritional and disease environment in childhood, has recently been linked to adult mortality, especially from cardiovascular diseases. Further research is needed, however, before causal mechanisms can be identified."


In vitro Bioaccessibility and Intestinal Absorption of Selected Bioactive Compounds in Terminalia ferdinandiana.
Terminalia ferdinandiana (or Kakadu plum), a native Australian fruit with potential health benefits, contains bioactive compounds such as ellagic acid (EA), ascorbic acid (AA) and calcium, and antinutrients such as oxalic acid (OA). However, few is known about the biological fate of these compounds following ingestion; therefore, the aim of this study was to evaluate in vitro bioaccessibility and intestinal absorption of T. ferdinandiana compounds using the INFOGEST static digestion model and Caco-2-HT29-MTX-E12 intestinal absorption model. No significant changes (p > 0.05) were observed in total AA content throughout in vitro digestion, whereas bioaccessibility of EA, OA, and calcium increased significantly from 33, 72, and 67% in the gastric phase to 48, 98, and 90% in the intestinal phase, respectively. The intestinal absorption study revealed variable rates of movement across the cell barrier. Findings reveal novel and important insights for the prediction of in vivo bioavailability of selected T. ferdinandiana compounds.


Effects of socioeconomic status on esophageal adenocarcinoma stage at diagnosis, receipt of treatment, and survival: A population-based cohort study.
The incidence of esophageal adenocarcinoma (EAC) is increasing worldwide and has overtaken squamous histology in occurrence. We studied the impact of socioeconomic status (SES) on EAC stage at diagnosis, receipt of treatment, and survival. A population-based retrospective cohort study was conducted using Ontario Cancer Registry-linked administrative health data. Multinomial logistic regression was used to examine the association between SES (income quintile) and stage at EAC diagnosis and EAC treatment. Survival times following EAC diagnosis were estimated using Kaplan-Meier method. Cox proportional-hazards regression analysis was used to examine the association between SES and EAC survival. Between 2003-2012, 2,125 EAC cases were diagnosed. Median survival for the lowest-SES group was 10.9 months compared to 11.6 months for the highest-SES group; the 5-year survival was 9.8% vs. 15.0%. Compared to individuals in the highest-SES group, individuals in the lowest-SES category experienced no significant difference in EAC treatment (91.6% vs. 93.3%, P = 0.314) and deaths (78.9% vs. 75.6%, P = 0.727). After controlling for covariates, no significant associations were found between SES and cancer stage at diagnosis and EAC treatment. Additionally, after controlling for age, gender, urban/rural residence, birth country, health region, aggregated diagnosis groups, cancer stage, treatment, and year of diagnosis, no significant association was found between SES and EAC survival. Moreover, increased mortality risk was observed among those with older age (P = 0.001), advanced-stage of EAC at diagnosis (P < 0.001), and those receiving chemotherapy alone, radiotherapy alone, or surgery plus chemotherapy (P < 0.001). Adjusted proportional-hazards model findings suggest that there is no association between SES and EAC survival. While the unadjusted model suggests reduced survival among individuals in lower income quintiles, this is no longer significant after adjusting for any covariate. Additionally, there is an apparent association between SES and survival when considering only those individuals diagnosed with stage 0-III EAC. These analyses suggest that the observed direct relationship between SES and survival is explained by patient-level factors including receipt of treatment, something that is potentially modifiable.


The influence of covalent immobilization conditions on antibody accessibility on nanoparticles.
The accessibility of particle-coupled antibodies is important for many analytical applications, but comprehensive data on parameters controlling the accessibility are scarce. Here we report on the site-specific accessibility of monoclonal antibodies, immobilized on magnetic nanoparticles (500 nm) by the widely used covalent EDC coupling method, with the variation of four key coupling parameters (surface activation and immobilization pH, crosslinker and antibody concentration ratios). By developing quantitative radio-labelled assays, the number of immobilized antibodies, the Fab domain accessibility (in a sandwich immunoassay), and the Fc domain accessibility (in a Protein G assay) were determined. For sub-monolayer surface coverage, the observed numbers of accessible Fab and Fc domains are equal and scale linearly with the antibody density. For above monolayer coverage, the fractions of accessible Fab and Fc domains decrease, in an unequal manner. The results show that the antibody accessibility is primarily determined by the antibody surface density, rather than by chemical reactivity or the charge state, and that crowded conditions affect Fab and Fc accessibility in an unequal manner.


CDKN2A-mediated molecular subtypes characterize the hallmarks of tumor microenvironment and guide precision medicine in triple-negative breast cancer.
Currently, breast cancer (BRCA) has become the most common cancer in the world, whose pathological mechanism is complex. Among its subtypes, triple-negative breast cancer (TNBC) has the worst prognosis. With the increasing number of diagnosed TNBC patients, the urgent need of novel biomarkers is also rising. Cyclin-dependent kinase inhibitor 2A (CDKN2A) has recently emerged as a key regulator associated with ferroptosis and cuproptosis (FAC) and has exhibited a significant effect on BRCA, but its detailed mechanism remains elusive. Herein, we conducted the first converge comprehensive landscape analysis of FAC-related gene CDKN2A in BRCA and disclosed its prognostic value in BRCA. Then, an unsupervised cluster analysis based on CDKN2A-correlated genes unveiled three subtypes, namely cold-immune subtype, IFN-γ activated subtype and FTL-dominant subtype. Subsequent analyses depicting hallmarks of tumor microenvironment (TME) among three subtypes suggested strong association between TNBC and CDKN2A. Given the fact that the most clinically heterogeneous TNBC always displayed the most severe outcomes and lacked relevant drug targets, we further explored the potential of immunotherapy for TNBC by interfering CDKN2A and constructed the CDKN2A-derived prognostic model for TNBC patients by Lasso-Cox. The 21-gene-based prognostic model showed high accuracy and was verified in external independent validation cohort. Moreover, we proposed three drugs for TNBC patients based on our model via targeting epidermal growth factor receptor. In summary, our study indicated the potential of CDKN2A as a pioneering prognostic predictor for TNBC and provided a rationale of immunotherapy for TNBC, and offered fresh perspectives and orientations for cancer treatment via inducing ferroptosis and cuproptosis to develop novel anti-cancer treatment strategies.


Responses to crizotinib and cabozantinib in patient with lung adenocarcinoma harboring mesenchymal-epithelial transition factor exon 14 skipping mutation: A case report.
Lung cancer is a leading cause of cancer-related mortality worldwide. Currently, targeted therapy has proved highly efficient in the treatment of advanced non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor (MET) is considered a validated molecular target in NSCLC. Given the low incidence of MET exon 14 skipping mutation, the planning of precision treatment for patients is a clinical problem that needs to be solved. In this report, we present a MET-positive case that benefited from crizotinib and cabozantinib treatment. A 77-year-old patient was diagnosed with lung adenocarcinoma in our hospital. Positron emission tomography-computed tomography (PET-CT) showed a right upper lobe mass (58 × 56 mm, SUVmax 15.6), right hilar enlarged lymph nodes, and multiple bone and left adrenal metastases (c-T3N1M1c). MET exon 14 mutation (exon14, c.2888-1G>C) was examined using the lung puncture sample by next generation sequencing. Therefore, the patient was diagnosed with late-stage lung adenocarcinoma with MET exon14 skipping gene mutation. Crizotinib was given as the first-line treatment from August 2019. Considering the resistance of crizotinib, cabozantinib was given for second-line treatment. Crizotinib was administered (250 mg bid) for 8 months, and her disease achieved partial regression (PR) and progression-free survival (PFS), which lasted for 8 months. The patient also reached PR after the second-line treatment with cabozantinib, and is currently under follow-up, with an overall survival (OS) of >12 months. As MET exon 14 skipping mutation is rare in clinical practices, MET-TKIs (tyrosine kinase inhibitors) treatment can boost curative effects and improve prognosis of patients with advanced lung adenocarcinoma. This case report supports a rationale for the treatment of lung adenocarcinoma patients with a MET exon 14 skipping mutation and provides alternative treatment options for these types of NSCLC patients.


Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts.
Topical application of pantothenate is widely used in clinical practice for wound healing. Previous studies identified a positive effect of pantothenate on migration and proliferation of cultured fibroblasts. However, these studies were mainly descriptive with no molecular data supporting a possible model of its action. In this study, we first established conditions for an in vitro model of pantothenate wound healing and then analysed the molecular effects of pantothenate. To test the functional effect of pantothenate on dermal fibroblasts, cells were cultured and in vitro proliferation tests were performed using a standardized scratch test procedure. For all three donors analysed, a strong stimulatory effect of pantothenate at a concentration of 20 microg/ml on the proliferation of cultivated dermal fibroblasts was observed. To study the molecular mechanisms resulting in the proliferative effect of pantothenate, gene expression was analysed in dermal fibroblasts cultivated with 20 microg/ml of pantothenate compared with untreated cells using the GeneChip Human Exon 1.0 ST Array. A number of significantly regulated genes were identified including genes coding for interleukin (IL)-6, IL-8, Id1, HMOX-1, HspB7, CYP1B1 and MARCH-II. Regulation of these genes was subsequently verified by quantitative real-time polymerase chain reaction analysis. Induction of HMOX-1 expression by pantothenol and pantothenic acid in dermal cells was confirmed on the protein level using immunoblots. Functional studies revealed the enhanced suppression of free radical formation in skin fibroblasts cultured with panthenol. In conclusion, these studies provided new insight in the molecular mechanisms linked to the stimulatory effect of pantothenate and panthenol on the proliferation of dermal fibroblasts.


[A clinical observation on urogenital tuberculosis].
A clinical observation was made on 25 cases of urogenital tuberculosis experienced at the urological department of Chiba Prefectural Sawara Hospital between January 1973 and December 1982. They accounted for 0.28% of the 8,945 outpatients. There were 17 cases of urinary tuberculosis and 13 cases of genital tuberculosis. In urinary tuberculosis, the age distribution showed a peak in the fifties. There was a predominance in males. The patients in their twenties and fifties comprised 60% of the cases of genital tuberculosis. The kidney affected was predominantly the left kidney. Bladder tuberculosis was found in 7 cases. The majority of the epididymal tuberculosis were found in the right side. Bladder and renal symptoms were the chief complaints for 41.2% and 17.6%, of the cases, respectively. Thirty two percent of the patients had a history of tuberculosis. In cystoscopy, typical findings of tuberculosis were found in only 25% of the cases. Mycobacterium in urine could be detected in 33.3%. Accelerated blood sedimentation rate was detected in 65% of the cases. Pyelography revealed ureteral abnormality in the majority of the cases. Three of the 16 patients with renal tuberculosis underwent nephrectomy, and orchiectomy was performed on 6 of the 13 patients with epididymal tuberculosis.


Long-term health experience of jet engine manufacturing workers: IV. A comparison of central nervous system cancer ascertainment using mortality and incidence data.
To compare ascertainment of central nervous system (CNS) neoplasms with the use of mortality and incidence data as part of an occupational epidemiology study. Deaths were identified by matching the cohort of 223,894 jet engine manufacturing employees to the U.S. Social Security Administration death files and the National Death Index. Incident cancer cases were identified by matching the cohort to 19 state cancer registries. We identified 718 cases overall: 59% by the use of both mortality and cancer incidence tracing; 24% by the use of only mortality tracing, and 17% by the use of only cancer incidence tracing. Compared with state cancer registries, death certificates missed 38% of the malignant, more than six times the benign and nearly 1.5 times the unspecified CNS cases. The positive predictive value of death certificates, with cancer registry as gold standard, was 6% for unspecified, 35% for benign, and 86% for malignant histologies. Death certificates seriously underascertained benign and unspecified CNS tumors; analyses determined with mortality data would not accurately capture the true extent of disease among the cohort. Most state cancer registries have only collected nonmalignant CNS tumor information since 2004, which currently limits the usefulness of state cancer registries as a source of nonmalignant CNS tumor identification. Underascertainment of CNS deaths could seriously affect interpretation of results, more so if examining nonmalignant CNS.


Copy number variations associated with idiopathic autism identified by whole-genome microarray-based comparative genomic hybridization.
Autism spectrum disorder (ASD) has been thought to have strong genetic background, but major contributing genes or associated molecular-genetic pathways are yet to be identified. To explore the idiopathic ASD-associated copy number variations (CNVs), we conducted case-control study using whole-genome copy number analysis. Whole-genome microarray-based comparative genomic hybridization was carried out on 28 children (24 boys and four girls) diagnosed as ASD and 62 Korean adults (45 males and 17 females) without any signs of abnormalities and family history of genetic disorders as normal controls. Fluorescence in-situ hybridization and capillary electrophoresis-single-strand conformational polymorphism were used for quantitative verification of the ASD-associated CNVs. Thirty-eight CNVs were identified. Among them, the distributions of copy number loss CNVs on 8p23.1 (odds ratio: 5.1, 95% confidence interval: 1.7-14.5, P=0.003) and on 17p11.2 (odds ratio: uncalculable because of zero cell, P=0.008) were found to be significantly different between ASD and control groups. DEFENSIN family occurs in a cluster at 8p23.1 region. Fluorescence in-situ hybridization and capillary electrophoresis-single-strand conformational polymorphism coherently showed reduced copy number of DEFENSIN in cases with 8p23.1 copy number loss CNV, which validated microarray-based comparative genomic hybridization results; but there are no known coding genes in the CNV on 17p11.2. Our approach as well as results can help to elucidate the genetic mechanism of idiopathic ASD.


Constitutive expression of insulin receptor substrate (IRS)-1 inhibits myogenic differentiation through nuclear exclusion of Foxo1 in L6 myoblasts.
Insulin-like growth factors (IGFs) are well known to play essential roles in enhancement of myogenic differentiation. In this report we showed that initial IGF-I signal activation but long-term IGF-1 signal termination are required for myogenic differentiation. L6 myoblast stably transfected with myc-epitope tagged insulin receptor substrate-1, myc-IRS-1 (L6-mIRS1) was unable to differentiate into myotubes, indicating that IRS-1 constitutive expression inhibited myogenesis. To elucidate the molecular mechanisms underlying myogenic inhibition, IGF-I signaling was examined. IGF-I treatment of control L6 cells for 18 h resulted in a marked suppression of IGF-I stimulated IRS-1 association with the p85 PI 3-kinase and suppression of activation of Akt that correlated with a down regulation of IRS-1 protein. L6-mIRS1 cells, in contrast, had sustained high levels of IRS-1 protein following 18 h of IGF-I treatment with persistent p85 PI 3-kinase association with IRS-1, Akt phosphorylation and phosphorylation of the downstream Akt substrate, Foxo1. Consistent with Foxo1 phosphorylation, Foxo1 protein was excluded from the nuclei in L6-mIRS1 cells, whereas Foxo1 was localized in the nuclei in control L6 cells during induction of differentiation. In addition, L6 cells stably expressing a dominant-interfering form of Foxo1, Δ256Foxo1 (L6-Δ256Foxo1) were unable to differentiate into myotubes. Together, these data demonstrate that IGF-I regulation of Foxo1 nuclear localization is essential for the myogenic program in L6 cells but that persistent activation of IGF-1 signaling pathways results in a negative feedback to prevent myogenesis.


Impacted Incus Foreign Body in the Eustachian Tube.
Foreign bodies in the external auditory canal are fairly common, and tend to be seeds, toys, or insects. However, foreign bodies in the middle ear are rarer and are generally accidental or iatrogenic. Although there are numerous reports regarding fascinating foreign bodies in the ear, the same cannot be said about foreign bodies in the Eustachian tube (ET). A 20-year-old male patient presented with right-sided active squamosal chronic otitis media (COM) persisting for 10 years. An incidental finding of a hyperintense foreign body (FB) located near the isthmus of the right ET was reported on high-resolution computed tomography (HRCT) of the temporal bones. The FB was bony (eroded incus), which was impacted near the isthmus of the ET and was extremely difficult to remove. A natural FB such as an eroded ossicle in the ET which aggravated the adhesive otitis and caused active squamosal COM has not been reported in the literature. We have reported this case not only for its rarity but also to make readers aware of such incidental findings which can be found only by imaging, and to suggest how they can be tackled with current equipment and technology.


Endogenous antioxidant status in neoplastic and adjacent tissues in 1,2-dimethylhydrazine-induced colon cancer in rats: effects of olsalazine.
There is much evidence suggesting a possible role of reactive oxygen-derived substances in the pathogenesis of both ulcerative colitis and colon cancer. The antioxidant effects of 5-aminosalicylic acid (the active moiety of olsalazine) on induction of colon cancer in an experimental model using 1,2-dimethylhydrazine were studied in male Wistar rats. The levels of reduced glutathione were significantly (P < 0.01) decreased (by approximately 50%) in neoplastic tissues of rats receiving 1,2-dimethylhydrazine alone and olsalazine treatment significantly (P < 0.01) reduced the extent of this alteration. Adjacent tissues from rats receiving either carcinogen alone or carcinogen and olsalazine showed comparable levels of glutathione and these were significantly (P < 0.01) lower than corresponding control values and higher than corresponding values from neoplastic tissues. Activity of the glutathione regenerating enzyme glutathione reductase was significantly (P < 0.01) decreased (by approximately 40%) in neoplastic colonic tissue and this alteration was unaffected by olsalazine treatment. Neither carcinogen nor olsalazine treatment caused alterations in activity of glutathione reductase in adjacent tissue as compared with corresponding control values. Activity of the glutathione utilizing enzyme glutathione peroxidase was significantly (P < 0.01) increased (almost doubled) in neoplastic tissue of rats treated with carcinogen alone. Olsalazine treatment significantly (P < 0.01) reduced the elevation in glutathione peroxidase activity in neoplastic tissues of rats treated with the carcinogen. Glutathione peroxidase showed comparable activity in adjacent tissue from rats treated with either carcinogen alone or a combination of carcinogen and olsalazine and these values were significantly (P < 0.01) lower than corresponding control values. Colonic neoplastic tissues from all experimental groups of animals showed a small, but statistically significant (P < 0.05), decrease in superoxide dismutase activity compared with that in corresponding tissues from control animals.


[Transcatheter aortic valve implantation (TAVI): update on the indications].
Although surgical aortic valve replacement has been the standard of care for patient with severe aortic stenosis, transcatheter aortic valve implantation (TAVI) is now a fair standard of care for patients not eligible or high risk for surgical treatment. The decision of therapeutic choice between TAVI and surgery considers surgical risk (estimated by the Euro-SCORE and STS-PROM) as well as many parameters that go beyond the assessment of the valvular disease's severity by echocardiography: a multidisciplinary assessment in "Heart Team" is needed to assess each case in all its complexity.


Progressive accumulation of lanthanum in the liver of normal and uremic rats.
The loss of renal function in chronic kidney disease (CKD) patients leads to a variety of metabolic disturbances that promote the development of secondary hyperparathyroidism (SH) and bone disease. One of these alterations, hyperphosphatemia, is a persistent problem in patients with CKD and is an important factor in the development and severity of SH as well as coronary artery and cardiac valve calcification. To help control serum phosphorus (P), phosphate binders are used to minimize intestinal absorption of P in these patients. Since the use of aluminum- and calcium-based phosphate binders can result in severe side effects, other phosphate binders have been proposed. One of these is lanthanum (La) carbonate. Since there is some controversy as to the degree La is absorbed by the intestine, whether it is deposited in tissues, and what effect its prolonged use would have in patients with chronic renal failure, we studied normal and uremic rats fed a control diet or a diet with La carbonate (1.5% elemental La) for 45, 90, or 110 days. As expected, plasma creatinine increased after the induction of uremia and continued to increase with time. At 45 and 90 days, dietary La produced a reduction in plasma P in normal rats (N + La) [45 days: 3.15 +/- 0.35 vs. normal control (NC) 4.41 +/- 0.15 mg/dL, P < 0.01; 90 days: 3.20 +/- 0.30 vs. 4.09 +/- 0.15 mg/dL, P < 0.05], but not at 110 days. Plasma P was initially lower (45 days) in both groups of La-treated rats (U + La: 3.47 +/- 0.28 vs. UC: 4.91 +/- 0.27 mg/dL, P < 0.01), but was not at 90 and 110 days. Whole blood La content was not increased in rats fed the La diet and is, therefore, not a good indicator of the La content of tissue. La was increased in kidney, femur, and especially liver in normal and uremic rats fed the La diet. Uremia markedly enhanced tissue accumulation of La (liver, 110 days: N + La: 849 +/- 152 vs. U + La: 2676 +/- 479 ng/g wet wt, P < 0.01), which increased in a time-dependent manner. The increase in La in the liver of normal rats was 44-fold compared to control and 98-fold in the liver of uremic rats compared to uremic control. La accumulates in tissues, most strikingly in the liver, and renal failure accelerates the accumulation. While this was a relatively short-term study, La accumulation increased in a time-dependent manner. The effect of long-term La treatment on patients with chronic renal insufficiency needs to be evaluated.


[Heilongjiang population drop].
Heilongjiang has scored remarkable achievements in planned parenthood. In 1980 Heilongjiang's rate of natural growth in population dropped to 8.6/1000 with 290,000 less babies compared with 1979. More than 3.73 million women in the province have adopted birth control measures. At present, over 528,000 couples have been issued 1 child only certificates.


Sacubitril/Valsartan Improves Sexual Function and Fibrosis of the Clitoral and Vaginal Tissues in Female Spontaneously Hypertensive Rats.
Female sexual dysfunction is common in hypertension. The effects of sacubitril/valsartan (SAC/VAL) as a potential therapy for hypertension and heart failure have not been studied in relation to sexual function and genital fibrosis in female spontaneously hypertensive rats (SHRs). Thirty female SHRs were administered VAL, SAC/VAL, or saline. Ten normotensive female Wistar-Kyoto (WKY) rats were included in the control group. We assessed estrous cyclicity and sexual behavior in the female rats. In addition, the morphology of clitoral and vaginal tissues was evaluated by histological analyses. Western blotting and enzyme-linked immunosorbent assays were used to assess the levels of fibrotic markers in vaginal and clitoral tissues. Furthermore, the protein levels of phosphatase and tensin homolog deleted from chromosome 10 (PTEN), phosphoinositide-3-kinase (PI3K), and AKT expression were measured by Western blotting. SAC/VAL treatment improved hypertension-induced sexual dysfunction, exhibited as a prolonged estrus phase, increased receptivity and proceptive events, and decreased aggressive events, compared with those of VAL treatment and control SHRs without treatments. In addition, SAC/VAL-treated SHRs had lower levels of fibrotic markers, estradiol, and estrogen receptor α/β than the levels of VAL-treated SHRs or SHRs without treatment. Moreover, SAC/VAL decreased p-PTEN expression and increased p-PI3K and p-AKT expression at the protein level compared with those in VAL treatment alone. VAL and SAC/VAL treatments have significantly increased sexual receptivity and proceptivity, decreased aggressiveness, and improved the fibrosis of vaginal and clitoral tissues in female SHRs. However, SAC/VAL treatment shows more effective results compared with VAL treatment, which may be related to the PTEN/PI3K/AKT pathway.


Being 'in sync'-is interactional synchrony the key to understanding the social brain?
The past couple of decades produced a surge of interest in interaction synchrony. Moving from the study of behavioral coordination to investigating the coordination of psychophysiological and brain activity, relevant research has tackled a broad range of interactional settings with a multitude of measurement and analysis tools. This method diversity produced a host of interesting results converging on the fact that individuals engaged in social exchange tend to temporally align external as well as internal processes. Moreover, there appears to be a reciprocal relationship between the individuals' affective bond and the extent of synchronization, which together benefit interaction outcomes. Notably, however, the current breadth of study approaches creates challenges for the field, including how to compare findings and how to develop a theoretical framework that unites and directs ongoing research efforts. More concerted efforts are called for to achieve the conceptual and methodological clarity needed to answer core questions and enabling a balanced pursuit of both synchronous and asynchronous processes.


No association between a transcription factor Activating Protein 2beta (AP-2beta) gene variant and schizophrenia.
Genetic components are involved in the aetiology of schizophrenia. Activating Protein 2 (AP-2) transcription factors are essential for neural gene expression and neural development. Transcription factor AP-2beta has also been connected with monoaminergic genes and monoamine levels in various brain regions. Thus, the AP-2beta gene is a suitable candidate taking both the neurodevelopmental and dopamine hypotheses of schizophrenia into account. We investigated 135 schizophrenic patients and 382 control subjects with regard to an intronic AP-2beta variant without evidence of any association. We conclude that the investigated AP-2beta variant is not of major importance to schizophrenia in the investigated Swedish population.


Cognitive rehabilitation: learning from experience and planning ahead.
Cognitive rehabilitation has evolved to be a common clinical practice, despite questions regarding the scientific basis for its effectiveness. A selective interpretation of existing studies suggests that non-specific treatment factors play an important role in the efficacy of cognitive rehabilitation. Some future directions for the science and practice of cognitive rehabilitation are discussed.


Licensing virus-specific T cells to secrete the neutrophil attracting chemokine CXCL-8 during hepatitis B virus infection.
T cell functional plasticity helps tailor antiviral immunity during different phases of infections. We tested whether, during different phases of HBV infection, virus-specific T cells can acquire specific proinflammatory functions that could drive granulocyte/mononuclear cell liver infiltration. Multifunctional analysis of HBV-specific T cells during acute and chronic HBV infection revealed that HBV-specific T cells had the capacity to produce the neutrophil chemokine CXCL-8 but not IL-17. CXCL-8 producing T cells were detectable in the liver of chronic HBV patients with active hepatitis; while in acute HBV patients CXCL-8 production by T cells was temporally limited to the acute phase of disease, concomitant with the peak of liver inflammation. Characterization of the conditions necessary for the development of CXCL-8 producing T cells showed a requirement for IL-7 and IL-15 during T cell expansion. These data show that functional plasticity of virus-specific T cells spontaneously occurs during HBV infection and that an environment rich IL-7 and IL-15 can license T cells with the ability to produce CXCL-8 and potentially influence liver pathology.


Experiences of Greek women of water immersion during normal labour and birth. A qualitative study.
There is scarce information on water births in Greece, as few women labour and give birth in water. The Greek public health system does not provide water immersion as a birthing option, and so women can only experience this option in private healthcare settings. The aim of this study was to explore the key concepts and themes identified from an analysis of the experiences of women who laboured and gave birth immersed in water. This was a qualitative study involving twelve women who used water immersion during labour, of which nine had also a water birth. Individual interviews were conducted and their content was analysed using thematic analysis. Three main themes were identified: Water use as a natural way of birth, Mixed messages from the healthcare professionals, and Partner's supportive role during water birth. All women reported a positive birth experience and water immersion helped them cope with the pain of labour. They felt greatly empowered following birth and this contributed to successful breastfeeding for more than one year, in the majority of cases. They reported difficulties in finding healthcare professionals that were in support of their choices. The women felt highly supported by the partner's role. Labouring and giving birth immersed in water was met with great satisfaction by all women. The findings of this study have added to the current body of midwifery knowledge on how water immersion can improve a woman's experience and so support a normal birth outcome.


Quantum Refrigeration with Indefinite Causal Order.
We propose a thermodynamic refrigeration cycle which uses indefinite causal orders to achieve nonclassical cooling. The cycle cools a cold reservoir while consuming purity in a control qubit. We first show that the application to an input state of two identical thermalizing channels of temperature T in an indefinite causal order can result in an output state with a temperature not equal to T. We investigate the properties of the refrigeration cycle and show that thermodynamically, the result is compatible with unitary quantum mechanics in the circuit model but could not be achieved classically. We believe that this cycle could be implemented experimentally using tabletop photonics. Our result suggests the development of a new class of thermodynamic resource theories in which operations are allowed to be performed in an indefinite causal order.


[Clinical and molecular cytogenetic analysis of a family with mental retardation caused by an unbalanced translocation involving chromosomes 3 and 22].
To explore the genetic cause of a Chinese boy with unexplained mental retardation, and analyze the pattern of inheritance for his family. Routine karyotyping, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH) were used to detect chromosome abnormalities in the patient and his families. Chromosome analysis suggested that the proband and 7 affected individuals had an identical karyotype 46,XN,der(22)t(3;22)(q28;q13)pat, while his father and 5 other relatives carried a same karyotype of 46,XN,t(3;22)(q28;q13). His mother and other family members were normal. CMA analysis confirmed that the patient had a 9.0 Mb duplication at 3q28q29, in addition with a 1.7 Mb deletion at 22q13.3. Above results were confirmed by FISH. The abnormal phenotypes of the proband and his family members from five generations have conformed to those of 3q duplication and 22q13.3 deletion caused by unbalanced translocation involving chromosomes 3q and 22q. The presence of multiple patients in this family may be attributed to abnormal gametes produced by parental balanced translocations involving 3q and 22q.


Mortality and Survival after Surgical Treatment of Colorectal Cancer in Patients Aged over 80 Years.
The purpose of this study was to identify the clinical factors and tumor characteristics that predict the outcome of colorectal cancer patients aged >80 years. The data of 186 patients aged >80 years with colorectal cancer were collected from a computer database, and the variables were analyzed by both uni- and multivariate analyses. The 30-day mortality was 4% and the 90-day mortality 10%. The 1-year survival was 76%, and 27 (61%) of the 44 deaths were unrelated to cancer. The overall 5-year survival was 36%, the median survival 38 months, and the cancer-specific survival 40%. The recurrence rate after radical surgery was 22% and it was not affected by age. Kaplan-Meier estimates indicated that age, number of underlying diseases, radical operation, Union for International Cancer Control stage of the tumor, tumor size, number of lymph nodes involved, venous invasion, and recurrent disease were significant predictors of survival, but in the Cox regression model, only radical operation and venous invasion were independent prognostic factors for survival. After good surgical selection, low early mortality and acceptable long-term survival can be achieved even in the oldest old patients with colorectal cancer. However, low early mortality seems to underestimate the effects of surgery during the first postoperative year.


A link between impaired lung function and increased cardiac stress.
Patients with impaired lung function often have systemic inflammation. C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are markers for inflammation and cardiac stress, respectively. To evaluate the association between both markers and the potential impacts of lung disease on this relationship. CRP and NT-proBNP were prospectively measured in 697 consecutive outpatients (57.5 +/- 16.4 years) with chronic dyspnea. The patients were stratified into quartiles according to CRP levels (quartile 1: median CRP 0.35 mg/l; quartile 2: 1.50 mg/l; quartile 3: 3.62 mg/l; quartile 4: 10.90 mg/l) and classified into 2 categories based on the presence (n = 176) or absence (n = 521) of heart disease. Patients with at least moderately severe airway obstruction and those with interstitial lung disease had higher CRP values than patients without lung disease (median 3.50 vs. 4.34 vs. 1.80 mg/l, respectively; p < 0.01). In patients without heart disease, NT-proBNP values increased from CRP quartiles 1-3 to quartile 4 (median 47.4 vs. 82.1 pg/ml; p < 0.01) after adjusting for important covariates such as age, sex, body mass index, renal function and arterial hypertension. Likewise, the values for NT-proBNP were lower in CRP quartiles 1-3 than in quartile 4 (median 212.0 vs. 647.7 pg/ml; p < 0.01) in patients with heart disease after additional adjustment for the type of cardiac disorder. Lung disease had no direct effect on the relationship between CRP and NT-proBNP. Systemic inflammation that originates in the lung places an excess burden on the heart, which may contribute to the functional impairment of patients with advanced pulmonary disease.


Occupational exposures to air contaminants at the World Trade Center disaster site--New York, September-October, 2001.
Amid concerns about the fires and suspected presence of toxic materials in the rubble pile following the collapse of the World Trade Center (WTC) buildings on September 11, 2001, the New York City Department of Health (NYCDOH) asked CDC for assistance in evaluating occupational exposures at the site. CDC's National Institute for Occupational Safety and Health (NIOSH) collected general area (GA) and personal breathing zone (PBZ) air samples for numerous potential air contaminants. This report summarizes the results of the assessment, which indicate that most exposures, including asbestos, did not exceed NIOSH recommended exposure limits (RELs) or Occupational Safety and Health Administration (OSHA) permissible exposure limits (PELs). One torch cutter was overexposed to cadmium; another worker was overexposed to carbon monoxide (CO) while cutting metal beams with an oxyacetylene torch or a gasoline-powered saw, and two more were possibly overexposed to CO. NIOSH recommended that workers ensure adequate on-site ventilation when using gas-powered equipment and use rechargeable, battery-powered equipment when possible.


Gaucher's disease type I: a disease masked by the presence of abnormal laboratory tests common to primary liver disease.
Gaucher's disease (GD) may go undiagnosed for many years, leading to severe complications that are preventable or reversible by enzyme replacement therapy with imiglucerase. GD is associated with cytopenia, bone complications, hepatosplenomegaly, hypermetabolism, and hyperactivity of the immune system manifested by polyclonal hyper gamma-globulinemia and an increased incidence of monoclonal gammopathies. High ferritin and presence of autoimmune antibodies may present and because of these abnormalities, clinical similarities with primary liver diseases may occur. We report on two patients who suffered diagnostic delay that could potentially lead to life-threatening manifestations of GD. Potential complications include: avascular necrosis, severe bleeding, chronic bone pain, life-threatening sepsis, pathologic fractures, growth failure, and liver pathology. Physician awareness will increase the likelihood of prompt detection of GD and improve its management.


Cantharidin toxicosis in 2 alpacas.
Two adult alpacas were presented for recumbency and reluctance to rise. Cantharidin toxicosis was suspected based on clinical and ancillary diagnostic findings. The diagnosis was confirmed by gas chromatography-mass spectrometry of gastric contents and urine. Despite medical treatment, neither alpaca survived. Blister beetle toxicosis has not been previously described in camelids. Challenges in treatment of affected ruminants or pseudoruminants are noted.


CXCL16 Stimulates Antigen-Induced MAIT Cell Accumulation but Trafficking During Lung Infection Is CXCR6-Independent.
Mucosa-associated invariant T (MAIT) cells are a unique T cell subset that contributes to protective immunity against microbial pathogens, but little is known about the role of chemokines in recruiting MAIT cells to the site of infection. Pulmonary infection with Francisella tularensis live vaccine strain (LVS) stimulates the accrual of large numbers of MAIT cells in the lungs of mice. Using this infection model, we find that MAIT cells are predominantly CXCR6+ but do not require CXCR6 for accumulation in the lungs. However, CXCR6 does contribute to long-term retention of MAIT cells in the airway lumen after clearance of the infection. We also find that MAIT cells are not recruited from secondary lymphoid organs and largely proliferate in situ in the lungs after infection. Nevertheless, the only known ligand for CXCR6, CXCL16, is sufficient to drive MAIT cell accumulation in the lungs in the absence of infection when administered in combination with the MAIT cell antigen 5-OP-RU. Overall, this new data advances the understanding of mechanisms that facilitate MAIT cell accumulation and retention in the lungs.


Numerical simulation of breast reduction with a new knitting condition.
Breast reduction is one of the most common procedures in breast surgery. The aim of this work is to develop a computational model allowing one to forecast the final breast geometry according to the incision marking parameters. This model can be used in surgery simulators that provide preoperative planning and training, allowing the study of the origin of the errors in breast reduction. From the mathematical point of view, this is a problem of calculus of variations with unusual boundary conditions, known as knitting conditions. The breast tissue is considered as a hyperelastic material, discretized with three-dimensional finite elements for the body, whereas the skin is modelled with two-dimensional finite elements on the curved surface. Although the model is of low precision, we show that it is sufficient for a satisfactory prediction of breast reduction surgery results, allowing an analysis of errors frequently performed during the surgery and giving an understanding of how to avoid or correct them. Copyright © 2016 John Wiley & Sons, Ltd.


Increased serum C-reactive protein levels are associated with shorter survival and development of second cancers in chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is characterized by a heterogeneous clinical course, ranging from stable to more aggressive disease. Herein, we determined the prognostic significance of serum C-reactive protein (CRP) levels in patients with CLL Methods: A retrospective cohort study reviewing the records of 107 consecutive treatment naïve patients with CLL and a control group comprised of apparently healthy individuals attending for periodic health examinations. The median CRP level of patients with CLL was 0.19 mg/dL (0-2.9). In univariate analysis, high-CRP levels (≥0.4 mg/dL) were significantly associated with an increased risk of mortality (HR = 3.97, 95%CI 1.64-9.62, p = .002) and development of second solid cancers (HR = 4.54, 95%CI 1.57-13.11, p = .005), compared to low-CRP values (<0.4 mg/dL). In multivariate analysis, high-CRP retained statistical significance for all-cause mortality (HR = 2.81, 95%CI 1.04-7.57, p = .04) and the development of second solid malignancies (HR = 4.54, 95%CI 1.57-13.11, p = .005). Moreover, when compared to an apparently healthy population, CLL patients with high CRP levels had more than an eightfold risk of cancer. Elevated baseline CRP levels are associated with shorter survival and development of second cancers in patients with CLL. We suggest that increased CRP in patients with CLL may justify a more rigorous search for second cancers. KEY MESSAGES Elevated CRP levels are associated with a shorter overall survival in CLL. Elevated CRP levels are associated with an increased risk of second cancers in CLL. Increased CRP in patients with CLL may justify a more rigorous search for second cancers.


Biochemistry and regulation of aurone biosynthesis.
Aurones are a group of flavonoids that confer a bright yellow coloration to certain ornamental flowers and are a promising structural target for the development of new therapeutic drugs. Since the first identification of the snapdragon aurone synthase as a polyphenol oxidase (PPO) in 2000, several important advances in the biochemistry and regulation of aurone biosynthesis have been achieved. For example, several other aurone synthases have been identified in distantly related plants, which not only include PPOs but also peroxidases. Elucidation of the subcellular localization of aurone biosynthesis in snapdragon led to the establishment of a method to genetically engineer novel yellow flowers. The crystal structure of an aurone-producing PPO was clarified and provided important insights into the structure-function relationship of aurone-producing PPOs. A locus (SULFUREA) that negatively regulates aurone biosynthesis in snapdragon was identified, illustrating the evolution of flower color pattern through selection on regulatory small RNAs.


Melittin-GM1 interaction: a model for a side-by-side complex.
We report here the interaction of melittin with ganglioside GM1 by steady-state fluorescence, one-dimensional (1)H NMR spectroscopy and molecular modeling. In the presence of GM1 the emission maximum of melittin is blue shifted and fluorescence quenching efficiencies of iodide and acrylamide are substantially reduced, indicating a shielding of tryptophan of melittin from aqueous environment. Significant line broadening of NMR resonances of melittin, suggestive of motional restriction, is observed. Molecular modeling indicates a melittin-GM1 complex with N-terminal hydrophobic stretch of melittin associating with the ceramide tail and C-terminal hydrophilic end of melittin having favorable electrostatic interaction with the carbohydrate head group of GM1.


The brain-artefact interface (BAI): a challenge for archaeology and cultural neuroscience.
Cultural neuroscience provides a new approach for understanding the impact of culture on the human brain (and vice versa) opening thus new avenues for cross-disciplinary collaboration with archaeology and anthropology. Finding new meaningful and productive unit of analysis is essential for such collaboration. But what can archaeological preoccupation with material culture and long-term change contribute to this end? In this article, I introduce and discuss the notion of the brain-artefact interface (BAI) as a useful conceptual bridge between neuroplastisty and the extended mind. I argue that a key challenge for archaeology and cultural neuroscience lies in the cross-disciplinary understanding of the processes by which our plastic enculturated brains become constituted within the wider extended networks of non-biological artefacts and cultural practices that delineate the real spatial and temporal boundaries of the human cognitive map.