Hematocrit interference of blood glucose meters for patient self-measurement.
Abnormal hematocrit levels may interfere with glucose readings of patient self-assessment blood glucose (BG) meters. The aim of this laboratory investigation was to assess the potential influence of hematocrit variations on a variety of BG meters applying different measurement technologies. Venous heparinized blood was manipulated to contain three different BG concentrations (50-90, 120-180, and 280-350 mg/dl) and five different hematocrit levels (25%, 35%, 45%, 55%, and 65%). After careful oxygenation to normal blood oxygen pressure (65-100 mmHg), each sample was measured (eight times) with the following devices: Accu-Chek® Aviva Nano and Active, Breeze®2 and Contour®, FreeStyle Freedom Lite®, GlucoDr. auto™, Glucofix® mio Plus, GlucoLab™, GlucoMen® LX Plus, Nova Max® Link, Nova Max® Plus, OneTouch® Ultra®2 and Verio®, On Call® Plus and Platinum, Optium Xceed®, Precision Xceed®, and TaiDoc Fora TD-4227. A YSI 2300 STAT Plus™ glucose analyzer served as reference method. Stability to hematocrit influence was assumed, with <10% mean glucose result bias between the highest and lowest hematocrit levels. Six of the investigated meters showed a stable performance in this investigation: Accu-Chek Active (7%), Glucofix mio Plus (5%), GlucoMen LX Plus (4%), Nova Max Plus (4%), Nova Max Link (7%), and OneTouch Verio (3%). All other meters failed this hematocrit interference test, with FreeStyle Freedom Lite (11%), and On Call Platinum (12%) being the better devices and On Call Plus (68%), GlucoLab (51%), TaiDoc Fora TD-4227 (39%), and Breeze 2 (38%) showing the worst performance. Hematocrit may affect BG meter performance in daily routine. In case of interference, low hematocrit values (<35%) result in too high readings. Our results encourage use of meters that are not affected by hematocrit interference.


Dose-response and time-course of α-tocoferol mediating the cytoprotection of dental pulp cells against hydrogen peroxide.
This in vitro study evaluated the potential protective effect of vitamin E alpha-tocopherol (α-T) isomer against the toxicity of hydrogen peroxide (HP) applied on dental pulp cells. Odontoblast-like MDPC-23 cells were seeded on 96-well plates for 72 h, treated with different concentrations of α-T (1, 3, 5, and 10 mM) for different times (1, 4, 8, and 24 h) and then exposed or not to a 0.018% HP solution for 30 min. In positive and negative control groups, cells were exposed to HP or culture medium (DMEM containing 5% DMSO), respectively. Cell viability was assessed by the MTT assay and the absorbance numeric data, expressed as percentage values, were subjected to the statistical analysis by Kruskal-Wallis and Mann-Whitney tests (α=5%). Considering the cells in the negative control as having 100% of cell viability, all combinations of α-T concentrations and pretreatment times showed a protective effect against HP cytotoxicity. Significant reduction of cell viability (59%) was observed in the positive control compared with the negative control. The highest values of pulp cell viability were obtained after pretreatment with 1 and 3 mM α-T concentrations for 24 h followed by exposure to HP (126% and 97% of cell viability, respectively). Under the tested conditions, the most effective cell protection against the cytotoxic effects of HP was provided by the lowest concentrations of α-T (1 and 3 mM) applied for 24 h.


Validity and reliability of the ankle-brachial index by oscillometric blood pressure and automated ankle-brachial index.
This study was conducted to assess the validity and reliability of ankle-brachial index (ABI) by oscillometric blood pressure (BP) measurement as compared with an automated ABI as a gold standard. This study was conducted at Golden Jubilee Medical Center, Thailand. All the data were collected from 303 patients at risk of peripheral arterial disease (PAD) who were 45 years of age or above and who underwent treatment at the outpatient medical clinic between June and December 2015. Patients who were followed up at the medical clinic had both oscillometric BP measurement (Terumo, ES-P600) and an automated ABI (oscillometric method) at the same time. Sensitivity, specificity, positive predictive value, and negative predictive value of the oscillometric BP measurements to predict an abnormal ABI (<0.90) were determined using the automated ABI as the gold standard. ABI values were similar between the two methods. The oscillometric BP method for determining an ABI (cutoff point <0.90) on the right side had a sensitivity of 88.89%, specificity of 99.32%, an accuracy of 99.01%, a positive predictive value of 80%, and a negative predictive value of 99.32% whereas ABI on the left side had a sensitivity of 69.23%, a specificity of 99.66%, an accuracy of 98.35%, a positive predictive value of 90%, and a negative predictive value of 98.63%. Reliability of the oscillometric BP method by Kappa statistics was 0.84 on the right side and 0.77 on the left side (P = 0.000). The oscillometric BP method is a reliable and useful alternative to conventional automated ABI determination in patients with no severe arterial occlusion for estimation of the prevalence and screening of PAD in primary health-care settings.


Clinical and angiographic outcomes after combined direct and indirect bypass in adult patients with moyamoya disease: A retrospective study of 76 procedures.
The present retrospective study was performed to evaluate the clinical outcome, as well as post-operative collateral formation and revascularization patterns in combined bypass. Surgical revascularization has been the mainstay of treatment for moyamoya patients. A total of 76 hemispheres from 64 moyamoya patients undergoing combined superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS) were retrospectively reviewed. Computed tomography perfusion and DSA were routinely performed. Modified Rankin scale (mRS) scoring and Kaplan-Meier analysis were performed, and post-operative collateral grading on digital subtraction angiography (DSA), reconstruction patterns and vessel diameter were measured to evaluate the revascularization area and vascular compensatory effect. During the follow-up period, the chief complaint was partially alleviated in 57/64 patients (89.1%). In all patients, mRS was significantly decreased after the operation. Good revascularization was established in most patients at 6 months after the surgery: 92.1% of sides were scored as 2 and 77.6% were scored as 3 by post-operative collateral grading on DSA. Dominant collateral revascularization originating from EDMS was more frequent than that from STA-MCA anastomosis (31 vs. 19 hemispheres) at 6-month follow-up. Morphologically, the calibers of the STA main trunk (2.60±0.65 mm) increased profoundly at the first 10 post-operative days (3.32±1.05 mm) and shrank back to pre-operative status at 6 months (2.20±1.01 mm) and 12 months (2.36±0.73 mm) according to DSA examination. Middle meningeal artery (MMA) and deep temporal artery (DTA) demonstrated continuous augmentation during the follow-up time (from 1.30±0.46 to 1.87±0.69 mm for MMA and 1.11±0.25 to 2.11±1.16 mm for DTA). These results strongly suggested that combined STA-MCA bypass and EDMS provided efficient revascularization and reduced acute cerebral events. The direct STA-MCA bypass provided early augmentation of cerebral perfusion, whereas the indirect EDMS provided a more durable long-term revascularization, indicating a complementary association between the two revascularization methods.


Boron-containing enamine and enamide linchpins in the synthesis of nitrogen heterocycles.
The use of α-boryl enamine and enamide linchpins in the synthesis of nitrogen heterocycles has been demonstrated. Boryl enamines provide ready access to the corresponding α-halo aldehydes, which undergo regioselective annulation to form borylated thiazoles. A condensation/amidation sequence converts α-boryl aldehydes into stable α-boryl enamides without concomitant C → N migration. We also show that palladium-catalyzed cyclization of α-boryl enamides leads to synthetically versatile isoindolones. These molecules can be subsequently used to access polycyclic scaffolds.


Chronic illness and early development. The parent's perspective.
While many chronic illnesses are diagnosed in infancy, there is little systematic study of the impact of chronic illness on early social development and how parental adjustment to a chronically ill infant contributes to subsequent outcomes. This paper outlines some of the factors which affect parents' ability to care for chronically ill infants and preschoolers. It draws upon studies of infants with other medical problems, ongoing longitudinal study of infants with cystic fibrosis and congenital heart disease by the authors; and the authors' clinical experience.


Modification of X-ray induced chromosome aberration frequency by pre- and postirradiation hyperthermia of human peripheral lymphocytes.
Human peripheral lymphocytes (HPL) were used to study the synergistic effects of hyperthermia and X-irradiation. The effects on the chromosome aberration frequencies of different combinations of heat and radiation exposure at different cell cycle phases were analysed at the first mitosis after irradiation. When unstimulated HPL were heated after irradiation with 2 and 3 Gy, respectively, the chromosomal aberration frequencies were significantly higher than following radiation exposure alone. Heat treatment during different phases of the cell cycle and irradiation during the G2 phase led to an increase in the aberration frequencies when the cells were heat-treated not later than 16 h before radiation. Furthermore we show that the number of breaks increased linearly with the duration of hyperthermia when HPL were heated for periods of 1-15 min at 45 degrees C 32 h before irradiation at 48 h after stimulation. Heat treatment alone during any phase of the cell cycle did not induce chromosome aberrations. The increased aberration frequencies are probably the result of inhibited repair of radiation-induced DNA strand breaks.


Horner syndrome: clinical perspectives.
Horner syndrome consists of unilateral ptosis, an ipsilateral miotic but normally reactive pupil, and in some cases, ipsilateral facial anhidrosis, all resulting from damage to the ipsilateral oculosympathetic pathway. Herein, we review the clinical signs and symptoms that can aid in the diagnosis and localization of a Horner syndrome as well as the causes of the condition. We emphasize that pharmacologic testing can confirm its presence and direct further testing and management.


[A case of miliary tuberculosis complicated with a tuberculous aneurysm of the aorta].
A 68-year-old man was admitted because of fever and weight loss. A chest high-resolution computed tomography (HRCT) scan revealed diffuse micronodular shadows, and an abdominal CT scan showed an aneurysm spreading from the root of the renal artery to the iliac bifurcation. His fever subsided without treatment and his general condition was good. However, histological studies of a transbronchial lung biopsy specimen and bone marrow aspirate clot revealed non-necrotizing epitheloid granulomas, and mycobacterium tuberculosis was cultured from sputum and bronchoalveolar lavage fluids. Military tuberculosis was diagnosed. One month after the initiation of chemotherapy, the abdominal aneurysm enlarged quickly despite the improvement of the thoracic findings, and graft replacement was performed. Histological findings in specimens of the resected aneurysm suggested that tuberculous inflammation of the surrounding lymph nodes had invaded the aortic wall, leading to the aneurysm. It should be borne in mind that symptoms in elderly patients with miliary tuberculosis may be mild, even when serious extrapulmonary lesions are present.


Cholinesterase inhibitory activities of Apai-sa-le recipe and its ingredients.
Acetylcholinesterase and butyrylcholoinesterase inhibitors are well-known drugs commonly used in the treatment ofAlzheimer's disease (AD) to improve cognitive function. These enzyme inhibitors were reported to be found in manyplants. Apai-sa-le recipe was a Thai tradition used as nootropic recipe and formerly claimed to improve memory. Therefore, it is interesting to investigate cholinesterase inhibitory activity ofthe recipe and its ingredients. To determine the whole recipe ofApai-sa-le and its ingredients for inhibitory effect on acetylcholinesterase (AChE) and human butyrylcholinesterase (BuChE) activities. Thirty grams of each plant and 181 grams of the whole recipe were separately extracted by 95% ethanol, after filtered the filtrate were evaporated and vacuum-dried at 45°C. By Elman method, the inhibitory activities of both enzymes were assessed. The volatile constituents ofeach extract were determined by GCMS. The constituents in the non- volatile extract were examined by TLC and the antioxidant activity was determined. Four plants exhibited specific BuChE inhibitor were Lepidium sativum Linn. (Ls), Piper nigrum L. (Pn), Angelica dahurica Benth (Ad) andAtractylodes lancea DC. (Al), which shown the lC50 of 5.59, 24.52, 73.23, 96.25 μg/ml, respectively whereas galantamine and the whole recipe showed IC50 of 0.59 and 236 μg/ml. Only Pn extract inhibited AChE at lCso of 25.46 μg/ml. By GCMS and TLC fingerprints revealed the main constituents in LS, Ad, Al andPn as apiol, cumialdehyde, furanodiene and piperine. Moreover nine plant extracts and the whole recipe showed antioxidant activity. Lepidium sativum Linn. (Ls) extract showed the most potency on BuChE inhibitory effect. Three ingredients and the whole recipe exhibited mild activity. Only Piper nigrum L demonstrated inhibition effect on both AChE and BuChE.


Testicular lymphoma: organ-specific treatment did not improve outcome.
To assess whether the use of an organ-specific treatment could improve event-free survival (EFS) and overall survival as endpoints in testicular lymphoma in the early stage: IE and IIE. Thirty-four patients were selected to be treated with orchiectomy following six cycles of anthracycline-based combined chemotherapy and radiotherapy (scrotum and contralateral testis in stage IE, contralateral testis and lymph nodes in stage IIE). Prophylaxis to the central nervous system was administered with four monthly cycles of a high dose of methotrexate: 6 g/m2. Complete response was achieved in 33 cases (97%). However, relapses continue to be the rule; at a median follow-up of 74 months (range 61-120), 21 patients relapsed. Thus, actuarial curves at 5 years were 32% for EFS and 30% for overall survival, because all patients with failure and relapse died of tumor progression. Relapses were observed in uncommon sites: lung, bone marrow and as disseminate disease; no relapses were observed in irradiated sites of the central nervous system. Testicular lymphomas remain a problem as regards defining the optimal treatment. The use of a specific treatment based on organ-involved sites did not show any improvement in outcome. It is evident that more specific therapies need to be explored.


STAT3 restrains RANK- and TLR4-mediated signalling by suppressing expression of the E2 ubiquitin-conjugating enzyme Ubc13.
The transcriptional regulator STAT3 curbs pro-inflammatory cytokine production mediated by NF-κB signalling in innate immune cells, yet the mechanism by which this occurs has been unclear. Here we identify STAT3 as a pivotal negative regulator of Ubc13, an E2 ubiquitin-conjugating enzyme that facilitates TRAF6 K63-linked ubiquitination and NF-κB activation. Ubc13 accumulates intracellularly in the absence of STAT3. Depletion of Ubc13 in Stat3-deficient macrophages subdues excessive RANKL- or LPS-dependent gene expression, indicating that Ubc13 overexpression mediates enhanced transcriptional responses in the absence of STAT3. In RANKL-activated macrophages, STAT3 is stimulated by autocrine IL-6 and inhibits accrual of Ets-1, Set1 methyltransferase and trimethylation of histone H3 lysine 4 (H3K4me3) at the Ube2n (Ubc13) promoter. These results delineate a mechanism by which STAT3 operates as a transcriptional repressor on Ube2n, thus modulating NF-κB activity by regulation of Ubc13 abundance. Our data suggest that this pathway plays important roles in bone homeostasis and restraint of inflammation.


Solid-state and solution-state coordination chemistry of lanthanide(III) complexes with (pyrazol-1-yl)acetic acid.
As a precursor of carboxyl-functionalized task-specific ionic liquids (TSILs) for f-element separations, (pyrazol-1-yl)acetic acid (L) can be deprotonated as a functionalized pyrazolate anion to coordinate with hard metal cations. However, the coordination chemistry of L with f-elements remains unexplored. We reacted L with lanthanides in aqueous solution at pH = 5 and synthesized four lanthanide complexes of general formula [Ln(L)3(H2O)2]·nH2O (1, Ln = La, n = 2; 2, Ln = Ce, n = 2; 3, Ln = Pr, n = 2; 4, Ln = Nd, n = 1). All complexes were characterized by single crystal X-ray diffraction analysis revealing one-dimensional chain formations. Two distinct crystallographic structures are governed by the different coordination modes of carboxylate groups in L: terminal bidentate and bridging tridentate (1-3); terminal bidentate, bridging bidentate, and tridentate coordination in 4. Comparison of the solid state UV-vis-NIR diffuse reflectance spectra with solution state UV-vis-NIR spectra suggests a different species in solution and solid state. The different coordination in solid state and solution was verified by distinctive (13)C NMR signals of the carboxylate groups in the solid state NMR.


Textile-Based Electronic Components for Energy Applications: Principles, Problems, and Perspective.
Textile-based electronic components have gained interest in the fields of science and technology. Recent developments in nanotechnology have enabled the integration of electronic components into textiles while retaining desirable characteristics such as flexibility, strength, and conductivity. Various materials were investigated in detail to obtain current conductive textile technology, and the integration of electronic components into these textiles shows great promise for common everyday applications. The harvest and storage of energy in textile electronics is a challenge that requires further attention in order to enable complete adoption of this technology in practical implementations. This review focuses on the various conductive textiles, their methods of preparation, and textile-based electronic components. We also focus on fabrication and the function of textile-based energy harvesting and storage devices, discuss their fundamental limitations, and suggest new areas of study.


Fusarium oxysporum f. sp. mori, a New Forma Specialis Causing Fusarium Wilt of Blackberry.
Fusarium oxysporum has recently been identified as the cause of a wilt disease affecting blackberry in California and Mexico. Thirty-six isolates of F. oxysporum obtained from symptomatic blackberry plants in California and Mexico were comprised of nine distinct somatic compatibility groups (SCGs). Phylogenetic analysis of a concatenated data set, consisting of sequences of the translation elongation factor 1-α and β-tubulin genes and the intergenic spacer of the ribosomal DNA, identified nine three-locus sequence types, each of which corresponded to an SCG. Six SCGs were present only in California, two only in Mexico, and one in both California and Mexico. An isolate associated with the most common SCG in California was tested for pathogenicity on blueberry, raspberry, strawberry, and lettuce. All blueberry, raspberry, and lettuce plants that were inoculated remained healthy, but two of the five strawberry cultivars tested developed symptoms. The three strawberry cultivars that were resistant to the blackberry pathogen were also resistant to F. oxysporum f. sp. fragariae, the cause of Fusarium wilt of strawberry. We propose to designate strains of F. oxysporum that are pathogenic to blackberry as Fusarium oxysporum f. sp. mori forma specialis nov.


Stage IV thymic carcinoma: a study of 20 patients.
This study was performed to investigate the clinical factors, tumor characteristics, treatment approach, and prognosis of patients with Stage IV thymic carcinoma (WHO type C). The records of 20 patients with histologically confirmed thymic carcinoma treated between 1988 and 2002 at the Division of Oncology at Taipei Veterans General Hospital were reviewed. Therapy consisted of surgical debulking, adjuvant radiotherapy, and chemotherapy in six patients (30%), surgical debulking with adjuvant chemotherapy in two patients (10%), surgical debulking with adjuvant radiotherapy in one patient (5%), radiotherapy with adjuvant chemotherapy in eight patients (40%), and chemotherapy alone in three patients (15%). After a median follow-up of 22 months (range, 5-72 months), three patients (15%) were alive. Eighteen patients (90%) experienced disease recurrence after a median of 9 months (range, 2-41 months); 12 (66%) of these patients initially had stage IVa disease, and 6 (33%) had stage IV b disease. Five patients had an undifferentiated type of histology. The median time to progression was 5 months. However, none of these patients was able to receive salvage therapy due to their poor performance status. For those patients with a lymphoepithelioma-like histology, the median survival was 36 months; there was tumor recurrence in five patients and they all received salvage chemotherapy. The median survival time for these five patients was 51 months. For patients with squamous cell type, the median time to progression was 10 months. Five patients received salvage chemotherapy and the median survival was 28 months. There was a significant difference (P < 0.0001) in the median survival between those who received chemotherapy (18 months) after tumor relapse and those who did not (1 month). Our results indicate that multidisciplinary treatment, including surgery, radiotherapy, and chemotherapy, is beneficial in treating primary thymic carcinoma. Chemotherapy plays an important role in both primary and relapsed stage IV thymic carcinoma in terms of prolonging the disease-free survival and median survival of patients with lymphoepithelioma-like or squamous cell histology types. For patients with an undifferentiated histology, multidisciplinary treatment or chemotherapy might not be helpful in either primary or relapsed stage IV thymic carcinoma.


'Flexible' or 'lifestyle' dialysis: is this the way forward?
Despite the advent of two new dialysis options, nocturnal home haemodialysis and short daily haemodialysis, many units are yet to build them into the modalities on offer to end-stage renal failure patients. The reasons behind this inertia are complex but primarily include anxieties about workload, budgetary implications and outcome data. The Geelong dialysis programme, where both nocturnal home haemodialysis and short daily haemodialysis are offered, is compared with Australian and New Zealand national profiles. Significant profile differences emerge when comparing sessions/week and h/week between the three groups. Most Australian (92.93%) and New Zealand (95.07%) haemodialysis patients dialyse for three sessions/week. This contrasts to Geelong where only 73.6% dialyse for three sessions/week. 18.8% of Geelong haemodialysis patients versus 1.8% (Australia) and 0.9% (New Zealand) dialyse for five or more sessions/week. Australia and New Zealand follow similar h/session patterns although more Australians (44.2%) dialyse for 4 h and fewer (24.2%) for 5 h than their New Zealand counterparts (39.6% and 29.8%, respectively), and few dialyse outside the 3.5-5 h window. In contrast, 6.7% of Geelong patients dialyse for 2-2.5 h/session versus Australia (0.9%) and New Zealand (0.2%). This represents the Geelong short daily dialysis programme. More Geelong patients (>15%) dialyse >/=8 h/week and represent the Geelong nocturnal home haemodialysis programme. The flexible Geelong programme has been supported without exceeding the budget applied to a conventional dialysis programme with the same patient numbers.


Hospital hypoglycemia: not only treatment but also prevention.
To propose a strategy, applicable on general hospital wards, for prevention of hypoglycemia in hospitalized patients. Although the mortality rate among hospitalized patients with hypoglycemia has been shown to be 22.2 to 27% in series that included patients with diabetes, some investigators have shown that hypoglycemia is not an independent predictor of mortality. Outside the critical care setting, the comparative risks of hyperglycemia and hypoglycemia and the relationship of hospital hypoglycemia to intensification of glycemic control have not been determined. The reported incidence of hospital hypoglycemia ranges from 1.2% for hospitalized adults to 20% for nonpregnant patients with diabetes admitted without a metabolic emergency. Among patients receiving antihyperglycemic therapy, the literature describes precipitating events--usually a sudden change of caloric exposure-- and predisposing conditions for hypoglycemic episodes. Hospital hypoglycemia is predictable, and it is preventable by measures other than undertreatment of hyperglycemia. Physician orders for antihyperglycemic therapy should be written and, if necessary, be revised so as to respond to the presence of predisposing conditions for hypoglycemia. A ward-based protocol or hospital-wide policy should establish the appropriate response to triggering events. Within the time frame of action of previously administered antihyperglycemic drugs (after abrupt interruption of caloric exposure), the threshold for preventive intravenous administration of dextrose is a glucose concentration of 120 mg/dL.


Quercetin and tin protoporphyrin attenuate hepatic ischemia reperfusion injury: role of HO-1.
Ischemia reperfusion (IR) injury occurs in many clinical situations such as organ transplantation and hepatectomies resulting in oxidative stress and immune activation. Heme oxygenase-1(HO-1) is the rate-limiting step in the heme-degradation pathway and has a critical cytoprotective role. Induction of HO-1 improves liver I/R injury. Quercetin, a plant pigment (flavonoid), is an antioxidant and HO-1 inducer. Tin protoporphyrin (SnPP) is a HO-1 inhibitor. This study was designed to investigate the protective effect of quercetin in hepatic I/R injury and the role of HO-1. Wister rats were randomly divided into four groups (sham, I/R, quercetin, and SnPP). Liver ischemia was induced for 45 min then reperfusion was allowed for 1 h. Quercetin and surprisingly SnPP ameliorate the deleterious effect of I/R by reducing the oxidative stress and hepatocyte degeneration. Both agents decreased the elevated inflammatory cytokines and improved the inhibition of the antiapoptotic marker, Bcl2. They induced HO-1 content and expression. Quercetin has better cytoprotective effect than SnPP. These findings suggest that quercetin has a hepatoprotective effect against I/R injury via HO-1 induction and unexpectedly, SnPP showed the similar effect. Quercetin has more prominent protective effect than SnPP because of its superior ability to induce HO-1.


Usability of and Satisfaction With Vocera Wireless Communication.
Qualitative reports of hands-free communication devices highlight numerous improvements in communication. The purpose of this study was to assess both usability and satisfaction scores at approximately 1 year after the implementation of a hands-free communication device at two different large military facilities. To do this, a survey that included the System Usability Scale and questions to assess satisfaction with regard to use, quality, and user satisfaction was provided to staff at both of these facilities. System usability scores indicated moderate satisfaction (61.7 at facility A, 63.8 at facility B). User satisfaction rated highest levels of agreement with the hands-free devices as an important system and being useful (35%-37% at facility A, 46% at facility B). Scores regarding improving the quality of work (A = 12%, B = 16%); safety of patients (A = 23%, B = 29%); and ability to do their job in a timely manner (A = 23%, B = 29%) were the lowest. The results highlight the potential benefits of Vocera for improving communication within the healthcare team. Given the large percentage of staff turnover at both of these facilities, the sustained benefit of hands-free devices will require ongoing training and continued evaluation of workflow processes.


The polymorphism of rs266729 in adiponectin gene and type 2 diabetes mellitus: A Meta-Analysis.
Genome-wide association studies and meta-analyses indicate that the polymorphism of rs266729 in adiponectin gene increases the risk of type 2 diabetes mellitus (T2DM); however, these study methods have not been able to identify the underlying genetic effect on the development of T2DM. A genetic model-free approach was conducted to determine the underlying genetic model of inheritance of T2DM because of rs266729 in adiponectin gene.We searched available studies on the association between the rs266729 in adiponectin gene and T2DM in accordance with the inclusion and exclusion criteria. Based on the information extracted from the studies, generalized odds ratio value (GOR) was used to evaluate whether the rs266729 polymorphism was a risk factor for T2DM. The parameter λ was calculated to estimate the genetic model, which was defined as the quotient of natural logarithm odds ratio of GC to CC divided by the natural logarithm odds ratio of GG to CC. Finally, binary logistic regression analysis was used to calculate the genetic effect of rs266729 on T2DM.Data from 7 studies were included in this meta-analysis. The total number of subjects was 12,323, comprising 5,948 cases and 6,395 controls. Mean (standard deviation) age of cases was 59.50 (11.53), and that of the controls was 53.80 (11.65), whereas the proportion of male was 40.9 and 50.0%, respectively. GOR was 1.13 (1.02, 1.25) and λ was 0.47 (0.29, 0.64). The result of logistic regression indicated that the G allele influenced the development of T2DM in the additive model, whereas the genetic effect was 1.13 (1.06, 1.19). Sources of control populations were the cause of between-study heterogeneity; nonetheless, there was no publication bias among studies.The G allele of rs266729 in adiponectin gene increases the risk of T2DM through an additive genetic model with an effect of 1.13 (1.06, 1.19).


Accelerated bilateral dynamic contrast-enhanced 3D spiral breast MRI using TSENSE.
To assess the ability of adaptive sensitivity encoding incorporating temporal filtering (TSENSE) to accelerate bilateral dynamic contrast-enhanced (DCE) 3D breast MRI. Bilateral DCE breast magnetic resonance imaging (MRI) exams were performed using a dual-band water-only excitation and a "stack-of-spirals" imaging trajectory. TSENSE was applied in the slab direction with an acceleration factor of 2. Four different techniques for sensitivity map calculation were compared by analyzing resultant contrast uptake curves qualitatively and quantitatively for 10 patient datasets. In addition, image quality and temporal resolution were compared between unaccelerated and TSENSE images. TSENSE can increase temporal resolution by a factor of 2 in DCE imaging, providing better depiction of contrast uptake curves and good image quality. Of the different methods tested, calculation of static sensitivity maps by averaging late postcontrast frames yields the lowest aliasing artifact level based on ROI analysis. TSENSE acceleration combined with 3D spiral imaging is very time-efficient, providing 11-second temporal resolution and 1.1 x 1.1 x 3 mm(3) spatial resolution over a 20 x 20 x 10 cm(3) field of view for each breast.


Toxic shock syndrome complicating influenza A in a child: case report and review.
Despite extensive literature on toxic shock syndrome, reports of its manifestations in children remain relatively uncommon. Similarly, toxic shock syndrome in association with influenza B or influenza-like illness has been reported in 12 patients, but it has been reported to occur following influenza A in only two patients to date. We report a third case of toxic shock syndrome in a child with influenza A and review the association between epidemic influenza and toxic shock syndrome ("the Thucydides syndrome").


[Chemical Exchange Saturation Transfer Imaging of Creatine Metabolites: a 3.0 T MRI Pilot].
To determine the feasibility of using chemical exchange saturation transfer (CEST) imaging to measure creatine (Cr) metabolites with 3.0 T MR. Phantoms containing different concentrations of Cr under various pH conditions were studied with CEST sequence on 3.0 T MR imaging. CEST effect and Z spectra were analyzed. Cr exhibited significant CEST effect (± 1.8 ppm, F = 99.08, P < 0.001) on 3.0 T MR imaging, and positive correlation was found between the signal intensity and concentration of Cr (r = 0.963, P < 0.001). The CEST effect showed pH dependency of Cr (r = 0.41, P = 0.035). Creatine CEST imaging can be performed on 3.0 T MR imaging. Creatine concentrations and pH influence CEST effect.


Validation of the Adolescent Drinking Expectancy Questionnaire and development of a short form.
This study aimed to validate the Drinking Expectancy Questionnaire-Adolescent version (DEQ-A) in a large adolescent sample and to develop and validate a brief measure, the Drinking Expectancy Questionnaire-Shortened Adolescent version (DEQ-SA). Cross-sectional survey of secondary school students (n = 2357, aged 13-16, M = 14.66 years, SD = 0.60). Students completed the DEQ-A in school, and measures of alcohol consumption including the Alcohol Use Disorders Identification Test-Consumption. The data were randomly split, and Exploratory Factor Analysis was performed using subsample 1, and Confirmatory Factor Analysis and reliability and validity testing were performed using subsample 2. The 24-item DEQ-A was successfully reduced to 12 items (DEQ-SA) without compromising psychometric properties. The DEQ-A and the DEQ-SA both demonstrated adequate-to-good fit to the data and very good internal reliability. The DEQ-A and DEQ-SA explained 20 and 18% of the variance in alcohol consumption. Adolescents who drank endorsed more positive alcohol expectancies, whereas alcohol-naïve adolescents scored higher on negative alcohol expectancies. As the DEQ-SA comprises two subscales of the DEQ-A, the endorsement rates are applicable to both scales. The DEQ-A and the short form of this scale developed in this study (DEQ-SA) show good reliability, internal structure and account for a large proportion of variance in alcohol consumption. Both scales can assist in targeting cognitive change processes within tailored alcohol prevention and treatment approaches, and investigating hypothesised mechanisms of change. The DEQ-SA is recommended for more time-limited environments. [Patton KA, Connor JP, Rundle-Thiele S, Dietrich T, Young RM, Gullo MJ. Validation of the Adolescent Drinking Expectancy Questionnaire and development of a short form.


The larva of Athripsodes genei (Rambur 1842) (Trichoptera, Leptoceridae).
This paper describes the previously unknown larva of Athripsodes genei (Rambur 1842). Information on the morphology of the 5th larval instar is given and the most important diagnostic features are illustrated. In the context of existing identification keys the larva of A. genei keys together with A. albifrons (Linnaeus 1758), A. commutatus (Rostock 1874), A. leucophaeus (Rambur 1842) and Athripsodes tavaresi (Navás 1916). These species differ in the number of ventral edge setae at the 1st tibia and in the shape and colour of the submentum. With respect to zoogeography, Athripsodes genei is a (micro-)endemic of the collin and planar regions of Sardinia and Corsica (Graf et al. 2008). According to mandible morphology, A. genei is a collector-gatherer, shredder and, to a minor extent, also a predator.


Integrated Analysis of the Roles of Long Noncoding RNA and Coding RNA Expression in Sheep (Ovis aries) Skin during Initiation of Secondary Hair Follicle.
Initiation of hair follicle (HF) is the first and most important stage of HF morphogenesis. However the precise molecular mechanism of initiation of hair follicle remains elusive. Meanwhile, in previous study, the more attentions had been paid to the function of genes, while the roles of non-coding RNAs (such as long noncoding RNA and microRNA) had not been described. Therefore, the roles of long noncoding RNA(LncRNA) and coding RNA in sheep skin during the initiation of sheep secondary HF were integrated and analyzed, by using strand-specific RNA sequencing (ssRNA-seq).A total of 192 significant differentially expressed genes were detected, including 67 up-regulated genes and 125 down-regulated genes between stage 0 and stage 1 of HF morphogenesis during HF initiation. Only Wnt2, FGF20 were just significant differentially expressed among Wnt, Shh, Notch and BMP signaling pathways. Further expression profile analysis of lncRNAs showed that 884 novel lncRNAs were discovered in sheep skin expression profiles. A total of 15 lncRNAs with significant differential expression were detected, 6 up-regulated and 9 down-regulated. Among of differentially expressed genes and LncRNA, XLOC002437 lncRNA and potential target gene COL6A6 were all significantly down-regulated in stage 1. Furthermore, by using RNAhybrid, XLOC005698 may be as a competing endogenous RNA ''sponges" oar-miR-3955-5p activity. Gene Ontology and KEGG pathway analyses indicated that the significantly enriched pathway was peroxisome proliferator-activated receptors (PPARs) pathway (corrected P-value < 0.05), indicating that PPAR pathway is likely to play significant roles during the initiation of secondary HF.Results suggest that the key differentially expressed genes and LncRNAs may be considered as potential candidate genes for further study on the molecular mechanisms of HF initiation, as well as supplying some potential values for understanding human hair disorders.


Difference on cone size preferences between two coniferous species by Great Spotted Woodpecker (Dendrocopos major).
The number of species that specialize in pre-dispersal seed predation is relatively small. Examples of specialized pre-dispersal seed predators adapted to feeding on closed cones include vertebrate species like Crossbills, Squirrels, Nutcrackers and Woodpeckers. Seed predation selects against certain phenotypic features of cones and favors another phenotypic features. In this study, we document preferences of the Great Spotted Woodpecker (Dendrocopos major) for specific traits in the cones of Norway spruce (Picea abies) and Scots pine (Pinus sylvestris). We found that the Great Spotted Woodpecker prefers to feed on medium sized Norway spruce cones. The results suggest a disruptive selection that favors the extreme cone lengths in Norway spruce. In Scots pine, the woodpeckers avoided cones with large apophyses. Further, the selectivity for the specific characteristics of the cones is probably related to the configuration of the anvil, a place at which woodpeckers extract seeds from the cones. We think that the Great Spotted Woodpecker preferences in relation to the morphological characteristics of cones are a key to the design of the anvil in order to maximize the use of it as a tool for processing cones of both the Norway spruce and the Scots pine.


Chemotherapy-related cognitive impairment or « chemobrain »: concept and state of art.
Cognitive complaints are frequent in patients who received chemotherapy for a non-CNS cancer. These observations have been described as « chemobrain ». However, studies results are contradictory concerning the implication of chemotherapy in the onset of cognitive defects. Moreover, other factors as mood, anxiety and fatigue are often associated in this population and could be confounding. This article present principal results of research in human experiencing chemobrain, concerning clinical presentation, neuropsychological examination, imaging techniques and treatment possibilities. Physiopathological hypothesis are presented. The implication of hormonotherapy is also discussed.


Upconversion Nanoparticles Intercalated in Large Polymer Micelles for Tumor Imaging and Chemo/Photothermal Therapy.
Frontiers in theranostics are driving the demand for multifunctional nanoagents. Upconversion nanoparticle (UCNP)-based systems activated by near-infrared (NIR) light deeply penetrating biotissue are a powerful tool for the simultaneous diagnosis and therapy of cancer. The intercalation into large polymer micelles of poly(maleic anhydride-alt-1-octadecene) provided the creation of biocompatible UCNPs. The intrinsic properties of UCNPs (core@shell structure NaYF4:Yb3+/Tm3+@NaYF4) embedded in micelles delivered NIR-to-NIR visualization, photothermal therapy, and high drug capacity. Further surface modification of micelles with a thermosensitive polymer (poly-N-vinylcaprolactam) exhibiting a conformation transition provided gradual drug (doxorubicin) release. In addition, the decoration of UCNP micelles with Ag nanoparticles (Ag NPs) synthesized in situ by silver ion reduction enhanced the cytotoxicity of micelles at cell growth temperature. Cell viability assessment on Sk-Br-3, MDA-MB-231, and WI-26 cell lines confirmed this effect. The efficiency of the prepared UCNP complex was evaluated in vivo by Sk-Br-3 xenograft regression in mice for 25 days after peritumoral injection and photoactivation of the lesions with NIR light. The designed polymer micelles hold promise as a photoactivated theranostic agent with quattro-functionalities (NIR absorption, photothermal effect, Ag NP cytotoxicity, and Dox loading) that provides imaging along with chemo- and photothermal therapy enhanced with Ag NPs.


Genetic Diversity of Pectobacterium carotovorum subsp. brasiliensis Isolated in Korea.
The plant pathogenic bacterial genus Pectobacteirum consists of heterogeneous strains. The P. carotovorum species is a complex strain showing divergent characteristics, and a new subspecies named P. carotovorum subsp. brasiliensis has been identified recently. In this paper, we re-identified the P. carotovorum subsp. brasiliensis isolates from those classified under the subspecies carotovorum and newly isolated P. carotovorum subsp. brasiliensis strains. All isolates were able to produce plant cell-wall degrading enzymes such as pectate lyase, polygalacturonase, cellulase and protease. We used genetic and biochemical methods to examine the diversity of P. carotovorum subsp. brasiliensis isolates, and found genetic diversity within the brasiliensis subsp. isolates in Korea. The restriction fragment length polymorphism analysis based on the recA gene revealed a unique pattern for the brasiliensis subspecies. The Korean brasiliensis subsp. isolates were divided into four clades based on pulsed-field gel electrophoresis. However, correlations between clades and isolated hosts or year could not be found, suggesting that diverse brasiliensis subsp. isolates existed.


Binding behaviors of p-sulfonatocalix[4]arene with gemini guests.
A dozen of homoditopic cations, possessing different spacer lengths and rigidities, as well as sizes, shapes, and charges of terminal groups, were synthesized as candidate gemini guests for the complexation of p-sulfonatocalix[4]arenes (SC4A). The 12 gemini guests are divided into five species according to the different terminal groups: imidazolium (G1-G3), pyridinium (G4-G6), quinolinium (G7), viologen (G8-G11), and 1,4-diazabicyclo[2.2.2]octane (DBO, G12). Their binding structures and stoichiometries with SC4A were examined by NMR spectroscopy, which is helpful to construct diverse highly ordered assemblies. The obtained results show that the length of the linkers, as well as the charge numbers on the end groups have a pronounced effect on the binding stoichiometry, whereas the size and shape of the terminal groups have no significant influence. Furthermore, both the stability constants and thermodynamic parameters of SC4A with the terminal subunits were determined by the isothermal titration calorimetry experiments, which are valuable to understand the binding behavior, giving quantitatively deep insight.


[Sudden cardiac death in athletes: is it always not preventable?].
Sudden cardiac death (SCD) in athletes is a rare but tragic event particularly considering that in some cases it is preventable. In young athletes with cardiovascular disease the risk of SCD is 2,5 times higher than in non-athletes. In young athletes (<35 years old), the most common causes of SCD are related to pre-existing cardiovascular disorders including hypertrophic cardiomyopathy, congenital coronary anomalies, arrhythmogenic right ventricular dysplasia, commotio cordis, some channelopathies and cardiac sarcoidosis. Actually there are two approches to pre-participation athletic screening: the American one based on anamnesis and physical examination and the European one based on anamnesis, physical examination and ECG at rest. However, some disorders responsible for SCD can't be suspected through these exams and it could be useful to implement preparticipation athletic screening.


Relationship between MGMT gene expression and treatment effectiveness and prognosis in glioma.
The expression of O6-methylguanine DNA methyltransferase (MGMT) in different grade gliomas were analyzed in relation to its therapeutic effect and impact on disease prognosis. In total, 62 patients with glioma, who were admitted by neurosurgery and received surgical treatment and postoperative conventional chemoradiation, were selected for this study. Expression of MGMT was greater with an increase in brain glioma grade. Gender, age, tumor size and Karnofsky performance status (KPS) score did not differ with MGMT expression (P>0.05). Expression of MGMT in normal brain tissue was slightly significantly different than expression of MGMT in glioma tissue (P<0.05). The short-term efficacy and survival time of the MGMT-negative expression group were better than those of MGMT-positive expression. MGMT was only treated as an index to monitor tumor recurrence or metastasis and a reference to judge the prognosis of patients. The expression level of MGMT in glioma had no relation with age, gender, tumor size, surgical approach and KPS score. For glioma patients with positive expression of MGMT, antineoplastic drugs of alkylating agent class should be avoided.


The Biomechanical Basis of the Claw Finger Deformity: A Computational Simulation Study.
Claw finger deformity occurs during attempted finger extension in patients whose intrinsic finger muscles are weakened or paralyzed by neural impairments. The deformity is generally not acutely present after intrinsic muscle palsy. The delayed onset, with severity progressing over time, suggests soft tissue changes that affect the passive biomechanics of the hand exacerbate and advance the deformity. Clinical interventions may be more effective if such secondary biomechanical changes are effectively addressed. Using a computational model, we simulated these altered soft tissue biomechanical properties to quantify their effects on coordinated finger extension. To evaluate the effects of maladaptive changes in soft tissue biomechanical properties on the development and progression of the claw finger deformity after intrinsic muscle palsy, we completed 45 biomechanical simulations of cyclic index finger flexion and extension, varying the muscle excitation level, clinically relevant biomechanical factors, and wrist position. We evaluated to what extent (1) increased joint laxity, (2) decreased mechanical advantage of the extensors about the proximal interphalangeal joint, and (3) shortening of the flexor muscles contributed to the development of claw finger deformity in an intrinsic-minus hand model. Of the mechanisms studied, shortening (or contracture) of the extrinsic finger flexors was the factor most associated with the development of claw finger deformity in simulation. These simulations suggest that adaptive shortening of the extrinsic finger flexors is required for the development of claw finger deformity. Increased joint laxity and decreased extensor mechanical advantage only contributed to the severity of the deformity in simulations when shortening of the flexor muscles was present. In both the acute and chronic stages of intrinsic finger paralysis, maintaining extrinsic finger flexor length should be an area of focus in rehabilitation to prevent formation of the claw finger deformity and achieve optimal outcomes after surgical interventions.


Orbital Fat Prolapse Into the Nasal Cavity in Orbital Blowout Fracture.
In this study, the authors describe the first report of 2 patients of fat prolapse into the nasal cavity by orbital blowout fracture. The patients were a 58-year-old male and an 86-year-old female. The patients could not attain binocular single vision in any eye position because of severe impairment of the extraocular muscle motility. Computed tomographic images of both patients revealed orbital blowout fractures with orbital fat prolapse into the nasal cavity. The fractures were reduced under transconjunctival/transcaruncular and endonasal endoscopic approaches. Six months postoperatively, the patients attained a binocular single vision field, including in the primary eye position.


Formation of highly ordered and orientated gold islands: effect of immersion time on the molecular adlayer structure of pentafluorobenzenethiols (PFBT) SAMs on Au(111).
Self-assembled monolayers (SAMs) of pentafluorobenzenethiol (PFBT) on Au(111) substrates, prepared with different immersion times (ITs) at room temperature, were studied using scanning tunneling microscopy (STM) and infrared reflection-absorption spectroscopy (IRRAS). In the present study, the focus was on several important points of interest in the field of SAMs. First, the gold islands formed upon adsorption of PFBT molecules on the gold surface were monitored at different ITs in terms of their size, density, and shape. After short ITs (5 to 30 min), small gold islands with rounded shape were formed. These gold islands were arranged in a rather regular fashion and found to be quite mobile under the influence of the STM-tip during the scanning. When the IT was increased to 16 h, the results revealed the formation of highly ordered and orientated gold islands with very unusual shapes with straight edges meeting at 60° or 120° running preferentially along the [11(-)0] substrate directions. The density of the gold islands was found to decrease with increasing IT until they almost disappeared from the SAMs prepared after 190 h of IT. On top of the gold islands, the PFBT molecules were found to adopt the closely packed (10√3 × 2) structure. Second, a number of structural defects such as disordered regions at the domain boundaries and dark row(s) of molecules within the ordered domains of the PFBT SAMs were observed at different ITs. The SAMs prepared after 190 h of IT were found to be free of these defects. Third, at low and moderate ITs, a variation in the PFBT molecular contrast was observed. This contrast variation was found to depend mainly on the tunneling parameters. Finally, our results revealed that the organization process of PFBT SAMs is IT-dependent. Consequently, a series of structural phases, namely, α, β, γ, δ, and ε were found. The α-, β-, γ-, and δ-phases were typically accompanied by the ε-phase that appeared on top of gold islands. With increasing IT, the α→β→ γ→δ→ε phase transitions took place. The resulting ε-phase, which covered the entire gold surface after 190 h of IT, yielded well-ordered self-assembled monolayers with large domains having a (10√3 × 2) superlattice structure.


Noninvasive and Highly Selective Monitoring of Intracellular Glucose via a Two-Step Recognition-Based Nanokit.
Accurate determination of intracellular glucose is very important for exploring its chemical and biological functions in metabolism events of living cells. In this paper, we developed a new noninvasive and highly selective nanokit for intracellular glucose monitoring via two-step recognition. The liposome-based nanokit coencapsulated the aptamer-functionalized gold nanoparticles (AuNPs) and the Shinkai's receptor together. When the proposed nanokit was transfected into living cells, the Shinkai's receptor could recognize glucose first and then changed its conformation to endow aptamers with binding and sensing properties which were not readily accessible otherwise. Then, the binary complexes formed by the intracellular glucose and the Shinkai's receptor can in situ displace the complementary oligonucleotide of the aptamer on the surface of AuNPs. The fluorophore-labeled aptamer was away from the AuNPs, and the fluorescent state switched from "off" to "on". Through the secondary identification of aptamer, the selectivity of the Shinkai's receptor could be greatly improved while the intracellular glucose level was assessed by fluorescence signal recovery of aptamer. In the follow-up application, the approach exhibits excellent selectivity and is noninvasive for intracellular glucose monitoring under normoxia and hypoxia. To the best of our knowledge, this is the first time that the advantages of organic receptors and nucleic acids have been combined and highly selective monitoring of intracellular glucose has been realized via two-step recognition. We expect it to open up new possibilities to integrate devices for diagnosis of various metabolic diseases and insulin delivery.


Toll-like receptor-9 is involved in the development of B cell stimulating factor-induced systemic lupus erythematosus.
The objective of the present study was to investigate the role of Toll-like receptor (TLR)-9 in B lymphocyte stimulating factor (BLyS)-induced systemic lupus erythematosus (SLE) in mice. The anti-double stranded (ds)DNA antibody titer, levels of complement proteins (C3 and C4), interleukin (IL)-10 and the disease activity [assessed by the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level] were measured. A total of 21 transgenic female mice (aged 8-10 weeks and weighing 30-40 g) expressing the Epstein-Barr virus membrane antigen, BLLF1, were studied. Mice were randomly divided into the control, the BLyS inhibition and the TLR-9 inhibition groups, with 7 mice in each group. Mice in the blank control group received intraperitoneal injections of normal saline, mice in the BLyS inhibition group received intraperitoneal injections of anti-BR3 monoclonal antibody (5,000 ng/day) and mice in the TLR-9 inhibition group received intraperitoneal injections of anti-human TLR-9 antibody (250 ng/day). The treatment regimens continued for 10 days, followed by the collection of peripheral venous blood. The relative levels of TLR-9 mRNA were measured by reverse transcription-quantitative polymerase chain reaction. Furthermore, the BLyS protein concentration and IL-10 levels were measured by ELISA. TLR-9 mRNA, BLyS, IL-10, anti-dsDNA antibody titer, C3, C4, ESR and CRP levels of the blank control group were significantly higher than those of the other two groups (P<0.05). The differences in comparison of these indexes between the BLyS inhibition and TLR-9 inhibition groups were not statistically significant (P>0.05), with the exception of TLR-9 mRNA and BLyS. In conclusion, the TLR-9 signaling pathway may be important for BLyS-induced SLE, and regulation of the inflammatory immune level.


Inhibitors of the sphingosine kinase pathway as potential therapeutics.
Sphingosine kinase (SK) 1 and 2 are lipid kinases that phosphorylate sphingosine to form sphingosine-1 phosphate, a potent signalling molecule with pleiotrophic effects. SK1 is commonly up-regulated in tumours and its inhibition or genetic ablation has been shown to slow tumour growth as well as sensitise cancer cells to other chemotherapeutics. Therefore, SK1 is of particular interest as a target therapeutic intervention in cancer. Initial SK inhibitors were sphingosine derivatives and displayed efficacy in a number of disease models, establishing a premise for SK inhibition for anti-proliferative and anti-inflammatory therapies, even though these compounds had questionable specificity. More recently, a number of new SK inhibitors have been developed that display higher affinities and greater specificity for the SKs. Here we summarise the current small molecule inhibitors and related approaches for targeting the SKs, and their in vitro and in vivo efficacy. Furthermore, we highlight findings demonstrating the success of SK inhibition in cancer and a range of other disease models that promotes the continued interest in targeting the SKs for therapeutic benefit.


Three-dimensional Printing in Reconstructive Oral and Maxillofacial Surgery.
Three-dimensional (3D) printing involves the process of constructing a 3D solid object from a digital file. Charles Hull was the first to introduce 3D printer in 1983 by using the technique of stereolithography.1 Since the 1990s 3D printing has gained attention in the field of medicine where more precision is required and has largely replaced the traditional technique in prosthetic works.2,3.


DNA microarray analysis of stage progression mechanism in myelodysplastic syndrome.
Myelodysplastic syndrome (MDS) is a clonal disorder of haematopoietic stem cells. Despite the high incidence of MDS in the elderly, effective treatment of individuals in its advanced stages is problematic. DNA microarray analysis is a potentially informative approach to the development of new treatments for MDS. However, a simple comparison of 'transcriptomes' of bone marrow mononuclear cells among individuals at distinct stages of MDS would result in the identification of genes whose expression differences only reflect differences in the proportion of MDS blasts within bone marrow. Such a 'population shift' effect has now been avoided by purification of haematopoietic stem-like cells that are positive for the cell surface marker AC133 from the bone marrow of healthy volunteers and 30 patients at various stages of MDS. Microarray analysis with the AC133+ cells from these individuals resulted in the identification of sets of genes with expression that was specific to either indolent or advanced stages of MDS. The former group of genes included that for PIASy, which catalyses protein modification with the ubiquitin-like molecule SUMO. Induction of PIASy expression in a mouse myeloid cell line induced apoptosis. A loss of PIASy expression may therefore contribute directly to the growth of MDS blasts and stage progression.


Pharmacodynamic evaluation of a reference and a generic toltrazuril preparation in broilers experimentally infected with Eimeria tenella or E. acervulina.
Abstract 1. The aim of this study was to investigate the effects on pigmentation, faecal oocyst output, immune responsiveness and reactive oxygen species (ROS) generation following treatment with either the reference toltrazuril (Baycox) or a generic preparation (gen-TTZ), during an experimental Eimeria tenella (Et) or E. acervulina (Ea) infection of 210 Ross broiler chickens. 2. Results showed a significant difference on the anticoccidial efficacy 6 d after treating infected animals with Baycox (Et: 99.69% and Ea: 99.52%) or gen-TTZ (Et:85.71% and Ea 81.81%). 3. Gen-TTZ-treated animals were less strongly carotenoid-pigmented than Baycox-treated broilers. Mean plasma carotenoid concentrations were significantly higher in groups treated with Baycox than in broilers given gen-TTZ. 4. Treatment of animals with Baycox led to a significant decrease in ability of the peripheral blood mononuclear cells to produce ROS in contrast to gen-TTZ-treated groups. Baycox, but not generic toltrazuril, increased IL-10 and decreased tumour necrosis factor alpha (TNF-α) concentrations in chickens infected with E. tenella and E. acervulina. 5. It is suggested that differences in anticoccidial efficacy may be observed when using a generic toltrazuril product. Hence, in addition to plasma profiles of drugs, standardised clinical control tests may be necessary for generic formulations, particularly if other parameters are important to achieve a better control of coccidiosis.


Label-Free and Real-Time Detection of Avian Influenza Using Nanowire Field Effect Transistors.
Real-time and label-free detection of antibodies from avian influenza (anti-AI) in an aqueous solution is demonstrated with the use of a nanowire field effect transistor. A real-time measurement system is constructed without leakage paths through the solution medium. The current through the nanowire changes significantly after an injection of an anti-AI solution onto the device, which was previously functionalized by the antigen of AI as a probe of anti-AI. In contrast, no significant response arises when an anti-AI solution is injected onto a non-functionalized device. Therefore, the real-time detection of specific antibody-antigen interaction of the AI is successfully implemented for a chip-based biosensor.


Post-traumatic stress disorder, drug dependence, and suicidality among male Vietnam veterans with a history of heavy drug use.
This study examines the roles of post-traumatic stress disorder (PTSD) and drug dependence in non-fatal suicidality, i.e., suicidal ideation and suicide attempt, among Vietnam veterans in their adult years. The sample includes male veterans deployed to Vietnam, including an oversample of those who tested positive for opiates at their return (n = 642). PTSD, substance abuse, suicidality, and other psychopathology are analyzed using three waves of survey and military data covering the time period from early adolescence to middle adulthood. Measures include the onset and recency of each of the lifetime DSM-IV PTSD symptom criteria, and yearly symptom measures of DSM-IV dependence for alcohol and eight classes of psychoactive substances. Survival and hazard models are applied to assess the effects of drug dependence, PTSD, and other psychopathology on the duration of suicidality. Longitudinal models estimate the casual relationships among PTSD, drug dependence, and suicidality over a 25-year period. Results show evidence of strong continuity of PTSD, drug dependence, and suicidality over time. The causal role of drug dependence on PTSD and suicidality is limited to young adulthood. Evidence is stronger for self-medication in later adulthood. The results indicate that a life course perspective is needed for the combined treatment of PTSD and drug dependence for severely traumatized populations.


A Novel Semiochemical Tool for Protecting Pinus contorta From Mortality Attributed to Dendroctonus ponderosae (Coleoptera: Curculionidae).
Verbenone (4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-one) is an antiaggregant of the mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae), a notable forest insect capable of causing extensive levels of tree mortality in western North America. Several formulations of verbenone are registered for tree protection, but failures in efficacy are not uncommon, particularly when applied during large infestations. A formulation of (-)-verbenone was developed (Specialized Pheromone & Lure Application Technology [SPLAT] Verb, ISCA Technologies Inc., Riverside, CA) and evaluated for protecting individual lodgepole pine, Pinus contorta Douglas ex Loudon, and small stands of P. contorta from mortality attributed to D. ponderosae. SPLAT Verb applied to individual P. contorta resulted in complete tree protection, while 93.3% mortality occurred in the untreated controls. Significantly fewer P. contorta were killed by D. ponderosae within 0.041-ha circular plots surrounding P. contorta treated with SPLAT Verb compared with the untreated control. In a second study, a smaller percentage of P. contorta were colonized and killed on 0.4-ha square plots treated with SPLAT Verb compared with the untreated control. No significant differences in levels of tree mortality were observed between the untreated control and another formulation of verbenone (7-g pouch) or between the 7-g pouch and SPLAT Verb. In a trapping bioassay, no significant differences were observed among captures in multiple-funnel traps at 1, 2, or 4 m from the point of release of SPLAT Verb. Significantly fewer D. ponderosae were collected at 1 and 2 m compared with 8 m. Significantly more D. ponderosae were captured at the farthest distance evaluated (16 m) than at any other distance. Our data indicate that SPLAT Verb is effective for protecting individual P. contorta and small stands of P. contorta from mortality attributed to D. ponderosae at moderate doses. The high levels of tree protection observed are attributed to the ability of applying release points (dollops) at high densities, and a larger zone of inhibition than reported for other formulations of verbenone. SPLAT Verb was registered by the U.S. Environmental Protection Agency for use on pines, Pinus spp., in 2013.


Distribution and Risk Factors of Multidrug-Resistant Bacteria Infection in Orthopedic Patients.
To study the distribution and risk factors of multidrug-resistant bacteria (MDROS) infection in orthopedic patients and to provide reference for clinical prevention and control measures. The data of 239 inpatients with orthopedic trauma from June 2019 to December 2020 were selected as the research objects, and the distribution characteristics of MDROS infection were analyzed through the real-time monitoring system of nosocomial infection. Logistic regression analysis was used to screen out the risk factors causing MDROS infection, and the preventive measures were put forward. 178 strains of pathogens were isolated from 239 patients, including 53 strains of MDROS, and the detection rate was 29.78%. The main pathogenic bacteria were ESBLs, MRSA, CRAB, CRE, and MDR/PDRPA. The main infection sites of MDROS in orthopedic patients were the respiratory tract and wound. No CRE1 was detected, and 64.39%, 17.42%, and 14.39% of ESBL-producing bacteria, MRSA, and MDR/PDRPA, respectively, were detected. Logistic multivariate analysis showed that the length of hospital stay, antibiotic use time, open injury, and serum albumin level were independent risk factors of MDROS infection in orthopedic trauma patients. To prevent MDROS infection in orthopedic patients, we should start from many aspects, focusing on reducing unnecessary hospitalization days, rationally preventing the use of antibacterial drugs, effectively treating basic diseases, etc., timely and effective thorough debridement, strengthening functional training, reducing bed rest, and strengthening targeted monitoring of related infections which are the keys to reduce MDROS infection in orthopedic patients.


Simple way to obtain pH-sensitive drug release from functional mesoporous silica materials.
A novel pH-sensitive drug release system has been synthesised by functional mesoporous silica materials. SBA-15, calcium modified SBA-15 (Ca-SBA-15) and phosphate modified SBA-15 (PO4-SBA-15) were synthesised using solvent evaporation method. It is a simple and feasible way to prepare the doping mesoporous silica materials. They show the large surface are, high pore volume and uniform pore size. Metformin hydrochloride was used as the model drug, and the control release behaviour was investigated. The functional mesoporous silica materials show the pH sensitive drug release behaviour because of the adjustable interaction between the drug molecule and the host.


Highly effective inhibition of lung cancer growth and metastasis by systemic delivery of siRNA via multimodal mesoporous silica-based nanocarrier.
Lung cancer has been the leading type of cancers with regard to mortality and mobility. New versions of RNAi-based therapy are greatly required to tackle the challenges of lung cancer. In this study, we developed a novel siRNA delivery vector based on our magnetic mesoporous silica nanoparticles (M-MSNs) platform. This nanocarrier was constructed by loading siRNAs into the mesopores of M-MSNs, followed by polyethylenimine (PEI) capping, PEGylation and fusogenic peptide KALA modification. The resultant delivery system exhibited prolonged half-life in bloodstream, enhanced cell membrane translocation and endosomal escapablity, and favorable tissue biocompatibility and biosafety. Systemic application of vascular endothelial growth factor (VEGF) siRNA via this nanocarrier resulted in remarkable tumor suppression, both in subdermal and orthotopic lung cancer models, while tumor metastasis was also significantly reduced, overall leading to improved survival. In addition, the magnetic core of the particles and the functionalized fluorescence markers conveniently enabled in vivo imaging of target tissues. Taken together, this M-MSNs-based siRNA delivery vehicle has shown very favorable applicability for cancer therapy.


Immortalization and transformation of human fibroblasts by regulated expression of polyoma virus T antigens.
We have established conditions for the immortalization of human fibroblasts by the large T antigen of the rodent virus polyoma. This allows the mechanism of immortalization to be studied, without interference by transformation events, in cells with relatively stable chromosomes. Large T antigen could immortalize human fibroblasts if expression was driven by a heterologous promoter like the immediate early promoter/enhancer of cytomegalovirus or the inducible mouse mammary tumour virus (MMTV) promoter. Using the latter promoter and dexamethasone, three clones were obtained, the immortalized phenotype of which was strictly dependent on the induction of T-antigen expression. At least one of these clones became mortal after removal of the inducing agent. The expression of large T antigen was paralleled by PCNA gene expression, as shown by nuclear run-off transcription, whereas none of a number of other known proto-oncogenes was influenced in its activity. Immortalized fibroblasts were readily transformed by polyoma virus middle T antigen expressed from the MMTV promoter or by the activated c-Ha-ras oncogene. The reversibility of immortalization and transformation is considered.


Adaptive evolution of the human fatty acid synthase gene: support for the cancer selection and fat utilization hypotheses?
Cancer may act as the etiological agent for natural selection in some genes. This selective pressure would act to reduce the success of neoplastic lineages over normal cell lineages in individuals of reproductive age. In addition, human's relatively larger brain and longer lifespan may have also acted as a selective force requiring new genotypes. One of the most important proteins in both processes is the fatty acid synthase (FAS) gene involved in fatty acid biosynthesis. A variety of other proteins, including PTEN, MAPK1, SREBP1, SREBP2 and PI are also involved in the regulation of fatty acid biosynthesis. We have specifically analysed variability in selective pressure across all these genes in human, mouse and other vertebrates. We have found that the FAS gene alone has signatures indicative of adaptive evolution. We did not find any signatures of adaptive evolution in any of the other proteins. In the FAS gene, we have detected an excess of non-synonymous over synonymous substitutions in approximately 6% of sites in the human lineage. Contrastingly, the substitution process at these sites in other available vertebrates and mammals indicates strong purifying selection. This is likely to reflect a functional shift in human FAS and correlates well with previously observed changes in FAS biochemical activities. We speculate that the role played by FAS either in cancer development or in human brain development has created this selective pressure, although we cannot rule out the various other functions of FAS.


Comparison of acute toxicities between contemporary forward-planned 3D conformal radiotherapy and inverse-planned intensity-modulated radiotherapy for whole breast radiation.
The use of inverse-planned intensity-modulated radiation therapy for whole breast radiation treatment has become more prevalent, but this may impose an increased cost on the health system. We hypothesized that when applied with the same treatment planning goals, tangential forward-planned field-in-field 3D conformal radiotherapy and tangential inverse-planned intensity-modulated radiotherapy would be associated with comparable toxicities. Women who underwent tangential whole breast irradiation at our institution from 2011 to 2015 planned using either forward-planned field-in-field 3D conformal radiotherapy or intensity-modulated radiotherapy were retrospectively analyzed. Grade 2+ Radiation dermatitis was the primary endpoint. A total of 201 and 212 women had undergone field-in-field 3D conformal radiotherapy and intensity-modulated radiotherapy, respectively. No differences were observed between the two modalities regarding acute radiation dermatitis, breast pain, or fatigue. In a multivariable logistic regression that incorporated the use of boost, hypofractionation, use of chemotherapy, patient positioning, use of a supraclavicular field, and breast planning target volume, intensity-modulated radiotherapy was not correlated with different rates of Grade 2+ radiation dermatitis. This study supports the routine first-line use of field-in-field 3D conformal radiotherapy for whole breast radiation instead of tangential intensity-modulated radiotherapy from the standpoint of equivalence in acute toxicity. Further investigation is needed to assess whether there are subgroups of women who may still benefit from intensity-modulated radiotherapy.


An unusual nail presentation in Marfan's syndrome.
Skin and nail lesions are very rare in Marfan's syndrome. We reported a 14-year-old boy who presented with pterygium in the nails of both the upper and lower limbs with chest deformity along with other features of Marfan's syndrome. Histopathological findings revealed hyperkeratosis with a scant perivascular inflammatory infiltrate. It was not clear whether this case is the first presentation of pterigium in Marfan's syndrome or congenital lichen planus. To our knowledge, this kind of feature is the first Marfan's syndrome case of its kind.


Rat kidney cells in primary culture: hormone-mediated desensitization of the adenosine 3',5'-monophosphate response to parathyroid hormone and calcitonin.
To investigate the direct actions and the possible cellular mechanisms of parathyroid hormone (PTH) and salmon calcitonin (sCT) action in inducing the desensitization of renal cAMP responses to these hormones, we studied kidney cells in primary culture. Renal cells isolated from neonatal rats were cultured in F-12 medium plus 100 microliters/ml calf serum. The cultured kidney cells reached confluent monolayer in 24 h and remained responsive to hormones, including PTH, sCT, vasopressin, and prostaglandin E1. Pretreatment of the cultured cells with PTH (2.5 X 10(-7) M) or sCT (3 X 10(-7) M) resulted in homologous desensitization in the cAMP responses to these hormones. Both PTH- and sCT-mediated desensitization were time and dose dependent. The EC50 for PTH-mediated desensitization was approximately 3.2 X 10(-9) M, and that for sCT was 2.0 X 10(-10) M. Cells that were desensitized to PTH or sCT showed normal responsiveness to cholera toxin, indicating that the catalytic and coupling units of the adenylate cyclase were not modified, suggesting that the locus for desensitization was at the receptor sites. We also found that the renal cell adenylate cyclase, after stimulation by PTH, was markedly different from that observed with sCT. The cAMP response to PTH was short-lived and readily reversible after removal of the hormone from the medium. Exposure to sCT resulted in stable activation of the adenylate cyclase system which was noted for several hours after the removal of sCT, sCT may form a stable complex with the receptors, thus activating the catalytic unit of the adenylate cyclase for a substantial period of time after removal of the hormone. This mechanism may account for the unique pharmacological efficacy of sCT.


Repeatability of dental plaque quantitation by light induced fluorescence technology in current, former, and never smokers.
The effects of smoking on the accumulation of dental plaque have not been studied in depth. We compared dental plaque quantitation obtained with a novel light induced fluorescence technology among current, former, and never smokers and verified measurements' repeatability. Dental plaque quantitation was objectively assessed by quantitative light induced fluorescence (QLF) technology on three separate study visits in current, former, and never smokers: baseline (day 0), day 7, day 30. Increase in the fluorescence intensity of at least 30% (ΔR30) and 120% (ΔR120) together with the simple oral hygiene (SOH) scoring were considered for analysis. The QLF parameters were highly repeatable in each study group (p < 0.0001, by regression analyses). All QLF parameters showed a significant difference between never smokers and current smokers (p = 0.041 for ΔR30; p = 0.027 for ΔR120; p = 0.04 for SOH). No significant differences were observed between never and former smokers and between current and former smokers except for ΔR120 (p = 0.033). Dental plaque measurements by QLF technology were highly reproducible and showed greater plaque formation among current smokers compared to non-smokers. Objective and reproducible quantitation of dental plaque can be a valuable clinical and regulatory science endpoint to investigate the effect of smoking cessation medications, combustion-free tobacco products, and consumer care products on oral health. There is a need to objectively evaluate the relationship between smoking and plaque build-up as well as maturation. Current smokers demonstrated greater and more mature plaque buildup when compared to never and former smokers. Differences in plaque build-up and maturation between current, former and non-smokers may be utilized as an effective tool for patient motivation, identifying therapeutic end-points, translational research as well as prognostication. The study is a pilot study parts of a larger project with registration ID: NCT04649645. As preliminary study, the pilot study referred into this paper started before the larger study registered in ClinicalTrials.gov.


Nutritional Status among Chinese Preschoolers in Subang Jaya, Selangor.
A nutritional status study was carried out among Chinese preschoolers (4- 6 years old) residing in Subang Jaya, Selangor. 91 preschoolers (48 boys and 43 girls) of Chinese descent participated in the study. Anthropometric measurements such as weight and height were taken and compared with the NCHS reference. Food habits and demographic background were also evaluated. The results indicated that the prevalence of underweight, wasting and stunting was 2% respectively, while the prevalence of overweight was 3%. Food habits data showed that most preschoolers consumed the daily main meals and snack once a day. Fruits were consumed between three to four times per week. Food items preferred by these preschoolers were milk, fish and fruits. In general, preschoolers in this study favoured foods, which were deep fried rather than steamed or roasted. Correlation analysis showed that there was no significant relationship between income, education of parents and anthropometric index (weight for age, height for age and weight for height). The nutritional status of these preschool children in Subang Jaya was satisfactory.


Identification and characterization of a Xenopus homolog of Dbf4, a regulatory subunit of the Cdc7 protein kinase required for the initiation of DNA replication.
Dbf4 is a regulatory subunit for the Cdc7 protein kinase that is required for the initiation of eukaryotic DNA replication, but the precise roles of Dbf4-Cdc7 remain to be determined. Here we identified a Xenopus homolog of Dbf4 (XDbf4) and characterized XDbf4 and Xenopus Cdc7 (XCdc7) in Xenopus egg extracts. XDbf4 formed a complex with XCdc7 in egg extracts and activated XCdc7 kinase activity in vitro. In contrast with Dbf4 in yeast and mammalian cultured cells, the XDbf4 levels in egg extracts did not change during the cell cycle progression. XDbf4 was a phosphoprotein in interphase extracts, and was apparently hyperphosphorylated in cytostatic factor (CSF)-mediated, metaphase-arrested extracts and in mitotic extracts. However, the hyperphosphorylation of XDbf4 did not seem to affect the level of kinase activation, or chromatin binding of the XDbf4-XCdc7 complex. Upon release from CSF-arrest, XDbf4 was partially dephosphorylated and bound to chromatin. Interestingly, XDbf4 was loaded onto chromatin before XCdc7 during DNA replication in egg extracts. These results suggest that the function of XDbf4-XCdc7 during the early embryonic cell cycle is regulated in a manner distinct from that during the somatic cell cycle.


Metaphyseal cones combined with diaphyseal impaction grafting provide good outcomes and survival in a complex revision total knee arthroplasty: a matched comparative analysis.
To compare clinical and radiological outcomes, implant survivorship at a minimum of 1-year follow-up using metaphyseal trabecular cones with or without impaction grafting in a complex revision TKA. A retrospective comparative matched analysis was performed and 15 patients who underwent revision surgery using the combination of porous trabecular metaphyseal cone and diaphyseal impaction grafting (MC-IBG) were matched with a group of 13 patients who also underwent revision surgery using metaphyseal cone (MC) without impaction grafting. All included patients presented severe bone defect (AORI 2,3) and a rotating-hinge prosthesis were implanted. Both groups were comparable regarding the baseline demographic and clinical data. Patients had previously undergone a mean of 4 (range, 2-12) and 3 (range, 2-5) previous procedures in the MC-IBG and MC groups, respectively. The indications for revision were aseptic loosening in 11 (73.3%) and 11 (84.6%) patients; prosthetic joint infection in 4 (26.7%) and 2 (15.4%) in the MC-IBG and MC groups, respectively. There was no significant difference in the mean postoperative Knee Society Score between the study groups (p = 0.806). Overall, 4 patients had further revision. Two patients were revised in the MC-IBG group, one patient for aseptic loosening and the second one after 2 episodes of instability. Two patients in the MC group presented prosthetic joint infection and underwent a two-stage reimplantation. No significant difference was observed between the study groups at comparison (p = 0.92). Trabecular metal cones with diaphyseal impaction grafting provide an alternative technique in a complex revision TKA surgery with early clinical and radiographic success.


Magnetically recoverable efficient demulsifier for water-in-oil emulsions.
A magnetically recoverable and efficient demulsifier is shown to demulsify surfactant-stable water-in-oil emulsions rapidly. Ferroferric oxide (Fe3 O4 ) particles are firstly coated by amorphous silicon dioxide (SiO2 ), and further functionalized with a commercial dodecyltrimethoxysilane solution (KH-1231). Owing to their paramagnetic properties, the demulsifier particles can be easily recovered with a magnet. Upon addition of demulsifier to emulsions and subsequent sonification, the supernatant becomes completely transparent and no droplets are observed in the micrographs. It was also demonstrated that this demulsifier is effective for emulsions prepared with a variety of oils. Moreover, magnetically recovered demulsifier can be recycled after simple treatment without any decline of efficiency. This work presents a feasible approach for demulsifying water-in-oil emulsions, and has potential value in industry.


[Vascular emergencies in childhood].
Vascular urgencies in childhood are rare and various in presentation. Authors report their experience regarding a wide range of vascular urgencies occurring in pediatric age. A number of cases of neonatal gangrene of extremities, vascular trauma, complicated vascular dysplasia, arterial and venous thrombosis both peripheric and visceral are described. Etiopathogenetic diagnostic and therapeutic features of these lesions are discussed.


The professional agenda and its effect on the implementation of telemedicine among primary care physicians: A qualitative study.
Studies show that physicians' attitudes are a major influential factor in the degree of implementation of telemedicine and that most of them identify much more opportunities in this type of visit than risks. These findings do not explain the observed decrease in the use of telemedicine in primary care with the decline of the COVID-19 pandemic. The aim of our study was to understand the gap between the attitudes that primary care physicians declare towards telemedicine and the extent to which they use it in practice. A qualitative research using a semi-structured phone interview with 33 primary care physicians experienced in telemedicine from Leumit Health Services, a health fund in Israel. A qualitative thematic analysis method was used to extract the main themes from all interviews, and descriptive statistical tests were used to analyze the demographic variables. The attitude of the physicians depended on the perception of their professional identity and their sense of control over telemedicine implementation. The more established their professional identity and the stronger the support from the organization in the technology integration, the more positive the physician's attitude towards this type of visit. Healthcare organizations that wish to improve the use of telemedicine in primary care should understand that this is more than just the implementation of new technology: they must find a way to properly support the profound change that doctors must undergo when defining their new role and professional status.


3D7-Derived Plasmodium falciparum erythrocyte membrane protein 1 is a frequent target of naturally acquired antibodies recognizing protein domains in a particular pattern independent of malaria transmission intensity.
Protection against Plasmodium falciparum malaria is largely mediated by IgG against surface Ags such as the erythrocyte membrane protein 1 family (PfEMP1) responsible for antigenic variation and sequestration of infected erythrocytes. PfEMP1 molecules can be divided into groups A, B/A, B, C, and B/C. We have previously suggested that expression of groups A and B/A PfEMP1 is associated with severe disease and that Abs to these molecules are acquired earlier in life than Abs to PfEMP1 belonging to groups B, B/C, and C PfEMP1. In this study, we compared the acquisition of IgG to 20 rPfEMP1 domains derived from 3D7 in individuals living under markedly different malaria transmission intensity and were unable to find differences in the Ab acquisition rate to PfEMP1 of different groupings (A, B, or C) or domain type (alpha, beta, gamma, delta, epsilon, or x). Abs were acquired early in life in individuals living in the high transmission village and by the age of 2-4 years most individuals had Abs against most constructs. This level of reactivity was found at the age of 10-20 years in the medium transmission village and was never reached by individuals living under low transmission. Nevertheless, the sequence by which individuals acquired Abs to particular constructs was largely the same in the three villages. This indicates that the pattern of PfEMP1 expression by parasites transmitted at the different sites was similar, suggesting that PfEMP1 expression is nonrandom and shaped by host-parasite relationship factors operating at all transmission intensities.


Competition between Raman and Kerr effects in microresonator comb generation.
We investigate the effects of Raman and Kerr gain in crystalline microresonators and determine the conditions required to generate mode-locked frequency combs. We show theoretically that a strong, narrowband Raman gain determines a maximum microresonator size allowable to achieve comb formation. We verify this condition experimentally in diamond and silicon microresonators and show that there exists a competition between Raman and Kerr effects that leads to the existence of two different comb states.


High degree of transferability of 86 newly developed zebra finch EST-linked microsatellite markers in 8 bird species.
High-resolution analysis for population genetic and functional studies requires the use of large numbers of polymorphic markers. The recent increase of available genetic tools is facilitated by the use of publicly available expressed sequence tag (EST) sequence databases that are a valuable resource for identifying gene-linked markers. In the present study, we applied bioinformatics analyses to identify microsatellite markers present in EST sequences from a zebra finch (Taeniopgia guttata) EST database and we explore the success of cross-species amplification of EST-linked microsatellite markers in 7 passerine and 1 nonpasserine species. Eighty-six zebra finch EST-linked microsatellite loci were screened for polymorphism revealing a high amplification success rate and adequate levels of polymorphism (33.3-51%) for relatively closely related species, whereas success decreased in the most distantly related species to zebra finch. EST-linked microsatellites appear to be more highly transferable between taxa than anonymous microsatellites as they revealed higher amplification and polymorphism success between different families indicating that they will be a useful source of gene-linked polymorphic markers in a broad range of avian species.


Primary choriocarcinoma of jejunum.
A 60-year-old man was admitted with pain in the abdomen and vomiting for one day; radiography revealed pneumoperitoneum. Laparotomy with excision of ulcer-bearing portion of the jejunum was done. Histology revealed choriocarcinoma with syncytiotrophoblastic and cytotrophoblastic cell differentiation. Postoperatively, urine and serum showed high levels of beta-human chorionic gonadotrophins. The patient expired after an unsatisfactory postoperative course.


Synthesis and anti-ulcer activity of new derivatives of glycyrrhetic, oleanolic and ursolic acids.
A review is made of the literature describing the structural changes to glycyrrhetic, oleanolic and ursolic acids and their influence on anti-ulcer activity. For the glycyrrhetic acid derivatives some analogues were prepared in which the ketonic group in position 11 was removed and the carboxylic function at position 30 was either intact, reduced to alcohol or transformed into ketone. This first series of compounds suggests the possibility of obtaining compounds devoid of the conjugated ketonic group, maintaining anti-ulcer activity but with reduced or lacking mineralocorticoid activity. Based on these findings, a series of carbenoxolone analogues in the beta-amyrin series of glycyrrhetic and oleanolic acid was prepared. In particular, the delta 9,11 unsaturated compounds 14b and 23b and the 11-methylene derivative 18 present advantages in terms of acute toxicity and mineralocorticoid activity as compared to the reference compound. The derivative 14b in the volunteer showed an increase of gastric PGE2 levels with minor pseudoaldosteronic effect. Among the ursolic acid derivatives, the dihemisuccinate sodium salt 35b demonstrated a good separation between anti-ulcer and mineralocorticoid activities. Nevertheless, kidney and liver toxicity was observed in the monkey thus jeopardizing its further development. Better results were obtained with the uvaol dihemiphthalate sodium salt and the diene analogue 39b. In particular, 38b and 39b showed a potent anti-ulcer activity, 3- to 25-fold higher than carbenoxolone. Furthermore, compound 38b does not show signs of liver toxicity in the monkey.


Is there a Möbius band in closed protein beta-sheets?
Protein beta-strands can form beta-barrels and other complicated structures. This paper defines bifurcations and pseudobifurcations of beta-sheets. They are important structural elements for protein folding. This paper also presents a characteristic number that can be used to test whether the surface of a closed beta-sheet is one- or two-sided. Searching the whole Protein Data Bank released in April 1997 with the definition of beta-structures given by the DSSP program, we do not find any one-sided beta-Möbius band. However, there are interesting structures such as beta-bands with odd number of antiparallel ladders and odd number of bifurcations. There are also beta-structures that are closed only at a singular point. Adding a small patch near the singular point in different ways can make it a one- or two-sided surface. The catalytic triad of a GMP synthetase (1GPM) is near the singular point of such a beta-sheet.


Multi-Targeted Anticancer Agents.
There is a great demand for the development of novel anticancer drugs, due to the increasing morbidity and high mortality of cancer. To date, chemotherapy still plays a central role in the clinical treatment of cancer, but this role is being reduced by targeted therapies. Since cancer is a complicated and multiple genes involved disease, drugs that act at multiple targets can enhance efficacy and lower drug resistance, and are thought to be the future of novel anticancer drug development. In this paper, we discuss the recent development of "single molecule, multi-target" anticancer agents that combine two or more pharmacophores in a single molecule, including organic multitargeted anticancer agents and metal based complexes such as platinum, ruthenium, iridium and rhodium complexes. These efforts will contribute to clinical cancer therapy and benefit patients in the future.


[Bevacizumab and taxanes in the first-line treatment of metastatic breast cancer : overall survival and subgroup analyses of the ATHENA study in France].
The international phase IIIb study, ATHENA assessed the combination of bevacizumab/taxane-based chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer (mBC) in real-life setting. Among the 365 patients included in France, median overall survival (OS) is 28.4 months (CI95% 24.8-33.0), with a median time from treatment start to end of study of 36,5 months (25,1-45,4). Exploratory analyses in three sub-groups show that the median OS in long responder patients (not progressing for at least one year; n = 116) is not reached. In responder patients (n = 308), median OS is 33.0 months (CI95% 28.6-37.4) and 12.4 months (CI95% 11.2-17.4) in non-responders (n = 41). In patients with mBC expressing hormone receptors (HR+), treated with first-line hormone therapy before inclusion (n = 87) median OS in is 23.2 months (CI95% 19.6-28.6), and 35.3 months (CI95% 32.2-not reached); P = 0.004 in patients treated first with chemotherapy + bevacizumab (n = 179). The safety analysis in the various sub-groups of grade 3-5 adverse events of particular interest to bevacizumab of this study was comparable to the safety data of randomized phase III studies.


Tumor necrosis factor α Inhibition for Alzheimer's Disease.
Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer's disease (AD). Food and Drug Administration-approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.


Clinical significance of radiation therapy combined with chemotherapy.
With the aim of reducing the side-effects in the surrounding healthy tissues, and/or improving the local control rate, radiotherapy combined with chemotherapy has been used to treat carcinoma of the esophagus, of the tongue, and of the paranasal sinuses. In the treatment of esophageal cancer, a dose of bleomycin too small to demonstrate clinical activity on its own is shown to potentiate the action of radiation with an enhancement ratio lying between 1.3 and 1.7 (Table 1). From the concept of 'therapeutic ratio' a 'two-phase' treatment modality (Table 2) was proposed, because many anticancer drugs or radiosensitizers available today influence not only the tumor tissue but also the surrounding healthy tissues. 'Two-phase' treatment was applied to cancer of the tongue (Table 3) and to cancer of the paranasal sinuses (Table 4). The appearance of the chronical complications such as the osteoradionecrosis of the mandible and the cataract of the lens could be prevented by the use of bleomycin or BUdR combined with radiotherapy.


Quality of life: perspectives of people with mental illnesses and family members.
Research studies that explore quality of life issues from the perspective of individuals living with mental illnesses, and from the perspective of their family members, are difficult to find in the literature. This study used qualitative strategies to assist policy makers in developing an appreciation of the perspectives of people with mental illnesses and family members on this very important topic. Results support the need for continued peer support and advocacy services; for a continued focus on promoting and supporting recovery for individuals living with mental illnesses; and for a service system that acknowledges and addresses the needs of family members.


Unusual clinical features of cutaneous tuberculosis in an immune compromised patient.
We report a case of an unusual form of cutaneous tuberculosis in an 82-year-old woman. She visited our hospital because of an intractable ulcer on the fifth finger of her right hand. While examining the ulcer surrounding half of her right fifth finger and covered with necrotic tissue, we also perceived a nodule with crust on the forearm, multiple subcutaneous nodules on the right forearm and upper arm, and a hen's-egg-sized agglomerative nodule on the axilla. All the lesions were located on her right arm. Skin biopsy specimens showed granulomatous tissue with necrosis in the lesions. Mycobacterium tuberculosis was identified by culture of a biopsied specimen, so the diagnosis was confirmed. Further examination revealed that she also had pulmonary tuberculosis. Cutaneous tuberculoses are classified morphologically with reference to host immune status, but no satisfactory classification exists. The present case can't be classified into any of the types which have been proposed so far. She is elderly and suffers from liver cirrhosis, hepatocellular carcinoma and myelodysplastic syndrome. The resulting acquired immunosuppression may have caused a unique form of cutaneous tuberculosis.