The regeneration capacity of caudal fin in the common tooth-carp, Aphanius dispar (Rí¼ppell, 1829) (Teleostei: Cyprinodontidae)

Regeneration ability is known for several Actinopterygii or ray-finned fishes. In order to assess the universality of regenerative potencies in this group of fishes, we have examined for the first time, caudal fin regeneration in tooth-carp, Aphanius dispar (Rí¼ppell, 1829). The caudal fin is used because of its accessibility, simple structure and fast regeneration. The results revealed the regeneration ability in caudal fin of A. dispar. The initiation of the regenerative outgrowth was differing in three examined water temperatures. It is started approximately 5 days post amputation (5 dpa) at room temperature, and 2 dpa at 25°Ð¡ and 28°Ð¡. Our finding indicates that water temperature more than 25°Ð¡ promotes procedure in caudal fin regeneration of A. dispar. By considering the high regeneration ability in A. dispar, and also the relatively short life span of the members of the genus Aphanius, we concluded that these fishes could probably be used in regeneration researches. However, details of this mechanism in Aphanius need further examinations

Isolation, characterization, and expansion of heterogeneous circulating tumor cell (CTC) populations from cancer patients using microfluidic technologies

Circulating tumor cells (CTCs) are cancerous cells that shed from a primary tumor, intravasate into blood, travel through the blood circulation, and then extravasate to distant organs and form secondary tumors. Hence, CTCs are critical to understand the biological process of metastasis and could serve as potential blood-based surrogate markers to noninvasively evaluate tumor progression and response to treatment. Although isolation of CTCs from pancreatic adenocarcinoma (PDAC) patients is feasible, investigating their clinical utility has proven less successful than in other cancers due to limitations of epithelial cellular adhesion molecule (EpCAM)-only based CTC assays. We developed a "Carpet Chip” using sequential immunoaffinity-based microfluidics to study the biological relevance of heterogeneous CTCs. Both epithelial (EpCs) and epithelial-to-mesenchymal transition (EMT)-like CTCs (EMTCs) were detected from the blood of PDAC patients (n=35). Thirty-four patients had ≥5 EpCs mL−1 and 35 patients had ≥15 EMTCs mL−1. Overall, significantly higher numbers of EMTCs than EpCs were recovered, reflecting the aggressive nature of PDAC. Furthermore, higher numbers of EMTCs were observed in patients with lymph node involvement compared to patients without. Gene expression profiling of CTCs from 17 patients revealed that CXCR1 is significantly upregulated in EpCs, while known stem cell markers POU5F1, or Oct-4 and MYC were upregulated in EMTCs. Thus, successful isolation and genomic profiling of heterogeneous CTC populations were demonstrated, revealing genetic signatures relevant to patient outcomes. Individualizing therapies targeting genes involved in EMT could reduce metastasis and improve patient survival. In further studies on PDAC patients, the utility of CTCs as a tool was validated for assessing tumor response to the only three therapy options currently available: surgery, chemotherapy, and radiotherapy. For all treatment options, we observed a statistically significant decrease in CTC counts after treatment completion, which was associated with prolonged OS. Orthogonally, in an effort to develop label-free technologies for CTC isolation, a microfluidic Labyrinth device for high throughput, label-free, size-based isolation of CTCs was applied to study CTCs from metastatic non-small cell lung cancer patients (NSCLC). Current methods for isolation of lung CTCs mostly rely on biomarker dependent antibody-based capture, missing populations that may be stem-like in nature. Using Labyrinth operating at a flow rate of 2.5 mL/min, heterogeneous CTC populations were isolated from NSCLC patients (n=21). Detected populations included CTCs (PanCK+ and CD45-), CTCs expressing EpCAM or Vimentin, and CTCs expressing both markers representing an EMT-like population of CTCs. We were able to isolate CTCs from 100% of patients with an average yield of 180±168 CTCs mL-1. Among captured CTCs, EpCAM- CTCs were significantly more common than EpCAM+ CTCs (115.7 vs. 39.1 CTCs mL-1 respectively). Cell clusters of 2 or more CTCs were also observed in 95% of patients; 79% of these clusters were negative for EpCAM expression, whereas 35% expressed Vimentin, suggestive of an EMT phenotype. Recovered CTCs from patients with RET, ROS1 and ALK rearrangements in tumors showed aberrations matching the primary tumor for each gene using FISH analysis. We successfully expanded CTCs in vitro and the cultured cells carried matched mutations. The Labyrinth device demonstrated the advantages of marker-independent separation methods for isolation of heterogonous CTC sub-populations in lung cancer for CTC expansion, allowing drug testing for therapies targeting specific driver mutations. The capability of collecting recovered CTCs from the device using a continuous processing technique opens up opportunities for not only CTC expansion off-chip, but also ex-vivo drug testing to direct patient-specific therapies

Provincial health accounts in Kerman, Iran: an evidence of a “mixed” healthcare financing system

Background: Provincial Health Accounts (PHA) as a subset of National Health Accounts (NHA) present financial information for health sectors. It leads to a logical decision making for policy-makers in order to achieve health system goals, especially Fair Financial Contribution (FFC). This study aimed to examine Health Accounts in Kerman Province. Methods: The present analytical study was carried out retrospectively between 2008 and 2011. The research population consisted of urban and rural households as well as providers and financial agents in health sectors of Kerman Province. The purposeful sampling included 16 provincial organizations. To complete data, the report on Kerman household expenditure was taken as a data source from the Governor-General’s office. In order to classify the data, the International Classification for Health Accounts (ICHA) method was used, in which data set was adjusted for the province. Results: During the study, the governmental and non-governmental fund shares of the health sector in Kerman were 27.22% and 72.78% respectively. The main portion of financial sources (59.41) was related to private household funds, of which the Out-of-Pocket (OOP) payment mounted to 92.35%. Overall, 54.86% of all financial sources were covered by OOP. The greatest portion of expenditure of Total Healthcare Expenditures (THEs) (65.19%) was related to curative services. Conclusion: The major portion of healthcare expenditures was related to the OOP payment which is compatible with the national average rate in Iran. However, health expenditure per capita, was two and a half times higher than the national average. By emphasizing on Social Determinant of Health (SDH) approach in the Iranian health system, the portion of OOP payment and curative expenditure are expected to be controlled in the medium term. It is suggested that PHA should be examined annually in a more comprehensive manner to monitor initiatives and reforms in healthcare s e c tor

A Radial Flow Microfluidic Device for Ultra‐High‐Throughput Affinity‐Based Isolation of Circulating Tumor Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110045/1/smll201400719.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110045/2/smll201400719-sup-0001-S1.pd

Ultra‐Specific Isolation of Circulating Tumor Cells Enables Rare‐Cell RNA Profiling

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134266/1/advs147_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134266/2/advs147-sup-0001-S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134266/3/advs147.pd

Profiling Heterogeneous Circulating Tumor Cells (CTC) Populations in Pancreatic Cancer Using a Serial Microfluidic CTC Carpet Chip

Although isolation of circulating tumor cells (CTCs) from pancreatic adenocarcinoma patients is feasible, investigating their clinical utility has proven less successful than other cancers due to the limitations of epithelial cellular adhesion molecule (EpCAM)‐only based CTC assays. An integrated technology‐ and biology‐based approach using a microfluidic “Carpet Chip” is presented to study the biological relevance of heterogeneous CTC populations. Both epithelial CTCs (EpCs) and epithelial‐to‐mesenchymal transition (EMT)‐like CTCs (EMTCs) are isolated simultaneously from the whole blood of pancreatic cancer (PaCa) patients (n = 35) by separately targeting two surface markers: EpCAM and CD133. Recovery of cancer cell lines spiked into whole blood is ≥97% with >76% purity. Thirty‐four patients had ≥5 EpCs mL−1 and 35 patients had ≥15 EMTCs mL−1. Overall, significantly higher numbers of EMTCs than EpCs are recovered, reflecting the aggressive nature of PaCa. Furthermore, higher numbers of EMTCs are observed in patients with lymph node involvement compared to patients without. Gene expression profiling of CTCs from 17 patients reveals that CXCR1 is significantly upregulated in EpCs, while known stem cell markers POU5F1/Oct‐4 and MYC are upregulated in EMTCs. In conclusion, successful isolation and genomic profiling of heterogeneous CTC populations are demonstrated, revealing genetic signatures relevant to patient outcomes.“Carpet Chip” uses sequential immunoaffinity‐based microfluidics to study the biological relevance of heterogeneous circulating tumor cell (CTCs). Both epithelial (EpCs) and epithelial‐to‐mesenchymal transition (EMT)‐like CTCs (EMTCs) are detectable from the blood of pancreatic cancer patients. Based on our observations of EMTCs and patient lymph node involvement, individualizing therapies targeting genes involved in EMT could reduce metastasis, thereby improving patient survival.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147173/1/adbi201800228-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147173/2/adbi201800228.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147173/3/adbi201800228_am.pd

High-Throughput Label-Free Isolation of Heterogeneous Circulating Tumor Cells and CTC Clusters from Non-Small-Cell Lung Cancer Patients.

(1) Background: Circulating tumor cell (CTC) clusters are emerging as clinically significant harbingers of metastases in solid organ cancers. Prior to engaging these CTC clusters in animal models of metastases, it is imperative for technology to identify them with high sensitivity. These clusters often present heterogeneous surface markers and current methods for isolation of clusters may fall short. (2) Methods: We applied an inertial microfluidic Labyrinth device for high-throughput, biomarker-independent, size-based isolation of CTCs/CTC clusters from patients with metastatic non-small-cell lung cancer (NSCLC). (3) Results: Using Labyrinth, CTCs (PanCK+/DAPI+/CD45-) were isolated from patients (n = 25). Heterogeneous CTC populations, including CTCs expressing epithelial (EpCAM), mesenchymal (Vimentin) or both markers were detected. CTCs were isolated from 100% of patients (417 +/- 1023 CTCs/mL). EpCAM- CTCs were significantly greater than EpCAM+ CTCs. Cell clusters of \u3e/=2 CTCs were observed in 96% of patients-of which, 75% were EpCAM-. CTCs revealed identical genetic aberrations as the primary tumor for RET, ROS1, and ALK genes using fluorescence in situ hybridization (FISH) analysis. (4) Conclusions: The Labyrinth device recovered heterogeneous CTCs in 100% and CTC clusters in 96% of patients with metastatic NSCLC. The majority of recovered CTCs/clusters were EpCAM-, suggesting that these would have been missed using traditional antibody-based capture methods

Provincial Health Accounts in Kerman, Iran: An Evidence of a “Mixed” Healthcare Financing System

Background Provincial Health Accounts (PHA) as a subset of National Health Accounts (NHA) present financial information for health sectors. It leads to a logical decision making for policy-makers in order to achieve health system goals, especially Fair Financial Contribution (FFC). This study aimed to examine Health Accounts in Kerman Province. Methods The present analytical study was carried out retrospectively between 2008 and 2011. The research population consisted of urban and rural households as well as providers and financial agents in health sectors of Kerman Province. The purposeful sampling included 16 provincial organizations. To complete data, the report on Kerman household expenditure was taken as a data source from the Governor-General’s office. In order to classify the data, the International Classification for Health Accounts (ICHA) method was used, in which data set was adjusted for the province. Results During the study, the governmental and non-governmental fund shares of the health sector in Kerman were 27.22% and 72.78% respectively. The main portion of financial sources (59.41) was related to private household funds, of which the Out-of-Pocket (OOP) payment mounted to 92.35%. Overall, 54.86% of all financial sources were covered by OOP. The greatest portion of expenditure of Total Healthcare Expenditures (THEs) (65.19%) was related to curative services. Conclusion The major portion of healthcare expenditures was related to the OOP payment which is compatible with the national average rate in Iran. However, health expenditure per capita, was two and a half times higher than the national average. By performing the Family Physician Program (FPP) and emphasizing Social Determinant of Health (SDH) approach in the Iranian health system, the portion of OOP payment and curative expenditure are expected to be controlled in the medium term. It is suggested that PHA should be examined annually in a more comprehensive manner to monitor initiatives and reforms in healthcare sector

Regenerative medicine in the treatment of specific dermatologic disorders: a systematic review of randomized controlled clinical trials

Abstract Aims and objectives The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study. Method Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events. Results In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte–keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP. Conclusion Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study

MRS Shimming: An Important Point Which Should not be Ignored

Introduction: Proton magnetic resonance spectroscopy (MRS) is a well-known device for analyzing the biological fluids metabolically. Obtaining accurate and reliable information via MRS needs a homogeneous magnetic field in order to provide well-defined peaks and uniform water suppression. There are lots of reasons which can disturb the magnetic field homogeneity which can be corrected by a process known as shimming. This study is intended to recall the importance of shimming and also the significant role of quality control (QC) in achieving an accurate quantification. Material and Method: An acrylic cylindrical quality control phantom was designed as an analog of brain MRS test phantoms in order to control the accuracy of the obtained signal of a 1.5 T Siemens MRI system which belonged to one of Shiraz hospitals. The signal of NAA, Cho, Cr, the combination of these metabolites and also the distilled water, which was used in this study, was evaluated using separate phantoms. A QC test was performed using Siemens QC phantom and a standard test phantom. Results: The spectrum of our home- made phantom had a significant difference with the expected spectrum. The results of checking the spectrum of metabolites separately also confirmed that there was a systemic problem that affects all the signals originated from all metabolites and even the pure distilled water. The MRS system could not pass QC tests, and peak broadening was common in all spectra. The complex spectrum of standard test phantom was not produced successfully by the MRS system. Discussion: By a simple check of the water peak characteristics, lots of information can be obtained, one of which is the status of shimming that has a considerable effect on the accuracy of the spectrum. Thus, performing an automatic or manual shimming is not a criterion of the spectrum accuracy, and performing a periodic quality control using a test phantom by a specialist is necessary. Conclusion: Briefly, the quality control of MRS and all the other clinical device must be taken seriously. Sometimes QC can be the boundary of a right or a wrong decision for the patient