Suspensions of healthy and pathological red blood cells (RBC) flowing in microfluidic devices are frequently used to perform in vitro blood experiments for a better understanding of human microcirculation hemodynamic phenomena. This work reports the development of particulate viscoelastic analogue fluids able to mimic the rheological and hemorheological behavior of pathological RBC suspensions flowing in microfluidic systems. The pathological RBCs were obtained by an incubation of healthy RBCs at a high concentration of glucose, representing the pathological stage of hyperglycaemia in diabetic complications, and analyses of their deformability and aggregation were carried out. Overall, the developed in vitro analogue fluids were composed of a suspension of semi-rigid microbeads in a carrier viscoelastic fluid made of dextran 40 and xanthan gum. All suspensions of healthy and pathological RBCs, as well as their particulate analogue fluids, were extensively characterized in steady shear flow, as well as in small and large amplitude oscillatory shear flow. In addition, the well-known cell-free layer (CFL) phenomenon occurring in microchannels was investigated in detail to provide comparisons between healthy and pathological in vitro RBC suspensions and their corresponding analogue fluids at different volume concentrations (5% and 20%). The experimental results have shown a similar rheological behavior between the samples containing a suspension of pathological RBCs and the proposed analogue fluids. Moreover, this work shows that the particulate in vitro analogue fluids used have the ability to mimic well the CFL phenomenon occurring downstream of a microchannel contraction for pathological RBC suspensions. The proposed particulate fluids provide a more realistic behavior of the flow properties of suspended RBCs when compared with existing non-particulate blood analogues, and consequently, they are advantageous for detailed investigations of microcirculation.

The endothelial glycocalyx is a complex network of glycoproteins, proteoglycans, and glycosaminoglycans; it lines the vascular endothelial cells facing the lumen of blood vessels forming the endothelial glycocalyx layer (EGL). This study aims to investigate the microvascular hemodynamics implications of the EGL by quantifying changes in blood flow hydrodynamics post-enzymatic degradation of the glycocalyx layer. High-speed intravital microscopy videos of small arteries (around 35 μm) of the rat cremaster muscle were recorded at various time points after enzymatic degradation of the EGL. The thickness of the cell free layer (CFL), blood flow velocity profiles, and volumetric flow rates were quantified. Hydrodynamic effects of the presence of the EGL were observed in the differences between the thickness of CFL in microvessels with an intact EGL and glass tubes of similar diameters. Maximal changes in the thickness of CFL were observed 40 min post-enzymatic degradation of the EGL. Analysis of the frequency distribution of the thickness of CFL allows for estimation of the thickness of the endothelial surface layer (ESL), the plasma layer, and the glycocalyx. Peak flow, maximum velocity, and mean velocity were found to statistically increase by 24, 27, and 25%, respectively, after enzymatic degradation of the glycocalyx. The change in peak-to-peak maximum velocity and mean velocity were found to statistically increase by 39 and 32%, respectively, after 40 min post-enzymatic degradation of the EGL. The bluntness of blood flow velocity profiles was found to be reduced post-degradation of the EGL, as the exclusion volume occupied by the EGL increased the effective volume impermeable to RBCs in microvessels. This study presents the effects of the EGL on microvascular hemodynamics. Enzymatic degradation of the EGL resulted in a decrease in the thickness of CFL, an increase in blood velocity, blood flow, and decrease of the bluntness of the blood flow velocity profile in small arterioles. In summary, the EGL functions as a molecular sieve to solute transport and as a lubrication layer to protect the endothelium from red blood cell (RBC) motion near the vessel wall, determining wall shear stress.

Clopidogrel (CP) is metabolized by CYPs to the active metabolite, or hydrolyzed by esterase to clopidogrel carboxylate (CPC) in liver, and CPC is partly excreted from urine. Therefore, the objective of the present study was to evaluate the interactions of CP and CPC with organic cation transporter 1 (OCT1) (in liver), and CPC with organic cation transporter 2 (OCT2) and organic anion transporter 1 (OAT1) (in kidney). Both CP and CPC inhibited the uptake of 1-methyl-4-phenylpyridinium (MPP(+)) and metformin, typical substrates of OCT1, in MDCK-hOCT1 cells with low IC₅₀ (0.307-14.0 μM). CPC (100 μM) reduced the uptake of MPP(+) and metformin mediated by OCT2 in MDCK-hOCT2 cells to 60.8% and 33.6% of the control, CPC (500 μM) decreased the uptake of 6-carboxyfluorescein (6-CFL) and para-aminohippuric acid (PAH), substrates of OAT1, in MDCK-hOAT1 cells to 64.6% and 79.4% of the control. CP and CPC were also found to inhibit other drugs of OCT1 substrates, such as lamivudine and amantadine, in MDCK-hOCT1 cells with the IC₅₀ of 1.97-4.15μM, except CPC on amantadine (IC₅₀>100 μM). The inhibition of CP and CPC on lamivudine uptake in primary rat hepatocytes was also confirmed with the IC₅₀ of 2.91 and 1.25μM, respectively. Additionally, CP and CPC were not substrates of OCT1 and OCT2, whereas CPC was a substrate of OAT1 with the Km of 5.61 μM. In conclusion, CP and CPC are strong inhibitors of OCT1, but weak inhibitors of OCT2 and OAT1, and CPC is a high affinity substrate of OAT1.

This article describes a surgical technique for reconstruction of the unstable ankle that uses a modification of the Elmslie procedure for anatomic augmentation of the anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL). Our technique is an anatomic reconstruction that uses a free graft of the gracilis tendon toreconstruct the CFL and A TFL.

A major challenge in developing anticancer therapies is determining the efficacies of drugs and their combinations in physiologically relevant microenvironments. We describe here our application of "constrained fuzzy logic" (CFL) ensemble modeling of the intracellular signaling network for predicting inhibitor treatments that reduce the phospho-levels of key transcription factors downstream of growth factors and inflammatory cytokines representative of hepatocellular carcinoma (HCC) microenvironments. We observed that the CFL models successfully predicted the effects of several kinase inhibitor combinations. Furthermore, the ensemble predictions revealed ambiguous predictions that could be traced to a specific structural feature of these models, which we resolved with dedicated experiments, finding that IL-1α activates downstream signals through TAK1 and not MEKK1 in HepG2 cells. We conclude that CFL-Q2LM (Querying Quantitative Logic Models) is a promising approach for predicting effective anticancer drug combinations in cancer-relevant microenvironments.

BACKGROUND

A lateral ankle sprain is one of the most frequent reasons for consultation at the emergency trauma unit. Numerous surgical procedures have been described with long-term outcomes that differ.

OBJECTIVE

The long-term results of anatomical repair of the anterior talofibular ligament (ATFL) and the calcaneofibular (CFL) ligament are better, with less secondary radiological osteoarthritis than non-anatomical repair.

METHODS

A review of the literature after a minimum follow-up of 10 years was performed to analyze the clinical and radiological results of direct anatomical repair (Broström, Duquennoy) and non-anatomical repair (Watson Jones, Evans, Castaing). Thirteen articles were selected.

RESULTS

Eight hundred and one ankles were evaluated after a mean follow-up of 15.3 years. The functional outcome was better after anatomical repair but with recurrent instability. Loss of range of motion and secondary osteoarthritis was more frequent after non-anatomical repair.

CONCLUSIONS

Anatomical repair of the lateral collateral ligament of the ankle resulted in a better functional outcome and less secondary osteoarthritis than non-anatomical repair.

METHODS

Review of the literature; level of proof IV.

From a previous field investigation in Yunnan, southwest China between 2001 and 2015, we selected two types of landscapes to make a retrospectively comparative study on the distribution of small mammals and their ectoparasitic chigger mites. One landscape is "mountainous uncultivated land (MUL)" with higher biodiversity, which is located in a famous "World Nature Heritage Site", the Three-Parallel-Rivers Region in the northwest of Yunnan. The other is "cultivated flatland landscape (CFL)" with lower biodiversity, which is located in the south of Yunnan. The landscapes with different biodiversity apparently influenced the distribution of small mammals and their ectoparasitic chigger mites. Much more species of small mammals and mites were found in MUL than in CFL. A total of 3,177 small mammals captured from MUL were identified as 55 species, 30 genera and 10 families in five orders. From these small mammal hosts, 5,882 chigger mites were collected and identified as 127 species, 15 genera and 3 subfamilies in two families. A total of 1,112 small mammals captured from CFL were identified as 19 species, 12 genera and 5 families in three orders. From these hosts, 17,742 chiggers were collected and identified as 86 species, 12 genera and 3 subfamilies in two families. Both the species diversity (S = 55) and community diversity (H = 2.673) of small mammals in MUL were much higher than those in CFL (S = 19; H = 0.926). There were also higher values of β diversity in MUL than in CFL. Different main reservoir rodent hosts of zoonoses (including tsutsugamushi disease) were found in two types of landscapes. Rattus tanezumi (one main reservoir host) was most abundant in CFL, which accounted for 80.22% of all the small mammals. Another two main reservoir hosts, Eothenomys miletus and Apodemus chevrieri were the dominant species in MUL, but they were not as abundant as R. tanezumi in CFL. Different vector species of chigger mites also existed in MUL and CFL. Leptotrombidium deliense (a main and powerful vector of tsutsugamushi disease in China) and Ascoschoengastia indica (a potential vector of tsutsugamushi disease) were the dominant species of chigger mites in CFL (Cr = 25.81% for A. indica; Cr = 23.47% for L. deliense). Leptotrombidium scutellare (also a main vector of tsutsugamushi disease in China) was the dominant chigger species in MUL (Cr = 26.09%). Higher infestation of vector mites on small mammals was found in the simple landscape with lower biodiversity (CFL) than in the complex landscape with higher biodiversity (MUL). The overall prevalence (P), mean abundance (MA) and mean intensity (MI) of chigger mites on small mammals were much higher in CFL than in MUL. The main vector mite species on their main rodent hosts also showed a higher P, MA and MI in CFL than in MUL.

The aim of this study was to identify candidate single-nucleotide polymorphisms (SNPs) that might play a role in susceptibility to neuroblastoma, elucidate their potential mechanisms, and generate SNP-to-gene-to-pathway hypotheses. A genome-wide association study (GWAS) dataset of neuroblastoma that included 442,976 SNPs from 1,627 neuroblastoma patients and 3,254 control subjects of European descent was used in this study. The identify candidate causal SNPs and pathways (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 15 candidate SNPs, 10 genes, and 31 pathways, which revealed 10 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was one wherein SNPrs40401 modulates the role of IL3 in several pathways and conditions, including the stem pathway, asthma (hsa05310), the dendritic cell pathway, and development (0.001 < p < 0.004; 0.001 < FDR < 0.033). The second strongest mechanism identified was that in which rs1048108 and rs16852600 alter the function of BARD1, which negatively regulates developmental process and modulates processes including cell development and programmed cell death (0.001 < p < 0.004; 0.001 < FDR < 0.033). The third mechanism identified was one wherein rs1939212 modulated CFLCFL, and 31 pathways were identified that might contribute to the susceptibility of patients to neuroblastoma.

Canavalia ensiformis (ConA), Canavalia brasiliensis (Conbr), and Cratylia floribunda (CFL) lectins have exhibited glucose-mannose binding specificity. We investigated the effect of fetal bovine serum (FBS) concentrations (1, 5, 10, and 20%) on the cytotoxic effect of these lectins against breast tumor cell line MCF-7. Cell viability was examined using the MTT reduction assay. When cells were grown in a medium supplemented with a higher serum concentration (10 or 20%), all lectins were much less toxic. When we used 1% FBS, it was possible to achieve a concentration-dependent activity by all examined lectins, with an IC(50) of 3.5, 25, and 60 µg/mL for ConA, Conbr, and CFL, respectively. All lectins incubated with 1% FBS induced apoptosis and DNA damage in MCF-7 cells. We conclude that ConA, Conbr, and CFL lectins' cytotoxic and genotoxic effects were observed only at low concentrations of serum.

BACKGROUND

This is the third study in a Phase 3 program evaluating onabotulinumtoxinA treatment of crow's feet lines (CFL).

OBJECTIVE

To assess the efficacy and safety of repeated onabotulinumtoxinA treatments of CFL alone or with glabellar lines (GL) in subjects with moderate-to-severe CFL and GL (maximum smile).

METHODS

This 5-month extension of a 7-month study randomized subjects who originally received onabotulinumtoxinA 24 U (CFL only; n = 227) or 44 U (24 U for CFL + 20 U for GL; n = 260) to retreatment with the same dose. Placebo-treated subjects were rerandomized to onabotulinumtoxinA 44 U (n = 101) or placebo (n = 96). Primary efficacy end point (Day 30) was the proportion of subjects who achieved a CFL severity rating of none or mild (maximum smile) on the investigator-assessed Facial Wrinkle Scale (FWS). Additional efficacy end points and adverse events were evaluated.

RESULTS

Responder rates (primary end point) were significantly greater in onabotulinumtoxinA-treated groups (24 U: 56.5%; 44 U: 63.6%; placebo: 1.1%; p < .001). Improvements on most patient-reported outcomes (PROs) favored the 44-U group over the 24-U group. Adverse events did not differ among groups; most were mild or moderate.

CONCLUSIONS

Repeated onabotulinumtoxinA treatments significantly reduce CFL severity based on FWS and PROs. Adverse event profiles remain consistent with approved GL labeling.

BACKGROUND

Cycling masticatory loads decrease the strength of particulate filler composites (PFCs) and initiate the failure process by fatigue. The life expectancy of a composite resin restoration under stress remains difficult to predict.

OBJECTIVE

The purpose of this study was to determine the fracture resistance and the compressive fatigue limits (CFL) of anterior crown restorations made of a short-fiber reinforced composite resin (SFC), to investigate selected mechanical properties of the material following standard test methods, and to observe their correlation with the CFL.

METHODS

Specimens (n=10) were fabricated either from SFC (everX Posterior, GC Corp) or PFC (G-ænial anterior, GC Corp). The properties investigated were flexural strength (FS), compression strength (CS), diametral-tensile strength (DTS), and single-edge-notched-bend fracture toughness (FT) following ISO standards. Fracture resistance was determined by static load (n=10) and the CFL at 10000 cycles was determined using a staircase approach (n=20), both on anterior composite resin crowns. The results were analyzed with 1-way ANOVA (α=.05) or 2-way ANOVA (α=.05) followed by a Tukey B post hoc test and the Pearson-correlation analysis.

RESULTS

The SFC crowns had higher fracture resistance (954 ±121 N) than the PFC crowns (415 ±75 N) (P<.001) and higher CFL (267 ±23 N) than the PFC crowns (135 ±64 N) (P<.001). SFC revealed also higher FT (2.6 ±0.6 MPa·m(1/2)) than the PFC (1.0 ±0.2 MPa·m(1/2)) (F=69.313, P<.001). A significant correlation was observed only between the FT and the CFL (r(2)=0.899; P<.001).

CONCLUSIONS

SFC crowns showed good performance under static and fatigue loading. FT was the only in vitro test method that filtered as a clinically relevant parameter.

OBJECTIVE

5-Fluorouracil (5-FU) plus cisplatin (C) can be considered a standard option for advanced gastric cancer (AGC). Irinotecan (Ir) and docetaxel (D) are active agents with no complete cross-resistance with C and 5-FU. Concomitant combination of Ir or D with C and 5-FU is feasible, but with substantial toxicities. A different way to include all active agents in first-line treatment of AGC may be to use them sequentially. We aimed to evaluate the activity and the safety profile of sequential chemotherapy with 5-FU-based doublets with C, Ir and D in the first-line treatment of AGC.

METHODS

We conducted a phase II study of first-line sequential chemotherapy in metastatic GC. Treatment consisted of 3 cycles of C + infused 5-FU and leucovorin (CFL) followed by 3 cycles of Ir + 5-FU/LV (IrFL) followed by 3 cycles of D + 5-FU/LV (DFL). Primary end-point was response rate.

RESULTS

Forty-six patients were enrolled, median age 60 years, sites of disease (single/multiple) = 9/37, PS 0/1 = 27/19, gastric/gastro-oesophageal junction = 39/7. Median number of cycles was 9. Main grade 3-4 toxicities were neutropenia (37%), febrile neutropenia (2%), diarrhoea (4%), stomatitis (9%). Response rate after the planned 9 cycles was 45% (15 partial and 5 complete responses among 43 evaluable patients). Median PFS and OS: 6.8 and 11.1 months, respectively.

CONCLUSIONS

This sequential treatment is feasible with a favourable safety profile and produced encouraging results in terms of activity and efficacy.

BACKGROUND

The traditional Brostrom repair and the modified Brostrom-Gould repair are 2 historically reliable procedures used to address lateral ankle instability. The purpose of this study was to evaluate the biomechanical stability conferred by the Brostrom repair as compared to the Brostrom-Gould modification in an unstable cadaveric ankle model.

METHODS

A total of 10 cadaveric specimens were placed in a Telos ankle stress apparatus in an anterior-posterior position and then in a lateral position, while a 170 N load was applied to simulate anterior drawer (AD) and talar tilt (TT) tests, respectively. In both circumstances, the ankle was held in 15 degrees of plantarflexion, neutral, and 15 degrees of dorsiflexion, while the movement of the sensors was measured using a video motion analysis system. Measurement of the translation between the talus and tibia in the AD test and the angle between the tibia and talus in the TT test were calculated for specimens in the (1) intact, (2) sectioned (division of the ATFL and CFL), (3) Brostrom repair and (4) Gould modification states.

RESULTS

When compared to both the repaired states and the intact states, the sectioned state demonstrated increased inversion and translation at all ankle positions during TT and AD testing. Furthermore, no significant differences were found between the intact state and either of the repaired states. Finally, no difference in the biomechanical stability could be identified between the traditional Brostrom repair and the modified Brostrom-Gould procedure.

CONCLUSIONS

Our findings indicate that there is no significant biomechanical difference in initial ankle stability conferred by augmenting the traditional Brostrom repair with the Gould modification in this time-zero cadaveric model.

CONCLUSIONS

These data suggest that the additional reinforcement of an ankle's lateral ligament complex repair of the ankle with the inferior extensor retinaculum may be marginal at the time of surgery.

BACKGROUND

Recently, studies have reported that protein glycosylation plays an important role in the occurrence and development of cancer. Gastric cancer is a common cancer with high morbidity and mortality owing to most gastric cancers are discovered only at an advanced stage. Here, we aim to discover novel specific serum glycanbased biomarkers for gastric cancer.

METHODS

A lectin microarray with 50 kinds of tumor-associated lectin was used to detect the glycan profiles of serum samples between early gastric cancer and healthy controls. Then lectin blot was performed to validate the differences.

RESULTS

The result of the lectin microarray showed that the signal intensities of 13 lectins showed significant differences between the healthy controls and early gastric cancer. Compared to the healthy, the normalized fluorescent intensities of the lectins PWA, LEL, and STL were significantly increased, and it implied that their specifically recognized GlcNAc showed an especially elevated expression in early gastric cancer. Moreover, the binding affinity of the lectins EEL, RCA-II, RCA-I, VAL, DSA, PHA-L, UEA, and CAL were higher in the early gastric cancer than in healthy controls. These glycan structures containing GalNAc, terminal Galβ 1-4 GlcNAc, Tri/tetraantennary N-glycan, β-1, 6GlcNAc branching structure, α-linked fucose residues, and Tn antigen were elevated in gastric cancer. While the two lectins CFL GNL reduced their binding ability. In addition, their specifically recognized N-acetyl-D-galactosamine structure and (α-1,3) mannose residues were decreased in early gastric cancer. Furthermore, lectin blot results of LEL, STL, PHA-L, RCA-I were consistent with the results of the lectin microarray.

CONCLUSIONS

The findings of our study clarify the specific alterations for glycosylation during the pathogenesis of gastric cancer. The specific high expression of GlcNAc structure may act as a potential early diagnostic marker for gastric cancer.

The 2008 EU regulation, which prohibits conventional incandescent light bulbs, is to be implemented in phases, completing in 2012. One of the possible substitutes is the compact fluorescent lamp (CFL), which, however, does contain up to 5 mg of mercury in its elemental or amalgamated form. The question arises as to the possible exposure of individuals to mercury as a result of lamp breakage during operation or when disconnected from the power supply. Therefore, an apparatus was built to shatter CFLs and drop the shards onto glycol-modified polyethylene terephthalate, a carpeted floor, or laminate floor under defined climatic parameters and operating conditions. Six CFLs of different types and mercury content were studied. After the breakage of a common CFL containing liquid mercury, concentrations up to 8000 ng/m(3) were reached in the chamber. Much lower peak values were obtained with amalgam-type lamps (414 ng/m(3)) or with lamps with a shatter-proof coating (60 ng/m(3)). It was found that ventilation can considerably reduce the indoor air concentration within 20 min. Acute health effects would only be expected if the mercury is not removed immediately. Careful collection and disposal of the lamp fragments would also prevent dwellers from the risk of long-term exposure.

CONCLUSIONS

After accidental breakage of a compact fluorescent lamp (CFL) indoors, dwellers could be exposed to high mercury concentrations. From the results of our studies in test chambers and real rooms using different lamp types and scenarios, it was possible to estimate the possible human uptake of mercury by inhalation. Immediate action is important to reduce indoor mercury concentrations to a minimum level. The first step is to maximize ventilation followed by careful collection of spilled mercury.

Lateral canthal lines or crow's feet lines (CFL) may be treated with onabotulinumtoxinA. We identified several key concepts important to understanding the use of onabotulinumtoxinA for treatment of moderate-to-severe CFL. To contextualize and integrate data on the recommended dose and injection patterns of onabotulinumtoxinA for treatment of CFL, we summarized data from pivotal clinical studies in the development of onabotulinumtoxinA for treatment of CFL. Data from key studies of onabotulinumtoxinA for CFL are presented. The efficacy and safety of onabotulinumtoxinA treatment of moderate-to-severe CFL were evaluated in 2 randomized, controlled phase 3 studies comprising 1362 patients. The 24U total dose of onabotulinumtoxinA used in these studies was based on a phase 2 dose-ranging trial. Two injection patterns were available to investigators; each involved 3 injection sites per side in the lateral orbicularis oculi muscle. A cross-sectional analysis of photographs from the phase 3 trials provided detailed information on the frequency of 4 distinct CFL patterns. In the primary efficacy analysis for each phase 3 trial, CFL responder rates were significantly greater with onabotulinumtoxinA vs placebo at day 30 (P< .001). Eyelid edema (1%) was the only adverse event reported in ≥ 1% of patients receiving onabotulinumtoxinA, occurring more frequently with onabotulinumtoxinA than with placebo. The studies showed that onabotulinumtoxinA is effective and generally well-tolerated for CFL treatment. Additionally, 2 different injection patterns allow physicians to tailor treatment based on a patient's CFL pattern.

BACKGROUND

Patterns of crow's feet lines (CFLs) vary among individuals.

OBJECTIVE

To characterize distribution and predictors of CFL patterns.

METHODS

Patterns of CFLs (full fan, lower fan, central fan, and upper fan) were evaluated at maximum smile and at rest from photographs of subjects with moderate-to-severe CFLs. Relationships between CFL pattern and severity, age, gender, and subject-reported outcomes were explored.

RESULTS

Evaluations of 2,699 photographs from 1,392 subjects were conducted; 1,389 and 1,310 had evaluable CFL patterns at maximum smile and at rest, respectively. Lower-fan, central-fan, and full-fan patterns were identified in 28.4% to 34.7% at maximum smile and 27.7% to 33.9% at rest; upper fan was found in ∼5%. The pattern distribution of CFLs demonstrated a relationship to baseline CFL severity, age, and gender; full-fan and lower-fan patterns were more common in severe versus moderate CFL at maximum smile; full fan increased with age. Lower fan was more common in males. Subjects with full fan at maximum smile were most dissatisfied with their appearance and perceived themselves to look older versus other patterns.

CONCLUSIONS

Baseline CFL severity, age, and gender may predict fan pattern. Patterns may progress with age from central to lower fan or full fan. Pattern heterogeneity of CFLs suggests that tailored treatment may be warranted.

Radioactive patients may expose others after radiopharmaceutical administrations, and evaluation of the absorbed dose or exposure rates close to patients is important in keeping radiation doses as low as reasonably achievable. Two theoretical exposure models, point source and line source models, are frequently used to calculate exposure or dose rates without the support of actual measurements. If measurements of exposure rates were performed near patients, an experimental exposure model could be implemented. When measurements of exposure rates are performed, these measurements are made inside therapy rooms or other confined places, in which case scattered radiation may significantly influence the measurements. In this study we measured exposure rates from radioactive patients without the influence of scattered radiation and determined correction factors for the theoretical exposure models. The exposure rates from a total of 110 radioactive patients were measured at 1.0 h after oral administration of Na131I for thyroid therapy; the results +/-1 SD at distances of 0.5, 1.0, 1.5, 2.0, 3.0, and 4.0 m in front of the patients were (29 +/- 6), (9.9 +/- 1.7), (4.6 +/- 0.9), (2.7 +/- 0.5), (1.31 +/- 0.25) and (0.74 +/- 0.12) x 10(-10) C kg(-1) MBq(-1) h(-1) [1.0 x 10(-10) C kg(-1) MBq(-1) h(-1) = 14.34 x 10(-6) R mCi(-1) h(-1)], respectively. To obtain more accurate estimates of the actual exposure rates from patients using the theoretical exposure models, we found that correction factors should be applied; the functions CFEM = 1.19 + 32.80e(5.92D) and CFLS = 0.022LnD + 0.639 describe these correction factors for distances less than or equal to 1.0 m from the patients for experimental and line source exposure models, respectively. The function that describes the correction factors to the point source model is CFPS = 0.224LnD + 0.638 at the same distances; applying these correction factors leads to a reduction from 56% to 1% in the difference between measured exposure rates and theoretical exposure rates calculated by the point source exposure model at a distance of 1.0 m from patients. The results given here provide more accuracy in evaluation of exposure rates and consequently absorbed doses near radioactive patients and allow for more effective radiological protection procedures during patient management.

OBJECTIVE

To prospectively evaluate and quantify the efficacy of cadaveric fascia lata (CFL) as an allograft material in pubovaginal sling placement to treat stress urinary incontinence (SUI).

METHODS

Thirty-one women with SUI (25 type II and six type III; mean age 63 years, range 40-75) had a CFL pubovaginal sling placed transvaginally. The operative time, blood loss, surgical complications and mean hospital stay were all documented. Before and at 4 months and 1 year after surgery each patient completed a 3-day voiding diary and validated voiding questionnaires (functional inquiry into voiding habits, Urogenital Distress Inventory and Incontinence Impact Questionnaire, including visual analogue scales).

RESULTS

The mean (range) operative time was 71 (50-120) min, blood loss 78.7 (20-250) mL and hospital stay 1.2 (1-2) days; there were no surgical complications. Over the mean follow-up of 13.5 months, complete resolution of SUI was reported by 29 (93%) patients. Overactive bladder symptoms were present in 23 (74%) patients before surgery, 21 (68%) at 4 months and two (6%) at 1 year; 80% of patients with low (< 15 cmH2O) voiding pressures before surgery required self-catheterization afterward, as did 36% at 4 months, but only one (3%) at 1 year. Twenty-four (77%) patients needed to adopt specific postures to facilitate voiding. After surgery there was a significant reduction in daytime frequency, leakage episodes and pad use (P < 0.05). The severity of leak and storage symptoms was also significantly less (P < 0.002), whilst the severity of obstructive symptoms remained unchanged. Mean subjective levels of improvement were 69% at 4 months and 85% at 1 year, with corresponding objective satisfaction levels of 61% and 69%, respectively. At 1 year, approximately 80% of the patients said they would undergo the procedure again and/or recommend it to a friend.

CONCLUSIONS

Placing a pubovaginal sling of CFL allograft is a highly effective, safe surgical approach for resolving SUI, with a short operative time and rapid recovery. Storage symptoms are significantly improved, and subjective improvement and satisfaction rates are high.

Herein we introduce a novel strategy based on capillary force lithography (CFL) to fabricate asymmetric polymeric ring structures by applying both shear and nomal forces to a poly(dimethylsiloxane) stamp. The mechanism for the formation of asymmetric rings is caused by the deflection of cylindrical PDMS pillars due to the shear load, which is therefore termed deflected CFL (dCFL). The asymmetric polymeric rings could be readily transferred to an underlying gold layer to generate split ring structures with tunable opening angles. Asymmetric structures based upon trigular and square-shaped pillars were also fabricated. These elements were formed into periodic arrays over surface areas as large as 1 cm(2) and may have optical and electromagnetic applications.

Mathematical models have substantially improved our ability to predict the response of a complex biological system to perturbation, but their use is typically limited by difficulties in specifying model topology and parameter values. Additionally, incorporating entities across different biological scales ranging from molecular to organismal in the same model is not trivial. Here, we present a framework called "querying quantitative logic models" (Q2LM) for building and asking questions of constrained fuzzy logic (cFL) models. cFL is a recently developed modeling formalism that uses logic gates to describe influences among entities, with transfer functions to describe quantitative dependencies. Q2LM does not rely on dedicated data to train the parameters of the transfer functions, and it permits straight-forward incorporation of entities at multiple biological scales. The Q2LM framework can be employed to ask questions such as: Which therapeutic perturbations accomplish a designated goal, and under what environmental conditions will these perturbations be effective? We demonstrate the utility of this framework for generating testable hypotheses in two examples: (i) a intracellular signaling network model; and (ii) a model for pharmacokinetics and pharmacodynamics of cell-cytokine interactions; in the latter, we validate hypotheses concerning molecular design of granulocyte colony stimulating factor.

Strategies for switching polymerizations between "ON" and "OFF" states offer new possibilities for materials design and fabrication. While switching of controlled radical polymerization has been achieve using light, applied voltage, allosteric effects, chemical reagents, pH, and mechanical force, it is still challenging to introduce multiple external switches using the same catalyst to achieve logic gating of controlled polymerization reactions. Herein, we report an easy-to-synthesize thermally responsive organo-/hydro-gel that features covalently bound 10-phenylphenothiazine (PTH). With this "Gel-PTH", we demonstrate switching of controlled radical polymerization reactions using temperature "LOW"/"HIGH", light "ON"/"OFF", and catalyst presence "IN"/"OUT". Various iniferters/initiators and a wide range of monomers including acrylates, methacrylates, acrylamides, vinyl esters, and vinyl amides were polymerized by RAFT/iniferter and ATRP methods using Gel-PTH and a readily available compact fluorescent light (CFL) source. In all cases, polymer molar masses increased linearly with conversion, and narrow molar mass distributions were obtained. To further highlight the utility of Gel-PTH, we achieved "AND" gating of controlled radical polymerization wherein various combinations of three stimuli were required to induce polymer chain growth. Finally, block copolymer synthesis and catalyst recycling were demonstrated. Logic-controlled polymerization with Gel-PTH offers a straightforward approach to achieve multiplexed external switching of polymer chain growth using a single catalyst without the need for addition of exogenous reagents.

OBJECTIVE

Volume scotomas are three-dimensional regions of space that are not visible to the observer. Volume perimetry maps volume scotomas. Volume scotomas predicted from combining monocular visual fields assume known fixation locus (mainly foveal). However, fixation loci are not always known, especially with central field loss (CFL). Here we demonstrate methods for measuring and calculating volume scotomas and discuss their practical implications.

METHODS

Three patients (bitemporal hemianopia, binasal scotoma, and CFL) were evaluated. Slices through the volume scotomas were measured at three distances: at the plane of fixation, at a plane anterior to fixation (representing anterior volume perimetry), and at a plane posterior to fixation (representing posterior volume perimetry). For anterior volume perimetry, patients fixated on a screen 100 cm away through a beamsplitter that reflected the perimetric stimulus (at 50 cm). For posterior volume perimetry, patients fixated on a near target (50 cm), while perimetric stimuli were presented on a screen 150 cm beyond fixation. At the plane of fixation, monocular visual fields under binocular viewing conditions were measured using a computerized dichoptic perimeter.

RESULTS

Posterior and anterior volume scotomas were documented in patients with bitemporal hemianopia and binasal scotomas, respectively. The CFL patient demonstrated both anterior and posterior volume scotomas. Scotoma magnitude was considered to determine its effect on visual function.

CONCLUSIONS

Direct measurement of volume scotomas can be performed. Anterior and posterior volume visual fields can vary substantially from conventional binocular perimetry measured at the fixation plane, revealing blind areas not otherwise identified. These volume scotomas are likely to impair functional vision such as driving (for bitemporal hemianopes) and near work with small hand tools (for binasal scotomas). Patients with CFL will have impaired functional vision for both distance and near tasks. Consideration of volume scotomas can help provide more effective vision rehabilitation and counseling.