CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth.

BACKGROUND: Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established. METHODS: To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter driven BrafV600E/Pten-/-/Cxcr2-/- and NRasQ61R/INK4a-/-/Cxcr2-/- melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated in BrafV600E/Pten-/- and NRasQ61R/INK4a-/- mice and in melanoma cell lines. Potential mechanisms by which Cxcr2 affects melanoma tumorigenesis in these murine models were explored using RNAseq, mMCP-counter, ChIPseq, and qRT-PCR; flow cytometry, and reverse phosphoprotein analysis (RPPA). RESULTS: Genetic loss of Cxcr2 or pharmacological inhibition of CXCR1/CXCR2 during melanoma tumor induction resulted in key changes in gene expression that reduced tumor incidence/growth and increased anti-tumor immunity. Interestingly, after Cxcr2 ablation, Tfcp2l1, a key tumor suppressive transcription factor, was the only gene significantly induced with a log2 fold-change greater than 2 in these three different melanoma models. CONCLUSIONS: Here, we provide novel mechanistic insight revealing how loss of Cxcr2 expression/activity in melanoma tumor progenitor cells results in reduced tumor burden and creation of an anti-tumor immune microenvironment. This mechanism entails an increase in expression of the tumor suppressive transcription factor, Tfcp2l1, along with alteration in the expression of genes involved in growth regulation, tumor suppression, stemness, differentiation, and immune modulation. These gene expression changes are coincident with reduction in the activation of key growth regulatory pathways, including AKT and mTOR.

Diagnostic Performance of Greyscale Ultrasound in Detecting Fatty Liver Disease in a Type 2 Diabetes Population Using FibroScan as the Reference Standard.

Introduction Brightness mode ultrasound (B-mode US) and FibroScan (Echosens, Paris, France) are the two ultrasound methods often recommended for screening non-alcoholic fatty liver disease (NAFLD) in persons with type 2 diabetes mellitus (T2DM). This study assessed the diagnostic performance of B-mode US using FibroScan as the reference standard. Methods Persons with a known history of T2DM were invited to screen for NAFLD using B-mode US and FibroScan on separate days within a one-month period. Assessors of B-mode US and FibroScan were blinded to each other's findings. Both B-mode US and FibroScan independently assessed and graded each participant for the presence of NAFLD. Using the diagnostic test findings of FibroScan as a reference standard, the sensitivity and specificity of B-mode US were analyzed. The area under the receiver operating characteristic curve (AUROC) was analyzed using Jamovi (version 2.3.21). A multinomial logistic regression of the B-mode US and FibroScan in predicting NAFLD grade was also analyzed. Results A total of 171 participants were assessed. B-mode US detected NAFLD in T2DM patients with 63.6% sensitivity, 65.6% specificity, and 0.646 AUROC. Sensitivity and specificity in overweight and obese participants were 36-43% and 76-85%, respectively. Multinomial logistic regression demonstrated an insignificant statistical relationship between FibroScan and B-mode US in predicting grade 1 steatosis (p-value = 0.397), which was significantly affected by a higher BMI (p-value = 0.034) rather than a higher liver fibrosis level (p-value = 0.941). The logistic regression further showed a significant relationship between B-mode US and FibroScan in predicting steatosis grade 2 (p-value = 0.045) and grade 3 (p-value < 0.001), which was not significantly affected by BMI (p-value = 0.091). Conclusion B-mode US can replace FibroScan for severe steatosis; however, it cannot be used to screen for NAFLD in T2DM patients due to lower sensitivity for early detection in the overweight.

CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth.

Background: Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established. Methods: To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter driven Braf V600E /Pten -/- /Cxcr2 -/- and NRas Q61R /INK4a -/- /Cxcr2 -/- melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated in Braf V600E /Pten -/- and NRas Q61R /INK4a -/- mice and in melanoma cell lines. Potential mechanisms by which Cxcr2 affects melanoma tumorigenesis in these murine models were explored using RNAseq, mMCP-counter, ChIPseq, and qRT-PCR; flow cytometry, and reverse phosphoprotein analysis (RPPA). Results: Genetic loss of Cxcr2 or pharmacological inhibition of CXCR1/CXCR2 during melanoma tumor induction resulted in key changes in gene expression that reduced tumor incidence/growth and increased anti-tumor immunity. Interestingly, after Cxcr2 ablation, Tfcp2l1 , a key tumor suppressive transcription factor, was the only gene significantly induced with a log 2 fold-change greater than 2 in these three different melanoma models. Conclusions: Here, we provide novel mechanistic insight revealing how loss of Cxcr2 expression/activity in melanoma tumor progenitor cells results in reduced tumor burden and creation of an anti-tumor immune microenvironment. This mechanism entails an increase in expression of the tumor suppressive transcription factor, Tfcp2l1, along with alteration in the expression of genes involved in growth regulation, tumor suppression, stemness, differentiation, and immune modulation. These gene expression changes are coincident with reduction in the activation of key growth regulatory pathways, including AKT and mTOR.

Do people with knee osteoarthritis use guideline-consistent treatments after an orthopaedic surgeon recommends nonsurgical care? A cross-sectional survey with long-term follow-up.

Objective: Describe "usual care" patterns of education, exercise, weight management, pain medication and other nonsurgical treatments for knee osteoarthritis (OA) in people recommended for nonsurgical care by an orthopaedic surgeon. Methods: We used a telephone-administered questionnaire to capture treatments people with knee OA used over the three to six years after an orthopaedic surgeon recommended nonsurgical care. The primary outcome, guideline-consistent nonsurgical treatments, was an aggregate measure defined as using education, exercise, weight management, and at least one recommended medication. Secondary outcomes were first-line (education, exercise, and weight management) and guideline-inconsistent treatments (orthoses, opioids, hyaluronic acid, platelet rich plasma, and stem cell therapy). Multivariable robust Poisson regression assessed the association between participant characteristics and use of guideline-consistent, first-line and guideline-inconsistent treatments. Results: 479 people were invited and 250 participated (52%). Participants were 58% female with a mean age 66.2 years. Participants received education by a healthcare professional (64%), exercised regularly (74%), used weight management (38%), and used recommended pain medications (91%). All guideline-consistent nonsurgical treatments were used by 19% of participants, 19% of participants used first-line treatments, and 42% used guideline-inconsistent treatments. Over six years, 34% had another consult then underwent arthroplasty. Older participants were less likely to use any treatment. People without post-secondary education were less likely to use first-line treatments (RR 0.54, 95% CI: 0.30-0.96), and females were less likely to use guideline-inconsistent treatments (RR 0.62, 95% CI:0.47-0.81). Conclusions: Nonsurgical usual care for people with knee OA was not consistent with international clinical guidelines.

Takotsubo cardiomyopathy in the setting of severe hyponatremia and beer potomania: A case report.

Takotsubo cardiomyopathy (TC), an acute cardiac event is often associated with acute emotional stress, usually in the setting of cardiovascular risk factors. This case report attempts to review one of the triggers of TC beer potomania-induce hyponatremia with imaging findings that shows the link between severe hyponatremia and TC.

Draft Genome Sequences of Lactobacillus delbrueckii subsp. bulgaricus Strains CBC-LB69 and CBC-LB8, Isolated from Homemade Dairy Foods in Bulgaria.

Here, we report the draft genome sequences of Lactobacillus delbrueckii subsp. bulgaricus strains CBC-LB69 and CBC-LB8. The strains were isolated from naturally processed, homemade dairy foods in Bulgaria. The two genome assemblies each resulted in 39 contigs with total lengths of 1,752,493 and 1,759,908 bp and GC contents of 49.80% and 49.90%, respectively.

Draft Genome Sequence of Streptococcus thermophilus Strain CBC-S77, Isolated from Homemade Dairy Foods in Bulgaria.

Here, we report the draft genome sequence of Streptococcus thermophilus strain CBC-S77. The strain was originally isolated from naturally processed, homemade dairy foods in West Rhode Mountain, Bulgaria. The genome was assembled in 148 contigs with a total length of 1,707,130 bp, with 1,563 coding genes and a GC content of 39.11%.

Draft Genome Sequence of Lactobacillus rhamnosus Strain CBC-LR1, Isolated from Homemade Dairy Foods in Bulgaria.

Here, we report the draft genome sequence of Lactobacillus rhamnosus strain CBC-LR1, which was isolated from naturally processed, homemade dairy foods in Bulgaria. The genome was assembled in 29 contigs with a total length of 2,892,155 bp and a GC content of 46.7%. Genome annotation predicted 2,638 coding genes and 49 tRNA genes.

Physical Activity Levels and Cardiometabolic Risks in Obese African American Adults: A Pilot Intervention Study.

Limited information is available regarding the effects of physical activity on risks of cardiometabolic diseases among obese African American adults. We conducted a church-based 12-week weight control and cardiometabolic risk reduction intervention (n=30, 22 females, 56.7±11.4 years old, BMI 37.4±6.7 kg/m2), after which body weight was slightly reduced (98.3±18.4 and 97.3±19 kg, p=.052); body fat percentage was significantly decreased among males (34.7±8.9 to 28.5±8.4 %; p=.049); and walking steps were increased, but not significantly. Among measured cardiometabolic risk biomarkers, hemoglobin A1c (HbA1c) was decreased significantly (6.8±1.1 to 6.1±1.1%; p=.0004) while time spent in sedentary behaviors was associated with less favorable change in total cholesterol (ß=11.49, SE=3.55, p=.003) and tumor necrosis factor (TNF-α, ß=0.3, SE=0.13, p=.038). Our study shows that adiposity reduction was feasible through a short-term healthy lifestyle program for obese African American adults, and suggests that reducing sedentary behaviors through light physical activity might lead to a decrease in cardiovascular risks.

An assessment of a 3D EPID-based dosimetry system using conventional two- and three-dimensional detectors for VMAT.

PURPOSE: To provide a 3D dosimetric evaluation of a commercial portal dosimetry system using 2D/3D detectors under ideal conditions using VMAT. METHODS: A 2D ion chamber array, radiochromic film and gel dosimeter were utilised to provide a dosimetric evaluation of transit phantom and pre-treatment 'fluence' EPID back-projected dose distributions for a standard VMAT plan. In-house 2D and 3D gamma methods compared pass statistics relative to each dosimeter and TPS dose distributions. RESULTS: Fluence mode and transit EPID dose distributions back-projected onto phantom geometry produced 2D gamma pass rates in excess of 97% relative to other tested detectors and exported TPS dose planes when a 3%, 3 mm global gamma criterion was applied. Use of a gel dosimeter within a glass vial allowed comparison of measured 3D dose distributions versus EPID 3D dose and TPS calculated distributions. 3D gamma comparisons between modalities at 3%, 3 mm gave pass rates in excess of 92%. Use of fluence mode was indicative of transit results under ideal conditions with slightly reduced dose definition. CONCLUSIONS: 3D EPID back projected dose distributions were validated against detectors in both 2D and 3D. Cross validation of transit dose delivered to a patient is limited due to reasons of practicality and the tests presented are recommended as a guideline for 3D EPID dosimetry commissioning; allowing direct comparison between detector, TPS, fluence and transit modes. The results indicate achievable gamma scores for a complex VMAT plan in a homogenous phantom geometry and contributes to growing experience of 3D EPID dosimetry.

Refining a Church-Based Lifestyle Intervention Targeting African-American Adults at Risk for Cardiometabolic Diseases: A Pilot Study.

OBJECTIVE: The pilot study was intended to test the feasibility of a multiple-component lifestyle intervention targeting African American adults in a weight control and cardiometabolic risk reduction program on diet, activity, and stress, using community-engagement principles. METHODS: Applying mixed qualitative and quantitative measures, the intervention had a two-part sequential study design consisting of 12 weekly small group sessions that provided individual and group counseling in nutrition, exercise, and mindfulness, while incorporating focus group and interactive techniques to learn about barriers and acceptable practices for this population. The program was implemented at an African-American church in Nashville, Tennessee. RESULTS: Thirty-four participants (aged 56.1 ± 11 years, body mass index (BMI) 36.7 ± 6.6 kg/m2) completed the intervention. Lifestyle changes after the 12 weekly sessions showed some positive trends including reduced sodium intake (from 2725.3 ± 326.5 to 2132 ± 330, mg/day, P = 0.008), increased walking steps (from 4392.1 ± 497.2 to 4895.3 ± 497.9, steps/day, not significant), and slightly decreased Perceived Stress Scale (PSS) scores (from 13.7 ± 1.4 to 12.4 ± 1.5, not significant). Body fat % among male participants decreased significantly (from 33.8 ± 2.6 to 28 ± 2.6, %, P = 0.043). Among cardiometabolic risk biomarkers, hemoglobin A1c (HbA1c) decreased significantly (from 6.6 ± 0.2 to 6.1 ± 0.2, %, P < 0.001). The baseline PSS score was positively associated with baseline adiposity levels (e.g., weight, ß = 2.4, P = 0.006). Twenty-one participants took part in focus groups during the program to identify barriers to healthy lifestyle changes. Primary barriers reported were price, time for preparing healthy meals, unfamiliarity with mindfulness activities, their health condition, and daily schedule available for physical activities. CONCLUSIONS: This church-based pilot intervention was proven feasible by showing modest progress in reducing adiposity and decreasing HbA1c levels. The focus group and interactive methods facilitated program direction. Future full-scale studies are warranted to identify key strategies that provide more personalized approaches and supportive environments to sustain a healthy lifestyle among these at risk minorities with limited resources.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

LASP-1: a nuclear hub for the UHRF1-DNMT1-G9a-Snail1 complex.

Nuclear LASP-1 (LIM and SH3 protein-1) has a direct correlation with overall survival of breast cancer patients. In this study, immunohistochemical analysis of a human breast TMA showed that LASP-1 is absent in normal human breast epithelium but the expression increases with malignancy and is highly nuclear in aggressive breast cancer. We investigated whether the chemokines and growth factors present in the tumor microenvironment could trigger nuclear translocation of LASP-1.Treatment of human breast cancer cells with CXCL12, EGF and HRG, and HMEC-CXCR2 cells with CXCL8 facilitated nuclear shuttling of LASP-1. Data from the biochemical analysis of the nuclear and cytosolic fractions further confirmed the nuclear translocation of LASP-1 upon chemokine and growth factor treatment. CXCL12-dependent nuclear import of LASP-1 could be blocked by CXCR4 antagonist, AMD-3100. Knock down of LASP-1 resulted in alterations in gene expression leading to an increased level of cell-junction and extracellular matrix proteins and an altered cytokine secretory profile. Three-dimensional cultures of human breast cancer cells on Matrigel revealed an altered colony growth, morphology and arborization pattern in LASP-1 knockdown cells. Functional analysis of the LASP-1 knockdown cells revealed increased adhesion to collagen IV and decreased invasion through the Matrigel. Proteomic analysis of immunoprecipitates of LASP-1 and subsequent validation approaches revealed that LASP-1 associated with the epigenetic machinery especially UHRF1, DNMT1, G9a and the transcription factor Snail1. Interestingly, LASP-1 associated with UHRF1, G9a, Snail1 and di- and tri-methylated histoneH3 in a CXCL12-dependent manner based on immunoprecipitation and proximity ligation assays. LASP-1 also directly bound to Snail1 which may stabilize Snail1. Thus, nuclear LASP-1 appears to functionally serve as a hub for the epigenetic machinery.

Field durability of the same type of long-lasting insecticidal net varies between regions in Nigeria due to differences in household behaviour and living conditions.

BACKGROUND: With the recent publication of WHO-recommended methods to estimate net survival, comparative analyses from different areas have now become possible. With this in mind, a study was undertaken in Nigeria to compare the performance of a specific long-lasting insecticidal net (LLIN) product in three socio-ecologically different areas. In addition, the objective was to assess the feasibility of a retrospective study design for durability. METHODS: In three states, Zamfara in the north, Nasarawa in the centre and Cross River in the south, four local government areas were selected one year after mass distribution of 100-denier polyester LLINs. From a representative sample of 300 households per site that had received campaign nets, an assessment of net survival was made based on rate of loss of nets and the physical condition of surviving nets measured by the proportionate hole index (pHI). Surveys were repeated after two and three years. RESULTS: Over the three-year period 98% of the targeted sample size of 3,720 households was obtained and 94% of the 5,669 campaign nets found were assessed for damage. With increasing time since distribution, recall of having received campaign nets dropped by 11-22% and only 31-87% of nets actually lost were reported. Using a recall bias adjustment, attrition rates were fairly similar in all three sites. The proportion of surviving nets in serviceable condition differed dramatically, however, resulting in an estimated median net survival of 3.0 years in Nasarawa, 4.5 years in Cross River and 4.7 years in Zamfara. Although repairs on damaged nets increased from around 10% at baseline to 21-38% after three years, the average pHI value for each of the four hole size categories did not differ between repaired and unrepaired nets. CONCLUSIONS: First, the differences observed in net survival are driven by living conditions and household behaviours and not the LLIN material. Second, recall bias in a retrospective durability study can be significant and while adjustments can be made, enough uncertainty remains that prospective studies on durability are preferable wherever possible. Third, repair does not seem to measurably improve net condition and focus should, therefore, be on improving preventive behaviour.

Methane emissions from beef cattle grazing on semi-natural upland and improved lowland grasslands.

In ruminants, methane (CH4) is a by-product of digestion and contributes significantly to the greenhouse gas emissions attributed to agriculture. Grazed grass is a relatively cheap and nutritious feed but herbage species and nutritional quality vary between pastures, with management, land type and season all potentially impacting on animal performance and CH4 production. The objective of this study was to evaluate performance and compare CH4 emissions from cattle of dairy and beef origin grazing two grassland ecosystems: lowland improved grassland (LG) and upland semi-natural grassland (UG). Forty-eight spring-born beef cattle (24 Holstein-Friesian steers, 14 Charolais crossbred steers and 10 Charolais crossbred heifers of 407 (s.d. 29), 469 (s.d. 36) and 422 (s.d. 50) kg BW, respectively), were distributed across two balanced groups that grazed the UG and LG sites from 1 June to 29 September at stocking rates (number of animals per hectare) of 1.4 and 6.7, respectively. Methane emissions and feed dry matter (DM) intake were estimated by the SF6 tracer and n-alkane techniques, respectively, and BW was recorded across three experimental periods that reflected the progression of the grazing season. Overall, cattle grazed on UG had significantly lower (P<0.001) mean daily DM intake (8.68 v. 9.55 kg/day), CH4 emissions (176 v. 202 g/day) and BW gain (BWG; 0.73 v. 1.08 kg/day) than the cattle grazed on LG but there was no difference (P>0.05) in CH4 emissions per unit of feed intake when expressed either on a DM basis (20.7 and 21.6 g CH4 per kg DM intake for UG and LG, respectively) or as a percentage of the gross energy intake (6.0% v. 6.5% for UG and LG, respectively). However, cattle grazing UG had significantly (P<0.001) greater mean daily CH4 emissions than those grazing LG when expressed relative to BWG (261 v. 197 g CH4/kg, respectively). The greater DM intake and BWG of cattle grazing LG than UG reflected the poorer nutritive value of the UG grassland. Although absolute rates of CH4 emissions (g/day) were lower from cattle grazing UG than LG, cattle grazing UG would be expected to take longer to reach an acceptable finishing weight, thereby potentially off-setting this apparent advantage. Methane emissions constitute an adverse environmental impact of grazing by cattle but the contribution of cattle to ecosystem management (i.e. promoting biodiversity) should also be considered when evaluating the usefulness of different breeds for grazing semi-natural or unimproved grassland.

Modification of properties of yttria stabilized zirconia epitaxial thin films by excimer laser annealing.

This study focuses on the ultrafast improvement of surface wettability, electrical, and room temperature magnetic characteristics of cubic zirconia single crystalline thin films after laser annealing. The point defects generated by the laser treatment are envisaged to play a critical role in altering the above properties. Yttria stabilized zirconia (YSZ) thin films were epitaxially grown on Si(100) substrates by pulsed laser deposition technique and subsequently annealed by a KrF excimer laser beam (τ = 25 ns) using low-energy laser pulses. An atomically sharp interface, parallel to the film free surface, between laser annealed layer and the pristine region was observed. The single crystalline nature of thin films was preserved following the laser treatment. The laser-solid interaction with YSZ led to the introduction of point defects, i.e., oxygen vacancies, resulting in a strained structure which, in turn, resulted in the formation of a tetragonal-like zirconia. With the increase of number of laser pulses the laser treated films got highly disordered due to the high concentration of the point defects, while maintaining their crystalline nature. Although the surface of the pristine sample showed weak hydrophilic characteristics (contact angle ∼ 73°), the laser annealed samples exhibited significantly improved hydrophilic characteristics. It was found that there is an optimum number of laser pulses where the maximum hydrophilicity (contact angle ∼ 22°) is obtained. The carrier concentration in the sample with the highest hydrophilicity was determined to be higher by about 5 orders of magnitude compared to the pristine sample. This sample possessed the lowest electrical resistivity. The laser annealed YSZ epilayers showed a superior room-temperature ferromagnetic behavior, compared to the pristine samples. A 2-fold enhancement in the magnetization of the samples was observed following the laser treatment which is a clear demonstration of the key role of defects and their transient distribution throughout the lattice. All these observations were correlated with the formation of point defects due to the photon interaction with YSZ and absorption of energy of the KrF laser photons to produce defects.

Engineered three-dimensional microfluidic device for interrogating cell-cell interactions in the tumor microenvironment.

Stromal cells in the tumor microenvironment play a key role in the metastatic properties of a tumor. It is recognized that cancer-associated fibroblasts (CAFs) and endothelial cells secrete factors capable of influencing tumor cell migration into the blood or lymphatic vessels. We developed a microfluidic device that can be used to image the interactions between stromal cells and tumor cell spheroids in a three dimensional (3D) microenvironment while enabling external control of interstitial flow at an interface, which supports endothelial cells. The apparatus couples a 200-µm channel with a semicircular well to mimic the interface of a blood vessel with the stroma, and the design allows for visualization of the interactions of interstitial flow, endothelial cells, leukocytes, and fibroblasts with the tumor cells. We observed that normal tissue-associated fibroblasts (NAFs) contribute to the "single file" pattern of migration of tumor cells from the spheroid in the 3D microenvironment. In contrast, CAFs induce a rapid dispersion of tumor cells out of the spheroid with migration into the 3D matrix. Moreover, treatment of tumor spheroid cultures with the chemokine CXCL12 mimics the effect of the CAFs, resulting in similar patterns of dispersal of the tumor cells from the spheroid. Conversely, addition of CXCL12 to co-cultures of NAFs with tumor spheroids did not mimic the effects observed with CAF co-cultures, suggesting that NAFs produce factors that stabilize the tumor spheroids to reduce their migration in response to CXCL12.

What happens to lost nets: a multi-country analysis of reasons for LLIN attrition using 14 household surveys in four countries.

BACKGROUND: While significant focus has been given to net distribution, little is known about what is done with nets that leave a household, either to be used by others or when they are discarded. To better understand the magnitude of sharing LLIN between households and patterns of discarding LLIN, the present study pools data from 14 post-campaign surveys to draw larger conclusions about the fate of nets that leave households. METHODS: Data from 14 sub-national post-campaign surveys conducted in Ghana, Senegal, Nigeria (10 states), and Uganda between 2009 and 2012 were pooled. Survey design and data collection methods were similar across surveys. The timing of surveys ranged from 2-16 months following their respective mass LLIN distributions. RESULTS: Among the 14 surveys a total of 14,196 households reported owning 25,447 nets of any kind, of which 23,955 (94%) were LLINs. In addition, a total of 4,102 nets were reported to have left the households in the sample: 63% were discarded, and 34% were given away. Only 255 of the discarded nets were reported used for other purposes, representing less than 1% of the total sample of nets. The majority (62.5%) of nets given away were given to or taken by relatives, while 31.1% were given to non-relatives. Campaign nets were almost six times (OR 5.95, 4.25-8.32, p < 0.0001) more likely to be given away than non-campaign nets lost during the same period. Nets were primarily given away within the first few months after distribution. The overall rate of net redistribution was 5% of all nets. DISCUSSION AND CONCLUSION: Intra-household re-allocation of nets does occur, but was sensitive to current household net ownership and the time elapsed since mass distribution. These factors can be addressed programmatically to further facilitate reallocation within a given community. Secondly, the overwhelming majority of nets were used for malaria prevention. Of the repurposed nets (<1% overall), the majority were already considered too torn, indicating they had already served out their useful life for malaria prevention. National programmes and donor agencies should remain confident that overall, their investments in LLIN are being appropriately used.