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Introduction: The outcomes of palliative radiation therapy (RT) for neuroendocrine neoplasms (NEN) are seldom reported. We investigated outcomes following palliative radiotherapy in a cohort of patients with NENs. We hypothesised that well‐differentiated NEN will be less likely to have a clinical response than poorly differentiated NEN. Methods: Patients who received at least one course of palliative RT were identified using the New Zealand NETwork! Registry. Patients with Merkel cell carcinoma, pulmonary small cell carcinoma or asymptomatic patients were excluded. Clinical response to RT within 90 days and overall survival were analysed alongside clinical variables (fractionation, RT site, tumour differentiation and tumour primary site). Results: The cohort comprised 79 patients, with 147 courses of palliative RT delivered. Clinical response was measurable for 100 courses, with clinical response rate of 76%. A course delivered to a well‐differentiated NEN was associated with 2.02‐fold (95% CI 0.67, 6.12; P = 0.21) increase in odds of a clinical response compared to a poorly differentiated NEN. Median overall survival from the first fraction of RT was 94 days (95% CI 80, 138 days). Overall survival was higher in well‐differentiated NEN than in poorly differentiated NEN (HR 0.2, 95% CI 0.10–0.40, P‐value < 0.001); 30‐day mortality was 7%. There were significantly reduced odds of clinical response for non‐bone sites, and for courses >10 fractions compared to a single fraction. Conclusion: Palliative RT is an appropriate option for management of symptoms in patients with both well‐ and poorly differentiated metastatic NEN. [ABSTRACT FROM AUTHOR]

BACKGROUND: Buccal fat pads are often used to repair oral and maxillofacial defects, which can rapidly differentiate the oral mucosa from the epithelium. Because the defect wound is exposed to saliva, it is believed that saliva may promote the epithelialization of adipose stem cells in the buccal fat pad. OBJECTIVE: To investigate the feasibility of promoting epithelial differentiation of rabbit adipose stem cells by induction of saliva in vitro. METHODS: Fat harvested from 2-3 months New Zealand white rabbit was isolated, cultured, generated adipose stem cells for passage. Passage 3 adipose stem cells were divided into three groups: negative control group, epidermal growth factor group and saliva group. Adipose stem cells were induced by 10 μg/L epidermal growth factor and 15% saliva in the epidermal growth factor group and saliva group. Cell morphology changes were observed under inverted microscope. The expression of cytokeratin 19 was detected by immunofluorescence and RT-PCR after 7 and 14 days of induction. RESULTS AND CONCLUSION: (1) After saliva induction, the morphology of adipose stem cells was gradually changed from long spindle shape to short spindle shape or even irregular oblate shape. (2) At 7 and 14 days, cytokeratin 19 was positively expressed in the epidermal growth factor and saliva groups, which was higher than that in the negative control group. The expression level of cytokeratin 19 in the 14-day induction group was significantly higher than that in the 7-day induction group. (3) The expression of cytokeratin 19 mRNA in epidermal growth factor and saliva groups was higher than that in negative control group (P < 0.01). The expression level at 14 days was significantly higher than that at 7 days (P < 0.01). (4) Results suggest that saliva can promote the epithelial differentiation of adipose stem cells to some extent. [ABSTRACT FROM AUTHOR]

To explore indicators that predict whether patients with extremity pain have a spinal or extremity source of pain. The data were from a prospective cohort study (n = 369). Potential indicators were gathered from a typical Mechanical Diagnosis and Therapy (MDT) history and examination. A stepwise logistic regression with a backward elimination was performed to determine which indicators predict classification into spinal or extremity source groups. A Receiver Operating Characteristic (ROC) curve was constructed to examine the number of significant indicators that could predict group classification. Five indicators were identified to predict group classification. Classification into the spinal group was associated with the presence of paresthesia [odds ratio (OR) 1.984], change in symptoms with sitting/neck or trunk flexion/turning neck/when still (OR 2.642), change in symptoms with posture change (OR 3.956), restrictions in spinal movements (OR 2.633), and no restrictions in extremity movements (OR 2.241). The optimal number of indicators for classification was two (sensitivity = 0.638, specificity = 0.807). This study provides guidance on clinical indicators that predict the source of symptoms for isolated extremity pain. The clinical indicators will allow clinicians to supplement their decision-making process in regard to spinal and extremity differentiation so as to appropriately target their examinations and interventions. [ABSTRACT FROM AUTHOR]

We aimed to generate human induced pluripotent stem cell (iPSC) lines from New Zealand donors. These lines are the first to be generated in New Zealand. Human dermal fibroblasts were collected from two individual donors and reprogrammed with the human OSKM transcription factors using the Sendai virus system. Emerging iPSC colonies were picked, expanded and karyotyped. Clones with normal karyotype were characterised for pluripotency marker expression, p53 mutational status and trilineage differentiation potential. The MANZ-2-2 and MANZ-4-37 iPSC lines showed normal karyotype and expressed pluripotency markers at RNA and protein levels without detectable transgene expression. Both lines differentiated into the three germ layers in vitro and passed the hPSC Scorecard assay for pluripotency and trilineage differentiation. Furthermore, both lines were susceptible to cell apoptosis mediated by nutlin-3a indicative of their wildtype p53 status. This study presents the successful derivation and characterisation of iPSC lines derived from New Zealand donors. These lines will facilitate iPSC-based research in New Zealand and beyond. [ABSTRACT FROM AUTHOR]

Pyroxene crystals from recent Central Plateau tephras are used to deduce their formation conditions through two-pyroxene thermobarometry. Crystals return pseudo-pressures and pseudo-temperatures that are artefacts of uptake of antecrysts formed at a range of crustal levels by isobaric cooling of previously intruded magmas. MELTS modelling of tephra glass compositions shows that pseudo-PT conditions are reproduced at oxygen fugacities above the nickel-nickel oxide buffer (NNO+1, NNO+2), mid- to upper crustal pressures (100–400 MPa), and temperatures between c. 900°C and >1100°C. Modelled crystals from the deep crust (800 MPa) are restricted to clinopyroxenes. However, these display chemical equilibrium with shallow orthopyroxenes at higher pseudo-PT conditions than observed in Central Plateau pyroxenes. The data indicate uptake of high-temperature pyroxenes at mid- to shallow crustal levels into ascending andesitic melts and thus preclude the presence of long-lived crustal mush zones (<1000°C) as a source for the crystal cargo of the Central Plateau tephras studied here. Further, the apparent absence of deep crustal pyroxene antecrysts does not preclude models of arc andesite genesis without a 'deep crustal hot zone' beneath the Central Plateau. Generation and ascent of primary andesites from a heterogeneous mantle wedge is therefore a possible scenario at the southern Hikurangi margin. [ABSTRACT FROM AUTHOR]

Objective: Glucagon-like peptide-1 (GLP-1) has attracted tremendous attention for treatment of diabetes. Likewise, it seems that active ingredients of chamomile oil might have anti-diabetic effects. This work was conducted to investigate the effects of the combination of GLP-1 and chamomile oil on differentiation of mesenchymal stem cells (MSCs) into functional insulin-producing cells (IPCs). Materials and Methods: In this experimental study, adipose MSCs derived from the adult male New Zealand white rabbits were assigned into four groups: control (without any treatment); GLP-1 (in which cells were treated with 10 nM GLP-1 every other day for 5 days); chamomile oil (in which cells were treated with 100 ug/ml Matricaria chamomilla L. flower oil every other day for 5 days); and GLP-1+ chamomile oil (in which cells were treated with 10 nM GLP-1 and 100 μg/ml M. chamomilla flower oil every other day for 5 days). Characterization of isolated MSCs was performed using flow cytometry, Alizarin red S staining and Oil red O staining. The expressions of genes specific for IPCs were measured using reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Measurement of insulin and the cleaved connecting peptide (C-peptide) in response to different concentrations of glucose, were performed using ELISA kits. Results: Our results demonstrated that isolated cells highly expressed MSC markers and were able to differentiate into osteocytes and adipocytes. Additionally, using GLP-1 in combination with chamomile oil exhibited higher levels of IPCs gene markers including NK homeobox gene 2.2 (NKX-2.2), paired box gene 4 (PAX4), insulin (INS) and pancreatic duodenal homeobox-1 (PDX1) as well as insulin and C-peptide secretion in response to different glucose concentrations compared to GLP-1 or chamomile oil alone (P<0.05). Conclusion: Collectively, these findings establish a substantial foundation for using peptides in combination with natural products to obtain higher efficiency in regenerative medicine and peptide therapy. [ABSTRACT FROM AUTHOR]

Keratocytes are the main cellular components of the corneal stroma. This cell is quiescent and cannot be cultured easily. The aim of this study was to investigate differentiate human adipose mesenchymal stem cells (hADSCs) into corneal keratocyte cells by combining natural scaffolds and conditioned medium (CM) and evaluating their safety in the rabbit's cornea. Keratocytes were cultured in an optimal culture medium and this medium was collected and kept as a CM. hADSCs were cultured on the decellularized human small incision lenticule extraction (SMILE) lenticule (SL), amniotic membrane (AM), and collagen-coated plates, and were exposed to keratocyte-CM (KCM) for 7, 14, and 21 days. Differentiation was evaluated using Real-time PCR and immunocytochemistry (ICC). hADSCs were cultured on the SL scaffolds and implanted in the corneal stroma of 8 New Zealand male rabbits. Rabbits were followed for 3 months and the safety was evaluated by clinical and histological variables. Real-time PCR results showed a significant increase in the expression of keratocyte-specific markers on the 21 day of differentiation compared to the control group. ICC also confirmed the induction of differentiation. Implantation of SLs containing differentiated cells in the cornea of animals showed no serious complications including neovascularization, corneal opacity, inflammation, or signs of tissue rejection. Furthermore, the evaluation of the presence of keratocyte-like cells after three months in the rabbit stroma was confirmed by Real-time PCR and immunohistochemistry (IHC) analysis. Our results showed that combination of combination of corneal extracellular matrix and KCM can induced keratocytes differentiation of hADSC and can be introduced as a alternative method to supply the required keratocytes in corneal tissue engineering. [Display omitted] • The conditioned medium contains natural and specific differentiation factors. • The use of cell niches plays an important role in inducing differentiation. • Simultaneous use of niche and conditioned medium increases differentiation. • The use of Stem cells differentiated by this method in the animal model is safe. • Differentiated stem cells have good survival in the cornea of animals. [ABSTRACT FROM AUTHOR]

Objective(s): Throughout evolution, mammalians have increasingly lost their ability to regenerate structures however rabbits are exceptional since they develop a blastema in their ear wound for regeneration purposes. Blastema consists of a group of undifferentiated cells capable of dividing and differentiating into the ear tissue. The objective of the present study is to isolate, culture expand, and characterize blastema progenitor cells in terms of their in vitro differentiation capacity. Materials and Methods: Five New Zealand white male rabbits were used in the present study. Using a punching apparatus, a 4-mm hole was created in the animal ears. Following 4 days, the blastema ring which was created in the periphery of primary hole in the ears was removed and cultivated. The cells migrated from the blastema were expanded through 3 successive subcultures and characterized in terms of their potential differentiation, growth characteristics, and culture requirements. Results: The primary cultures tended to be morphologically heterogeneous having spindly-shaped fibroblast-like cells as well as flattened cells. Fibroblast-like cells survived and dominated the cultures. These cells tended to have the osteogenic, chondrogenic, and adipogenic differentiation potentials. They were highly colonogenic and maximum proliferation was achieved when the cells were plated at density of 100 cells/cm2 in a medium which contained 10% fetal bovine serum (FBS). Conclusion: Taken together, blastema tissue-derived stem cells from rabbit ear are of mesenchymal stem cell-like population. Studies similar to this will assist scientist better understanding the nature of blastema tissue formed at rabbit ear to regenerate the wound. [ABSTRACT FROM AUTHOR]

Tissue engineering is clinically promising for missing and damaged tissues. Adipose-derived stem cells (ASCs), a type of mesenchymal stem cells, represent a reliable source of seed cells for tissue engineering with multiple merits such as minimal invasion, abundant yield, little immunity, low morbidity, easy isolation, and rapid expansion. However, because the properties of adipose tissue-derived cells differ depending on the fat depot from which they are derived, we compared the ASCs from three anatomic sites of New Zealand white rabbits: subcutaneous inguinal (SI), subcutaneous dorsocervical (SD), and retroperitoneal perinephric (RP) regions. We investigated cellular behaviors including proliferation, viability, and differentiation. The ASCs of the subcutaneous regions (SI and SD) had higher performances in all assessments compared to those of the RP region. Moreover, the SI and SD ASCs had significant differences, with SI ASCs having better properties than SD ASCs. We conclude that the different anatomic distributions of fat contribute to the different behaviors of ASCs. The SI region offers the most applicable cell source reservoir for ASC tissue engineering. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Using the explanatory conceptual framework developed as part of the South Africa--Norway Tertiary Education Development Project, the Bachelor of Natural Medicine at the South Pacific College of Natural Therapies (SPCNT) was analysed in order to distinguish between different forms of knowledge, curriculum logics, and cognitive complexity within the curriculum. The findings suggest that the Bachelor of Natural Medicine at SPCNT has an overall contextual curriculum logic. There is a strong core of proceduralised conceptual knowledge base (with overarching contextual coherence). A significant proportion of proceduralised conceptual knowledge (with overarching conceptual coherence) can also be detected. The cognitive complexity increases from Years 1 to 3. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a tissue culture system which closely mimics the in situ lacrimal gland for improved study of lacrimal acinar cell physiology. Highly purified preparations of lacrimal acinar cells from adult female New Zealand White rabbits were isolated and grown in suspension culture in the form of Matrigel ‘rafts’, i.e., aggregates of acinar cells enclosed within a Matrigel coating. The rafts were seeded onto Matrigel-coated culture plates and their growth was followed for up to 28 days. Immunohistochemistry was used to demonstrate the cellular sites of prolactin (PRL), epidermal growth factor (EGF), basic fibroblast growth factor (FGF-2), secretory component (SC) and major histocompatibility complex class-II molecules (MHC-II) within the acinar cells. By 3 days the cultures contained numerous, well-formed acini enclosed within the Matrigel. The acinar epithelial cells demonstrated histotypic polarity, with large, pale-staining, secretory granules aggregated adjacent to the lumen, and exocytotic release of secretory material into the lumen. From 5–10 days the pale-staining secretory granules decreased in number, while the lumenal contents of the acini increased in staining density. Throughout the culturing period as the pale-staining, secretory granules decreased in number, smaller more densely stained, secretory granules increased in number. The number of cells and size of acinar clusters increased steadily throughout the culturing period, and acini frequently achieved dimensions in excess of 0.5 mm. Increases in the size of acinar clusters were often accompanied by an increase in the size of the lumen. Frequently the lumen and its contents bulged asymmetrically towards one edge of the acinus. Immunhistochemistry demonstrated PRL and EGF within the lumens and within the apical cytoplasm of the acinar cells. Acini were strongly immunopositive for SC throughout the 28 day culture period, whereas immunopositivity for MHC-II molecules was strong initially, but diminished dramatically by 21 days. Immunostaining for FGF-2 was most intense on days 1 and 3, with staining throughout the cytoplasm, but became progressively more localized to the periphery of the acini as the culture period lengthened. In cultures of 1–28 days duration, Western blots of cell lysates demonstrated a major band (approximately 40 kDa) for PRL in 3–28 day preparations; a major band (approximately 80 kDa) for SC in 3 day and 7 day preparations that decreased in intensity in 14–28 day preparations; and a major band (approximately 23 kDa) for MHC-II protein in 1–21 day preparations that decreased in intensity in 28 day preparations. Lysosomes increased in number with time in culture, becoming a dominant cytoplasmic feature in 21 and 28 day cultures. Carbachol stimulation of 4 day rafts resulted in increased release of β-hexosaminidase and SC from the rafts. The authors conclude that Matrigel rafts containing purified lacrimal gland acinar cells offer a highly advantageous system for study of lacrimal acinar cell function and one that correlates well with the in situ gland. [ABSTRACT FROM AUTHOR]