Toward facilitating microalgae cope with effluent from anaerobic digestion of kitchen waste: the art of agricultural phytohormones.
Although numerous studies have used wastewater as substitutes to cultivate microalgae, most of them obtained weaker algal viability than standard media. Some studies demonstrated a promotion of phytohormones on algal growth in standard media. For exploiting a strategy to improve algal biomass accumulation in effluent from anaerobic digestion of kitchen waste (ADE-KW), the agricultural phytohormones gibberellin, indole-3-acetic acid, and brassinolide (GIB) were applied to Chlorella SDEC-11 and Scenedesmus SDEC-13 at different stages of algal growth. Previous studies have demonstrated a promotion of phytohormones on algal growth in standard media, but attempts have been scarce, focusing on wastewater cultivation system. In addition, the effects of wastewater on algal morphology and ultrastructure have not been revealed so far, much less on the mechanism of the role of phytohormones on algae. ADE-KW disrupted the membranes of nuclear and chloroplast in ultrastructural cell of SDEC-11, and reduced the room between chloroplast and cell membrane and increased the starch size of SDEC-13. This reduced algal growth and biocompound accumulation, but SDEC-13 had greater adaptation to ADE-KW than SDEC-11. Moreover, inoculation with an algal seed pretreated with GIB aided the adaptability and viability of algae in ADE-KW, which for SDEC-13 was even promoted to the level in BG11. GIB mitigated the inhibition of ADE-KW on algal cell division and photosynthetic pigments and apparatus, and increased lipid droplets, which might result from the change in the synthesis and the fate of nicotinamide adenine dinucleotide phosphate. GIB addition significantly promoted lipid productivity of the two algal species, following 13 mg L-1 d-1 of SDEC-11 in B+ADE-KW and especially 13 mg L-1 d-1 of SDEC-13 achieved during the priming of algal seed with the hormones, which is 139% higher than 5 mg L-1 d-1 achieved in ADE-KW control. Agricultural phytohormones could be applied as a strategy for promoting biomass and biocompound accumulation of algae in ADE-KW, in which pretreatment of the algal inoculum with hormones is a unique way to help algae survive under stress. Considering our results and treatment technology for kitchen waste, a more feasible and economic plant can be built incorporating anaerobic digestion, algae cultivation with ADE-KW assisted with phytohormones, and biodiesel production.


Jamming at zero temperature, zero friction, and finite applied shear stress.
Shear stress, as temperature, induces particle motion, and affects the jamming transition from a fluid to a disordered solid state. Here, we show that at finite shear stress, the jamming transition is characterized by the presence of hysteresis, as in a given range of control parameters a flowing or a jammed state can be found, depending on whether the system is prepared coming from the fluid or the jammed phase. At small shear stress, where the hysteresis is negligible, the jamming transition has a mixed first-order second-order character close to that found at the glass transition of thermal systems, with discontinuities in the asymptotic values of two time quantities such as the self-intermediate scattering function.


Evaluation of efficacy of peribulbar block with the combination of 2% lidocaine and 0.5% bupivacaine in comparison with 2% lidocaine and 0.75% ropivacaine in cataract surgery.
Cataract surgery is performed under peribulbar or retrobulbar block. Majority of the patients posted for cataract have some form of medical diseases like diabetes, hypertension, angina, ischaemic heart disease etc. Lidocaine and bupivacaine are the most commonly used local anesthetic for the block procedure. Here we compare the efficacy of peribulbar block in cataract surgery using the combination of 1:1 mixture of 2% lidocaine with 0.5% bupivacaine and 1:1 mixture of 2% lidocaine with 0.75% ropivacaine. It is a prospective, randomized, double blinded study including 60 patients were devided into two groups of 30 each, Group-R received 8 ml of 1:1 mixture of 4 ml of 2% lidocaine, 4 ml of 0.75% ropivacaine and 15 IU/ml of hyaluronidase and group-B received 8 ml of 1:1 mixture of 4 ml of 2% lidocaine, 4 ml of 0. 5% bubivacaineand 15 IU/ml of hyaluronidase. Peribulbar block was performed as per Bloomberg's modification of the Davis and Mandel technique where 5 ml of local anesthetic was injected in the infero temporal region and 3 ml of drug was injected in the superi nasal area. Patients were assessed for sensory block, eyelid and occular movements at an interval of 2 minutes. Systolic, diastolic and mean arterial pressures, heart rate, oxygen saturation, ECG were monitored non invasively at 1,3,5,8,10,15 and then every 10 minutes till the end of the surgery. Mean time for the onset of sensory blockade was 2.70 ± 6.5 minutes in Group B and 2.63 ± 0.57 minutes in group R with P-value 0.671, showing no significant difference in the onset of sensory blockade. Onset of motor blockade was 6.53 ± 1.81 minutes in group B, and 7.57 ± 1.46 minutes in the group R, the P-value being 0.018 was statistically significant. Regarding the duration of analgesia, our study showed mean time for analgesia lasted for 295 ± 54.63 minutes in group B and 414.67 ± 99.47 in group R with P value 0.001 showing statistically significant prolongation of duration of analgesia with group R. We observed a significant increase of mean IOP in bupivacaine group from 13.333 ± 1.582 mm Hg to 21.966 ± 2.697 mm Hg, whereas in ropivacaine group it increased from 12.766 ± 1.222 mm Hg to 13.0 ± 1.341 mm Hg after peribulbar anaesthesia.


Autophagy Induced FHL2 Upregulation Promotes IL-6 Production by Activating the NF-κB Pathway in Mouse Aortic Endothelial Cells after Exposure to PM2.5.
Epidemiological and clinical studies have increasingly shown that fine particulate matter (PM2.5) is associated with cardiovascular morbidity and mortality, which share the common feature of PM2.5-induced vascular inflammation; however, the underlying mechanisms of how PM2.5 triggers increased inflammatory response in vascular endothelial cells are not well understood. After treating mouse aortic endothelial cells (MAECs) with different concentrations of PM2.5, we assessed interleukin (IL)-6 and four and a half LIM domains 2 (FHL2) expression in cell supernatant by enzyme-linked immunosorbent assay and Western blot, respectively, as well as activation of nuclear factor (NF)-κB and immune-response signaling pathways. Additionally, changes in pathway activation, IL-6 expression, and autophagy were evaluated under PM2.5 exposure, following FHL2 knockdown with small interfering RNA. Our results indicated that PM2.5 exposure induced FHL2 expression and IL-6 secretion, as well as activation of pathways associated with immune response. Additionally, following FHL2 knockdown, the activation of NF-κB-related pathways and IL-6 secretion was inhibited under PM2.5 exposure, although the Akt- and p38-signaling pathways were not affected. Furthermore, PM2.5 exposure induced autophagy, whereas autophagy inhibition eventually inhibited PM2.5-induced FHL2 expression. These findings suggested a novel link between autophagy induced FHL2 upregulation and IL-6 production in MAECs under PM2.5 exposure.


A synthetic biology approach to engineering circuits in immune cells.
A synthetic circuit in a biological system involves the designed assembly of genetic elements, biomolecules, or cells to create a defined function. These circuits are central in synthetic biology, enabling the reprogramming of cellular behavior and the engineering of cells with customized responses. In cancer therapeutics, engineering T cells with circuits have the potential to overcome the challenges of current approaches, for example, by allowing specific recognition and killing of cancer cells. Recent advances also facilitate engineering integrated circuits for the controlled release of therapeutic molecules at specified locations, for example, in a solid tumor. In this review, we discuss recent strategies and applications of synthetic receptor circuits aimed at enhancing immune cell functions for cancer immunotherapy. We begin by introducing the concept of circuits in networks at the molecular and cellular scales and provide an analysis of the development and implementation of several synthetic circuits in T cells that have the goal to overcome current challenges in cancer immunotherapy. These include specific targeting of cancer cells, increased T-cell proliferation, and persistence in the tumor microenvironment. By harnessing the power of synthetic biology, and the characteristics of certain circuit architectures, it is now possible to engineer a new generation of immune cells that recognize cancer cells, while minimizing off-target toxicities. We specifically discuss T-cell circuits for antigen density sensing. These circuits allow targeting of solid tumors that share antigens with normal tissues. Additionally, we explore designs for synthetic circuits that could control T-cell differentiation or T-cell fate as well as the concept of synthetic multicellular circuits that leverage cellular communication and division of labor to achieve improved therapeutic efficacy. As our understanding of cell biology expands and novel tools for genome, protein, and cell engineering are developed, we anticipate further innovative approaches to emerge in the design and engineering of circuits in immune cells.


Evaluation of a semi-automated workflow for fragment growing.
Intelligent Automatic Design (IADE) is an expert system developed at Novartis to identify nonclassical bioisosteres. In addition to bioisostere searching, one could also use IADE to grow a fragment bound to a protein. Here we report an evaluation of IADE as a tool for fragment growing. Three examples from the literature served as test cases. In all three cases, IADE generated close analogues of the published compounds and reproduced their crystallographic binding modes. This exercise validated the use of the IADE system for fragment growing. We have also gained experience in optimizing the performance of IADE for this type of application.


[The preliminary report of a registration clinical trial of proton and heavy ion irradiation].
Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions: IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.


New technique for measurement of left ventricular pressure in conscious mice.
Concern about the effects of anesthesia on physiological measurements led us to develop methodology to assess left ventricular (LV) pressure in conscious mice. Polyethylene-50 tubing filled with heparinized saline was implanted in the LV cavity through its apex via an abdominal approach and exteriorized to the back of the animal. This surgery was done under anesthesia with either an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (5 mg/kg) (K+X) in 11 mice or isoflurane (ISF; 1.5 vol%) by inhalation in 14 mice. Postoperatively, mice were trained daily to lie quietly head first in a plastic cone. LV pressure, the first derivative of LV pressure (dP/dt), and heart rate (HR) in the conscious state were compared between the two groups at 3 days and 1 wk after recovery from surgery using a 1.4-Fr Millar catheter inserted into the LV through the tubing, with the mice lying quietly in the plastic cone. Acutely during anesthesia, K+X decreased HR (from 698 to 298 beats/min), LV systolic pressure (from 107 to 65 mmHg), and maximal dP/dt (dP/dt(max)) (from 15,724 to 4,445 mmHg/s), all P < 0.01. Similar but less marked negative chronotropic and inotropic effects were seen with ISF. HR and dP/dt(max) were decreased significantly in K+X mice 3 days after surgery compared with those anesthetized with ISF (655 vs. 711 beats/min, P < 0.05; 14,448 vs. 18,048 mmHg/s, P < 0.001) but increased to the same level as in ISF mice 1 wk after surgery. In ISF mice, recovery of function occurred rapidly and there were no differences in LV variables between 3 days and 1 wk. LV pressure and dP/dt can be measured in conscious mice with a micromanometer catheter inserted through tubing implanted permanently in the LV apex. Anesthesia with either K+X or, to a lesser extent, ISF, depressed LV function acutely. This depression of function persisted for 3 days after surgery with K+X (but not ISF) and did not recover completely until 1 wk postanesthesia.


Unsuccessful transjugular intrahepatic portosystemic shunt for a patient with right heart failure and portal hypertension.
A 60-year-old women with a history of congenital pulmonary valve stenosis developed right heart failure, cardiac cirrhosis and end-stage renal disease requiring renal replacement therapy. Cirrhosis was complicated by portal hypertension, resulting in intractable gastro-intestinal bleedings despite optimal treatment with beta-blockers and endoscopic band ligation. Because of fears for worsening right heart failure, a decision for placement of a transjugular intrahepatic portosystemic shunt (TIPS) was initially turned down. However, as intractable bleeding problems persisted and caused heavy transfusion needs, TIPS was ultimately performed as a rescue procedure. Although TIPS successfully reduced the hepatic venous pressure gradient from 16 mmHg to 4 mmHg, portal pressure remained high at 14 mmHg because of persisting right heart failure with elevated central venous pressure. Hepatic encephalopathy soon developed after TIPS placement and culminated in multi-organ failure after another episode of gastro-intestinal bleeding. At this point, the family of the patient decided to withdraw care and the patient died subsequently. This case illustrates how important it is to diagnose and optimally treat right heart failure before cardiac cirrhosis with its impending complications emerges. Although TIPS may effectively treat complications of portal hypertension in the context of cirrhosis, persisting right heart failure may abrogate its beneficial effects.


Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics.
The authors investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS). ACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known. Seventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFRCT], change in FFRCT across the lesion [△FFRCT], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFRCT, △FFRCT, WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC). The culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p < 0.001) and higher prevalence of APC (80.3% vs. 42.0%; p < 0.001) than nonculprit lesions. Regarding hemodynamic parameters, culprit lesions showed lower FFRCT and higher △FFRCT, WSS, and axial plaque stress than nonculprit lesions (all p values <0.01). Among the 3 models, model 3, which included hemodynamic parameters, showed the highest c-index, and better discrimination (concordance statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001). Noninvasive hemodynamic assessment enhanced the identification of high-risk plaques that subsequently caused ACS. The integration of noninvasive hemodynamic assessments may improve the identification of culprit lesions for future ACS. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamic [EMERALD]; NCT02374775).


A novel surgical approach for feline stenotic nares: Bilateral wedge resection of the dorsal lateral nasal cartilage in seven cases.
Surgical correction of stenotic nares, one component of brachycephalic obstructive airway syndrome (BOAS), is not referenced as often in cats as it is in dogs. Similar to dogs, stenotic nares emerge as a significant contributor in the development of BOAS in cats. In this study, we propose that stenotic nares in brachycephalic cats arise from an elongated dorsal lateral nasal cartilage. The aim of this paper is to illustrate a novel surgical technique to alleviate stenosis-associated clinical signs by performing full-thickness bilateral wedge resection of the excessive cartilage. Seven cats that underwent rhinoplasty with full-thickness bilateral wedge resection along the dorsal lateral nasal cartilage between 2019 and 2022 at Pan-Asia Veterinary Clinic in Taipei, Taiwan. Clinical data of all cats included in the study were retrospectively reviewed. Surgical procedures were recorded. A full-thickness bilateral wedge resection was made along the dorsal lateral nasal cartilage adjacent to the non-hairy area. The full-thickness wedge resection was then apposed and closed, resulting in the abduction of the wing of the nostrils. Postoperative outcomes were evaluated according to follow-up sessions by the authors, and an owner survey was conducted at least 6 months post-surgery. All cats included in this study had a favourable outcome with no complications reported following surgery. The degree of nostril stenosis was improved, and relapse of clinical signs was not reported. Overall, the quality of life of cats that underwent rhinoplasty was significantly improved. The results support that the innovative procedure described in this study is highly promising and holds great potential in restoring quality of life and halting disease progression of cats with BOAS.


Summary measures for evaluating the evidence for linkage.
Two summary measures for evaluating the evidence for linkage are the maximum lod score and the average of the likelihood function (antilod score). The average antilod score can be used to calculate an exact probability of there being no linkage. Use of subjective prior probabilities in the calculation will only influence the final conclusion in any important way if evidence from the sample is not particularly conclusive. It is shown how results from two-point analyses for linkage of the test locus with each marker locus can be easily combined to give an approximate probability of there being no linkage. Some examples using bipolar affective disorder data and marker loci are presented.


Exploring the biomechanics of taurodontism.
Taurodontism (i.e. enlarged pulp chamber with concomitant apical displacement of the root bi/trifurcation) is considered a dental anomaly with relatively low incidence in contemporary societies, but it represents a typical trait frequently found in Neandertal teeth. Four hypotheses can be envisioned to explain the high frequency in Neandertals: adaptation to a specific occlusal loading regime (biomechanical advantage), adaptation to a high attrition diet, pleiotropic or genetic drift effects. In this contribution we used finite element analysis (FEA) and advanced loading concepts based on macrowear information to evaluate whether taurodontism supplies some dental biomechanical advantages. Loads were applied to the digital model of the lower right first molar (RM1 ) of the Neandertal specimen Le Moustier 1, as well as to the digital models of both a shortened and a hyper-taurodontic version of Le Moustier RM1 . Moreover, we simulated a scenario where an object is held between teeth and pulled in different directions to investigate whether taurodontism might be useful for para-masticatory activities. Our results do not show any meaningful difference among all the simulations, pointing out that taurodontism does not improve the functional biomechanics of the tooth and does not favour para-masticatory pulling activities. Therefore, taurodontism should be considered either an adaptation to a high attrition diet or most likely the result of pleiotropic or genetic drift effects. Finally, our results have important implications for modern dentistry during endodontic treatments, as we observed that filling the pulp chamber with dentine-like material increases tooth stiffness, and ultimately tensile stresses in the crown, thus favouring tooth failure.


Network medicine in ovarian cancer: topological properties to drug discovery.
Network medicine provides network theoretical tools, methods and properties to study underlying laws governing human interactome to identify disease states and disease complexity leading to drug discovery. Within this framework, we investigated the topological properties of ovarian cancer network (OCN) and the roles of hubs to understand OCN organization to address disease states and complexity. The OCN constructed from the experimentally verified genes exhibits fractal nature in the topological properties with deeply rooted functional communities indicating self-organizing behavior. The network properties at all levels of organization obey one parameter scaling law which lacks centrality lethality rule. We showed that $\langle k\rangle $ can be taken as a scaling parameter, where, power law exponent can be estimated from the ratio of network diameters. The betweenness centrality $C_B$ shows two distinct behaviors one shown by high degree hubs and the other by segregated low degree nodes. The $C_B$ power law exponent is found to connect the exponents of distributions of high and low degree nodes. OCN showed the absence of rich-club formation which leads to the missing of a number of attractors in the network causing formation of weakly tied diverse functional modules to keep optimal network efficiency. In OCN, provincial and connector hubs, which includes identified key regulators, take major responsibility to keep the OCN integrity and organization. Further, most of the key regulators are found to be over expressed and positively correlated with immune infiltrates. Finally, few potential drugs are identified related to the key regulators.


2-pyrazoline derivatives in neuropharmacology: Synthesis, ADME prediction, molecular docking and in vivo biological evaluation.
A novel series of 1,3,5-trisubstituted-2-pyrazoline derivatives (PFC-1 to PFC-16) were synthesized in a three step reaction using conventional and microwave assisted green chemistry approach. The synthesized derivatives were characterized and their chemical structures were established by various physicochemical methods such as IR, Mass, 1H-NMR, 13C-NMR and elemental analysis. The synthesized compounds were tested for their neuropharmacological potential. The compounds exhibited significant antidepressant and anti-anxiety activities against various behavioral in vivo models. Compounds PFC-3 and PFC-12 were found to be the most active derivatives in the series. The 2-pyrazoline analogs, having 2-hydroxyphenyl and anthracen-9-yl substitution at 3rd position while 4-benzyloxyphenyl and 4-methylphenyl substitution at 5th position, were decisive in eliciting good antidepressant and anxiolytic properties, respectively. The docking experiments revealed that the synthesized derivatives were potential inhibitors of MAO-A protein, which plays a central role in managing depression and anxiety disorders. The most potent derivatives were found to be involved in some key interactions with Tyr407, Tyr444, Phe352 and Ala68 amino acid residues at the binding site of MAO-A protein. All the synthesized derivatives successfully passed the pharmacokinetic barriers of absorption, distribution, metabolism and elimination as predicted using in silico techniques without showing any substantial indication of acute and neurotoxicity. This was further confirmed in the laboratory by performing acute toxicity studies as per OECD guidelines.


Nano-Zinc Oxide and Arbuscular mycorrhiza Effects on Physiological and Biochemical Aspects of Wheat Cultivars under Saline Conditions.
Saline soils are restrictive factors to agriculture in arid and semi-arid regions, plant growth and productivity. Thus, it was important to consider how, nano-zinc oxide or bulk zinc oxide alleviates the oxidative salt stress in the presence of Arbuscular mycorrhiza (AM) fungi by two wheat cultivars (Sids 13 and Sakha 94). A field experiment was carried out during two winter successive seasons to study the beneficial role of nano-zinc oxide or bulk zinc oxide with different concentrations (5 and 10 mg L-1) in enhancing growth, some biochemical and physiological of two wheat cultivars under saline soil. Soaking both wheat cultivars with nano-zinc oxide or bulk zinc oxide in the presence of AM improved growth parameters. All treatments increased significantly photosynthetic pigments, IAA, phenols contents, organic antioxidant enzyme activities and significant decrease in lipid peroxidation. some changes are observed in protein patterns, so several proteins were disappear, but others were selectively improved and synthesis of the new groups of protein was formed, some of these responses were observed through the effect of nano-zinc oxide or bulk zinc oxide and AM. Nano-ZnO (10 mg L-1) in the presence of AM was the most effective treatments on both cultivars. Results showed superiority of Sakha 94 cultivar in most growth parameters and biochemical aspects than Sids 13 cultivar.


Modelling survival data of thalassaemia patients in Pakistan.
Fatimid Foundation with its centers serves as a charitable organization for millions of blood disease carriers in Pakistan. This retrospective survival study is an analysis of the Thalassaemia patients registered in Multan centre who are followed up to nine years to assess the gender risk of death. Data on 120 patients of Thalassaemia during 1994-2002 was analyzed. The standard Kaplan-Meier and Nelson-Aalen procedures were used to compare the survival function of the male and female patients of Thalassaemia. The statistical significance was also assessed using log rank test. The Cox Proportional Hazards (PH) model using a forward selection procedure was used to identify the potential factors associated with the increase risk of death. By ignoring the censoring, the average survival time of males and females were calculated to be 1308.1 and 1574.7 days respectively. The average hazard rate for the female group was 0.00033 and for the male group it was 0.00061. The median survival time was estimated from the Kaplan-Meier survival curves (Males: 1400 days, Females: 1785 days). Under the censoring mechanism, the mean survival time for males was calculated to be 1465.82 days with standard error of 146 days, where as for females it was calculated to be 1855.26 with standard error of 151.82 days. When considering death as event of interest Under the Cox modelling approach, we found a male patient of Thalassaemia was 1.484 times more likely to die when compared to his female counterpart. When considering the iron over load as the event of interest, we found a male patient of Thalassaemia was 1.753 fold more likely to reach excessive Haemochromatosis level compared to female patient. The analysis reinforces that female group prognosis is better than the male group. Further, our analysis of real survival data set shows that the high status of Haemochromatosis level is associated with the increased risk of death in patients with Thalassaemia with other possible confounders.


Factors associated with weaning in the first 3 months postpartum.
To determine the demographic, behavioral, and clinical factors associated with breastfeeding termination in the first 12 weeks postpartum. This was a prospective cohort study. Breastfeeding women in Michigan and Nebraska were interviewed by telephone at 3, 6, 9, and 12 weeks postpartum or until breastfeeding termination. We measured associations of demographic, clinical, and breastfeeding variables with weaning during the first 12 weeks postpartum. A total of 946 women participated; 75% breastfed until 12 weeks. Women older than 30 years and women with at least a bachelor's degree were more likely to continue breastfeeding in any given week. Mastitis, breast or nipple pain, bottle use, and milk expression in the first 3 weeks were all associated with termination. Beyond 3 weeks, women who expressed breast milk were 75% less likely to discontinue breastfeeding than women who did not. Women who used a bottle for some feedings during weeks 4 to 12 were 98% less likely to discontinue breastfeeding than women who did not use a bottle. "Not enough milk" was the most common reason given for termination in weeks 1 through 3 (37%) and weeks 4 through 6 (35%); "return to work" was the most common reason given in weeks 7 through 9 (53%) and weeks 10 through 12 (58%). Younger women and less educated women need additional support in their breastfeeding efforts. Counseling and assistance should be provided to women with pain and mastitis. Exclusive breastfeeding for the first 3 weeks should be recommended. After the first 3 weeks, bottles and manual expression are not associated with weaning and may improve the likelihood of continuing breastfeeding, at least until 12 weeks.


Screening and structural and functional investigation of a novel ferritin from Phascolosoma esculenta.
Ferritins are primary iron storage proteins and play a crucial role in iron storage and detoxification. Yeast two-hybrid method was employed to screen the cDNA library of Phascolosoma esculenta. Sequence of positive colony FER147 was analyzed. The higher similarity and conserved motifs for ferritin indicated that it belonged to a new member of ferritin family. The interaction between Ferritin and Fer147 was further confirmed through co-immunoprecipitation. The pET-28a-FER147 prokaryotic expression vector was constructed. The expressed recombinant Fer147 was then isolated, purified, and refolded. When ferritins were treated by different heavy metals, several detection methods, including scanning electron microscopy (SEM), circular dichroism (CD), and inductively coupled plasma-mass spectrometry (ICP-MS) were applied to examine the structures and functions of the new protein Fer147, recombinant P. esculenta ferritin (Rferritin), and natural horse-spleen ferritin (Hferritin). SEM revealed that the three ferritin aggregates changed obviously after different heavy metals treatment, meanwhile, a little different in aggregates were detected when the ferritins were trapped by the same heavy metal. Hence, changes in aggregation structure of the three proteins are related to the nature of the different heavy metals and the interaction between the heavy metals and the three ferritins. CD data suggested that the secondary structure of the three ferritins hardly changed after different heavy metals were trapped. ICP-MS revealed that the ferritins exhibit different enrichment capacities for various heavy metals. In particular, the enrichment capacity of the recombinant Fer147 and Rferritin is much higher than that of hferritin.


Combretastatin A-1 phosphate a novel tubulin-binding agent with in vivo anti vascular effects in experimental tumours.
In view of the clinical potential of a number of natural products, Combretastatin A-1 phosphate was developed as a water-soluble derivative of combretastatin A-1. This study examined the anti-tumour activity of this compound against an experimental colon tumour (MAC29) in mice. A comparison was made with the clinically active combretastatin A-4 phosphate. The new compound was well-tolerated up to a dose of 250 mg/kg and was more effective at producing tumour growth delays than the A-4 analogue. Significant growth delays were seen at a dose of 50 mg/kg whereas the A-4 phosphate produced no measurable growth delay until a dose of 150 mg/kg was administered. Histological examination of treated tumours indicated that combretastatin A-1 phosphate caused very severe haemorrhagic necrosis in the tumour tissue and analysis of the sections indicated that almost 94 percent of the tumour was dead within 24 hours of treatment. The mechanism of action of combretastatin A-1 phosphate appears to be similar to the A-4 phosphate in that tumour vascular shutdown occurs within 4 hours of treatment. In summary combretastatin A-1 phosphate, the water-soluble analogue of combretastatin A-1, is more potent against a well-vascularised murine colon tumour than its predecessor, combretastatin A-4 phosphate. These data suggest this compound may have potential for clinical development.


Are individuals with higher psychopathic traits better learners at lying? Behavioural and neural evidence.
High psychopathy is characterized by untruthfulness and manipulativeness. However, existing evidence on higher propensity or capacity to lie among non-incarcerated high-psychopathic individuals is equivocal. Of particular importance, no research has investigated whether greater psychopathic tendency is associated with better 'trainability' of lying. An understanding of whether the neurobehavioral processes of lying are modifiable through practice offers significant theoretical and practical implications. By employing a longitudinal design involving university students with varying degrees of psychopathic traits, we successfully demonstrate that the performance speed of lying about face familiarity significantly improved following two sessions of practice, which occurred only among those with higher, but not lower, levels of psychopathic traits. Furthermore, this behavioural improvement associated with higher psychopathic tendency was predicted by a reduction in lying-related neural signals and by functional connectivity changes in the frontoparietal and cerebellum networks. Our findings provide novel and pivotal evidence suggesting that psychopathic traits are the key modulating factors of the plasticity of both behavioural and neural processes underpinning lying. These findings broadly support conceptualization of high-functioning individuals with higher psychopathic traits as having preserved, or arguably superior, functioning in neural networks implicated in cognitive executive processing, but deficiencies in affective neural processes, from a neuroplasticity perspective.


Correction: Virtual microwells for digital microfluidic reagent dispensing and cell culture.
Correction for 'Virtual microwells for digital microfluidic reagent dispensing and cell culture' by Irwin A. Eydelnant et al., Lab Chip, 2012, 12, 750-757, https://doi.org/10.1039/C2LC21004E.


Achievement of higher thresholds of clinical responses and lower levels of disease activity is associated with improvements in workplace and household productivity in patients with axial spondyloarthritis.
Patients with active axial spondyloarthritis (axSpA) exhibit more absences and lower levels of productivity in the workplace and household than the general population, which can improve upon treatment. The objective of this study is to determine the long-term impact of achieving different levels of clinical response or disease activity on workplace and household productivity in patients with axSpA. RAPID-axSpA (NCT01087762) was a 204-week phase III trial evaluating the safety and efficacy of certolizumab pegol (CZP) in adult patients with active axSpA. The impact of axSpA on workplace and household productivity was evaluated using the validated arthritis-specific Work Productivity Survey. Outcomes included the percentage of patients achieving Assessment of SpondyloArthritis International Society (ASAS) response and Ankylosing Spondylitis Disease Activity Score (ASDAS) thresholds. This post hoc study used a generalised estimating equations model to determine the association between the threshold of clinical response achieved and patient productivity. Of 218 CZP-randomised patients, 65.1% completed week 204. At baseline, 72.0% were employed outside the home. Of the patients who were unemployed, 42.6% were unable to work due to arthritis. Achievement of higher treatment response thresholds, such as clinical remission, was associated with fewer days affected by workplace absenteeism (ASAS-partial remission: 4.0 days, ASAS40: 8.6 days, ASAS20 but not reaching ASAS40 response: 29.4 days, ASAS20 non-response: 69.2 days; ASDAS-inactive disease: 5.0 days, ASDAS-low disease activity: 15.6 days, ASDAS-high disease activity: 32.7 days, ASDAS-very high disease activity: 93.4 days). Similar associations were found for workplace presenteeism, and household absenteeism and presenteeism. Over 4 years, achievement of higher clinical response thresholds and lower levels of disease activity was associated with fewer cumulative days affected by absenteeism or presenteeism, with clinical remission associated with the greatest improvements in productivity. This highlights the importance of targeting these thresholds to limit the burden of axSpA on society and on patients' daily lives.


Synthesis and antimicrobial evaluation of 3-methanone-6-substituted-benzofuran derivatives.
Seventeen benzofuran derivatives were synthesized and screened for their antibacterial activities against Escherichia coli, Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Seven of them have showed excellent antibacterial activities compared to the positive controls (Cefotaxime and Sodium Penicillin). The substitutions at C-6 and C-3 positions of these derivatives were found to greatly impact on the antibacterial activity and strains specificity, respectively. Specifically, compounds bearing a hydroxyl group at C-6 (5a, 5b, 5c and 12) offered excellent antibacterial activities against all five above-mentioned strains (MIC(80) = 0.78-12.5 ug/mL), and those with imine (15) and (3, 4, 5-trimethoxyphenyl) methanone (7e), respectively, at C-3 position showed selective activity against S. aureus among five tested strains with great MIC(80) values (3.12-12.5 ug/mL).


Clinical characteristics of melon (Cucumis melo) allergy.
Although melon is a frequent allergy-eliciting fruit, allergic reactions to melon have rarely been reported. To evaluate and describe the clinical characteristics of melon allergy in melon-allergic patients. We evaluated patients allergic to melon and a control group of patients allergic to pollen. The diagnosis of melon allergy was based on a convincing clinical history, positive skin test results (prick-by-prick test), and positive results on oral challenge tests to melon. A total of 161 patients were included in the study: 66 in the melon allergy group and 95 in the pollen control group. The melon allergy group included 35 female and 31 male patients with a mean age of 26.6 +/- 2.7 years (range, 5-61 years). Although all patients had oral symptoms, 13 (19.7%) of the patients had extraoral symptoms and none experienced generalized urticaria or anaphylaxis. Excluding other Cucurbitaceae fruits, peach, fig, and kiwi most frequently elicited positive skin test results and symptoms. Up to 23% of melon-allergic patients had a concomitant latex sensitization. Melon allergy was especially linked to pollen allergy, since all the melon-allergic patients were also allergic to pollen. Some differential features with respect to the pollen allergy control group were a higher prevalence of asthma (odds ratio [OR], 2.13; P < 0.05) and a statistical increase in the frequency of sensitization to several tree and weed pollens, including Ulmus (OR, 42.8) and Ambrosia (OR, 22.4). The most important conditions linked to melon allergy are pollen allergy (100%), allergy to other nonrelated fruits, mainly peach (up to 62%), and latex sensitivity (up to 23%). Some differential features of the pollinosis in melon allergy were a higher prevalence of asthma and a higher frequency of sensitization to several weed and tree pollens.


A Novel Risk Model for lncRNAs Associated with Oxidative Stress Predicts Prognosis of Bladder Cancer.
Oxidative stress (OS) reactions are closely related to the development and progression of bladder cancer (BCa). This project aimed to identify new potential biomarkers to predict the prognosis of BCa and improve immunotherapy. We downloaded transcriptomic information and clinical data on BCa from The Cancer Genome Atlas (TCGA). Screening for OS genes was statistically different between tumor and adjacent normal tissue. A coexpression analysis between lncRNAs and differentially expressed OS genes was performed to identify OS-related lncRNAs. Then, differentially expressed oxidative stress lncRNAs (DEOSlncRNAs) between tumors and normal tissues were identified. Univariate/multivariate Cox regression analysis was performed to select the lncRNAs for risk assessment. LASSO analysis was conducted to establish a prognostic model. The prognostic risk model could accurately predict BCa patient prognosis and reveal a close correlation with clinicopathological features. We analyzed the principal component analysis (PCA), immune microenvironment, and half-maximal inhibitory concentration (IC50) in the risk groups. We constructed a model containing eight DEOSlncRNAs (AC021321.1, AC068196.1, AC008750.1, SETBP1-DT, AL590617.2, THUMPD3-AS1, AC112721.1, and NR4A1AS). The prognostic risk model showed better results in predicting the prognosis of BCa patients and was strongly correlated with clinicopathological characteristics. We found great agreement between the calibration plots and prognostic predictions in this model. The areas under the receiver operating characteristic (ROC) curve (AUCs) at 1, 3, and 5 years were 0.792, 0.804, and 0.843, respectively. This model also showed good predictive ability regarding the tumor microenvironment and tumor mutation burden. In addition, the high-risk group was more sensitive to eight therapeutic agents, and the low-risk group was more responsive to five therapeutic agents. Sixteen immune checkpoints were significantly different between the two risk groups. Our eight DEOSlncRNA risk models provide new insights into predicting prognosis and clinical progression in BCa patients.


Quantitation of postexercise lung thallium-201 uptake during single photon emission computed tomography.
To test the hypothesis that analysis of lung thallium uptake measured during single photon emission computed tomography (SPECT) yields supplementary clinical information as reported for planar imaging, quantitative analysis of lung thallium uptake following maximal exercise was performed in 40 clinically normal subjects (Group 1) and 15 angiographically normal subjects (Group 2). Lung thallium uptake was measured from anterior projection images using a ratio of heart-to-lung activities. Seventy subjects with coronary artery disease (CAD) (Group 3) determined by angiography (greater than or equal to 70% luminal stenosis) underwent thallium perfusion SPECT. Thirty-nine percent of these subjects had multivessel and 61% had single vessel CAD. Lung thallium uptake was elevated in 47 of 70 (67%) Group 3 subjects. Group 3 subjects with elevated lung thallium uptake did not differ from Group 3 subjects with normal lung thallium uptake with respect to extent or distribution of coronary artery disease, left ventricular function, or severity of myocardial ischemia as determined by exercise and redistribution thallium SPECT. Thus, the measurement of thallium lung uptake from anterior projection images obtained during SPECT frequently identifies patients with CAD, but it may not provide supplementary information regarding the extent of myocardial ischemia or ventricular dysfunction.


Renal Cell Carcinoma: The Evolving Role of Imaging in the 21st Century.
Kidney lesions are commonly an incidental finding on cross sectional studies carried out for a variety of reasons. The detection of renal cell carcinoma (RCC) has increased accordingly. There are a variety of different contrast-enhanced CT imaging protocols that have been developed to help diagnose and stage RCC. More recently, renal MRI and contrast-enhanced ultrasound have also been used as problem-solving tools. This paper describes the epidemiology of RCC and the role of imaging in diagnosis and follow-up.


Combining instruction prefetching with partial cache locking to improve WCET in real-time systems.
Caches play an important role in embedded systems to bridge the performance gap between fast processor and slow memory. And prefetching mechanisms are proposed to further improve the cache performance. While in real-time systems, the application of caches complicates the Worst-Case Execution Time (WCET) analysis due to its unpredictable behavior. Modern embedded processors often equip locking mechanism to improve timing predictability of the instruction cache. However, locking the whole cache may degrade the cache performance and increase the WCET of the real-time application. In this paper, we proposed an instruction-prefetching combined partial cache locking mechanism, which combines an instruction prefetching mechanism (termed as BBIP) with partial cache locking to improve the WCET estimates of real-time applications. BBIP is an instruction prefetching mechanism we have already proposed to improve the worst-case cache performance and in turn the worst-case execution time. The estimations on typical real-time applications show that the partial cache locking mechanism shows remarkable WCET improvement over static analysis and full cache locking.


Current pharmacotherapy for the treatment of chronic hepatitis B.
The virological profile of infection with the hepatitis B virus (HBV) is changing in many parts of the world from the classical hepatitis B e antigen (HBeAg)-positive serological pattern to a HBeAg-negative pattern, linked to the replacement of wild-type HBV by HBV variants with mutations in the core-promoter and in the precore region that prevent the secretion of HBeAg. The wild-type HBV disease is characterised by steady levels of alanine aminotransferase (ALT) and high HBV-DNA levels, responding relatively well to IFN treatment (3 - 5 MU/day or 10 MU every other day for 16 weeks), which induces anti-HBe seroconversion and normalises ALT levels in approximately 30% of the adults, with a minimal risk of relapse. Pegylated-IFN appears to have superior efficacy over conventional IFN-alpha. Mutant-type disease (anti-HBe-positive/HBeAg-negative) is less responsive to IFN given for 6 - 12 months. This has led to the use of novel nucleoside analogues, of which the prototype is lamivudine. The response to lamivudine therapy shares with IFN a rapid decline in ALT accompanied by an improvement in histology; at variance with IFN, in HBeAg-positive chronic hepatitis B (CHB) there is delayed seroconversion to anti-HBe which accumulates over time, the switch to anti-HBs is more rare and in the long-term, the activity of the drug is abolished by the emergence of viral mutations (YMDD-motif mutants) that may rekindle the disease. The combination of IFN plus lamivudine may be more efficacious than IFN or lamivudine monotherapy. Lamivudine therapy needs to be prolonged in HBeAg-negative CHB. Short-term lamivudine-therapy is highly efficacious in preventing HBV reinfection in liver transplants. Recent data suggest that long-term IFN therapy (24 months) may achieve a response in 30% of HBeAg-negative patients. The advent of adefovir, an analogue of adenosine monophosphate, may provide a safer alternative to lamivudine in the control of HBV disease; the drug is well-tolerated and treatment raises drug-resistant mutants in < 2% of the patients over 2 years of therapy. Adefovir provides rescue therapy against YMDD mutants raised by lamivudine therapy.


Who Am I: The Conscious and the Unconscious Self.
Who am I? What is the self and where does it come from? This may be one of the oldest problems in philosophy. Beyond traditional philosophy, only very recently approaches from neuroscience (in particular imaging studies) have tried to address these questions, too. So what are neural substrates of our self? An increasing body of evidence has demonstrated that a set of structures labeled as cortical midline structures are fundamental components to generate a conscious self. Moreover, recent theories on embodied cognition propose that this conscious self might be supplemented by additional structures, for example, in the somatosensory cortices, which enable our brain to create an "embodied mind". While the self based on cortical midline structures may be related to a conscious self, we here propose that the embodied facet of the self may be linked to something we call unconscious self. In this article we describe problems of this model of a conscious and unconscious self and discuss possible solutions from a theoretical point of view.


Valence-change of Eu and its effects on the luminescent properties of Sr2MgSi2O7:Eu,Dy.
Long afterglow phosphors of Sr2MgSi2O7:Eu,Dy were prepared by high temperature solid state reaction in oxidation atmospheres, and then were treated sequentially in reducing atmosphere --> oxidation atmosphere --> reducing atmosphere. The crystal structure of the samples was investigated by using powder X-ray diffraction (XRD). The measurements of the photoluminescence and the thermoluminescence properties suggest the difference in the luminescent properties between Eu2+ and Eu3+. Eu3+ ions occupy two different sites, and their emission spectra consist of four discrete line spectra, due to the 5D0 --> 7F1 (590 nm), 5D0 --> 7F2 (618 nm), 5D0 --> 7F4 (703 nm) and the 5D2 --> 7F3 (510 nm) transitions. But in contrast, the emission spectrum of Eu2+ is characteristic of a broadband spectrum due to the 4f(7) --> 4f(6) 5d(1) transition. The luminescence of Sr2MgSi2O7:Eu2+,Dy3+ displays both higher intensity and longer decay than that of Sr2MgSi2O7:Eu3+,Dy3+. The emissions from Dy3+ are detected in all samples, indicating that Dy3+ ions act not only the trap center but also the luminescence center in the host lattice of Sr2MgSi2O7.


Fractional Chern Insulators in Harper-Hofstadter Bands with Higher Chern Number.
The Harper-Hofstadter model provides a fractal spectrum containing topological bands of any integer Chern number C. We study the many-body physics that is realized by interacting particles occupying Harper-Hofstadter bands with |C|>1. We formulate the predictions of Chern-Simons or composite fermion theory in terms of the filling factor ν, defined as the ratio of particle density to the number of single-particle states per unit area. We show that this theory predicts a series of fractional quantum Hall states with filling factors ν=r/(r|C|+1) for bosons, or ν=r/(2r|C|+1) for fermions. This series includes a bosonic integer quantum Hall state in |C|=2 bands. We construct specific cases where a single band of the Harper-Hofstadter model is occupied. For these cases, we provide numerical evidence that several states in this series are realized as incompressible quantum liquids for bosons with contact interactions.


Manual dexterity and keyboard use in spastic hemiparesis: a comparison between the impaired hand and the 'good' hand on a number of performance measures.
To assess the functional deficits in tapping performance of subjects with spastic hemiparesis. In a pilot study, typing performance on a computer keyboard was examined on a number of performance measures. Department of Research and Development at the Werkenrode Institute. Four subjects (mean age 16.4 years, standard deviation 1.8 years) with cerebral palsy and diagnosed as having spastic hemiparesis. Subjects had to type a sequence of one or more keys as quickly as possible within an 8 second period with the fingers of both hands separately. The average number of good and false responses were calculated. Within the false response category, four, mutually exclusive, types of errors were distinguished; wrong key, repetition, registrations under 75 ms and holding. Speed and regularity of the typing responses were also established. The 'good' hand outperformed the impaired hand on all performance measures except on the amount of repetition errors made. The holding error was only present for the impaired hand, and there was an increase in holding errors from the index to the little finger in this hand. In addition, the impaired hand performed the task with a slower speed and in a more irregular fashion. The results are discussed with reference to keyboard design. It is concluded that the standard 'QWERTY' keyboard hampers typing performance extensively, especially for subjects with left spastic hemiparesis. A learning method is presented in which the role of an external pacer (e.g. metronome) is discussed. This device can initially be used to decrease movement variability and, eventually, for increasing movement speed.


Colloidal aspects of dispersion and digestion of self-dispersing lipid-based formulations for poorly water-soluble drugs.
Self-dispersing lipid-based formulations, particularly self-microemulsifying drug delivery systems (SMEDDS) have gained an increased interest in recent times as a means to enhance the oral bioavailability of poorly water-soluble lipophilic drugs. Upon dilution, SMEDDS self-emulsify in an aqueous fluid and usually form a kinetically stable oil-in-water emulsion or in some rare cases a true thermodynamically stable microemulsion. The digestion of the formulation leads to the production of amphiphilic digestion products that interact with endogenous amphiphilic components and form self-assembled colloidal phases in the aqueous environment of the intestine. The formed colloidal phases play a pivotal role in maintaining the lipophilic drug in the solubilised state during gastrointestinal transit prior to absorption. Thus, this review describes the structural characterisation techniques employed for SMEDDS and the recent literature studies that elucidated the colloidal aspects during dispersion and digestion of SMEDDS and solid SMEDDS. Possible future studies are proposed to gain better understanding on the colloidal aspects of SMEDDS and solid SMEDDS.


Larval morphology of Plagiosterna adamsii (Baly) and P. aenea (Linnaeus) with resurrection of Gastrolinoides Chûjô & Kimoto and P. formosana (Bates) (Coleoptera: Chrysomelidae: Chrysomelinae).
Larvae of Plagiosterna adamsii (Baly, 1864) and P. aenea (Linnaeus, 1758) are redescribed and illustrated in detail, with discussion of the previous misinterpretations. The first instar larva of Plagiosterna adamsii is described for the first time. The original name and citation of P. adamsii is confirmed. The genus Gastrolinoides Chûjô & Kimoto, 1960 is resurrected from synonymy with Plagiosterna Motschulsky, 1860. Plagiosterna formosana (Bates, 1866) is resurrected from synonymy with P. aenea. A key to the larvae of the Palaearctic Plagiosterna is provided. Tubercular pattern, pigmentation and sclerotized platelets of the integument are used as diagnostic characters for particular species.


[Surgical management of inverted papillomas of the nose and paranasal sinuses].
Inverted papillomas require radical resection because of their high recurrence rate and expansive growth and the risk of malignant degeneration. Since the late 1980s surgical resection has been performed predominantly as an endoscopy-/microscopy-aided procedure through an endonasal approach. The extranasal approach is only used in the case of papillomas in unusual locations or ones that have expanded to an exceptional degree. The goal of the present study was a comparative evaluation of the results of this relatively new treatment strategy and of external sinus surgery in our own patients, with particular reference to the recurrence rate. Since 1989 a total of 80 patients have undergone surgery for inverted papilloma and have been followed up at regular intervals by means of endoscopic examinations. In any patients with a recurrence the revision operation was carried out through an extranasal approach when the papilloma was in the anterior or laterocaudal maxillary sinus or in the frontal sinus; in all other cases an endonasal approach was used for the revision surgery. The mean period of follow-up was 43 months (range 15 months to 16years). In most patients (n=64, 80%) the endonasal surgical approach was used for the primary surgical treatment, while in 16 patients (20%) an extranasal approach was used initially. In 2 patients (2.6%) a squamous cell carcinoma was discovered adjacent to the papilloma. These two therapeutic special cases were not considered evaluable in the analysis of recurrences. Recurrences were seen in 14 patients (17.9%, n=78), in 11 patients after endonasal surgery (17.5%, n=11) and in 3 (20%, n=15) after extranasal resection. The majority of recurrences developed in patients with T3 papillomas. The recurrence rates observed after endonasal resection are comparable to those after extranasal surgery. Thus, a primary endonasal approach does not mean any prognostic disadvantage. This approach should therefore be given preference over extranasal approaches whenever possible, because there are fewer side-effects and recovery is faster than after extranasal surgery.


The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry.
The implementation of continuous flow processing as a key enabling technology has transformed the way we conduct chemistry and has expanded our synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient and reproducible manufacture. This review article aims to illustrate the holistic systems approach and diverse applications of flow chemistry to the preparation of pharmaceutically active molecules, demonstrating the value of this strategy towards every aspect ranging from synthesis, in-line analysis and purification to final formulation and tableting. Although this review will primarily concentrate on large scale continuous processing, additional selected syntheses using micro or meso-scaled flow reactors will be exemplified for key transformations and process control. It is hoped that the reader will gain an appreciation of the innovative technology and transformational nature that flow chemistry can leverage to an overall process.


Aggregation of yeast cells: direct measurement of discrete lectin-carbohydrate interactions.
Aggregation of microbial cells mediated by specific interactions plays a pivotal role in the natural environment, in medicine and in biotechnological processes. Here we used atomic force microscopy (AFM) to measure individual lectin-carbohydrate interactions involved in the flocculation of yeast cells, an aggregation event of crucial importance in fermentation technology. AFM probes functionalized with oligoglucose carbohydrates were used to record force-distance curves on living yeast cells at a rate of 0.5 micro m s(-1). Flocculating cells showed adhesion forces of 121+/-53 pN, reflecting the specific interaction between individual cell-surface lectins and glucose residues. Similar adhesion forces, 117+/-41 pN, were measured using probes functionalized with the lectin concanavalin A and attributed to specific binding to cell-surface mannose residues. By contrast, specific interaction forces were not observed in non-flocculating conditions, i.e. in the presence of mannose or when using non-flocculating cells, pointing to their involvement in yeast flocculation. The single molecule force spectroscopy measurements presented here provide a means to study a variety of cellular interactions at the molecular level, such as the adhesion of bacteria to animal and plant tissues.


Approaching Intra- and Interchain Charge Transport of Conjugated Polymers Facilely by Topochemical Polymerized Single Crystals.
Charge transport of small molecules is measured well with scanning tunneling microscopy, conducting atomic force microscopy, break junction, nanopore, and covalently bridging gaps. However, the manipulation and measurement of polymer chains remain a long-standing fundamental issue in conjugated polymers and full of challenge since conjugated polymers are naturally disordered materials. Here, a fundamental breakthrough in generating high-quality conjugated-polymer nanocrystals with extended conjugation and exceptionally high degrees of order using a surface-supported topochemical polymerization method is demonstrated. In the crystal the conjugated-polymer chains are extended along the long axis of the crystal with the side chains perpendicular to the long axis. Devices with conducting channels along the polymer chains show efficient charge transport, nearly two orders of magnitude greater than the interchain charge transport along the π-π stacking direction. This is the first example to clarify intra- and interchain charge transport based on an individual single crystal of conjugated polymers, and demonstrate the importance of intrachain charge transport in plastic electronics.


Transgenes consisting of a dsRNA of an RNAi suppressor plus the 3' UTR provide resistance to Citrus tristeza virus sequences in Nicotiana benthamiana but not in citrus.
In an attempt to utilize post-transcriptional gene silencing (PTGS) as a means to impart resistance against Citrus tristeza virus (CTV) into citrus plants, the p23 + 3'UTR sequence (p23U) of the VT strain of CTV was engineered to fold into a double-stranded (ds) RNA structure. The resulting construct (p23UI) was introduced into Nicotiana benthamiana and Alemow (Citrus macrophylla) plants by Agrobacterium-mediated transformation. Transgenic p23UI- N. benthamiana were resistant to infection with a viral vector made of Grapevine virus A (GVA) + p23U (GVA-p23U), as indicated by the absence of the chimeric virus from inoculated plants. Inoculation of transgenic p23UI Alemow plants with CTV resulted in delayed appearance of symptoms in 9 out of the 70 transgenic plants. However, none of the plants showed durable resistance, as indicated by the obtaining of similar Northern hybridization signals from both transgenic and non-transgenic citrus plants. The possible causes for the failure of transgenic citrus plants to confer durable resistance to CTV are discussed.


Circadian disruption induced by light-at-night accelerates aging and promotes tumorigenesis in young but not in old rats.
We evaluated the effect of exposure to constant light started at the age of 1 month and at the age of 14 months on the survival, life span, tumorigenesis and age-related dynamics of antioxidant enzymes activity in various organs in comparison to the rats maintained at the standard (12:12 light/dark) light/dark regimen. We found that exposure to constant light started at the age of 1 month accelerated spontaneous tumorigenesis and shortened life span both in male and female rats as compared to the standard regimen. At the same time, the exposure to constant light started at the age of 14 months failed to influence survival of male and female rats. While delaying tumors in males, constant light accelerated tumors in females. We conclude that circadian disruption induced by light-at-night started at the age of 1 month accelerates aging and promotes tumorigenesis in rats, however failed affect survival when started at the age of 14 months.


[Neuroendocrine tumor of the breast--metastasis or primary breast carcinoma? Case report].
A 74-year-old women with a history of neuroendocrine tumor in the terminal ileum presented on screening mammography with an irregular hypoechogenic mass in the upper outer quadrant of the left breast. A core biopsy showed a neuroendocrine tumor, interpreted as a probable metastasis from the intestinal primary. Other masses were found in the right lobe of the liver. Resection of the masses in the breast and liver was performed at the same time. Morphological and immunohistochemical findings (positive neuroendocrine markers, estrogene receptors and negative cytokeratine 7, mammaglobin, GCDFP-15, cytokeratine 20 and progesterone receptors) were consistent with a diagnosis of a metastatic well-differentiated neuroendocrine tumor, despite some estrogen receptor positivity. Issues of primary and metastatic breast neuroendocrine tumors are discussed in detail.


Ectodermal Differentiation of Wharton's Jelly Mesenchymal Stem Cells for Tissue Engineering and Regenerative Medicine Applications.
Mesenchymal stem cells (MSCs) from Wharton's jelly (WJ) of the human umbilical cord are perinatal stem cells that have self-renewal ability, extended proliferation potential, immunosuppressive properties, and are accordingly excellent candidates for tissue engineering. These MSCs are unique, easily accessible, and a noncontroversial cell source of regeneration in medicine. Wharton's jelly mesenchymal stem cells (WJMSCs) are multipotent and capable of multilineage differentiation into cells like adipocytes, bone, cartilage, and skeletal muscle upon exposure to appropriate conditions. The ectoderm is one of the three primary germ layers found in the very early embryo that differentiates into the epidermis, nervous system (spine, peripheral nerves, brain), and exocrine glands (mammary, sweat, salivary, and lacrimal glands). Accumulating evidence shows that MSCs obtained from WJ have an ectodermal differentiation potential. The current review examines this differentiation potential of WJMSC into the hair follicle, skin, neurons, and sweat glands along with discussing the potential utilization of such differentiation in regenerative medicine.


Incorporating nicotine dependence into addiction treatment.
An addiction treatment program devoted two years to preparing to become a smokefree treatment unit that addressed nicotine dependence as another drug dependency. Data collected from September 1990 to July 1995 on 263 admissions before becoming smokefree and 2182 admissions after making the transition revealed that going smokefree did not affect the incidence of premature discharges or aggressive behavior, and did not change the overall rate of program completion by either smokers or nonsmokers. During the first three months after going smokefree, the program completion rate dropped for both smokers and nonsmokers; by the fourth month, it had returned to previous levels. Seventeen months after going smokefree, the program completion rate was higher than it had ever been. This suggests that the drop in the program completion rate was due to the disruption caused by a significant programmatic change and not due to the unit's smokefree status, and that the increasing experience of staff in treating nicotine dependence resulted in improved patient outcomes.


Expression of adipose differentiation-related protein: a predictor of cancer-specific survival in clear cell renal carcinoma.
We recently found that adipose differentiation-related protein (ADFP) is a potential diagnostic and prognostic biomarker for clear cell subtype renal cell carcinoma (RCC). To further evaluate the correlation between ADFP expression levels and clinicopathologic characteristics and patient outcome, we retrospectively examined patients with clear cell RCC. A series of 432 consecutive patients with sporadic clear cell RCC who underwent nephrectomy between March 1986 and June 2004 were enrolled in the study. ADFP expression levels in the primary tumors and in 18 metastases were measured by real-time quantitative PCR. The clinicopathologic and prognostic data were collected, as well as the von Hippel-Lindau disease (VHL) gene alteration status in selected cases. ADFP expression was apparently high in cases without a symptomatic presentation, as well as in cases of low-stage, low-grade, or VHL alteration-positive clear cell RCC, whereas it was down-regulated in undifferentiated tumors with a spindle/pleomorphic component or metastatic lesions. Univariate analyses showed that high ADFP expression was associated with better cancer-specific survival and cancer-free survival. Further Cox multivariate analyses combined with the split-sample validation method showed that ADFP expression still remains an independent predictor for cancer-specific survival in all tumor stages and in advanced metastatic cases, whereas the predictive value of ADFP expression for cancer recurrence is rather weak. The ADFP expression may represent the tumor differentiation status, and the detection of the expression levels provides useful prognostic information for cancer-specific survival in patients with clear cell RCC.


[Bone adaptive digital analysis for femur bone being in disuse and overload condition].
Mature femur bone, through the process of bone remodeling, renews itself and adapts to mechanical load. In this study, a biomechanical model involving strain and other variable parameters was developed for bone remodeling and used to simulate the removal of bone mass and bone regeneration in the disuse and overload condition. The results exhibit that elastic modulus in bone lateral portion is decreasing and porosity is increasing for acquiring equilibrium strain. The conclusion of simulation for reality femur model is more accurate than what is obtained from simplified model or from only one volume element. These indicate the significance of acquiring scientific data to the development of consummate simulation model.


Advantages and disadvantages of neurological scales.
The neurological features demonstrated by a patient form a valid measurement for the level of impairment experienced following a stroke. These features can be assessed using neurological scores, which assign values to the many deficits exhibited by such patients and allow a prognosis to be made on patient outcome. Several stroke scales have been produced, most of which are based on normative scaling. While these stroke scales provide effective patient assessment, they do have some associated disadvantages. The analysis of multiple minor deficits can lead to the same scoring as a few major deficits, some scales assess stroke only on a small number of items. In addition, most scales operate best in the middle range of stroke severity and have limited value in mild and severe cases. Despite these drawbacks, neurological scores give an earlier and more sensitive response to the outcome of stroke than functional scales. They are powerful prognostic indicators in stroke. Most of them are equivalent, which allows comparison between studies.


[Recurrence and survival rate of advanced gastric cancer after preoperative EAP-II intra-arterial infusion therapy].
Ninety-eight patients with advanced gastric cancers underwent gastrectomy from Jan. 1989 to Dec. 1991. For these patients, preoperative intra-arterial injection therapy using EAP-II (etoposide 100 mg, epirubicin 20 mg, carboplatin 100 mg) was given to 24 patients. In this report, the recurrence and survival rate of these patients were investigated. After curative resection, the survival rate of patients with EAP-II 36 months after operation was 76.9%, while that of patients without EAP-II was 78.6%. There were no significant differences between these two groups. Two peritoneal carcinomatoses and two liver metastases were seen in patients with EAP-II (recurrence rate, 30.7%). Eight recurrences were observed in patients without preoperative injection therapy (peritoneal dissemination, 4; local recurrence, 3; lymph node recurrence, 1). Previously, we reported that drugs were remarkably accumulated in gastric cancer tissue and regional lymph nodes after EAP-II intra-arterial injection therapy. This high accumulation might cause no local or lymph node recurrence was seen in patient with EAP-II. Thus, it was concluded that preoperative EAP-II intra-arterial injection may prevent local and lymph node recurrences, and that further study of the combination and dose of anti-cancer drug needed to improve the postoperative survival rate in advanced gastric cancer patients.


Liquid-liquid phase transition in supercooled yttria-alumina.
The structure and thermal characteristics of aerodynamically levitated samples of yttria-alumina in the liquid, supercooled liquid and solid phases were explored in an extensive series of high energy x-ray diffraction, small angle neutron scattering, and pyrometric cooling measurements. Particular focus was placed on the compound (Y2O3)(x)(Al2O3)(1-x) with x = 0.2 for which a liquid-liquid phase transition at a temperature of 1788 K has recently been reported. No structural or thermal signature in support of this metastable phase transition could be found.


Aeromonas hydrophila Sepsis Associated with Consumption of Raw Oysters.
Introduction. Aeromonas hydrophila is a gram negative bacillus that is native to aquatic environments that is increasingly reported in humans. This case is remarkable for A. hydrophila with an initial presentation of acute pancreatitis. Case Presentation. A 61-year-old male presented to the emergency department with nausea, vomiting, and abdominal pain for two days. His past medical history was significant for alcohol abuse. Initial laboratory examination showed an elevated white blood cell count, elevated lipase, and elevated liver function tests (LFT). Computer tomography (CT) showed peripancreatic inflammatory changes and retroperitoneal free fluid, suggestive of acute pancreatitis. The patient was treated with intravenous (IV) fluids and IV meropenem. After two days, the patient developed sepsis and respiratory failure and was intubated. Blood cultures were positive for Aeromonas hydrophila sensitive to ciprofloxacin which was added to his treatment. Additionally, it was discovered that this patient had recently vacationed in Florida where he consumed raw oysters. He was discharged home on the eighth day of the hospital admission. Conclusion. This is a rare case of A. hydrophila sepsis in an elderly patient with acute pancreatitis and a history of consumption of raw oysters. This case suggests that A. hydrophila can cause disseminated infection in immunocompetent individuals.


Dietary K regulates ROMK channels in connecting tubule and cortical collecting duct of rat kidney.
The activity of ROMK channels in rat kidney tubule cells was assessed as tertiapin-Q (TPNQ)-sensitive current under whole cell clamp conditions. With an external K(+) concentration of 5 mM and an internal K(+) concentration of 140 mM and the membrane potential clamped to 0 mV, TPNQ blocked outward currents in principal cells of the cortical collecting duct (CCD) outer medullary collecting duct and connecting tubule (CNT). The apparent K(i) was 5.0 nM, consistent with its interaction with ROMK. The TPNQ-sensitive current reversed at voltages close to the equilibrium potential for K(+). The currents were reduced when the pipette solution contained ATP. In the CCD, the average TPNQ-sensitive outward current (I(SK)) was 476 +/- 48 pA/cell in control animals on a 1% KCl diet. I(SK) increased to 1,255 +/- 140 pA when animals were maintained on a high-K (10% KCl) diet for 7 days and decreased to 314 +/- 46 pA after 7 days on a low-K (0.1% KCl) diet. In the CNT, I(SK) was 360 +/- 30 pA on control, 1,160 +/- 110 on high-K, and 166 +/- 16 pA on low-K diets. The results indicate that ROMK channel activity is highly regulated by dietary K in both the CCD and the CNT.


Phosphoproteome analysis of HeLa cells using stable isotope labeling with amino acids in cell culture (SILAC).
Identification of phosphorylated proteins remains a difficult task despite technological advances in protein purification methods and mass spectrometry. Here, we report identification of tyrosine-phosphorylated proteins by coupling stable isotope labeling with amino acids in cell culture (SILAC) to mass spectrometry. We labeled HeLa cells with stable isotopes of tyrosine, or, a combination of arginine and lysine to identify tyrosine phosphorylated proteins. This allowed identification of 118 proteins, of which only 45 proteins were previously described as tyrosine-phosphorylated proteins. A total of 42 in vivo tyrosine phosphorylation sites were mapped, including 34 novel ones. We validated the phosphorylation status of a subset of novel proteins including cytoskeleton associated protein 1, breast cancer anti-estrogen resistance 3, chromosome 3 open reading frame 6, WW binding protein 2, Nice-4 and RNA binding motif protein 4. Our strategy can be used to identify potential kinase substrates without prior knowledge of the signaling pathways and can also be applied to profiling to specific kinases in cells. Because of its sensitivity and general applicability, our approach will be useful for investigating signaling pathways in a global fashion and for using phosphoproteomics for functional annotation of genomes.


Comparative evaluation of bioactivity change of crystalline trypsin during compression by chemoinformatics and 2-D Fourier-transform infrared spectroscopy.
The purpose of this study is to develop a method of evaluating the enzymatic activity of trypsin in a solid-state based on Fourier transform infrared (FT-IR) spectra using chemoinformatics and two-dimensional (2-D) correlation spectroscopy. Crystalline trypsin powders are compressed at 0-4000 kg cm-2 by a compression/tension tester. The enzymatic activity of trypsin is assayed by the kinetic degradation method. Spectra of 10 calibration sample sets are recorded 3 times with a FT-IR spectrometer. The maximum intensity of FT-IR spectra and enzymatic activity of trypsin decrease as the compression pressure increases. The FT-IR spectra of trypsin samples are subjected to a principal component regression (PCR). A plot of the calibration data obtained is made between the actual and predicted trypsin activity based on a two-component model with gamma2=0.909 (n=30). The regression vector is almost the same as the loading vector for PC1. On the other hand, a generalized two-dimensional (2-D) correlation spectroscopic method is applied to FT-IR spectra of compressed trypsin. The result is consistent with that of the chemoinformatics method. The FT-IR chemoinformatics method allows for solid-state quantitative analysis of the bioactivity of the bulk powder of a polypeptide drug.


Functional Outcomes After Temporary Bridging With Locking Plates in Lisfranc Injuries.
The standard operative treatment of Lisfranc fracture dislocations currently consists of open reduction and transarticular fixation. Recently, bridge plating has been used more often. Using joint spanning, the reduced fracture dislocation is temporary stabilized to minimize articular damage. The present study describes the outcomes of patients treated with bridge plating after tarsometatarsal fracture dislocations compared with transarticular screw fixation. A retrospective cohort study was performed. Patients with an isolated tarsometatarsal injury who had been treated operatively from June 2000 to October 2013 were included. The primary functional outcome was measured using the American Orthopaedic Foot and Ankle Society midfoot score and the Foot Function Index. The secondary outcome was patient satisfaction, which was measured using the EuroQol 5 dimensions questionnaire and a visual analog scale. A total of 34 patients were included. Bridge plating was used in 21 patients. In 13 patients, Kirschner wires or transarticular screws or a combination were used. The median follow-up period was 49 (interquartile range 18 to 89) months. The implants were removed in 10 of 13 patients in the transarticular group and 17 of 21 patients in the bridge plating group. The incidence of wound complications was comparable in both groups. The median American Orthopaedic Foot and Ankle Society score was lower in the transarticular group (77 versus 66). The Foot Function Index score was 18 in both groups. Patient satisfaction was 90% in the bridge plating group and 80% in the transarticular group. Bridge plating for Lisfranc injuries led to at least similar results compared with transarticular fixation in terms of functional outcomes and patient satisfaction. Longer follow-up is necessary to determine whether the prevention of secondary damage to the articular surface leads to less post-traumatic arthritis and better functional outcomes.


Hip fracture incidence in Lund, Sweden, 1966-1986.
The hip fracture incidence in the city of Lund and its rural surroundings was studied for the years 1966, 1972, 1981, and 1986. The total incidence increased from 3.3 to 5.1 per 1,000 inhabitants above 50 years of age. For persons more than 80 years old, the incidence almost doubled from 13.2 to 25.5, i.e., this group represented the entire increase in incidence. In the urban population, men with cervical fractures had an increased incidence. A smaller increase in incidence for both men and women was found in the rural area. Compared with larger cities, the incidence increase in the urban population in Lund was lower over time, but in 1986 the figures were comparable to those in Gothenburg in 1981. The total incidence in the mixed urban and rural population was as of 1981 higher than in Denmark and Finland, but lower than in Norway. If the incidence in the elderly continues to increase to 1995, there will be three times as many hip fractures as there were in 1966.


Heterogeneous distribution of monomeric elements from the globular domain (NC1) of type IV collagen in renal basement membranes as revealed by high resolution quantitative immunocytochemistry.
Heterogeneity in the distribution of major components, namely laminin, entactin/nidogen, heparan sulfate proteoglycan and type IV collagen among renal basement membranes, was previously demonstrated (Desjardins and Bendayan, J Histochem Cytochem 37:885-897, 1989). To further investigate the nature of basement membranes, we applied high resolution immunocytochemistry to reveal monomers M1, M2* and M3 composing the NC1 domain of type IV collagen of various rat renal basement membranes. Labeling for the three monomers was confined to basement membranes. Quantitative morphometrical analysis demonstrated that the labeling for each monomer was not evenly distributed among the various basement membranes. Labeling for M1 was intense over the proximal tubule and the Bowman's capsule basement membranes. In the glomerulus, the mesangial matrix was highly labeled, whereas the glomerular basement membrane was labeled with a lower intensity. In contrast, labeling for M2* and M3 were high in the glomerular basement membrane, while very low in the mesangial matrix. Labeling intensities were intermediate in the other renal basement membranes. The ultrastructural distribution analysis made over the glomerular basement membrane showed a preferential subendothelial localization of M1 monomers. M2 and M3 on the other hand, were found throughout the entire thickness of the basement membrane. M1 monomers being associated to alpha 1(IV) and alpha 2(IV) chains of type IV collagen, and M2* and M3 to alpha 3(IV) and alpha 4(IV) chains respectively, our results thus demonstrate the existence of an heterogeneity in the collagenous nature of renal basement membranes, particularly the glomerular one. This heterogeneity must reflect variations in the structural arrangement of basement membranes and therefore in their functional properties.


Substance P in the ventrolateral medulla oblongata regulates ventilatory responses.
Local injection of substance P (SP) into the ventral portion of the nucleus gigantocellularis, nucleus reticularis lateralis, and nucleus retrofacialis of the ventrolateral medulla oblongata (VLM) or direct application on the ventral surface of the medulla oblongata caused marked stimulation of tidal volume (VT) and/or minute ventilation (VE). The ventilatory response to hypoxia was significantly blunted after SP in the VLM but not in the dorsal medulla oblongata (DM) (nucleus tractus solitarius). The SP antagonist [D-Pro2,D-Trp7,9]SP almost completely inhibited this response when applied locally to a wide area of the superficial layer of the VLM but not of the DM. Unilateral or bilateral application of 0.3-1.5 nmol of the SP antagonist in the VLM (corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment) markedly attenuated the response to a 5% CO2 inhalation. The inhibition of the CO2 response was seen after [D-Pro2,D-Trp7,9]SP in the rostral areas of the medulla oblongata corresponding to the corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment of the cervical cord. Electric somatosensory-induced ventilatory stimulation could be depressed by approximately 70% by [D-Pro2,D-Trp7,9]SP locally applied on the surface of the VLM. We conclude that SP is involved in the hypoxic, hypercapnic, and somatosensory ventilatory responses in the rat. However, these respiratory reflexes are mediated via different neuronal pools in the medulla oblongata, mainly the VLM.


Magnetic Nanomaterials and Their Applications.
This Special Issue of Nanomaterials is dedicated to the development of new magnetic nanomaterials and their applications in biomedicine, catalysis, spintronics and other areas. The publications in this Issue demonstrate that the interest in magnetic nanomaterials is continuously growing and their realm is expanding rapidly. Some highlights of the publications in this issue are discussed below. [...].


Overexpression of mir-183 and mir-494 promotes proliferation and migration in human breast cancer cell lines.
Breast cancer (BC) is a leading cause of cancer-associated mortality in females worldwide. MicroRNAs (miRNAs or miRs), a type of non-coding RNA, have been reported to be important in the regulation of BC onset and progression. Several studies have implicated the role of miR-183 and miR-494 in different types of cancer. However, the biological functions of these miRNAs in BC remain largely unknown. In the present study, the expression of both miRNAs was assessed in the MDA-MB-231 and MDA-MB-468 BC cell lines. It was hypothesized that miR-183 and miR-494 serve an important role in regulating the expression of key genes associated with the metastatic phenotype of BC cells. To further understand their role, the expression of these miRNAs was restored in selected BC cell lines. Functional assays revealed that overexpression of miR-183 or miR-494 modulated the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells in vitro. Additionally, retinoblastoma 1 (RB1) was identified to be a downstream target of both miRNAs by in silico analysis. Western blotting revealed that upregulation of miR-183 was associated with downregulation of RB1 protein in MDA-MB-231 cells. In conclusion, the present results support the hypothesis that miR-183 and miR-494 serve a pivotal role in BC metastasis, and that miR-183 may act as an oncogene by targeting RB1 protein in MDA-MB-231 cells.


Patterns of physical activity and metabolic syndrome among adult Koreans: a cross sectional study.
The purpose of this study was to determine whether leisure time physical activity (PA) affects risk for developing metabolic syndrome (MetS) among Korean adults. We studied 1728 Korean adults over age 20 years who visited a public health promotion center in Seoul, Korea. All subjects completed an International Physical Activity Questionnaire, and were examined for MetS criteria as defined by National Cholesterol Education Program's Adult Treatment Panel III criteria. The association between PA and MetS was assessed using multivariate logistic regression analysis. The odds ratios (95% confidence interval) for having MetS and engaging in vigorous PA, moderate PA or light PA (walking) compared with having MetS and not engaging in vigorous PA, moderate PA or light PA (walking) were 0.482 (0.322-0.721, p < 0.001), 0.547 (0.370-0.810, p = 0.003) and 0.482 (0.318-0.731, p < 0.001) for PA once a week; 0.763 (0.468-1.243, p = 0.277), 0.697 (0.419-1.160, p = 0.165) and 0.674 (0.403-1.128, p = 0.134) for PA twice a week; 0.449 (0.248-0.815, p = 0.008), 0.568 (0.338-0.954, p = 0.033) and 0.451 (0.260-0.780, p = 0.004) for PA 3 times a week; 0.321 (0.123-0.835, p = 0.020), 0.737 (0.362-1.502, p = 0.401) and 0.411 (0.185-0.916, p = 0.030) for PA 4 times a week; and 0.216 (0.064-0.727, p = 0.013), 0.390 (0.166-0.915, p = 0.031) and 0.318 (0.181-0.558, p < 0.001) for PA 5 or more times a week, respectively. These findings indicate vigorous PA, moderate PA and light PA may reduce the risk of MetS among Korean adults.


Advantages and disadvantages of using human cells for pharmacological and toxicological studies.
1. Marked species differences in the distribution and affinity of drug receptors, and in the patterns of biotransformation and susceptibility to the toxicity of xenobiotics, provide the impetus for using human tissues for pharmacological and toxicological studies. 2. Studies with intact cells facilitate the correlation of xenobiotic metabolism with cellular indices of toxicity, which can provide the mechanistic basis for understanding species differences in toxicity. 3. Human cells in suspension or primary culture reflect the variability in susceptibility to toxicity in a population. 4. The current limitation to these studies is scarcity of human material, the need for improved (cryo)preservation techniques for human hepatocytes/precision-cut slices and difficulties in predicting in vivo exposure-risk relationships from in vitro dose-response relationships.


Spatiotemporal change of sky polarization during the total solar eclipse on 29 March 2006 in Turkey: polarization patterns of the eclipsed sky observed by full-sky imaging polarimetry.
Using 180 degrees field-of-view (full-sky) imaging polarimetry, we measured the spatiotemporal change of the polarization of skylight during the total solar eclipse on 29 March 2006 in Turkey. We present our observations here on the temporal variation of the celestial patterns of the degree p and angle alpha of linear polarization of the eclipsed sky measured in the red (650 nm), green (550 nm), and blue (450 nm) parts of the spectrum. We also report on the temporal and spectral change of the positions of neutral (unpolarized, p = 0) points, and points with local minima or maxima of p of the eclipsed sky. Our results are compared with the observations performed by the same polarimetric technique during the total solar eclipse on 11 August 1999 in Hungary. Practically the same characteristics of celestial polarization were encountered during both eclipses. This shows that the observed polarization phenomena of the eclipsed sky may be general.


The alterations of innate immunity and enhanced severity of infections in diabetes mellitus.
Diabetes mellitus (DM) is a metabolic inflammatory disease with a high incidence worldwide. Patients with DM are at a high risk for all types of infections. Type 1 DM is characterised with immune destruction of pancreatic β cells, while type 2 diabetes is characterised with insulin resistance and β cell dysfunction, both of which result in disorders of glucose and lipid metabolism. This metabolic disorder causes functional defects of immune cells, aberrant production of inflammatory cytokines, dysregulated immune responses, advanced pathophysiological injury of the body, and increased mortality in populations with DM upon infections. Starting with the change of natural immune system in patients with DM, this paper focused on the enhanced severity of infections in DM and the underlying innate immune alterations in preclinical and clinical studies, aiming to better understand the influence of DM on the susceptibility, pathophysiology, and clinical outcomes in infections.


Improved Protein Toxin Delivery Based on ATTEMPTS Systems.
Ribosome-inactivating proteins (RIPs) are wildly found in multiple species of plants, bacteria and fungi. As a special family of protein toxins, RIPs can inhibit protein synthesis and induce cell death via inactivating ribosome in eukaryotic cells. Thus, RIPs have been applied for anti-tumor therapy in the past two decades. However, because of poor cell permeability, nonselective mode of action for tumor cells, poor pharmacokinetic profiles and immunogenicity, their clinical application has been severely constrained. As an effort to overcome these obstacles, tumor-specific monoclonal antibodies (mAb) have been conjugated to RIPs (forming so called "immunotoxins") specifically to increase their cytotoxicity and provide tumor targeting. Nevertheless, immunotoxins yet have not fully resolved all the issues and critical challenges still remain, such as immunogenicity and inability to penetrate into the deep site of tumor. To overcome the constrain of immunotoxins, the novel cell-penetrating peptide (CPP)- modified ATTEMPTS systems based on combination of CPP-mediated penetration and antibodymediated tumor targeting, with triggerable drug release function, were developed to achieve effective and safe delivery of protein toxin. The CPP-modified ATTEMPTS systems showed effective protamine-triggered CPP-toxin release and thus enhanced CPP-mediated cellular uptake and cytotoxicity. It also showed antibodymediated in vivo tumor targeting and significantly increased in vivo tumor growth suppression with limited systematic toxicity. The CPP-modified ATTEMPTS systems were developed and demonstrated as a proof-ofconcept for CPP-based protein toxin delivery with triggerable antibody targeting to improve the druggability of protein toxin drugs. The systems showed the potential application of protein toxin clinical translation in anticancer treatment.


Preventing the onset of depressive disorders in low-and middle-income countries: An overview.
Depressive disorders constitute an important and costly public health problem and worldwide most of the disease burden is suffered in low-and middle-income countries (LMICs). Treatments only have limited possibilities to reduce the disease burden of depressive disorders. Prevention may be one of the alternative ways to further reduce the disease burden of depressive disorders. In this paper, the results of a subgroup analysis of a previous meta-analysis on the effect of preventive interventions on the incidence of depressive disorders was undertaken. Only 6% of all trials examining the possibility to prevent the onset of major depression have been conducted in LMICs, and these studies find significantly smaller effects than those in high-income settings. It is too early, therefore, to consider implementing and disseminating preventive interventions in LMICS. However, in optimal conditions and assuming that evidence-based preventive interventions will be developed, investments should be made into treatment, universal, selective and indicated prevention, as well as in social institutions focusing on larger risk factors for mental health problems.


Promoting pneumococcal immunizations among rural Medicare beneficiaries using multiple strategies.
Vaccine-preventable diseases among adults are major contributing causes of morbidity and mortality in the United States. However, adult immunizations continue to be underutilized in both urban and rural areas. To evaluate the effectiveness of a community-wide education campaign and mailed reminders promoting pneumococcal immunizations to rural Medicare beneficiaries. We implemented a community-wide education campaign, and mailed reminders were sent to Medicare beneficiaries in 1 media market in Montana to increase pneumococcal immunizations. In a second distinct media market, mailed reminders only were sent to beneficiaries. The proportion of respondents aged 65 years and older aware of pneumococcal immunizations increased significantly from baseline to follow-up among respondents both in the education-plus-reminder (63% to 78%, P = 0.04) and the reminder-only (64% to 74%, P = 0.05) markets. Overall from 1998 to 1999, there was a 3.7-percentage-point increase in pneumococcal immunization claims for Medicare beneficiaries in the education-plus-reminder market and a 1.5-percentage-point increase in the reminder-only market. Medicare beneficiaries sent reminders in the education-plus-reminder market compared to those in the reminder-only market were more likely to have a claim for pneumococcal immunization in 1999 (odds ratio 1.18, 95% confidence interval 1.08 to 1.28). The results suggest that these quality improvement strategies (community education plus reminders and reminders alone) modestly increased pneumococcal immunization awareness and pneumococcal immunization among rural adults. Mailed reminder exposure was associated with an increased prevalence of pneumococcal immunizations between 1998 and 1999 and was augmented somewhat by the education campaign.