Grade Components Research Articles

Perioperative outcomes following reoperation for recurrent insular gliomas.

Greater extent of resection (EOR) improves overall survival and progression-free survival for patients with low- and high-grade glioma. While resection for newly diagnosed insular gliomas can be performed with minimal morbidity, perioperative morbidity is not clearly defined for patients undergoing a repeat resection for recurrent insular gliomas. In this study the authors report on tumor characteristics, tumor EOR, and functional outcomes in patients undergoing reoperation for recurrent insular glioma. Adult patients with insular gliomas (WHO grades II-IV) who underwent index resection followed by reoperation were identified through the University of California San Francisco Brain Tumor Center. Treatment history and functional outcomes were collected retrospectively from the electronic medical record. Pre- and postoperative tumor volumes were quantified using software with region-of-interest analysis based on FLAIR and T1-weighted postgadolinium sequences from pre- and postoperative MRI. Forty-four patients (63.6% male, 36.4% female) undergoing 49 reoperations for recurrent insular tumors were identified with a median follow-up of 741 days. Left- and right-sided tumors comprised 52.3% and 47.7% of the cohort, respectively. WHO grade II, III, and IV gliomas comprised 46.9%, 28.6%, and 24.5% of the cohort, respectively. Ninety-five percent (95.9%) of cases involved language and/or motor mapping. Median EOR of the insular component of grade II, III, and IV tumors were 82.1%, 75.0%, and 94.6%, respectively. EOR during reoperation was not impacted by Berger-Sanai insular zone or tumor side. At the time of reoperation, 44.9% of tumors demonstrated malignant transformation to a higher WHO grade. Ninety-day postoperative assessment confirmed that 91.5% of patients had no new postoperative deficit attributable to surgery. Of those with new deficits, 3 (6.4%) had a visual field cut and 1 (2.1%) had hemiparesis (strength grade 1-2/5). The presence of a new postoperative deficit did not vary with EOR. Recurrent insular gliomas, regardless of insular zone and pathology, may be reoperated on with an overall acceptable degree of resection and safety despite their anatomical and functional complexities. The use of intraoperative mapping utilizing asleep or awake methods may reduce morbidity to acceptable rates despite prior surgery.

MMR deficient undifferentiated/dedifferentiated endometrial carcinomas showing significant programmed death ligand-1 expression (sp 142) with potential therapeutic implications

BackgroundUterine undifferentiated (UEAC)/dedifferentiated (DEAC) carcinomas are rare malignant neoplasms. They appear to pursue an aggressive clinical course with an advanced stage at presentation. Recently, it was discovered that the use of immunotherapeutic drugs targeting programmed cell death protein 1 (PD1)/programmed death ligand-1 (PD-L1) was associated with improved survival in several types of cancer (especially in patients with mismatch-repair (MMR) deficient patients). Whether these findings can be applied to UEAC/DEAC remains a question. Herein, the aim of this study is to evaluate the expression of PD-L1/PD-1 in UEAC/DEAC and its relationship to MMR status. This could offer useful therapeutic information. DesignReview of endometrial carcinoma (EC) diagnosed over the period of 2011 to 2017 in our institution identified 14 UEAC/DEAC cases (n=14). All cases had immunohistochemistry performed for MMR (MLH1, PMS2, MSH2 and MSH6), PD-L1 and PD-1. The protein expression was examined and in DEAC cases both the undifferentiated component and the low grade component were recorded separately. The expression of PD-L1 and PD-1 was scored in both the tumor and the peritumoral lymphocyte infiltration. ResultsOverall variable degrees of tumoral or immune stromal PD-L1 staining (from 1% to 5%), was present in 50.0% (7/14) of UC/DEACs. Seven cases (50%) were PD-1 positive (immune stromal). Five cases (35.7%) showed co-expression of PD-1 and PD-L1 (Figure 1). Worth noting is that PD-1 staining was exclusively present in peritumoral immune cells. Following this the 14 cases were further divided into MMR deficient and MMR proficient groups (Table 1). A total of 8 cases had MMR deficiency (57.1%). There was a statistically significant association for PD-L1 positivity in the MMR deficiency group (p=0.05). However there was no statistically significant differences regarding PD-1 positivity between MMR groups. ConclusionsPD-L1 and PD-1 were expressed in majority of MMR-deficient UEAC /DEAC cases. PD-L1 was not expressed in MMR-proficient carcinomas. These findings might help support potential immunotherapy trials in MMR-deficient UEAC /DEAC.

The reduction of quadcopter propeller noise

Fan affinity laws are combined with a simple scaling relationship for fan noise to show that truly significant reductions in propeller noise can be achieved by increasing the propeller diameter while reducing its rotational speed, thereby reducing its blade tip speed, while maintaining a given level of static thrust. Fan affinity laws are also used to show that efficiency improvements accompany the reductions in radiated noise. The significant reductions in noise and increases in efficiency predicted from the scaling relationships are verified experimentally by measuring the radiated noise and power requirements for both large, slowly rotating propellers and small, high-speed propellers, at equivalent static thrusts, where the large propellers serve as possible replacements for the small propellers in typical quadcopter applications. The bulk of the noise reductions offered by large and slowly rotating propellers compared with small, high-speed propellers are shown to be maintained at equivalent net force (thrust minus weight) conditions, as required for practical implementation into a quadcopter UAV, even using readily available hobby grade components. Further significant noise reductions are possible with lightweight and custom engineered components. © 2019 Institute of Noise Control Engineering

On asymptotic vanishing behavior of local cohomology

Let R be a standard graded algebra over a field k, with irrelevant maximal ideal $$\mathfrak {m}$$, and I a homogeneous R-ideal. We study the asymptotic vanishing behavior of the graded components of the local cohomology modules $$\{{\text {H}}^{i}_{\mathfrak {m}}(R/I^n)\}_{n\in {\mathbb {N}}}$$ for $$i<\dim R/I$$. We show that, when $${{\,\mathrm{{{char}}}\,}}k= 0$$, R / I is Cohen–Macaulay, and I is a complete intersection locally on $${{\,\mathrm{{Spec}}\,}}R {\setminus }\{\mathfrak {m}\}$$, the lowest degrees of the modules $$\{{\text {H}}^{i}_{\mathfrak {m}}(R/I^n)\}_{n\in {\mathbb {N}}}$$ are bounded by a linear function whose slope is controlled by the generating degrees of the dual of $$I/I^2$$. Our result is a direct consequence of a related bound for symmetric powers of locally free modules. If no assumptions are made on the ideal or the field k, we show that the complexity of the sequence of lowest degrees is at most polynomial, provided they are finite. Our methods also provide a result on stabilization of maps between local cohomology of consecutive powers of ideals.

Efficacy and Safety of Surgery for Mild Degenerative Cervical Myelopathy: Results of the AOSpine North America and International Prospective Multicenter Studies.

BACKGROUNDThere is controversy over the optimal treatment strategy for patients with mild degenerative cervical myelopathy (DCM).OBJECTIVETo evaluate the degree of impairment in baseline quality of life as compared to population norms, as well as functional, disability, and quality of life outcomes following surgery in a prospective cohort of mild DCM patients undergoing surgical decompression.METHODSWe identified patients with mild DCM (modified Japanese Orthopaedic Association [mJOA] 15 to 17) enrolled in the prospective, multicenter AOSpine CSM-NA or CSM-I trials. Baseline quality of life Short Form-36 version 2 (SF-36v2) was compared to population norms by the standardized mean difference (SMD). Outcomes, including functional status (mJOA, Nurick grade), disability (NDI [Neck Disability Index]), and quality of life (SF-36v2), were evaluated at baseline and 6 mo, 1 yr, and 2 yr after surgery. Postoperative complications within 30 d of surgery were monitored.RESULTSOne hundred ninety-three patients met eligibility criteria. Mean age was 52.4 yr. There were 67 females (34.7%). Patients had significant impairment in all domains of the SF-36v2 compared to population norms, greatest for Social Functioning (SMD –2.33), Physical Functioning (SMD –2.31), and Mental Health (SMD –2.30). A significant improvement in mean score from baseline to 2-yr follow-up was observed for all major outcome measures, including mJOA (0.87, P < .01), Nurick grade (–1.13, P < .01), NDI (–12.97, P < .01), and SF-36v2 Physical Component Summary (PCS) (5.75, P < .01) and Mental Component Summary (MCS) (6.93, P < .01). The rate of complication was low.CONCLUSIONMild DCM is associated with significant impairment in quality of life. Surgery results in significant gains in functional status, level of disability, and quality of life.

Quadcopter propeller noise and its control

Simple scaling analysis is used to show that truly significant reductions in propeller noise are possibly by increasing the propeller diameter while reducing its rotational speed, thereby reducing its blade tip speed, while maintaining a given level of static thrust. The scaling analysis is also used to show that efficiency improvements accompany the reductions in radiated noise. The significant reductions in noise and the increase in efficiency predicted were verified experimentally by measuring the radiated noise and power requirements for both large, slowly rotating propellers and small, high speed propellers, at equivalent static thrusts, where the large propellers serve as possible replacements for the small propellers in typical quadcopter applications. The bulk of the noise reductions offered by large and slowly rotating propellers compared with small, high speed propellers is shown to be maintained at equivalent net force (thrust minus weight conditions), as required for practical implementation into a quadcopter, even using readily available hobby grade components. Further significant noise reductions are possible with lightweight and custom engineered components.

Abstract P4-02-13: Inter- and intra-laboratory variation in grading of invasive breast cancer: A nationwide study in the Netherlands

Abstract Background Histologic grading is one of the best established prognostic factors in invasive breast cancer (IBC) and is used to guide patient management. Yet, the level of inter- and intra-observer agreement does not reach high enough clinical standards. To improve standardization, we aimed to gain insight into laboratory-specific variation in histologic grading. Methods All synoptic pathology reports of IBC resection specimens between 2013-2016 were retrieved from PALGA, the nationwide Dutch Pathology Registry. All lesions were graded according to the modified Bloom and Richardson guideline, which combines assessment of cell morphology (nuclear polymorphism), measurement of differentiation (tubular differentiation) and assessment of proliferation (mitotic count). Absolute differences in proportions of grade I-III and the three components of grading between laboratories were compared to the national distributions. For logistic regression analyses, grade was dichotomized into high- and low-grade by two alternative definitions for high-grade IBC (either solely grade III or grade II-III). Multivariable logistic regression, to correct for case mix (age, tumor size, type of surgery, histologic subtype, ER/PR-receptor status, HER2-receptor status), provided two laboratory-specific odds ratios (ORs) and 95% confidence intervals (CI) for high versus low-grade IBC compared to the reference laboratory. Findings In total 33.792 IBC cases from 39 laboratories were included, of which 28.1% were reported as grade I (range 16.3-43.3%), 47.6% as grade II (range 38.4-57.8%), and 24.3% as grade III (range 15.5-34.3%). More than half of the laboratories (22/39) showed proportions outside the 95% confidence limits of the national proportion for both grade I and grade III, followed by 41.0% of the laboratories for grade II. After case mix correction, 20 laboratories (51.3%) showed at least one significantly higher or lower OR than the reference laboratory. Four laboratories (10.3%) showed significantly deviant ORs on both analyses. Most variation between laboratories was observed for nuclear polymorphism. Significant grading differences were also observed between pathologists within 62.5% of the laboratories that could be analyzed. Overall, the indication for adjuvant chemotherapy was dependent on histologic grade in 29.9% of patients. Conclusion We observed substantial inter- and intra-laboratory variation in the histologic grading of IBC, which may likely influence treatment decisions and subsequently patient outcome as the indication for chemotherapy depends on histologic grade in almost every one in three patients. Citation Format: van Dooijeweert C, van Diest PJ, Willems SM, Kuijpers CC, Overbeek LI, Deckers IA. Inter- and intra-laboratory variation in grading of invasive breast cancer: A nationwide study in the Netherlands [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-13.

Development of dehydrated products from peach palm-tucupi blends with edible film characteristics using refractive window.

This study aimed to obtain a dehydrated product with film characteristics with superior functional and technological quality, prepared from different varieties of peach palm (Bactris gasipaes) using the refractance window drying (RW) process. The experiments were carried out at 70°C and drying was fully performed at an increasing rate. The physicochemical characteristics and mechanical, technological, and morphological properties were determined and the moisture and water activity curves of the different peach palm varieties were assessed. The dehydrated product by refractance window have good visual appearance and bright yellowish color due to the carotenoid content found in the samples used as raw material. All dehydrated products had non-homogenous microstructure, however, the products had low tensile strength, percent elongation, hygroscopicity, and water absorption and solubility, desired properties to obtain a food product. The presence of components such as proteins, lipids, and fibers had important effects on the mechanical properties of the products because the mechanical resistance of the biopolymers is influenced by the cohesion of the constituents of the polymer matrix. The production of a dehydrated product with film characteristics through the RW technique presented some advantages over conventional casting drying as such as short drying times, lower costs and without addition of plasticizers or non-food grade components. In general, the products dehydrated by RW are promising and can be consumed immediately after production as snacks or in the substitution of other ingredients, such as algae in sushi.

Dedifferentiated endometrial adenocarcinoma with neuroendocrine differentiation and ballooning-cell features: Report of a rare entity with an unusual histology

A 63-year-old Caucasian woman underwent total hysterectomy with bilateral salpingo-oophorectomy due to abnormal uterine bleeding. Gross examination of the hysterectomy specimen revealed a large polypoid mass filling the endometrial cavity. Histological examination revealed a tumor with two unique morphologic patterns with no overlap or transition from one pattern to the other. The low-grade component consisted of FIGO grade 1 endometrioid adenocarcinoma with unusual “balloon-cell” change, while the high grade component was an undifferentiated carcinoma with neuroendocrine features. Both components exhibited MLH1 and MSH6 loss by immunohistochemistry. To our knowledge, the current case is only the 5th documented case of dedifferentiated endometrioid carcinoma with neuroendocrine features.

Ovarian seromucinous tumor: A case series of WHO newly introduced entity

Introduction: Ovarian epithelial tumors account for the majority of female ovarian neoplasms but seromucinous tumors are rare and not adequately described in the literature. The recent World Health Organization (WHO) 2014 classification of tumors of female reproductive organs introduced this new category of ovarian neoplasm as “seromucinous tumors. Materials and Method: Sectioning of tissue followed by staining and immunohistochemistry. Results: Four of our cases which were diagnosed as cystic lesion clinically and radiologically , on histopathological examination two of them reported as seromucinous cystadenoma and rest two as seromucinous borderline tumors (SMBT). One of the case of SMBT also showed microinvasion along with focal areas of intraepithelial carcinoma high grade and clear cell component. Conclusion: Proper histopathological diagnosis is very important for better treatment and to reduce the use of aggressive therapies.

Graph-based approach to model the dependency information of graduate attributes for supporting the accreditation process

In the accreditation of an engineering program, the criterion of graduate attributes is particularly challenging due to its outcome-based nature, which involves diverse instructors to collect and analyze data on students’ skills and competencies in course activities. Also, the amount of data can be vast, causing the issues of relevance and consistency of the collected data. In this context, the purpose of this paper is to facilitate the relevant process by modeling the information dependency concerning the measurements of graduate attributes and the responsibilities of stakeholders. The modeling approach is based on the graph representation that focuses on the nodes and their relations. In the graph-based model, information contents are treated as nodes, which are classified into five types: graduate attribute (GA), attribute indicator (AI), program course (PC), learning outcome (LO), and grading component (GC). Then, the contextual interpretation of the GA assessments is specified by the relations that connect these content types. In this work, three types of content relations are defined: refine, measure and associate. Further, three types of stakeholders are identified (i.e., accreditor, administrator, and instructor), along with their relations to specify their responsibilities to the content types. To demonstrate the application of the proposed graph-based model, this paper overviews the use of the Integrated Course Design Tool (ICDT) and the course outline template in the accreditation process. Based on the graph-based model, suggestions are provided toward the development of quality function deployment and software tools.

How Does Pretesting for PubMed Knowledge Spark Student Learning?

Predoctoral students enter dental school with varying skill levels for searching biomedical databases and a tendency to overestimate their abilities. Accordingly, PubMed instruction is embedded within a required dental course and includes a graded component. This article describes a pretest/intervention/posttest developed for the PubMed session. The expectation for this new assessment was that motivation to learn PubMed would increase during the intervention if pretesting objectively showed students the difference between their self-perceived versus actual PubMed abilities. The goals were to help students better self-assess their genuine searching abilities, spark learning during the instruction session, and elicit measurable improvement in skills.

Variation of surgery clerkship grades in US medical schools

BackgroundDespite efforts at standardization, evaluation and reporting of clerkships remains highly variable. This study reviews the current spectrum of surgical clerkship grading. MethodsData were reviewed for every medical school from which an application was received to a single surgery residency program in 2017 and were evaluated for core surgical clerkship grading systems, distributions, and components. Fischer's exact tests and Wilcoxon-Mann-Whitney tests were used for analysis. Results133 (49 private) schools were evaluated. Geographic distribution:34 Northeast, 50 South, 31 Midwest and 18 West. 120 reported grading tiers, with public schools (95%) more likely than private (80%) to report this (p = 0.02). The number of grading categories ranged from 2 to 11; 90% with 3–5. Over 25% of the schools gave ≥40% of students the highest grade; median of 30% in the highest tier. ConclusionsSignificant variation exists in core surgery clerkship grading between schools. Similarly, a sizeable difference exists in how grades are calculated and the reporting systems used. Standardizing grading schemes across medical schools would be beneficial.

Nonlocal Symmetries of Integrable Linearly Degenerate Equations: A Comparative Study

We continue the study of Lax integrable equations. We consider four three-dimensional equations: (1) the rdDym equation uty = uxuxy − uyuxx, (2) the Pavlov equation uyy = utx + uyuxx − uxuxy, (3) the universal hierarchy equation uyy = utuxy − uyutx, and (4) the modified Veronese web equation uty = utuxy − uyutx. For each equation, expanding the known Lax pairs in formal series in the spectral parameter, we construct two differential coverings and completely describe the nonlocal symmetry algebras associated with these coverings. For all four pairs of coverings, the obtained Lie algebras of symmetries manifest similar (but not identical) structures; they are (semi)direct sums of the Witt algebra, the algebra of vector fields on the line, and loop algebras, all of which contain a component of finite grading. We also discuss actions of recursion operators on shadows of nonlocal symmetries.

Friday, September 28, 2018 4:05 PM–5:05 PM abstracts: cervical myelopathy and deformity: 259. The influence of cervical spondylolisthesis on clinical presentation and surgical outcome in patients with degenerative cervical myelopathy: analysis of a global cohort

BACKGROUND CONTEXT Cervical Spondylolisthesis (CS) presents in ∼12% of patients with Degenerative Cervical Myelopathy (DCM). However, its impact on clinical presentation and surgical outcome have not been well-described. Using a prospective and multicenter cohort, we compare patients with and without CS on MRI undergoing surgical treatment for DCM. PURPOSE To determine the influence of cervical spondylolisthesis in patients with DCM. STUDY DESIGN/SETTING Retrospective review of prospectively collected data from multiple global sites. PATIENT SAMPLE A total of 458 patients with MRIs and clinical data. OUTCOME MEASURES The modified Japanese Orthopedic Association score (mJOA), Nurick grade, SF-36 Mental and Physical Component Scores, and the Neck Disability Index. METHODS A total of 458 MRIs from the AOSpine North America and International Studies were reviewed. Patient demographics and baseline neurological and functional status were also obtained. CS was identified using T2 MRI. Patients with DCM were divided into two cohorts, those with CS and those without. Patient demographics, neurological and functional status at baseline and outcome at 2-year follow-up were compared using independent t-tests, chi square tests, Fischer exact tests, and multivariate analysis. RESULTS In comparison to the nonspondylolisthesis cohort (n=404), CS patients (n=54) were on average 8.8 years older (p CONCLUSIONS CS patients are older and present with worse neurological and functional impairment. Furthermore, they receive surgery on more levels and more commonly from the posterior. CS may indicate a more advanced state of DCM pathology and is more likely to result in a suboptimal surgical outcome.

Post-operative albumin-bilirubin grade predicts long-term outcomes among Child–Pugh grade A patients with hepatocellular carcinoma after curative resection

Although Child-Pugh grade A patients with hepatocellular carcinoma (HCC) are candidates for curative resection, some may have a poor prognosis. The albumin-bilirubin (ALBI) grade, a measure of liver function based on albumin and bilirubin, has the potential to detect Child-Pugh grade A HCC patients with poor prognosis. Because components of the ALBI grade can be measured easily even after surgery, we explored the predictive values of ALBI in patient prognosis after HCC resection. In this retrospective case-control study, we included 136 HCC patients who underwent curative resection between January 2004 and December 2013 at our hospital. ALBI grade was calculated from laboratory data recorded the day before surgery and at post-operative day 5. Pre- and post-operative ALBI grade predicted patients' long-term outcomes (P = 0.020 and P < 0.001, respectively, for overall survival, and P = 0.012 and P = 0.015, respectively, for recurrence-free survival). Post-operative ALBI grade was associated with patients' surgical factors of repeated hepatic resection (P = 0.012), intra-operative bleeding (P = 0.006), and surgery duration (P = 0.033). Furthermore, post-operative ALBI grade, rather than pre-operative ALBI grade, was an independent predictive factor of long-term outcome of Child-Pugh grade A patients with HCC. Post-operative ALBI grade is useful to predict the prognosis in patients after HCC resection.

Autophagy defects and related genetic variations in renal cell carcinoma with eosinophilic cytoplasmic inclusions

The relationship between autophagy and tumour is well studied, but tumour cell morphological changes associated with autophagy defects are rarely reported, especially in renal cell carcinoma (RCC). We collected 10 renal tumour samples with characteristic eosinophilic cytoplasmic inclusions (ECIs) and found that the ECIs were majorly composed of sequestosome 1/P62, neighbor of BRCA1 gene 1 (NBR1), PEX14, and CATALASE1 (CAT1). Further, transmission electron microscopy analysis revealed that ECIs were aggregates of proteinaceous material and peroxisomes. These results confirmed that ECIs in RCCs were the products of autophagy defects. The presence of ECIs was correlated with high Fuhrman grade components of RCCs. Whole-exome sequencing (WES) and Sanger sequencing confirmed that tumours with ECIs showed somatic mutations or high frequency of genetic variations in autophagy-related (ATG) genes, such as ATG7, ATG5, and ATG10. These results indicate that nucleotide changes in ATG genes are associated with autophagy defect, ECI formation, and even tumour grade in RCCs.

PO-324 Interferon regulatory factor 1 (IRF1) regulates inflammatory and metabolic phenotypes in pancreatic ductal adenocarcinoma

IntroductionPancreatic Ductal Adenocarcinoma (PDAC) is the most frequent neoplasia of the exocrine pancreas. This tumour is and is characterised by a pervasive heterogeneity, with the coexistence of a range of histological grades, from epithelial-like to mesenchymal-like features. We previously dissected the transcriptional and epigenetic networks underlying PDAC grading. We identified the association of low grade phenotypes with a cell-autonomous interferon-related signature. Therefore, we set out to investigate the sustainment of inflammatory and interferon-related signatures in well-differentiated pancreatic cancer cells, and to determine the role of this network in PDAC biology.Material and methodsWe used cell-line based models of cancer differentiation, xenografts and human samples. We used CRISPR-Cas9 mediated genome editing to delete the transcription factor IRF1 (Interferon Regulatory Factor 1) in low-grade PDAC cells. RNA-seq, metabolic assays (oxygraphy, steady state metabolomics, fluxomics) and cell biology assays were carried out in IRF1 wt and knock-out cell lines. Data validation in human PDAC samples was carried out by immunohistochemistry.Results and discussionsWe found that IRF1 is a transcription factor differentially expressed between low- and high-grade PDACs, both in cell lines and in human tumours. IRF1 deletion in low-grade cell lines reduced the expression of genes in the antigen processing and presentation pathways, while its overexpression promoted the expression of the same genes in high-grade cells, where they are normally not expressed. Furthermore, xenografted IRF1-deficient cell lines recruited fewer immune cells in vivo. IRF1 deletion also affected epithelial phenotypes, including growth rate, cell shape, motility and collagen remodelling ability. Alongside, we unveiled a role of IRF1 in the control of the metabolism of low-grade PDAC cells, consisting in the control of mitochondrial respiration and lipogenesis as well as of the overall lipid profile of these cells.ConclusionTo conclude, our results provide hints on the regulatory networks controlling cell differentiation in human PDACs. We show that IRF1 acts as a pleiotropic regulator in the low grade component of PDACs, with wide effects on immunological and metabolic features of this cancer population. Our work reinforces the body of knowledge needed for the development of those therapeutic strategies aiming at exploiting immunological or metabolic pitfalls.

Correcting for motion artifact in handheld laser speckle images

Laser speckle imaging (LSI) is a wide-field optical technique that enables superficial blood flow quantification. LSI is normally performed in a mounted configuration to decrease the likelihood of motion artifact. However, mounted LSI systems are cumbersome and difficult to transport quickly in a clinical setting for which portability is essential in providing bedside patient care. To address this issue, we created a handheld LSI device using scientific grade components. To account for motion artifact of the LSI device used in a handheld setup, we incorporated a fiducial marker (FM) into our imaging protocol and determined the difference between highest and lowest speckle contrast values for the FM within each data set (Kbest and Kworst). The difference between Kbest and Kworst in mounted and handheld setups was 8% and 52%, respectively, thereby reinforcing the need for motion artifact quantification. When using a threshold FM speckle contrast value (KFM) to identify a subset of images with an acceptable level of motion artifact, mounted and handheld LSI measurements of speckle contrast of a flow region (KFLOW) in in vitro flow phantom experiments differed by 8%. Without the use of the FM, mounted and handheld KFLOW values differed by 20%. To further validate our handheld LSI device, we compared mounted and handheld data from an in vivo porcine burn model of superficial and full thickness burns. The speckle contrast within the burn region (KBURN) of the mounted and handheld LSI data differed by <4 % when accounting for motion artifact using the FM, which is less than the speckle contrast difference between superficial and full thickness burns. Collectively, our results suggest the potential of handheld LSI with an FM as a suitable alternative to mounted LSI, especially in challenging clinical settings with space limitations such as the intensive care unit.

Lipid Nanocarriers for Oral Delivery of Serenoa repens CO2 Extract: A Study of Microemulsion and Self-Microemulsifying Drug Delivery Systems.

The aim of this study was the development and characterization of lipid nanocarriers using food grade components for oral delivery of Serenoa repens CO2 extract, namely microemulsions (MEs) and self-microemulsifying drug delivery systems (SMEDDSs) to improve the oral absorption. A commercial blend (CB) containing 320 of S. repens CO2 extract plus the aqueous soluble extracts of nettle root and pineapple stem was formulated in two MEs and two SMEDDSs. The optimized ME loaded with the CB (CBM2) had a very low content of water (only 17.3%). The drug delivery systems were characterized by dynamic light scattering, transmission electron microscopy, and high-performance liquid chromatography (HPLC) with a diode-array detector analyses in order to evaluate the size, the homogeneity, the morphology, and the encapsulation efficiency. β-carotene was selected as marker for the quantitative HPLC analysis. Additionally, physical and chemical stabilities were acceptable during 3 wk at 4 °C. Stability of these nanocarriers in simulated stomach and intestinal conditions was proved. Finally, the improvement of oral absorption of S. repens was studied in vitro using parallel artificial membrane permeability assay. An enhancement of oral permeation was found in both CBM2 and CBS2 nanoformulations comparing with the CB and S. repens CO2 extract. The best performance was obtained by the CBM2 nanoformulation (~ 17%) predicting a 30 - 70% passive oral human absorption in vivo.