Less is more-A pilot study evaluating one to three intradetrusor sites for injection of OnabotulinumtoxinA for neurogenic and idiopathic detrusor overactivity.
To determine if minimizing the number of onabotulinumtoxinA (BTX) injection sites to one to three locations provides similar clinical efficacy and duration of effect compared to the established technique in treating patients with neurogenic (NDO) or idiopathic detrusor overactivity (IDO). Prospective data were collected on BTX naïve patients with NDO or IDO who were intolerant or refractory to oral medications. Patients were treated with 100-300 U of BTX via one to three injection sites. Patients completed the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) prior to and after treatment. The primary endpoint was defined as ICIQ-SF score improvement of >5 points. Secondary endpoints included subjective success, complete continence, quality of life score, post void residual (PVR), duration of effect and adverse events. Fourty-five patients (22 IDO, 23 NDO) were included. ICIQ-SF score improvement of >5 points was achieved in 73% (IDO 55%, NDO 91%) and the subjective success rate was 69% (50% IDO, 87% NDO). 52% of NDO patients attained complete continence. PVR increased by a mean of 32 and 156 ml in the IDO and NDO groups. Hematuria occurred in 6.7% and symptomatic urinary tract infection occurred in 11.1%. No systemic BTX adverse events occurred. Mean duration of effect was 31 weeks. Our technique for administering BTX via one to three intradetrusor injection sites has similar clinical efficacy and rates of adverse events compared to the established technique for treating patients with IDO and NDO. Neurourol. Urodynam. 36:1104-1107, 2017. © 2016 Wiley Periodicals, Inc.


In vivo evaluation of a Poly-2p barrier cream protective effect.
Theoretically, skin barrier creams reduce or even prevent the penetration into the skin by building up a physical barrier, like a thin film between the skin and the irritant. Practically, controversial experiences concerning the effectiveness of barrier creams exist. For this, we propose an in vivo method to evaluate the efficacy of barrier creams trough clinical scoring and instrumental analysis. Nineteen housewives with hand dermatitis in remission phase were enrolled in the study. Every patient was evaluated clinically and an arbitrary score was assigned by the investigator considering erythema, exudation, lichenification and xerosis. A score was also assigned by every patient to itching and burning. As measurement of the functional state of the skin and of the effectiveness of the barrier cream, transepidermal water loss (TEWL), corneometry, colorimetry and visco-elasticity determination were performed. To investigate the protection properties against irritant products, the 24-h irritancy patch test with sodium lauryl sulphate 1% in water was used. Through the patch test technique the efficacy of the barrier cream was tested compared to other topical products containing corticosteroids, lipids, humectants or urea, with already known anti-inflammatory, lenitive or protective properties. The results showed this methods easy and fast in handling, non-invasive, standardized, and in vivo applicable for evaluation and ranking of barrier creams. The study preparation demonstrated high tolerability and indubitable efficacy in improving the skin barrier function even towards a very well known irritant.


Oral health and access to dental care - a comparison of elderly migrants and non-migrants in Germany.
To compare oral health, access barriers to dental care, oral health behavior and oral hygiene behavior of elderly German residents with and without immigration background. In this cross-sectional explorative study, a convenience sample (N = 112, age ≥ 60 years, 54% immigrants) was recruited in four dental practices in Hamburg, Germany. Oral health was assessed with Decayed/Missing/Filled Teeth (DMFT), Papillary Bleeding Index (PBI), and Approximal Plaque Index (API). Dental health was operationalized as number of decayed teeth, and poor oral hygiene based on a PBI ≥ 40%. Access barriers and oral health behavior were assessed with a standardized questionnaire. While caries experience was similar in migrants and non-migrants (DMFT mean: 24.8 vs. 23.4, n.s.), significantly more teeth were decayed (5.3 vs. 2.1, p < 0.001), and API (55.3% vs. 33.0%, p = 0.002) and PBI (46.3% vs. 30.5%, p = 0.016) were significantly higher in migrants. After adjusting for age, sex, income, education, and number of teeth, migrants still had on average 3 decayed teeth more than non-migrants. However, impact of migration background on poor oral health changed from OR = 3.61 (p = 0.007) to OR = 1.05 (n.s.) after adjusting for confounders, mainly due to lower income in migrants. Fewer migrants had visited a dentist within the past 12 months, and migrants were less likely to have a regular dentist that they visit and more often indicated language or cost barriers than non-migrants. Elderly German migrants have higher treatment needs than non-migrants. Likely causes are poorer oral hygiene and lower utilization of dental care services. Specific prevention programs targeting migrants are warranted to improve oral health in this disadvantaged group.


The Ilizarov method for complex fracture nonunions.
Nonunion of complex fractures continues to challenge orthopedic trauma surgeons. Although traditional management results in a successful outcome in 50% to 80% of cases, the Ilizarov method has been reported to be more effective. We evaluated the efficacy of the Ilizarov method for treatment of nonunions. Patients were selected based on the presence of nonunion associated with osteomyelitis, treatment failure, or extensive segmental bone loss. Treatment principles include surgical debridement, stabilization, and bone regeneration for correction of defects. Patients were given maximum mobility and were required to function as normally as possible during the course of treatment. Seventeen patients were treated for complex nonunions with the Ilizarov method during a 33-month period. Seven patients were facing the alternative of amputation. Causes of nonunion were osteomyelitis (65%), failure of conventional treatment (23%), and segmental bone loss (12%). Fractures involved the lower (82%) and upper (18%) extremities. Using the Ilizarov method, union was achieved in 94% (16 of 17) of patients over an average time of 6 months. Our results indicate that the Ilizarov method is superior to traditional techniques of managing complex nonunions.


Post-natal management of antenatally detected, bilateral hydronephrosis.
26 children, with antenatally detected, isolated, bilateral hydronephrosis (thus consistent with pelvi-ureteric junction obstruction), were investigated for up to 7 years. The aim was to avoid operation. 34 kidneys were never operated on. Despite initially often severe hydronephrosis and poor isotope wash-out on the renogram, half of the kidneys improved or even normalized during follow-up. The final glomerular filtration rate (GFR) was always normal or almost normal. 18 kidneys came to surgery, because of poor filtration, symptoms or social reasons. At the end of the follow-up, GFR was normal in all but 2 kidneys. In a subgroup of the kidneys, with initially severe reduction in filtration, half were operated on and half were not; at the end, the GFR was normal in all of the non-operated kidneys (and in all but 1 of the operated kidneys). Total GFR was at the end normal or almost normal also in the children with persistingly filtration-reduced kidneys (always unilaterally), because of compensation by the contralateral, although hydronephrotic kidney. Thus, in this study the renographic parameters were not very helpful in predicting the prognosis. There was no consistent difference between operative and non-operative treatments on final filtration. Also hydronephrotic kidneys possessed a substantial capacity for contralateral compensation. It is concluded that the initial approach to bilateral, antenatally diagnosed hydronephrosis may safely be non-operative. This allows time for the clear expression of sustained impairment of renal filtration requiring surgical intervention.


FOLFOX and intensified split-course chemoradiation as initial treatment for rectal cancer with synchronous metastases.
Optimal initial management of rectal carcinoma with synchronous metastases (RCSM) is controversial - both for patients being treated with curative and palliative intent. This study aims to evaluate the use of an upfront treatment strategy combining FOLFOX chemotherapy with split-course pelvic chemoradiation (FOLFOX + CRT) for patients with RCSM. An analysis of all patients who commenced treatment with FOLFOX + CRT at our institutions between January 2009 and June 2014 was performed. The regimen consisted of a total of 12 weeks of treatment with split-course pelvic chemoradiation (50.4Gy with concurrent oxaliplatin and 5-FU) alternating with FOLFOX chemotherapy. Restaging imaging was performed following treatment, with subsequent management as per local standard of care. 78 patients (15 with resectable liver-only metastases) were identified. 77 (99%) completed at least 45Gy of radiation and 87% completed ≥75% of planned dose intensity of both oxaliplatin and 5FU. Two (2.6%) patients died within 30 days of treatment. Rates of radiological complete or partial response for local and metastatic disease were 90% and 66%, respectively. 24% patients had radiological disease progression of metastatic disease. Median overall survival for patients with unresectable metastatic disease at baseline was 23 months (95%CI: 19-28). 12 patients underwent radical surgery to both the rectum and liver and had an estimated 3-year overall survival rate of 62% (95%CI: 37-100). For those patients who did not proceed to rectal surgery, only 7% required palliative re-irradiation or surgery at a later date and all >20months from initial treatment. In patients with unresectable metastatic disease, FOLFOX + CRT provides durable pelvic control for the majority without the need for additional local treatment. For patients with an advanced primary tumor and synchronous resectable liver-only metastases, FOLFOX + CRT can be considered a feasible and tolerable upfront treatment option.


Decomposition of hydrogen peroxide and organic compounds in the presence of dissolved iron and ferrihydrite.
This work examines the contribution of solution phase reactions, especially those involving a chain reaction mechanism, to the decomposition of hydrogen peroxide (H2O2) and organic compounds in the presence of dissolved iron and ferrihydrite. In solutions at pH 4, where Fe was introduced as dissolved Fe(III), both H2O2 and 14C-labeled formic acid decomposed at measurable rates that agreed reasonably well with those predicted by a kinetic model of the chain reaction mechanism, using published rate constants extrapolated to pH 4. The ratio of the formic acid and H2O2 decomposition rates, as well as the dramatic effect of tert-butyl alcohol on these rates, confirmed that a solution chain reaction mechanism involving *OH controlled the decomposition kinetics of both compounds. In the presence of ferrihydrite as the iron source, the ratio of the rate of formic acid decomposition to that of H2O2 decomposition was significantly lower than that observed in the presence of only dissolved Fe. Moreover, neither rate diminished drastically upon addition of tert-butyl alcohol, indicating that the solution phase chain reaction is not a dominant decomposition pathway of H2O2 and formic acid. Relative decomposition rates of formic acid and a second *OH probe, benzoic acid, were consistent with oxidation of these compounds by *OH. These observations can be reproduced by a kinetic model including (a) decomposition of H2O2 at the iron oxide surface, producing *OH with lower yield than the reaction sequence with dissolved Fe, and (b) low concentrations of dissolved Fe in the presence of ferrihydrite, preventing propagation of the solution phase chain reaction.


[Expression of mitochondrial ferritin in K562 leukemic cell during ATRA-induced cell differentiation].
To investigate the expression of MtF, transferrin receptor 1 (TfR1) and ferritin (Fn) mRNAs in K562 leukemic cells during ATRA-induced cell differentiation and to explore the interrelationship between the expression levels of these iron metabolism-related molecules. K562 cells cultured with or without ATRA (1 micromol/L) were collected at 24, 72 and 120 hours respectively. Cell differentiation toward granulocyte lineage was confirmed by microscopic study (Wright's staining) and flowcytometry. Expression levels of MtF, TfR1 and Fn were evaluated with semiquantitative RT-PCR, while K562 cells cultured without ATRA as control. Over 21.2% of K562 cells demonstrated features of granulocyte, and the expression of CD13 on cell surface increased significantly at day 5 with ATRA treatment (P < 0.05, compared with control). K562 cells could express a certain level of MtF before ATRA-induced differentiation. With increase of ATRA-induced cell differentiation, MtF mRNA expressions were downregulated progressively. After 5 days of induced cell differentiation, expression levels of MtF and TfR1 mRNA were just 86.5% and 79.2% of that before ATRA treatment. While Fn mRNA expression increased to 1.21 folds of that before ATRA treatment. MtF expression is downregulated during ATRA-induced K562 cell differentiation, with concomitant downregulation of TfR1 and upregulation of Fn. The coordinated expression regulation of these key iron metabolism-related molecules during cell differentiation may in turn inhibit TfR1-mediated iron uptake via endocytosis and thus adversely affect cell proliferation potential.


[Questions of liability in unsuccessful voluntary sterilization (author's transl)].
Since the June 29, 1976, decision of the Federal High Court of the Federal Republic of Germany, voluntary sterilization is permitted under certain, limited, circumstances. After the physician has thoroughly instructed the patient, the patient must give written consent in agreement with S 226 of the penal code. The physician cannot then later be charged with commiting bodily injury according to S 224 of the penal code. Recently, the German courts have tended more and more to consider the unplanned birth of a child following unsuccessful sterilization as a damage case for which the attending physician is held responsible under civil law. For most physicians, this means that the financial compensation set by the court is not, or at least not fully, covered by their medical indemnity insurance. A corresponding increase in the medical indemnity coverage or a release from all damage claims overagainst the attending physician signed by the patient is urgently indicated.


Direct proportional relationship between endometrioma size and ovarian parenchyma inadvertently removed during cystectomy, and its implication on the management of enlarged endometriomas.
The aim of this study was to estimate whether or not the size of an endometrioma is related to the thickness of the ovarian parenchyma inadvertently excised along with the cyst wall. We performed a retrospective study including 35 women who had undergone endometrioma cystectomy, using an ovarian tissue sparing procedure. In total 38 specimens were studied by three pathologists as three women presented bilateral localizations, and all cyst diameters measured at least 30 mm. For each endometrioma, serial sections were performed, and on each section four different sites were randomly chosen to measure the thickness of glandular epithelium and stroma, of subjacent fibrosis, depending on the cyst, and of the ovarian parenchyma removed with the cyst. The diameter of the ovary was measured preoperatively either by MRI or ultrasound, and the area of the internal wall was then calculated. The relationships between the mean thickness of ovarian parenchyma removed and the variables were estimated and a multiple regression model identified independent predictors for ovarian parenchyma thickness. Adjacent ovarian tissue was found in 37 cases (97%). The mean thickness of ovarian tissue removed was 1173 +/- 711 microm and that of the cyst wall was 851 +/- 499 microm. The thickness of the ovarian parenchyma removed presented a direct proportional relationship with cyst diameter (P = 0.015), and consequently with cyst wall area (P = 0.032). This relationship with cyst diameter was independent after adjustment on other variables (P = 0.032). Endometrioma cystectomy even though performed with an accurate surgical technique leads to significant ovarian tissue removal, the thickness of which increases proportionally with cyst diameter.


XVSAP1 from Xerophyta viscosa improves osmotic-, salinity- and high-temperature-stress tolerance in Arabidopsis.
XVSAP1, a gene isolated from a dehydrated Xerophyta viscosa cDNA library, was transformed into Arabidopsis thaliana by Ti plasmid-mediated transformation under the control of a cauliflower mosaic virus 35S promoter, a nos terminator and bar gene selection. Expression of XVSAP1 in Arabidopsis led to constitutive accumulation of the corresponding protein in the leaves. Transgenic Arabidopsis grown in tissue culture maintained higher growth rates during osmotic, high-salinity and high temperature stress, respectively. Non-transgenic plants had shorter roots, leaf expansion was inhibited and leaves were more chlorotic than those of the transgenic plants. This study demonstrates that XVSAP1 has a significant impact on dehydration, salinity and high-temperature stress tolerance in Arabidopsis.


Treatment of ectopic pregnancy with prostaglandin E2.
In 10 patients the treatment of ectopic pregnancy consisted of the use of 0.75 to 2.25 mg of prostaglandin E2 (Prostin E2, 1 mg/ml, Upjohn). In 8 patients PGE2 was injected in the tubal wall under laparoscopic control, in 2 under the control of vaginal ultrasound probe. The effect of the treatment was controlled by serial determinations of serum beta HCG. In 8 patients with PGE2 injected laparoscopically, negativization of beta HCG took place in 14 +/- 8 days which meant successful treatment of ectopic pregnancy. For persistently elevated beta HCG concentrations in both patients with PGE2 applied under the ultrasound control, laparotomy had to be performed.


Comparison of oral versus intra-articular tranexamic acid in enhanced-recovery primary total knee arthroplasty without tourniquet application: a randomized controlled trial.
Although randomized controlled trials have confirmed oral tranexamic acid (TXA) can provide similar blood-sparing efficacy compared with intravenous (IV) TXA in total knee arthroplasty (TKA), some concerns do remain about thromboembolic events after such systemic administration. Many studies have confirmed that intra-articular (IA) application of TXA can show similar blood-saving efficacy with minimal levels of systemic absorption compared with IV TXA. However, it remains unclear whether the efficacy and safety of oral TXA administration is equal to or less than that of IA administration in TKA without the use of a tourniquet and drain. Thus, this study was to verify non-inferior efficacy and safety of oral TXA compared with IA TXA in primary TKA. A double-blind, randomized, controlled trial was performed to compare three oral doses of TXA (2 g of TXA 2 h before incision, and 1 g of TXA 6 and 12 h after surgery, respectively) with IA TXA (3 g of TXA in 100 mL of saline solution). One hundred forty-seven patients scheduled for TKA were randomized to one of the two interventions. The primary outcome was total blood loss. The secondary outcomes included reduction of hemoglobin concentration, clinical outcomes, blood coagulation values, thromboembolic complications, and transfusion rates. The mean total blood loss was 788.8 mL in the oral TXA group compared with 872.4 mL in the IA TXA group, with no statistical significance (p > 0.05). There were no significant differences in reduction of hemoglobin level, blood coagulation level, and clinical outcomes. The transfusion rates were 4% in oral group and 5% IA group, respectively. Also, no significant differences were identified in thromboembolic complications. Oral TXA according to the described protocol demonstrated non-inferiority for primary TKA, with no safety concerns and a greatly reduced cost, compared with the IA TXA. This randomized controlled trial supports the oral administration of TXA in TKA. The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR-INR-17010968 ) dated 23rd March 2017.


Competitive Spiking Neural P Systems With Rules on Synapses.
This paper proposes an extension of spiking neural P systems with rules on synapses (SNP-RS systems) working in competitive strategy, called competitive SNP-RS (CSNP-RS systems). In CSNP-RS systems, the spikes are viewed as a kind of competitive resources, and the rules on different synapses will compete the spikes (resources) in neurons. A new strategy is considered: the total amount of spikes consumed by these rules should be greater than or equal to the generated amount of spikes. There are two cases to chosen one rule non-deterministically: 1) two or more rules on the same synapse are enabled; and 2) two or more rules on the different synapses are enabled, and the number of spikes contained in neuron is smaller than the number of spikes consumed by these rules. CSNP-RS systems are a kind of distributed parallel computing models. The computational power of CSNP-RS systems is investigated. Specifically, we prove that CSNP-RS systems are turing universal as number generating/accepting devices and function computing device.


Suffering: etiology and treatment.
Suffering comes in many forms. Certain psychological therapies rooted in the work of Victor Frankl have been shown to alleviate suffering at the end of life. Frankl asserted, with subsequent agreement from secular and religious authors, that it is important to include the transcendent when working with those who suffer. This article explores some of the causes for and treatments of suffering. It briefly argues for the importance of addressing and even embracing the transcendent.


Klebsiella pneumoniae causes bacteremia using factors that mediate tissue-specific fitness and resistance to oxidative stress.
Gram-negative bacteremia is a major cause of global morbidity involving three phases of pathogenesis: initial site infection, dissemination, and survival in the blood and filtering organs. Klebsiella pneumoniae is a leading cause of bacteremia and pneumonia is often the initial infection. In the lung, K. pneumoniae relies on many factors like capsular polysaccharide and branched chain amino acid biosynthesis for virulence and fitness. However, mechanisms directly enabling bloodstream fitness are unclear. Here, we performed transposon insertion sequencing (TnSeq) in a tail-vein injection model of bacteremia and identified 58 K. pneumoniae bloodstream fitness genes. These factors are diverse and represent a variety of cellular processes. In vivo validation revealed tissue-specific mechanisms by which distinct factors support bacteremia. ArnD, involved in Lipid A modification, was required across blood filtering organs and supported resistance to soluble splenic factors. The purine biosynthesis enzyme PurD supported liver fitness in vivo and was required for replication in serum. PdxA, a member of the endogenous vitamin B6 biosynthesis pathway, optimized replication in serum and lung fitness. The stringent response regulator SspA was required for splenic fitness yet was dispensable in the liver. In a bacteremic pneumonia model that incorporates initial site infection and dissemination, splenic fitness defects were enhanced. ArnD, PurD, DsbA, SspA, and PdxA increased fitness across bacteremia phases and each demonstrated unique fitness dynamics within compartments in this model. SspA and PdxA enhanced K. pnuemoniae resistance to oxidative stress. SspA, but not PdxA, specifically resists oxidative stress produced by NADPH oxidase Nox2 in the lung, spleen, and liver, as it was a fitness factor in wild-type but not Nox2-deficient (Cybb-/-) mice. These results identify site-specific fitness factors that act during the progression of Gram-negative bacteremia. Defining K. pneumoniae fitness strategies across bacteremia phases could illuminate therapeutic targets that prevent infection and sepsis.


Demonstration of the in vitro phagocytosis of Treponema denticola by human polymorphonuclear neutrophils.
A method has been developed for the study of phagocytosis of the oral treponeme T. denticola by human polymorphonuclear neutrophils. T. denticola was labelled with 32P-orthophosphate, and phagocytosis, expressed as counts per mg cell protein, was measured after 15, 60 and 120 min of interaction between neutrophils and treponemes. Four different cell cultures were used as controls, and phagocytosis of E. coli was used as reference. The uptake of radiolabelled T. denticola was significantly larger with the PMNs than with any of the control cells. An increase of uptake was observed from 15 to 120 min. The addition of autologous human serum or rabbit T. denticola antiserum enhanced the phagocytosis 2-3 fold, and phagocytosis was decreased under an anaerobic atmosphere. Scanning electron microscopic studies also indicated that phagocytosis had taken place.


Evolution of Ni nanofilaments and electromagnetic coupling in the resistive switching of NiO.
Resistive switching effect in conductor/insulator/conductor thin-film stacks is promising for resistance random access memory with high-density, fast speed, low power dissipation and high endurance, as well as novel computer logic architectures. NiO is a model system for the resistive switching effect and the formation/rupture of Ni nanofilaments is considered to be essential. However, it is not clear how the nanofilaments evolve in the switching process. Moreover, since Ni nanofilaments should be ferromagnetic, it provides an opportunity to explore the electromagnetic coupling in this system. Here, we report a direct observation of Ni nanofilaments and their specific evolution process for the first time by a combination of various measurements and theoretical calculations. We found that multi-nanofilaments are involved in the low resistance state and the nanofilaments become thin and rupture separately in the RESET process with subsequent increase of the rupture gaps. Theoretical calculations reveal the role of oxygen vacancy amount in the evolution of Ni nanofilaments. We also demonstrate electromagnetic coupling in this system, which opens a new avenue for multifunctional devices.


Tyrosine phosphorylation of WIP releases bound WASP and impairs podosome assembly in macrophages.
Podosomes are integrin-containing adhesion structures commonly found in migrating leukocytes of the monocytic lineage. The actin cytoskeletal organisation of podosomes is based on a WASP- and Arp2/3-mediated mechanism. WASP also associates with a second protein, WIP (also known as WIPF1), and they co-localise in podosome cores. Here, we report for the first time that WIP can be phosphorylated on tyrosine residues and that tyrosine phosphorylation of WIP is a trigger for release of WASP from the WIP-WASP complex. Using a knockdown approach together with expression of WIP phosphomimics, we show that in the absence of WIP-WASP binding, cellular WASP is rapidly degraded, leading to disruption of podosomes and a failure of cells to degrade an underlying matrix. In the absence of tyrosine phosphorylation, the WIP-WASP complex remains intact and podosome lifetimes are extended. A screen of candidate kinases and inhibitor-based assays identified Bruton's tyrosine kinase (Btk) as a regulator of WIP tyrosine phosphorylation. We conclude that tyrosine phosphorylation of WIP is a crucial regulator of WASP stability and function as an actin-nucleation-promoting factor.


Potential pitfall of FDG PET/CT in assessing residual masses postchemotherapy.
A 22-year-old man with primary mediastinal choriocarcinoma and bilateral lung metastases underwent an FDG PET/CT scan after completing chemotherapy. Serum beta-human chorionic gonadotropin had normalized. PET/CT showed increased FDG uptake in the anterior mediastinal and lung lesions, suspicious for residual disease. After resection of the mediastinal and lung lesions, histopathology revealed necrosis and fibrohistiocytic reaction with no viable tumor. There was discordance between beta-human chorionic gonadotropin (negative) and FDG PET/CT (positive) findings, with PET/CT findings being false positive. Awareness of this potential pitfall of FDG PET/CT is important, and caution should be exercised when using FDG PET/CT to assess residual masses after chemotherapy.


[Clinical aspects and therapy of congenital pseudarthrosis of the lower limb. 2 case reports].
Congenital pseudarthrosis of the lower leg is described with reference to recent findings regarding its pathogenesis, development, treatment and prognosis; the condition is explained on the basis of the authors' personal experience with two cases.


Robotic hand illusion with tactile feedback: Unravelling the relative contribution of visuotactile and visuomotor input to the representation of body parts in space.
The rubber hand illusion describes a phenomenon in which participants experience a rubber hand as being part of their body by the synchronous application of visuotactile stimulation to the real and the artificial limb. In the recently introduced robotic hand illusion (RobHI), a robotic hand is incorporated into one's body representation due to the integration of synchronous visuomotor information. However, there are no setups so far that combine visuotactile and visuomotor feedback, which is expected to unravel mechanisms that cannot be detected in experimental designs applying this information in isolation. We developed a robotic hand, controlled by a sensor glove and equipped with pressure sensors, and varied systematically and separately the synchrony for motor feedback (MF) and tactile feedback (TF). In Experiment 1, we implemented a ball-grasping task and assessed the perceived proprioceptive drift of one's own hand as a behavioral measure of the spatial calibration of body coordinates as well as explicit embodiment experiences by a questionnaire. Results revealed significant main effects of both MF and TF for proprioceptive drift data, but we only observed main effects for MF on perceived embodiment. Furthermore, for the proprioceptive drift we found that synchronous feedback in one factor compensates for asynchronous feedback in the other. In Experiment 2, including a new sample of naïve participants, we further explored this finding by adding unimodal conditions, in which we manipulated the presence or absence of MF and/or TF. These findings replicated the results from Experiment 1 and we further found evidence for a supper-additive multisensory effect on spatial body representation caused by the presence of both factors. Results on conscious body perception were less consistent across both experiments. The findings indicate that sensory and motor input equally contribute to the representation of spatial body coordinates which for their part are subject to multisensory enhancing effects. The results outline the potential of human-in-the-loop approaches and might have important implications for clinical applications such as for the future design of robotic prostheses.


Identification of functional domains in the cytoskeletal protein talin.
The cytoskeletal protein talin potentially plays a key role in actin-membrane linkage. It is able to nucleate actin filament growth in vitro while binding simultaneously to lipid bilayers. Thrombin digestion of human platelet talin yields tow polypeptide domains of 200 kDa and 47 kDa. We have purified these fragments and analyzed their functional properties: the 200-kDa fragment was active in nucleating actin filament formation and reduced the viscosity of filamentous actin, comparable to the effects of the intact protein. The 47-kDa fragment was inactive in this respect. However, the 47-kDa polypeptide, but not the 200-kDa fragment, interacted specifically with large liposomes containing acidic phospholipids. This is demonstrated by selective, hydrophobic photolabeling of the 47-kDa fragment using phosphatidylserine liposomes containing trace amounts of a photoactivable phospholipid analogue and by selective co-sedimentation of this domain with the liposomes. The 200-kDa fragment, whether alone or in conjunction with the small fragment, neither incorporated significant amounts of label nor co-sedimented with the liposomes. We thus are able to attribute specialized functions to distinct domains on the talin molecule. These enable the protein to interact simultaneously with actin filaments and lipid membranes.


Sodium-Dependent Glucose Transporter 1 (SGLT1) Stabled by HER2 Promotes Breast Cancer Cell Proliferation by Activation of the PI3K/Akt/mTOR Signaling Pathway in HER2+ Breast Cancer.
Aerobic glycolysis is a hallmark of tumor cells. SGLT1 plays a vital role in glucose metabolism. However, whether SGLT1 could promote cell growth and proliferation in breast cancer remains unclear. Here, we investigated the expression of SGLT1 in breast cancer and examined its role in malignant behavior and prognosis. Further, we examined the SGLT1 expression in breast cancer tissues and its relationship with clinicopathologic characteristics. We clarified that SGLT1 was overexpressed in HER2+ breast cancer cell lines and was affected by HER2 status. We further found that SGLT1 affected breast cancer cell proliferation and patient survival by mediating cell survival pathway activation. SGLT1 was overexpressed in HER2+ breast cancers and associated with lymph node metastasis and HER2+ status. Inhibition of HER2 decreased SGLT1 expression, and the extracellular acidification rate was also reduced in the UACC812 and SKBR3 cell lines. These changes could be reversed by proteasome inhibitor treatment. Knockdown of SGLT1 blocked PI3K/Akt/mTOR signaling, thereby inhibiting cell proliferation. Further, we demonstrated that high SGLT1 was significantly correlated with shorter survival in all breast cancer patients and specifically in HER2+ breast cancer patients. Therefore, we conclude that SGLT1 is overexpressed in HER2+ breast cancer, thereby promoting cell proliferation and shortening survival by activating PI3K/Akt/mTOR signaling. This study submits that SGLT1 is promising not only as a novel biomarker of HER2+ breast cancer subtype but also as a potential drug target.


Circadian Rhythms in Fear Extinction Recall Depend on the Time of Day of Extinction Recall, Not the Time of Day of Extinction Learning.
The recall of conditioned fear extinction exhibits a circadian rhythm in humans and rodents, with optimal extinction recall occurring during the early active phase. However, it remains unclear whether this rhythm depends on the circadian modulation of mechanisms supporting memory consolidation versus memory maintenance and retrieval. Here, adult male rats underwent conditioned fear extinction at one of four times throughout the day and then, starting 24 h after extinction, were repeatedly tested for extinction recall over the next 24 h. Rats undergoing extinction learning during the early active phase tended toward accelerated extinction learning compared with rats in other groups, pointing to rhythms in mechanisms that support extinction memory encoding. The next day, the strength of extinction recall followed a 24-h cycle that depended not on the time of day of extinction learning but, instead, on the time of day of extinction recall. This latter finding indicates a rhythm in mechanisms supporting extinction memory maintenance and/or retrieval. Subsequent testing for fear relapse in the conditioning context suggested reduced fear in rats tested during the early active phase. These results lay the groundwork for mechanistic investigations of circadian rhythms in fear extinction memory.


Enhancement of human lymphocyte transformation by aggregated human gamma globulin.
The effect of heat-aggregated human gamma globulin (aggFII) on the induction of in vitro lymphocyte transformation, measured by the uptake of tritiated thymidine into newly synthesized DNA, was studied with peripheral blood lymphocytes derived from 12 patients with rheumatoid arthritis (RA), six with ankylosing spondylitis (AS), two with systemic lupus erythematosus (SLE), and seven normal subjects. It was found that 200 mug aggFII induced significant transformation of the lymphocytes of eight patients with RA, five with AS, one with SLE, and one normal subject. Neither deaggregated FII nor heat-aggregated human serum albumin induced significant transformation of the lymphocytes of any subject tested. A source of complement appeared necessary to support aggFII-induced blastogenesis, since enhanced transformation occurred only in the presence of fresh plasma. Heat-inactivated plasma and fetal calf serum (FCS), and FCS devoid of hemolytic complement, failed to support enhanced blastogenesis in the presence of aggFII. Since substrates similar to those employed in these studies are present in vivo in the rheumatoid joint, it is suggested that aggFII may enhance intra-articular lymphocyte transformation in subjects with RA.


[Determinants of prognosis in acute pulmonary embolism: the role of serum troponins].
In-hospital mortality in patients with acute pulmonary embolism ranges between about 1% and over 30%. Due to a particularly high mortality, hemodynamically unstable patients with pulmonary embolism should receive thrombolytic treatment. The role of thrombolytic treatment in hemodynamically stable patients with pulmonary embolism is controversial and should be restricted to those at high risk for in-hospital mortality. Prognostic stratification is crucial in hemodynamically stable patients as mortality in this group ranges between 1 and 10%. Serum troponin levels have been shown to be associated with in-hospital mortality and clinical deterioration. Studies on the prognostic value of serum troponin in patients with acute pulmonary embolism have been included in a meta-analysis that shows a 5-fold in hospital mortality in patients with high troponin compared to those with normal troponin levels. The prognostic value of elevated serum troponin levels have also been shown in studies including only hemodynamically stable patients with pulmonary embolism. Future studies will evaluate the clinical benefit of thrombolytic treatment in hemodynamically stable patients with acute pulmonary embolism at high risk for adverse outcome.


The Infection Returns: A Case of Pulmonary Sporotrichosis Relapse after Chemotherapy.
Pulmonary sporotrichosis is a rare disease caused by a dimorphic fungus, Sporothrix schenckii. It is rarely found in association with malignancy. We present a case of pulmonary sporotrichosis recurrence after chemotherapy. A 44-year-old man, treated for pulmonary sporotrichosis in the past, presented with dysphagia and was found to have squamous cell carcinoma of the esophagus. After undergoing chemotherapy, extensive cavitary lesions were observed on thoracic computed tomography scan. A bronchoalveolar lavage revealed the presence of Sporothrix schenckii sensu lato. Despite treatment with itraconazole, he eventually required a left pneumonectomy for progressive destructive cavitary lesions involving the left lung. This case highlights the importance of considering past fungal infections, albeit cured, in patients initiating immunosuppressive therapy.


Conjugal mobilization of plasmid DNA: termination frequency at the origin of transfer of plasmid R1162.
Conjugal transfer of plasmid R1162 is initiated and terminated at a 38-bp origin of transfer (oriT). Plasmids containing two directly repeated copies of oriT were used to determine the actual frequency of termination at this site. This frequency was calculated both for oriTnic, a mutated origin that cannot act as the initiation site of transfer, and for an unmutated oriT where transfer had been initiated. In both cases, the termination frequency decreased as the distance between the initiation and termination sites became greater and was significantly less than one for plasmids the size of R1162. A substantial proportion of recipient cells received more than one plasmid copy during transfer. Our results indicate that termination is inefficient but that this is partly compensated for by the transmission of multiple plasmid copies.


Effects of stromal fibroblasts and fat cells and an environmental factor air exposure on invasion of laryngeal carcinoma (HEp-2) cells in a collagen gel invasion assay system.
To clarify the invasion mechanism of laryngeal carcinoma (HEp-2) cells. Human HEp-2 cells were cultured on a collagen gel containing fibroblasts and/or fat cells. The HEp-2 cells were also treated with air exposure as the local environment of the laryngeal epithelial mucosa. A collagen gel invasion assay was conducted under these culture conditions. No invasion of HEp-2 cells was found in the stromal cell-free collagen gel, but a slight invasion was observed in the fibroblast-embedded gel. A deeper invasion of HEp-2 cells occurred in the fibroblast- and fat cell-coembedded gel and in the fibroblast-embedded gel with air exposure. The most extensive invasion of HEp-2 cells was observed under the fibroblast- and fat cell-coembedded gel in combination with air exposure. Fat cells and air exposure clearly increase the invasive effect of fibroblasts in squamous cell carcinoma of the larynx. The combined effect of these 3 factors (ie, fat cells, fibroblasts, and air exposure) plays a very important role in the invasive growth of the carcinoma cells. This observation suggests that both tumor cell-stromal cell interaction and tumor cell-local environmental factor interaction should be taken into account in an investigation of the invasive and proliferative mechanisms of laryngeal carcinoma.


In vitro and in vivo neutralizing activity of human colostrum and milk against purified toxins A and B of Clostridium difficile.
The neutralizing activity (NA) of supernates of colostral samples collected postpartum from 55 women and tested against a 50% cytopathic dose of purified toxins A and B of Clostridium difficile was evaluated in Y1 adrenal cells. Thirty-one (56%) of the samples had NA against one or both toxins. Samples of breast milk were collected postpartum from five women-three had colostral NA and two did not. All milk specimens from the three women with colostral NA had NA titers of 1:1-1:4 throughout the study (609 days in one case). Samples from the two women without colostral NA did not exhibit NA during a 60-day follow-up period. In suckling mice either toxin plus human milk with in vitro NA elicited significantly less fluid accumulation than did toxin plus diluent or toxin plus milk without in vitro NA (P less than .025 to P less than .05). Twelve (63%) of 19 milk samples with in vitro NA against toxin A and 15 (65%) of 23 with in vitro NA against toxin B inhibited fluid accumulation caused by the corresponding toxin. In vitro NA against toxin A appeared to reside in the secretory IgA fraction of one milk sample assessed by immune precipitation. The results suggest that human milk may protect newborn infants against toxins A and B of C. difficile.


Bio-Inspired Antioxidant Heparin-Mimetic Peptide Hydrogel for Radiation-Induced Skin Injury Repair.
Radiotherapy is one of the most important means of cancer treatment, however, radiation can also cause adverse reactions and even serious injuries to the skin. Radiation-induced excess reactive oxygen species (ROS) production and inflammatory infiltration make skin wounds difficult to heal compared to normal skin injuries. Herein, an antioxidant heparin-mimetic peptide hydrogel (K16, KYKYEYEYAGEGDSS-4Sa) is designed for radiation-induced skin injury (RISI) repair. First, the K16 peptide can self-assemble into a hydrogel with a 3D mesh-like porous nanofiber structure, which can provide certain physical support for skin repair like extracellular matrix (ECM). Then, K16 hydrogel not only scavenges ROS and prevents radiation damage to cellular DNA, but also promotes cell proliferation, migration, and angiogenesis. Meanwhile, 4-sulfobenzoic acid (4Sa) modified at the N-terminal end of the K16 peptide can adsorb inflammatory cytokines, thus acting to eliminate inflammation at the wound site. In vivo experiments showed that K16 hydrogel can inhibit early wound degradation, reduce inflammatory infiltration, and promote angiogenesis and collagen deposition, thus promoting wound healing. Therefore, the K16 hydrogel designed in this study has good potential for application in the field of radiation-induced skin injury repair.


Unobtrusive measurement of indoor energy expenditure using an infrared sensor-based activity monitoring system.
The purpose of this study was to develop an unobtrusive energy expenditure (EE) measurement system using an infrared (IR) sensor-based activity monitoring system to measure indoor activities and to estimate individual quantitative EE. IR-sensor activation counts were measured with a Bluetooth-based monitoring system and the standard EE was calculated using an established regression equation. Ten male subjects participated in the experiment and three different EE measurement systems (gas analyzer, accelerometer, IR sensor) were used simultaneously in order to determine the regression equation and evaluate the performance. As a standard measurement, oxygen consumption was simultaneously measured by a portable metabolic system (Metamax 3X, Cortex, Germany). A single room experiment was performed to develop a regression model of the standard EE measurement from the proposed IR sensor-based measurement system. In addition, correlation and regression analyses were done to compare the performance of the IR system with that of the Actigraph system. We determined that our proposed IR-based EE measurement system shows a similar correlation to the Actigraph system with the standard measurement system.


Negative Birefringence in the Higher Homologs of the 5O.m Series of Liquid Crystals.
A detailed study of the different parameters of the higher homologs of the 5O.m (m = 14, 16) series of liquid-crystalline compounds is reported. These are interdigitated compounds with unsymmetrical alkyl chain length. The compounds have a unique nature, unlike the other members of the nO.m series. The molecular structure reported in this article is not purely uniaxial; it has a bending tendency. In this article, we report that both the compounds exhibit negative birefringence. For the optical study, the refractive indices, ne and no, of the sample are measured by the thin-prism technique, using a He-Ne laser beam of wavelength 633 nm. A four-parameter model was used for fitting the experimental results. From the experimentally measured refractive indices, it is possible to compare different parameters with those of the theoretical models.


Plant mycorrhizal associations mediate the zoogeochemical effects of calving subsidies by a forest ungulate.
Animals interact with and impact ecosystem biogeochemical cycling-processes known as zoogeochemistry. While the deposition of various animal materials (e.g. carcasses and faeces) has been shown to create nutrient hotspots and alter nutrient cycling and storage, the inputs from parturition (i.e. calving) have yet to be explored. We examine the effects of ungulate parturition, which often occurs synchronously during spring green-up and therefore aligns with increased plant nitrogen demand in temperate biomes. Impacts of zoogeochemical inputs are likely context-dependent, where differences in material quality, quantity and the system of deposition modulate their impacts. Plant mycorrhizal associations, especially, create different nutrient-availability contexts, which can modify the effects of nutrient inputs. We, therefore, hypothesize that mycorrhizal associations modulate the consequences of parturition on soil nutrient dynamics and nitrogen pools. We established experimental plots that explore the potential of two kinds of zoogeochemical inputs deposited at ungulate parturition (placenta and natal fluid) in forest microsites dominated by either ericoid mycorrhizal (ErM) or ectomycorrhizal (EcM) plants. We assess how these inputs affect rates of nutrient cycling and nitrogen content in various ecosystem pools, using isotope tracers to track the fate of nitrogen inputs into plant and soil pools. Parturition treatments accelerate nutrient cycling processes and increase nitrogen contents in the plant leaf, stem and fine root pools. The ecosystem context strongly modulates these effects. Microsites dominated by ErM plants mute parturition treatment impacts on most nutrient cycling processes and plant pools. Both plant-fungal associations are, however, equally efficient at retaining nitrogen, although retention of nitrogen in the parturition treatment plots was more than two times lower than in control plots. Our results highlight the potential importance of previously unexamined nitrogen inputs from animal inputs, such as those from parturition, in contributing to fine-scale heterogeneity in nutrient cycling and availability. Animal inputs should therefore be considered, along with their interactions with plant mycorrhizal associations, in terms of how zoogeochemical dynamics collectively affect nutrient heterogeneity in ecosystems.


Detection of endophyte toxins in the imported perennial ryegrass straw.
From 1997 to 1999, 29 cases of disorders were detected in cattle and horses that had been fed ryegrass straw imported from the U.S.A. These animals showed symptoms resembling ryegrass staggers and the clinical signs disappeared after removal of the straw. Endophytic hyphae were detected in the seeds of all straw samples that were responsible for the clinical cases. Lolitrem B concentrations in the straw ranged between 972 and 3740 ppb. Ergovaline concentrations were between 355 and 1300 ppb. Even though the concentrations of lolitrem B were lower than the toxic threshold proposed by Oregon State University in better part of the cases, our observations suggest the possibility that lolitrem B lower than the proposed threshold can bring disorders to sensitive individuals.


State insurance mandates and off-label use of chemotherapy.
Access to cancer drugs used off-label is important to cancer patients but may drive up healthcare costs with little evidence of clinical benefit. We hypothesized that state health insurance mandates for private insurers to provide coverage for off-label use of cancer drugs cause higher rates of off-label use. We used Truven MarketScan data from 1999 to 2007 on utilization of 35 infused chemotherapy drugs in private health plans in the United States, covering the period when eight states implemented off-label coverage laws. We studied trends in off-label use of drugs, distinguishing between appropriate and inappropriate off-label use according to drug compendia, and estimated difference-in-difference regressions of the effect of state laws on off-label use. We estimate 41% of utilization was off-label, including 17% of use conservatively defined as inappropriate. Trends show gradual declines in off-label use over time. We also find no discernable effect of state laws mandating coverage of off-label use of cancer drugs on utilization patterns under multiple empirical specifications. Our conclusion is that policymakers should consider shifting away from mandating coverage as a way to ensure access to drugs off-label and towards incentivizing adherence to clinical practice guidelines to improve the quality and value of off-label use.


Towards targeted combinatorial therapy design for the treatment of castration-resistant prostate cancer.
Prostate cancer is one of the most prevalent cancers in males in the United States and amongst the leading causes of cancer related deaths. A particularly virulent form of this disease is castration-resistant prostate cancer (CRPC), where patients no longer respond to medical or surgical castration. CRPC is a complex, multifaceted and heterogeneous malady with limited standard treatment options. The growth and progression of prostate cancer is a complicated process that involves multiple pathways. The signaling network comprising the integral constituents of the signature pathways involved in the development and progression of prostate cancer is modeled as a combinatorial circuit. The failures in the gene regulatory network that lead to cancer are abstracted as faults in the equivalent circuit and the Boolean circuit model is then used to design therapies tailored to counteract the effect of each molecular abnormality and to propose potentially efficacious combinatorial therapy regimens. Furthermore, stochastic computational modeling is utilized to identify potentially vulnerable components in the network that may serve as viable candidates for drug development. The results presented herein can aid in the design of scientifically well-grounded targeted therapies that can be employed for the treatment of prostate cancer patients.


Alteration of surface properties in a Tn5 mutant strain of Rhizobium trifolii 0403.
A symbiotically defective mutant strain of Rhizobium trifolii, UR251, was obtained by transposon Tn5 mutagenesis of R. trifolii 0403 rif and recognized by its partially ineffective (Fix +/-) phenotype on white clover plants. UR251 had a single Tn5 insertion in plasmid DNA, a wild-type plasmid pattern, and no detectable Mu DNA sequences originally present in the vector used for Tn5 mutagenesis. Agglutination by the clover lectin trifoliin A and attachment to clover root hairs was higher with UR251 than with the wild-type strain. The capsular polysaccharide (CPS) of UR251 was altered, as shown by a slower rate of CPS depolymerization with a CPS beta-lyase, PD-I; more pyruvate and less acetate and 3-hydroxybutanoate noncarbohydrate substitutions as quantitated by 1H nuclear magnetic resonance; and a higher pyruvyl transferase activity (enzymatic pyruvylation of lipid-bound saccharides). The site of increased pyruvylation in the CPS of UR251 was on the terminal galactose of the branch of the repeating oligosaccharide unit. These results show that the level of noncarbohydrate substitutions of the CPS as well as pyruvyl transferase activity are altered in R. trifolii UR251 and that trifoliin A-binding ability and clover root hair attachment are improved in this mutant strain of R. trifolii 0403 rif.


SNRPD1/E/F/G Serve as Potential Prognostic Biomarkers in Lung Adenocarcinoma.
Objectives: Sm proteins (SNRPB/D1/D2/D3/E/F/G), involved in pre-mRNA splicing, were previously reported in the tumorigenesis of several cancers. However, their specific role in lung adenocarcinoma (LUAD) remains obscure. Our study aims to feature abnormal expressions and mutations of genes for Sm proteins and assess their potential as therapeutic targets via integrated bioinformatics analysis. Methods: In this research, we explored the expression pattern and prognostic worth of genes for Sm proteins in LUAD across TCGA, GEO, UALCAN, Oncomine, Metascape, David 6.8, and Kaplan-Meier Plotter, and confirmed its independent prognostic value via univariate and multivariate cox regression analysis. Meanwhile, their expression patterns were validated by RT-qPCR. Gene mutations and co-expression of genes for Sm proteins were analyzed by the cBioPortal database. The PPI network for Sm proteins in LUAD was visualized by the STRING and Cytoscape. The correlations between genes for Sm proteins and immune infiltration were analyzed by using the "GSVA" R package. Results: Sm proteins genes were found upregulated expression in both LUAD tissues and LUAD cell lines. Moreover, highly expressed mRNA levels for Sm proteins were strongly associated with short survival time in LUAD. Genes for Sm proteins were positively connected with the infiltration of Th2 cells, but negatively connected with the infiltration of mast cells, Th1 cells, and NK cells. Importantly, Cox regression analysis showed that high SNRPD1/E/F/G expression were independent risk factors for the overall survival of LUAD. Conclusion: Our study showed that SNRPD1/E/F/G could independently predict the prognostic outcome of LUAD and was correlated with immune infiltration. Also, this report laid the foundation for additional exploration on the potential treatment target's role of SNRPD1/E/F/G in LUAD.


Antimicrobial use in the surgical patient.
Antimicrobials are often used in the surgical patient in an effort to prevent infection (prophylactic) or to treat established infection (therapeutic). To be effective, prophylactic antimicrobials at appropriate concentrations must be present in tissues at the surgical site at the time of contamination to prevent bacterial growth and subsequent infection. Therapeutic antimicrobials are used to treat established localized or systemic infection. Selection of antimicrobial agents for prophylactic or therapeutic use should be based on knowledge of expected flora, ability of the antimicrobial to reach the target tissue at appropriate concentrations, bacterial resistance patterns, drug pharmacokinetics, and culture and susceptibility testing results (therapeutic use). Failure of antimicrobial therapy to prevent or treat infection in the surgical patient may result from poor antimicrobial selection, inappropriate dosage or frequency, or inappropriate duration of therapy.


Protection of feruloylated oligosaccharides from corn bran against oxidative stress in PC 12 cells.
Feruloylated oligosaccharides (FOs) were prepared by autoclaving corn bran in oxalic acid (0.6%) solution, and their protection effects against oxidative stress in pheochromocytoma cells (PC 12) cells were investigated. The FOs samples, which comprised a mixture of feruloylated mono- and dipentoses with 4.88% bound ferulic acid (FA), as well as xylose, arabinose, galactose, and glucose amounting to 46.43, 40.46, 3.76, and 8.68% of the total sugars, respectively, were prepared by autoclaving the pretreated corn bran in 0.6% oxalic acid and then further separated. Antioxidant activity was tested by 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH) scavenging and oxygen radical absorbance capacity (ORAC) methods. Oxidative stress was induced by H2O2 in PC 12 neuronal cell culture model. The results showed that FOs exhibited higher antioxidant activity than free ferulic acid, with an IC50 value of 11 versus 128 μM for DPPH and an ORAC value of 4.77 versus 2.62 μmol Trolox/μmol. Tetrazolium blue assay showed that the addition of FOs with an FA concentration >50 μM significantly increased cell viability after treatment with H2O2. Flow cytometry analysis showed that the addition of FOs at concentrations of 800, 200, and 50 μM significantly decreased the apoptosis rate at the sub-G0 phase from 37.5 to 12.7, 16.2, and 20.9% (P < 0.01), respectively. FOs also significantly decreased the malonic dialdehyde content and lactate dehydrogenase (LDH) activity, but increased superoxide dismutase activity in PC 12 cells treated with H2O2 and prevented the damage of cellular membranes by decreasing the release of LDH to the cultures. The addition of FA at 800 μM showed an effect similar to that of FOs at 200 μM. Therefore, the FOs prepared from corn bran are potential functional ingredients for protection against oxidative stress.


Depletion of tumor suppressor Kank1 induces centrosomal amplification via hyperactivation of RhoA.
Chromosome instability, frequently found in cancer cells, is caused by a deficiency in cell division, including centrosomal amplification and cytokinesis failure, and can result in abnormal chromosome content or aneuploidy. The small GTPase pathways have been implicated as important processes in cell division. We found that knockdown of a tumor suppressor protein Kank1 increases the number of cells with a micronucleus or bi-/multi-nuclei, which was likely caused by centrosomal amplification. Kank1 interacts with Daam1, known to bind to and activate a small GTPase, RhoA, in actin assembly. Knockdown of Kank1 or overexpression of Daam1, respectively, hyperactivates RhoA, potentially leading to the modulation of the activity of Aurora-A, a key regulator of centrosomal functions, eventually resulting in centrosomal amplification. Kank1 is also associated with contractile ring formation in collaboration with RhoA, and its deficiency results in the interruption of normal daughter cell separation, generating multinucleate cells. Such abnormal segregation of chromosomes may cause further chromosomal instability and abnormal gene functions, leading to tumorigenesis. Thus, Kank1 plays a crucial role in regulating the activity of RhoA through retrieving excess Daam1 and balancing the activities of RhoA and its effectors.


Mitochondria in brain hypoxia.
Neurons vary widely in shape, size, type of neurotransmitters and number of synapses. Their common characteristic is a very high sensitivity to changes in oxygen concentration. The consequence of hypoxia is to launch a series of biochemical reactions called the ischemic cascade. The term is a bit misleading, because it suggests that there is a succession of events, in a linear fashion. In fact, the ischemic cascade involves very complex processes that take place simultaneously and interact with each other. The key role in neuronal responses to hypoxia is played by changes related to mitochondria, which occur immediately after hypoxia, at the beginning of the ischemic cascade. Disturbances in the mitochondrial functions are recognized as an essential element not only in acute but also in chronic hypoxia, as well as neurodegenerative diseases.


On the experimental estimation of surface enhanced raman scattering (SERS) cross sections by vibrational pumping.
We present an in-depth analysis of the experimental estimation of cross-sections in surface enhanced raman scattering (SERS) by vibrational pumping. The paper highlights the advantages and disadvantages of the technique, pinpoints the main aspects and limitations, and provides the underlying physical concepts to interpret the experimental results. Examples for several commonly used SERS probes are given, and a discussion on future possible developments is also presented. Obtaining good estimates of SERS cross-sections is, in general, an extremely hard problem and has been a longstanding ambition of the SERS community for reasons that go from the purely applied (quantification of signals) to the more fundamental (comparisons of theoretical electromagnetic enhancement factors with experiment). Any method that can produce a standard protocol for the estimation of cross-sections is, accordingly, of great interest and an effort to understand its principles and limitations is required.


Prosthetic management of neuromuscular rehabilitation in hemimandibulectomy patients. A case report.
The radio-surgical treatments for carcinomas involving the oral cavity are often destructive in order to limit as much as possible the high rate of recidivism. The outcome of the combined treatment is represented by lesions on hard and soft healthy tissues besides naturally by a more or less important mandibular deviation depending on greater or lesser quantity of basal bone excised. In some cases it is possible to surgically restore the defective mandible through bone grafting; this means a quite perfect restitutio ad integrum of the mandibular arch; instead, in other cases, because of bone and soft tissue biology, general healthy state and age of the patient prosthetic management would be better as it is less invasive even if less resolutive. For a right tonsillar cavity carcinoma the patient, T. F., female, 73-year old, had undergone radical neck dissection and hemisection of the homolateral mandible. A guide-device was realized for "guiding" the residual mandible into the physiological centric occlusion position, and then a removable partial denture was realized as a definitive prosthesis. After 3 months therapy the patient was easily able to spontaneously reposition the hemimandible itself, also with considerable improvement of the masticatory function. Neuromuscular re-education of hemimandibulectomy patients via the use of a guide flange on a removable prosthesis applied to the residual mandible represents a fundamental condition for permanent prosthetic rehabilitation.


Sarcoidosis: a rheumatologist's perspective.
Sarcoidosis is a systemic disorder of unknown etiology, which may involve various tissues and organs and is characterized by a noncaseating granuloma reaction. While pathogenesis is not yet clear, cellular immune system activation and nonspecific inflammatory response occur secondarily to several genetic and environmental factors. T helper 1-cells and macrophage-derived pro-inflammatory cytokines stimulate the inflammatory cascade and formation of granuloma occurs as a result of tissue permeability, cell influx, and local cell proliferation. The different prevalence, clinical results, and disease course observed in different races and ethnic groups, is an indicator of the heterogeneous nature of the disease. Sarcoidosis may mimic and/or may occur concomitantly with numerous primary rheumatic diseases. This disease most commonly presents with bilateral hilar lymphadenopathy, pulmonary infiltrations, and skin and eye lesions. Locomotor system involvement is observed at a range of 15% and 25%. Two major joint involvements have been described: acute and chronic form. The most common form, the acute form, may be the first sign of sarcoidosis and present with arthralgia, arthritis, or periarthritis. Chronic sarcoid arthritis is usually associated with pulmonary parenchymal disease or other organ involvement and occurs rarely. While asymptomatic muscular involvement is reported between 25% and 75%, symptomatic muscular involvement is very rare. Symptomatic myopathy may present as three different types: chronic myopathy, palpable nodular myositis, or acute myositis. Even if rare, 2-5% of cases may exhibit osseous involvement and it is frequently associated with lupus pernio, chronic uveitis, and multisystemic disease. Sarcoidosis was reported together with different rheumatologic diseases. There are studies showing that sarcoidosis may mimic the clinical and laboratory findings of these disorders. Nonsteroidal anti-inflammatory drugs and corticosteroids are used for treating the symptoms of rheumatologic findings. In patients who are unresponsive to corticosteroids, immunosuppressive and anti-tumor necrosis factor alpha drugs may be used. In this review, the incidence of rheumatologic symptoms, the clinical findings, and the treatment of rheumatologic manifestations of sarcoidosis are discussed.


An assessment of rubber dam usage amongst specialists in paediatric dentistry practising within the UK.
Rubber dam is recommended by the British Society of Paediatric Dentistry (BSPD) for various restorative and endodontic procedures. To date, there has been no report of actual usage of rubber dam within the speciality of paediatric dentistry. The aim of this study was to assess the usage of rubber dam amongst paediatric dentistry specialists within the UK. A postal questionnaire was distributed to all practitioners registered on the UK General Dental Council's 2004 specialist list in paediatric dentistry. Data were available for 162 questionnaires (a 75% response rate), and of these, 85% of respondents worked in the National Health Service (NHS), 4% were private practitioners and the remainder had a mixed NHS/private practice. Regarding the benefits of rubber dam, 65% and 52% of respondents quoted patient safety and moisture control, respectively. Perceived difficulties of dam usage were lack of patient cooperation and the non-necessity for a particular treatment, as quoted in 64% and 36% of the completed questionnaires, respectively. The most common modes of isolation for anterior and posterior teeth were Dry Dam(R) (58%), and clamp and dam (80%), respectively. Current BSPD guidelines recommend rubber dam usage for many restorative procedures; however, it would appear that there is wide variability in the application, as well as under-use, of rubber dam.


Infrared spectroscopy of gas phase alpha hydroxy carboxylic acid homo and hetero dimers.
New gas phase infrared spectroscopy is reported for an aromatic alpha hydroxy carboxylic acid homo dimer of 9-hydroxy-9-fluorene carboxylic acid (9HFCA)2, and the hetero dimer of 9HFCA with glycolic acid. In terms of the 9-hydroxy stretching frequency, the 16 cm-1 blue-shift in the homo dimer and the 17 cm-1 blue-shift in the hetero dimer, relative to that in 9HFCA monomer, are attributed to collective effects with anti-cooperativity stronger than cooperativity. Furthermore, for the hetero dimer, the two alpha hydroxy groups' stretching frequencies are clearly resolved, and differ by 30 cm-1. This difference represents a modest, quantitative enhancement of the intramolecular H-bond by the fluorene moiety in 9HFCA monomer, as opposed to that in glycolic acid. Accurate vibrational frequencies of the alpha OH, 3568 cm-1 in the bare glycolic acid, and 3584 cm-1 in the glycolic acid homo dimer are determined for the first time by comparison to 9HFCA monomer, homo and hetero dimers. The quantitative studies by infrared spectroscopy reveal subtle interactions among intra- and intermolecular H-bonds in the alpha hydroxyl acid dimers, which are also uniquely extended to probe each monomer's subtle intramolecular interactions.


Sequence-Specific Recognition of HIV-1 DNA with Solid-State CRISPR-Cas12a-Assisted Nanopores (SCAN).
Nucleic acid detection methods are crucial for many fields such as pathogen detection and genotyping. Solid-state nanopore sensors represent a promising platform for nucleic acid detection due to its unique single molecule sensitivity and label-free electronic sensing. Here, we demonstrated the use of the glass nanopore for highly sensitive quantification of single-stranded circular DNAs (reporters), which could be degraded under the trans-cleavage activity of the target-specific CRISPR-Cas12a. We developed and optimized the Cas12a assay for HIV-1 analysis. We validated the concept of the solid-state CRISPR-Cas12a-assisted nanopores (SCAN) to specifically detect the HIV-1 DNAs. We showed that the glass nanopore sensor is effective in monitoring the cleavage activity of the target DNA-activated Cas12a. We developed a model to predict the total experimental time needed for making a statistically confident positive/negative call in a qualitative test. The SCAN concept combines the much-needed specificity and sensitivity into a single platform, and we anticipate that the SCAN would provide a compact, rapid, and low-cost method for nucleic acid detection at the point of care.


Survey statistics of automated segmentations applied to optical imaging of mammalian cells.
The goal of this survey paper is to overview cellular measurements using optical microscopy imaging followed by automated image segmentation. The cellular measurements of primary interest are taken from mammalian cells and their components. They are denoted as two- or three-dimensional (2D or 3D) image objects of biological interest. In our applications, such cellular measurements are important for understanding cell phenomena, such as cell counts, cell-scaffold interactions, cell colony growth rates, or cell pluripotency stability, as well as for establishing quality metrics for stem cell therapies. In this context, this survey paper is focused on automated segmentation as a software-based measurement leading to quantitative cellular measurements. We define the scope of this survey and a classification schema first. Next, all found and manually filteredpublications are classified according to the main categories: (1) objects of interests (or objects to be segmented), (2) imaging modalities, (3) digital data axes, (4) segmentation algorithms, (5) segmentation evaluations, (6) computational hardware platforms used for segmentation acceleration, and (7) object (cellular) measurements. Finally, all classified papers are converted programmatically into a set of hyperlinked web pages with occurrence and co-occurrence statistics of assigned categories. The survey paper presents to a reader: (a) the state-of-the-art overview of published papers about automated segmentation applied to optical microscopy imaging of mammalian cells, (b) a classification of segmentation aspects in the context of cell optical imaging, (c) histogram and co-occurrence summary statistics about cellular measurements, segmentations, segmented objects, segmentation evaluations, and the use of computational platforms for accelerating segmentation execution, and (d) open research problems to pursue. The novel contributions of this survey paper are: (1) a new type of classification of cellular measurements and automated segmentation, (2) statistics about the published literature, and (3) a web hyperlinked interface to classification statistics of the surveyed papers at https://isg.nist.gov/deepzoomweb/resources/survey/index.html.


Allogenic Adipose Derived Stem Cells Transplantation Improved Sciatic Nerve Regeneration in Rats: Autologous Nerve Graft Model.
We examined the effect of transplantation of allogenic adipose-derived stem cells (ADSCs) with properties of mesenchymal stem cells (MSCs) on posttraumatic sciatic nerve regeneration in rats. We suggested an approach to rat sciatic nerve reconstruction using the nerve from the other leg as a graft. The comparison was that of a critical 10 mm nerve defect repaired by means of autologous nerve grafting versus an identical lesion on the contralateral side. In this experimental model, the same animal acts simultaneously as a test model, and control. Regeneration of the left nerve was enhanced by the use of ADSCs, whereas the right nerve healed under natural conditions. Thus the effects of individual differences were excluded and a result closer to clinical practice obtained. We observed significant destructive changes in the sciatic nerve tissue after surgery which resulted in the formation of combined contractures in knee and ankle joints of both limbs and neurotrophic ulcers only on the right limb. The stimulation of regeneration by ADSCs increased the survival of spinal L5 ganglia neurons by 26.4%, improved sciatic nerve vascularization by 35.68% and increased the number of myelin fibers in the distal nerve by 41.87%. Moreover, we have demonstrated that S100, PMP2, and PMP22 gene expression levels are suppressed in response to trauma as compared to intact animals. We have shown that ADSC-based therapy contributes to significant improvement in the regeneration.


Hyperglycemic hemianopia: A case report.
Nonketotic hyperglycemia (NKH) is characterized by hyperglycemia with little or no ketoacidosis. Diverse neurological symptoms have been described in NKH patients, including choreoathetosis, hemiballismus, seizures, and coma in severe cases. Homonymous hemianopia, with or without occipital seizures, caused by hyperglycemia is less readily recognized. We describe a 54-year-old man with NKH, who reported seeing round, colored flickering lights with right homonymous hemianopia. Cranial magnetic resonance imaging demonstrated abnormalities in the left occipital lobe, with decreased T2 signal of the white matter, restricted diffusion, and corresponding low signal intensity in the apparent diffusion coefficient map. He responded to rehydration and a low-dose insulin regimen, with improvements of his visual field defect. Patients with NKH may present focal neurologic signs. Hyperglycemia should be taken into consideration when making an etiologic diagnosis of homonymous hemianopia.


Evolution of the Fermi surface of BaFe2(As1-xPx){2} on entering the superconducting dome.
Using the de Haas-van Alphen effect we have measured the evolution of the Fermi surface of BaFe2(As1-xPx){2} as a function of isoelectric substitution (As/P) for 0.41<x<1 (T{c} up to 25 K). We find that the volumes of electron and hole Fermi surfaces shrink linearly with decreasing x. This shrinking is accompanied by a strong increase in the quasiparticle effective mass as x is tuned toward the maximum T{c}. These results are not explained by simple band structure calculations, and it is likely that these trends originate from the same many-body interactions which give rise to superconductivity.


Anti-ICAM-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat.
Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein expressed on endothelial cells that facilitates leukocyte adhesion. To test the hypothesis that reduction of leukocytes in an ischemic lesion reduces ischemic brain damage, we measured the effect of administration of an anti-ICAM-1 monoclonal antibody on ischemic brain damage after transient middle cerebral artery occlusion in the rat. ICAM-1 expression increased in the ischemic lesion, and the lesion volume was significantly reduced by 41% in the anti-ICAM-1 antibody group compared with the control group (p < 0.05). Numbers of polymorphonuclear leukocytes (PMNs) were significantly reduced in the cortices of the anti-ICAM-1 antibody group compared with the control animals (p < 0.05). Our data indicate that administration of anti-ICAM-1 antibody results in a significant reduction of ischemic brain damage concomitant with a reduction of PMNs in the lesion after transient focal cerebral ischemia in the rat.


Anti-RO anti-LA anti-RNP antibodies and eletrocardiogram's PR interval in adult patients with systemic lupus erythematosus.
Children born from mothers with anti-Ro La or RNP autoantibodies may develop neonatal lupus. One of the manifestations of neonatal lupus is congenital atrio ventricular block. To study EKG PR interval in adult systemic lupus erythematosus (SLE) patients with anti-Ro anti-La and anti-RNP autoantibodies. PR intervals and the presence of anti-Ro La and RNP antibodies were studied in 61 SLE patients and compared with 61 controls. 36.6% of SLE patients were anti-Ro positive 20% were anti-La and 22.9% were anti-RNP positive. All studied PR intervals were within normal limits (upper limit of 0.2 sec). We did not find any association between PR interval length and the presence of anti-Ro (p=0.54) anti-La (p=0.45) or anti-RNP autoantibodies (p=0.36). The presence of anti-Ro La and RNP autoantibodies does not influence PR interval in adult SLE patients.


Changes in incremental weight and well-being of children with rampant caries following complete dental rehabilitation.
The purposes of this study were to determine if young children with rampant dental caries that received complete dental rehabilitation under general anesthesia: 1.) weighed less preoperatively compared to national norms; and 2.) demonstrated significant improvement postoperatively in percentile weight gain and/or quality of life indicators. The preoperative and postoperative percentile weights based on national norms were calculated for children, aged 2-7 years old, with non-significant medical histories (absence of systemic illness) that underwent rehabilitation for rampant dental caries under general anesthesia. Changes in the quality of the children's life following dental rehabilitation under general anesthesia were determined from parental report. The results showed that there was a slight, non-significant increase in the mean percentile weight following dental rehabilitation under general anesthesia. There was no significant effect on the mean net percentile weight change based on the chronological age or weighing interval. There was, however, a significant improvement in the children's quality of life as reported by their parents. Contrary to previous reports, the mean percentile weight of children with rampant dental caries was not below the 50th percentile and the slight gain in percentile weight following dental rehabilitation under general anesthesia was not indicative of a "catch-up growth" phenomenon. There was, however, a significant improvement in the children's quality of life as based upon parental report and confirmed in a previous investigations.


Further evidence for an association between affective disorders and anxiety disorders: review and case reports.
The relationship between anxiety and affective disorders continues to be debated in the literature. The authors report a case of identical twins concordant for attention deficit disorder and somnambulism but discordant for major depression and agoraphobia with panic attacks. The authors discuss the implications of this "finding in nature." Results from neuroendocrinological, family, and twin studies are also reviewed that either lend support or question the existence of a relationship between anxiety disorders and affective disorders.


[Quality analysis and evaluation of Rhizoma Coptidis under different cultivation conditions].
To develop methods for the fingerprint analysis of Rhizoma Coptidis and the determination of berberine, palmatine and jatrorrhizine in Rhizoma Coptidis, and analyze the contents of these three alkaloids in Rhizoma Coptidis under different cultivation conditions, from different areas and processed with different methods. Two methods (HPLC-UV and HPLC-MS) have been developed and used in fingerprint analysis of Rhizoma Coptidis. An HPLC method was used to determine the contents of three alkaloids. With HPLC-MS techniques, seven major chromatographic peaks in the fingerprint analysis of Rhizoma Coptidis were identified by their MS spectra and compared with the reference standards. In different cultivation conditions, shading conditions and growing ages have obvious influence on the contents of three alkaloids in Rhizoma Coptidis, while planting density was not the major factor that influenced the contents of three alkaloids. The contents of three alkaloids of Coptidis samples were almost higher than those of Coptidis reference material. For Coptidis samples from different cultivation area, the contents of these three alkaloids were different greatly. For Coptidis samples processed with different methods, the contents of three alkaloids were not influenced obviously by processing methods. The results showed that the ecology cultivation method to replace the traditional shading method was feasible and provided the theoretical foundation for scientifically processing Rhizoma Coptidis.


The Incidence of Infection Complicating Snakebites in Tropical Australia: Implications for Clinical Management and Antimicrobial Prophylaxis.
To define the incidence of infection following snakebite in tropical Australia and the resulting implications for the routine prescription of prophylactic antibiotics. A retrospective study of all individuals presenting to Cairns Hospital, a tertiary referral hospital in tropical Australia, after a snakebite between December 2013 and October 2020. There were 732 hospitalisations, 720 (98.4%) patients presented within 8 hours of the snakebite, and 29/732 (4.0%) were envenomated. Envenomated patients were more likely to receive empirical antibiotics than nonenvenomated patients (8/29 (27.6%) versus 14/703 (2.0%), p < 0.001), although this was frequently as a bundle of care for critically ill individuals. Superficial skin infection was diagnosed by clinicians in 6/732 (0.8%) patients during their hospitalisation; infection was diagnosed more commonly in envenomated than in nonenvenomated patients (3/29 (10.3%) versus 3/703 (0.4%), p = 0.001). All 3 envenomated individuals diagnosed with infection were believed to have taipan (genus Oxyuranus) bites. Five (83%) of the six patients diagnosed with infection had received empirical antibiotics at presentation; only 1/710 (0.1%) patients who received no antibiotics developed a (superficial) infection. Infection is a very uncommon complication of snakebite in tropical Australia. Individuals bitten by snakes in tropical Australia should not routinely receive antibiotic prophylaxis.


Fast Algorithms for Structured Least Squares and Total Least Squares Problems.
We consider the problem of solving least squares problems involving a matrix M of small displacement rank with respect to two matrices Z 1 and Z 2. We develop formulas for the generators of the matrix M (H) M in terms of the generators of M and show that the Cholesky factorization of the matrix M (H) M can be computed quickly if Z 1 is close to unitary and Z 2 is triangular and nilpotent. These conditions are satisfied for several classes of matrices, including Toeplitz, block Toeplitz, Hankel, and block Hankel, and for matrices whose blocks have such structure. Fast Cholesky factorization enables fast solution of least squares problems, total least squares problems, and regularized total least squares problems involving these classes of matrices.


Sexual differentiation in the terminal ganglion of the moth Manduca sexta: role of sex-specific neuronal death.
In the insect Manduca sexta the genitalia on the terminal abdominal segments are sexually dimorphic structures but they arise during metamorphosis from segments that are monomorphic in the larva. The motoneurons in the terminal ganglion that innervate these structures were examined by cobalt backfills of peripheral nerves. In the larval stage the population of motoneurons innervating the terminal segments was identical in both sexes. By contrast, the motoneuron populations in the terminal ganglia of adult males and females were strikingly different. No new motoneurons were produced during metamorphosis. Rather, this difference was the result of sex-specific cell death which occurred primarily during the early stages of adult differentiation. Possible mechanisms underlying this sex-specific degeneration of neurons are discussed.


Association between vasomotor rhinitis and irritable bowel syndrome.
Vasomotor rhinitis (VMR) and irritable bowel syndrome (IBS) are two of the most widespread pathologies in industrialized countries, and they have a substantial impact on health-related quality of life. To investigate the relationship between VMR and IBS to provide evidence to classify VMR and IBS as a sole disorder. The study included 150 patients from San Salvatore Hospital, L'Aquila: 50 with VMR, 50 with IBS, and 50 healthy volunteers. With regard to a probable link between VMR and IBS, 62 patients of the whole population, 150 patients (41.3%) were affected by both VMR and IBS, 33 subjects (22%) were not affected by VMR or IBS, 25 patients (16.67%) only had VMR, and 30 patients (20%) only had IBS. When considering the 87 subjects affected by VMR, 62 of them also had IBS (71.26%). In turn, when considering all 92 subjects with IBS, 62 (67.39%) had VMR. We found a significant association among IBS and nasal obstruction, rhinorrhea, and turbinates, and among VMR and a change in stool consistency and abdominal pain. Among the patients affected by nonallergic rhinitis (NAR), we found a prevalence of NAR with eosinophils (31%) compared with the other cytologic types. This study expanded the knowledge of the link between VMR and IBS, also the correlation between typical VMR symptoms and IBS, and about the correlation between typical IBS symptoms and VMR. For future implications, the diagnosis of NAR indicated the need to check for the presence of IBS, by using the Rome III criteria, and a diagnosis of IBS indicated the need to check for the presence of VMR. More studies are needed to find the pathogenetic mechanisms to explain the clinical correlation between VMR and IBS as seen in the present study.


The uptake of O3 by myristic acid-oleic acid mixed particles: evidence for solid surface layers.
The oleic acid ozonolysis in mixed oleic and myristic acid particles was studied in a flow tube reactor using single particle mass spectrometry. The change in reactivity was investigated as a function of the myristic acid concentration in these 2 micron particles. For pure oleic acid aerosol, the reactive ozone uptake coefficient, gamma, was found to be 3.4 (+/-0.3) x 10(-4) after taking secondary reactions into account. At the myristic acid crystallization point, where only 2.5% of the particle is in the solid phase, the uptake coefficient was reduced to 9.7 (+/-1.0) x 10(-5). This dramatic drop in the uptake coefficient is explained by the presence of a crystalline monolayer of myristic acid, through which ozone diffusion is reduced by several orders of magnitude, relative to liquid oleic acid. Scanning electron microscope images of the mixed particles confirm that the particle surface is crystalline when the myristic acid mole fraction exceeds 0.125. The findings of these experiments illustrate that particle morphology is important to understanding the reactivity of species in a mixed particle. The decay of myristic acid during the course of ozonolysis is explained in terms of a reaction with stabilized Criegee intermediates, which attack the acidic groups of the oleic and myristic acids with equal rate constants.


An event-coding account of attitudes.
Attitudes (or opinions, preferences, biases, stereotypes) can be considered bindings of the perceptual features of the attitudes' object to affective codes with positive or negative connotations, which effectively renders them "event files" in terms of the Theory of Event Coding. We tested a particularly interesting implication of this theoretical account: that affective codes might "migrate" from one event file to another (i.e., effectively function as a component of one while actually being part of another), if the two files overlap in terms of other features. We tested this feature-migration hypothesis by having participants categorize pictures of fictitious outer space characters as members of two fictitious races by pressing a left or right key, and to categorize positive and negative pictures of the International Affective Picture System (IAPS) as positive and negative by using the same two keys. When the outer space characters were later rated for likability, members of the race that was categorized by means of the same key as positive IAPS pictures were liked significantly more than members of the race that was categorized with the same key as negative IAPS pictures - suggesting that affective feature codes from the event files for the IAPS pictures effectively acted as an ingredient of event files for the outer space characters that shared the same key. These findings were fully replicated in a second experiment in which the two races were replaced by two unfamiliar fonts. These outcomes are consistent with the claim that attitudes, opinions, and preferences are represented in terms of event files and created by feature binding.


Myocardial infarction and older people.
Nurses have a central role to play in the care of older people who have suffered a myocardial infarction. This article points out that such patients may not present with typical symptoms so it is important to be aware of signs that indicate problems. It suggests that following diagnosis it is vital that older people are offered evidence-based treatment and that secondary prevention and rehabilitation are considered.


Molecular detection of extensively drug-resistant Salmonella Typhi and carbapenem-resistant pathogens in pediatric septicemia patients in Pakistan - a public health concern.
Aim: To determine the prevalence of multidrug (MDR) and extensively drug-resistant (XDR) pathogens from pediatric blood samples Methods: In total, 4543 children's blood samples were processed in the BacT/ALERT system. Confirmation of the isolates and MIC was determined in VITEK® 2 system. Molecular identification of blaIMP, blaVIM and blaOXA-48 was done by PCR. Results: Of 4543 blood cultures, 458 (10%) were positive for bacterial growth and Salmonella Typhi (415; 90%) remained the primary pathogens. Antibiogram revealed 208 (50.1%) and 137 (33%) were MDR and XDR S. Typhi, respectively. Klebsiella pneumoniae displayed 46% resistance to imipenem. One hundred twelve (81.7%) XDR Typhi were positive for blaCTXM, whereas 14 (66.6%) blaVIM were found in carbapenem-resistant bacteria. Conclusion: A high prevalence of MDR and XDR pathogens was found in peads blood culture.


Cholinesterase-responsive supramolecular vesicle.
Enzyme-responsive, amphiphilic self-assembly represents one of the increasingly significant topics in biomaterials research and finds feasible applications to the controlled release of therapeutic agents at specific sites where the target enzyme is located. The supramolecular approach, using "superamphiphiles", provides a smart way to fabricate drug delivery systems responsive to enzymatic catalysis. In this work based on the concept of supramolecular chemistry, we report an enzyme-responsive vesicle using p-sulfonatocalix[4]arene as the macrocyclic host and natural enzyme-cleavable myristoylcholine as the guest molecule. The complexation of p-sulfonatocalix[4]arene with myristoylcholine directs the formation of a supramolecular binary vesicle, which is dissipated by cholinesterase with high specificity and efficiency. Cholinesterase is a key protein overexpressed in Alzheimer's disease, and therefore, the present system may have potential for the delivery of Alzheimer's disease drugs.


Interaction of laxatives with enzymes of cyclic AMP metabolism from human colonic mucosa.
The mechanism by which laxatives such as dioctyl sodium sulfosuccinate and ricinoleic acid evoke colonic fluid secretion has been suggested to involve mucosal cyclic AMP. Ricinoleic acid and dioctyl sodium sulfosuccinate were tested for their capacity to modulate the key enzymes of cAMP-metabolism--adenylate cyclase and cAMP-phosphodiesterase--in human colonic mucosa. Both laxatives were ineffective stimuli of human colonic adenylate cyclase. In contrast to ricinoleic acid, dioctyl sodium sulfosuccinate was a competitive inhibitor of soluble cAMP-phosphodiesterase activity. These experiments suggest that the cathartic properties of dioctyl sodium sulfosuccinate in human colonic mucosa might be mediated by cyclic AMP via inhibition of soluble phosphodiesterase activity.


Analysis of the response of Candida albicans cells to Silver(I).
The response of the pathogenic yeast Candida albicans to the silver(I) perchlorate salt (AgClO(4)) was assessed. By employing an anti-phospho-p38 MAPK antibody, dual phosphorylation of a high osmolarity protein (Hog1p) in C. albicans in the presence of AgClO(4) was demonstrated. Phosphorylation of C. albicans Hog1p in response to hydrogen peroxide or AgClO(4) resulted in the translocation of this mitogen-activated protein (MAP) kinase to the nucleus. Nuclear translocation of C. albicans activating protein-1 (Cap1p) was demonstrated by Western blot analysis and detected using polyclonal anti-Cap1p antibody. Upon AgClO(4)-induced translocation of Cap1p there was a concomitant activation of genes coding for glutathione reductase-1 and Mn-superoxide dismutase but no increase in the expression of flavin oxidoreductase or mitochondrial processing protease was recorded. In addition, exposure to AgClO(4) increased the activity of superoxide dismutase, glutathione reductase and catalase. The activation of C. albicans oxidative stress response genes and enzymes following exposure to AgClO(4) is evidence of the generation of oxidative stress within this medically important yeast.


Steady-state EB cap size fluctuations are determined by stochastic microtubule growth and maturation.
Growing microtubules are protected from depolymerization by the presence of a GTP or GDP/Pi cap. End-binding proteins of the EB1 family bind to the stabilizing cap, allowing monitoring of its size in real time. The cap size has been shown to correlate with instantaneous microtubule stability. Here we have quantitatively characterized the properties of cap size fluctuations during steady-state growth and have developed a theory predicting their timescale and amplitude from the kinetics of microtubule growth and cap maturation. In contrast to growth speed fluctuations, cap size fluctuations show a characteristic timescale, which is defined by the lifetime of the cap sites. Growth fluctuations affect the amplitude of cap size fluctuations; however, cap size does not affect growth speed, indicating that microtubules are far from instability during most of their time of growth. Our theory provides the basis for a quantitative understanding of microtubule stability fluctuations during steady-state growth.


Bacillus subtilis RNase Y activity in vivo analysed by tiling microarrays.
RNase Y is a key endoribonuclease affecting global mRNA stability in Bacillus subtilis. Its characterization provided the first evidence that endonucleolytic cleavage plays a major role in the mRNA metabolism of this organism. RNase Y shares important functional features with the RNA decay initiating RNase E from Escherichia coli, notably a similar cleavage specificity and a preference for 5' monophosphorylated substrates. We used high-resolution tiling arrays to analyze the effect of RNase Y depletion on RNA abundance covering the entire genome. The data confirm that this endoribonuclease plays a key role in initiating the decay of a large number of mRNAs as well as non coding RNAs. The downstream cleavage products are likely to be degraded by the 5' exonucleolytic activity of RNases J1/J2 as we show for a specific case. Comparison of the data with that of two other recent studies revealed very significant differences. About two thirds of the mRNAs upregulated following RNase Y depletion were different when compared to either one of these studies and only about 10% were in common in all three studies. This highlights that experimental conditions and data analysis play an important role in identifying RNase Y substrates by global transcriptional profiling. Our data confirmed already known RNase Y substrates and due to the precision and reproducibility of the profiles allow an exceptionally detailed view of the turnover of hundreds of new RNA substrates.