Hydroxyapatite promotes superior adhesion and proliferation of telomerase transformed keratocytes in comparison with inert plastic skirt materials used in leading contemporary keratoprostheses

Aim: Published clinical series suggest the osteoodontokeratoprosthesis (OOKP) may have a lower extrusion rate than current synthetic keratoprostheses. The OOKP is anchored in the eye wall by autologous tooth. The authors’ aim was to compare adhesion, proliferation, and morphology for telomerase transformed keratocytes seeded on calcium hydroxyapatite (the principal mineral constituent of tooth) and materials used in the anchoring elements of commercially available synthetic keratoprostheses. Methods: Test materials were hydroxyapatite, polytetrafluoroethylene (PTFE), polyhydroxyethyl methacrylate (HEMA), and glass (control). Cell adhesion and viability were quantified at 4 hours, 24 hours, and 1 week using a calcein-AM/EthD-1 viability/cytotoxicity assay. Focal contact expression and cytoskeletal organisation were studied at 24 hours by confocal microscopy with immunoflourescent labelling. Further studies of cell morphology were performed using light and scanning electron microscopy. Results: Live cell counts were significantly greater on hydroxyapatite surfaces at each time point (p<0.04). Dead cell counts were significantly higher for PTFE at 7 days (p<0.002). Β1 integrin expression was highest on hydroxyapatite. Adhesion structures were well expressed in flat, spread out keratocytes on both HA and glass. Keratocytes tended to be thinner and spindle shaped on PTFE. The relatively few keratocytes visible on HEMA test surfaces were rounded and poorly adherent. Conclusions: Keratocyte adhesion, spreading, and viability on hydroxyapatite test surfaces is superior to that seen on PTFE and HEMA. Improving the initial cell adhesion environment in the skirt element of keratoprostheses may enhance tissue integration and reduce device failure rates

Health of Philippine Emigrants Study (HoPES): study design and rationale.

BackgroundImmigrants to the United States are usually healthier than their U.S.-born counterparts, yet the health of immigrants declines with duration of stay in the U.S. This pattern is often seen for numerous health problems such as obesity, and is usually attributed to acculturation (the adoption of "American" behaviors and norms). However, an alternative explanation is secular trends, given that rates of obesity have been rising globally. Few studies of immigrants are designed to distinguish the effects of acculturation versus secular trends, in part because most studies of immigrants are cross-sectional, lack baseline data prior to migration, and do not have a comparison group of non-migrants in the country of origin. This paper describes the Health of Philippine Emigrants Study (HoPES), a study designed to address many of these limitations.MethodsHoPES is a dual-cohort, longitudinal, transnational study. The first cohort consisted of Filipinos migrating to the United States (n = 832). The second cohort consisted of non-migrant Filipinos who planned to remain in the Philippines (n = 805). Baseline data were collected from both cohorts in 2017 in the Philippines, with follow-up data collection planned over 3 years in either the U.S. for the migrant cohort or the Philippines for the non-migrant cohort. At baseline, interviewers administered semi-structured questionnaires that assessed demographic characteristics, diet, physical activity, stress, and immigration experiences. Interviewers also measured weight, height, waist and hip circumferences, blood pressure, and collected dried blood spot samples.DiscussionMigrants enrolled in the study appear to be representative of recent Filipino migrants to the U.S. Additionally, migrant and non-migrant study participants are comparable on several characteristics that we attempted to balance at baseline, including age, gender, and education. HoPES is a unique study that approximates a natural experiment from which to study the effects of immigration on obesity and other health problems. A number of innovative methodological strategies were pursued to expand the boundaries of current immigrant health research. Key to accomplishing this research was investment in building collaborative relationships with stakeholders across the U.S. and the Philippines with shared interest in the health of migrants

The effect of increased microporosity on bone formation within silicate-substituted scaffolds in an ovine posterolateral spinal fusion model

This study compared the bone forming capacity of the same formulation of silicate-substituted bone graft substitute materials with different microporosity in an instrumented posterolateral spinal fusion ovine model. Materials with a strut porosity of (i) 22.5% (SiCaP) or (ii) 36.0% (SiCaP(+)) were packed along either side of the spine. Bone apposition rates, % new bone formation, % bone-implant contact, and % graft resorption were quantified at 8, 12, and 24 weeks post surgery. Computed Tomography (CT) was used to grade the formation of fusion bridges between vertebrae. Results showed no significant difference in bone apposition rates, % new bone formation, and % bone-implant contact when the two materials were compared. However, at 8 weeks, a significantly higher CT score was obtained in the SiCaP(+) group (0.83±0.17) when compared with the SiCaP group (0.17±0.17; p=0.027). Significantly less scaffold remained in the SiCaP(+) group at 12 weeks (p=0.018). Both SiCaP and SiCaP(+) formulations augmented bone formation. Increasing the strut porosity did not significantly increase bone formation however, at 8 weeks it promoted the formation of more highly mineralized bone resulting in a significantly higher CT score, suggesting the bone tissue formed was more mature

New interleukin-15 superagonist (IL-15SA) significantly enhances graft-versus-tumor activity.

Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors. Herein, we evaluated the effects of IL-15SA in recipients of allogeneic hematopoietic stem cell transplantation. Weekly administration of IL-15SA to transplant recipients significantly increased the number of CD8+ T cells (specifically CD44+ memory/activated phenotype) and NK cells. Intracellular IFN-γ and TNF-α secretion by CD8+ T cells increased in the IL-15SA-treated group. IL-15SA also upregulated NKG2D expression on CD8+ T cells. Moreover, IL-15SA enhanced proliferation and cytokine secretion of adoptively transferred CFSE-labeled T cells in syngeneic and allogeneic models by specifically stimulating the slowly proliferative and nonproliferative cells into actively proliferating cells.We then evaluated IL-15SA\u27s effects on anti-tumor activity against murine mastocytoma (P815) and murine B cell lymphoma (A20). IL-15SA enhanced graft-versus-tumor (GVT) activity in these tumors following T cell infusion. Interestingly, IL-15 SA administration provided GVT activity against A20 lymphoma cells in the murine donor leukocyte infusion (DLI) model without increasing graft versus host disease. In conclusion, IL-15SA could be a highly potent T- cell lymphoid growth factor and novel immunotherapeutic agent to complement stem cell transplantation and adoptive immunotherapy

Generating compact classifier systems using a simple artificial immune system

Current artificial immune system (AIS) classifiers have two major problems: 1) their populations of B-cells can grow to huge proportions, and 2) optimizing one B-cell (part of the classifier) at a time does not necessarily guarantee that the B-cell pool (the whole classifier) will be optimized. In this paper, the design of a new AIS algorithm and classifier system called simple AIS is described. It is different from traditional AIS classifiers in that it takes only one B-cell, instead of a B-cell pool, to represent the classifier. This approach ensures global optimization of the whole system, and in addition, no population control mechanism is needed. The classifier was tested on seven benchmark data sets using different classification techniques and was found to be very competitive when compared to other classifiers

Sprouty2 loss‐induced IL6 drives castration‐resistant prostate cancer through scavenger receptor B1

Metastatic castration‐resistant prostate cancer (mCRPC) is a lethal form of treatment‐resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre‐clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self‐sufficient form of CRPC. Mechanistically, HER2‐IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1‐mediated cholesterol uptake in SPRY2‐deficient tumours. Systemically, IL6 elevated the levels of circulating cholesterol by inducing host adipose lipolysis and hepatic cholesterol biosynthesis. SPRY2‐deficient CRPC is dependent on cholesterol bioavailability and SRB1‐mediated tumoral cholesterol uptake for androgen biosynthesis. Importantly, treatment with ITX5061, a clinically safe SRB1 antagonist, decreased treatment resistance. Our results indicate that cholesterol transport blockade may be effective against SPRY2‐deficient CRPC

Abundance and stomach content analysis of threadfin shad in Lake Mead, Nevada: Do invasive quagga mussels affect this prey species?

Lake Mead, Nevada is the largest reservoir by volume in the United States, as well as a popular sport fishing destination. In January 2007, the invasive quagga mussel Dreissena rostriformis bugensis (Andrusov, 1897) was discovered in the reservoir and concerns began to arise about potential alterations to the aquatic environment. The Lake Mead sport fishery is reliant on the sustainability of prey species like the threadfin shad [Dorosoma petenense (Günther, 1867)]. This study examined 20-year trends in historic abundance of the threadfin shad, before, and shortly after, the discovery of quagga mussels in the system. Larval shad trawl data collected in Las Vegas Bay and Overton Arm portions of Lake Mead were analyzed in the present study. Two-way analysis of variances showed that the abundance of this prey fish has not changed following quagga mussel invasion (P \u3e 0.05). Post-quagga mussel discovery collections of adult threadfin shad from Las Vegas Bay ranged from 113 to 212 mm total length (TL) (mean = 184 mm; n = 170). Shad from Overton Arm ranged from 131 to 197 mm TL (mean = 150 mm; n = 27). Stomach contents were analyzed. The proportion of cladocerans in stomach contents differed significantly from spring to winter in Las Vegas Bay (P = 0.008); whereas the proportion of copepods did not show statistically relevant differences regarding seasonality (P = 0.562). Initial trends in lower trophic level dynamics in response to quagga mussel invasion has yet to reveal significant effects in Las Vegas Bay or Overton Arm. Long-term monitoring on threadfin shad is needed to evaluate potential impacts from invasive quagga mussels in Lake Mead

Physiological Profile of Male Competitive and Recreational Surfers

Surfing consists of both high- and low-intensity paddling of varying durations, using both the aerobic and anaerobic systems. Surf-specific physiological studies lack adequate group sample sizes, and V[Combining Dot Above]O2peak values are yet to determine the differences between competitive and recreational surfers. The purpose of this study was therefore to provide a comprehensive physiological profile of both recreational and competitive surfers. This multisite study involved 62 male surfers, recreational (n = 47) and competitive (n = 15). Anthropometric measurements were conducted followed by dual-energy x-ray absorptiometry, anaerobic testing and finally aerobic testing. V[Combining Dot Above]O2peak was significantly greater in competitive surfers than in recreational surfers (M = 40.71 ± 3.28 vs. 31.25 ± 6.31 ml·kg·min, p \u3c 0.001). This was also paralleled for anaerobic power (M = 303.93 vs. 264.58 W) for competitive surfers. Arm span and lean total muscle mass was significantly (p ≤ 0.01) correlated with key performance variables (V[Combining Dot Above]O2peak and anaerobic power). No significant (p ≥ 0.05) correlations were revealed between season rank and each of the variables of interest (V[Combining Dot Above]O2peak and anaerobic power). Key performance variables (V[Combining Dot Above]O2peak and anaerobic power) are significantly higher in competitive surfers, indicating that this is both an adaptation and requirement in this cohort. This battery of physiological tests could be used as a screening tool to identify an athlete\u27s weaknesses or strengths. Coaches and clinicians could then select appropriate training regimes to address weaknesses