Clinical evaluation of a fully electronic microfluidic white blood cell analyzer.

The White Blood Cell (WBC) count is one of the key parameters signaling the health of the immune system. Abnormal WBC counts often signal a systemic insult to the body such as an underlying infection or an adverse side effect to medication. Typically, the blood collected is sent to a central lab for testing, and results come back within hours, which is often inconvenient and may delay time-sensitive diagnosis or treatment. Here, we present the CytoTracker, a fully electronic, microfluidic based instant WBC analyzer with the potential to be used at point-of-care. The CytoTracker is a lightweight, portable, affordable platform capable of quantifying WBCs within minutes using only 50 µl of blood (approximately one drop of blood). In this study, we clinically evaluated the accuracy and performance of CytoTracker in measuring WBC and granulocyte counts. A total of 210 adult patients were recruited in the study. We validated the CytoTracker against a standard benchtop analyzer (Horiba Point of Care Hematology Analyzer, ABX Micros 60). Linear dynamic ranges of 2.5 k/µl- 35 k/µl and 0.6 k/µl- 26 k/µl were achieved for total WBC count and granulocyte count with correlation coefficients of 0.97 and 0.98. In addition, we verified CytoTracker's capability of identifying abnormal blood counts with above 90% sensitivity and specificity. The promising results of this clinical validation study demonstrate the potential for the use of the CytoTracker as a reliable and accurate point-of-care WBC analyzer.

The Disruption of Mage-11 Gene via CRISPR/Cas9 Method Induced Apoptosis in the in vitro Model of Prostate Cancer.

BACKGROUNDS AND AIMS: Prostate cancer is the most common malignant cancer among men and is the second deadliest cancer in men after lung cancer. Understanding the molecular mechanisms involved in development and progression of prostate cancer is essential to improve both diagnostic and therapeutic strategies in this regard. In addition, using novel gene therapy-based methods for treatment of cancers has gotten increasing attention during the recent years. Accordingly, this study was aimed to evaluate the inhibitory effect of MAGE-A11 gene, as an important oncogene involved in the pathophysiology of prostate cancer invitro model. The study was also aimed to evaluate the downstream genes related to MAGE-A11. MATERIALS AND METHODS: First, MAGE-A11 gene was knocked out in PC-3 cell line using "Clustered regularly interspaced short palindromic repeats" (CRISPR)/ "CRISPR-associated genes 9" (CRISPR/Cas9) method. Next, the expression levels of MAGE-A11, survivin and Ribonucleotide Reductase Small Subunit M2 (RRM2) genes were determined by quantitative polymerase chain reaction (qPCR) technique. The levels of proliferation and apoptosis were also analyzed in PC-3 cells using CCK-8 and Annexin V-PE/7-AAD assays. RESULTS: The results showed that the disruption of MAGE-A11 by CRISPR/Cas9 method significantly decreased proliferation (P< 0.0001) and enhanced apoptosis (P< 0.05) in PC-3 cells compared to control group. Moreover, the disruption of MAGE-A11 significantly down regulated the expression levels of survivin and RRM2 genes (P< 0.05). CONCLUSION: Our results demonstrated that knocking out MAGE-11 gene by CRISPR/CAS9 technique could efficiently inhibit cell proliferation and induce apoptosis in PC3 cells. Survivin and RRM2 genes might also participated in these processes.

A Multi-Criteria Approach for Comparison of Ginger Extract and Conventional Irrigants in Root Canal Treatment.

Background Considering the importance of irrigation in dental root canal treatment, there is an urgent need to find a risk-free bioactive and antibacterial endodontic solution. Enterococcus faecalis, an anaerobic gram-positive coccus, has been identified as the main reason for endodontic infections. Several studies have been conducted on E. faecalis and periapical infection. Nowadays, plants used in traditional medicine play a role that is widely appreciated by researchers. One of these herbs is ginger which shows an acceptable antimicrobial effect on E. faecalis. Due to the highly crucial role that irrigation plays in the success of endodontic treatment, a comprehensive survey based on several criteria, namely, scientific, technical, and empirical, is required to address the goal of determining the best endodontic solution. Methodology The most important criteria are antibacterial activity, risks and hazards, cost, and availability. In this study, the analytical network process (ANP), which is a multi-criteria decision-making method, was applied to determine the best endodontic irrigant. Results Several alternatives were investigated using the ANP. In this study, 5.25% sodium hypochlorite (NaOCl) and 2% chlorhexidine were at the top of the list. According to the sensitivity analysis, 10% ethanolic ginger extract showed comparable results to 2.5% NaOCl. Conclusions To carefully prioritize endodontic irrigants a wide range of standards and criteria should be considered. Considering the low risk, great wettability, and active compounds of ginger extract, it can be a promising viable risk-free solution for root canal treatments.

Over-expression of survivin could prevent the oxidative stress and toxicity of rotenone in SH-SY5Y cells.

Objectives: It is important to find novel therapeutic molecular targets for curing Parkinson's disease (PD). Accordingly, this study aimed to evaluate the effect of over-expression of the survivin gene, a gene frequently reported as neuroprotective, on the in vitro model of PD. Materials and Methods: Survivin was over-expressed in SH-SY5Y cells. Next, the cells were treated with rotenone (500 nM) for 24 hr. Then, viability and the total antioxidant capacity were assessed. The expression levels of 15 important genes of key cellular processes (oxidative stress, apoptosis, cell cycle, and autophagy) were assessed. The studied genes included survivin, superoxide dismutase, catalase, BAX, bcl2, caspase 3, caspase 8, caspase 9, p53, SMAC, ß-catenin, mTOR, AMPK, ATG7, RPS18. The apoptosis level and the frequency of cell cycle stages were assessed by flow cytometry. For analyzing the data, the ANOVA test followed by Tukey's test was used to evaluate the significant differences between the experimental groups. P<0.05 was considered significant. Results: Survivin could significantly decrease the rotenone-induced apoptosis in SH-SY5Y cells. The rotenone treatment led to down-regulation of catalase and up-regulation of bax, bcl2, caspase 3, caspase 8, P53, ß-catenin, and ATG7. Survivin could significantly neutralize the effect of rotenone in most the genes. It could also increase the total antioxidant capacity of SH-SY5Y cells. Conclusion: Survivin could prevent the toxic effect of rotenone on SH-SY5Y cells during the development of in vitro PD model via regulating the genes of key cellular processes, including anti-oxidation, apoptosis, cell cycle, and autophagy.

Feeding role of mouse embryonic fibroblast cells is influenced by genetic background, cell passage and day of isolation.

Mouse embryonic fibroblast (MEF) cells are commonly used as feeder cells to maintain the pluripotent state of stem cells. MEFs produce growth factors and provide adhesion molecules and extracellular matrix (ECM) compounds for cellular binding. In the present study, we compared the expression levels of Fgf2, Bmp4, ActivinA, Lif and Tgfb1 genes at the mRNA level and the level of Fgf2 protein secretion and Lif cytokine secretion at passages one, three and five of MEFs isolated from 13.5-day-old and 15.5-day-old embryos of NMRI and C57BL/6 mice using real-time PCR and enzyme-linked immunosorbent assay. We observed differences in the expression levels of the studied genes and secretion of the two growth factors in the three passages of MEFs isolated from 13.5-day-old and 15.5-day-old embryos, respectively. These differences were also observed between the NMRI and C57BL/6 strains. The results of this study suggested that researchers should use mice embryos that have different genetic backgrounds and ages, in addition to different MEF passages, when producing MEFs based on the application and type of their study.

CRISPR-Cas9-mediated knockout of the Prkdc in mouse embryonic stem cells leads to the modulation of the expression of pluripotency genes.

Prkdc encodes for the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) playing a key role in nonhomologous end joining pathway during DNA double-strand break repair and also influencing the homologous recombination (HR) repair system by phosphorylation of proteins involved in HR. In addition, Prkdc has other critical functions in biological processes, such as transcriptional regulation, telomere stability, apoptosis, and metabolism. DNA-PKcs upregulates during in vitro differentiation of mouse embryonic stem cells (mESCs). To address the potential role of Prkdc in mESCs pluripotency and in vitro differentiation into ectoderm, mesoderm, and endoderm germ layers under normal physiological conditions, a bi-allelic Prkdc-knockout cell line was generated in the present study by employing CRISPR/Cas9 system, and subsequently, its potential role in stemness and development was studied. The results of the study showed that the expression of pluripotency-associated genes, including Nanog and Sox-2 were overexpressed in the bi-allelic Prkdc-knockout cell line. Also, bi-allelic Prkdc-knockout cell line was shown to have typical mESCs cell morphology, cell cycle distribution, and alkaline phosphatase activity. Furthermore, the results of the study revealed that the expression of several germ layer markers is modulated in Prkdc-knockout lines. In conclusion, the findings of our study demonstrated the role of Prkdc during differentiation and development of ESCs.

Ratiometric enhanced fluorometric determination and imaging of intracellular microRNA-155 by using carbon dots, gold nanoparticles and rhodamine B for signal amplification.

An ultrasensitive and highly reliable ratiometric assay is described for the determination of microRNA-155. It works at the attomolar concentration level and has high selectivity which warrants its potential application in cancer biomarker tracking. The excellent performance of this method results from (a) the use of a hybrid conjugate prepared from Rhodamine B (RhB), carbon dots (CDs) and probe-microRNA, and (b) from the measurement of fluorescence resonance energy transfer (FRET) that is observed in the AuNP/target-microRNA system as a result of RNA hybridization. The dye RhB (emission peak at 580 nm) serves as an internal reference. The sensitivity of this assay is increased by about 30% because of the broad emissions of CDs (489 nm and 665 nm) through a sequential FRET phenomenon. RhB-CDs were covalently bio-conjugated to probe microRNA. In the presence of AuNPs, the fluorescence of the CDs is quenched, while in the presence of microRNA-155, the ratio of fluorescences at 489 and 665 nm (I489/I665) is enhanced again. A linear relationship exists between the ratio of fluorescence and the concentration of microRNA-155 in the range from 1 aM to 0.1 µM, and the detection limit is 0.3 aM. The assay was applied to quantitative studies of target microRNA-155 in multiple pathways associated with cancer progression in biological fluids include human serum samples and cancer cells. The nanoprobe also deliver clear signal to microRNA target in fixed and lived MDA-MB-231 cells. Graphical abstract A ratiometric FRET sensing method used for microRNA-155 detection at aM concentration level using CDs and AuNPs as donor-acceptor respectively and Rhodamine B as amplification reagent. The application of assay for imaging of microRNA-155 in fixed and live MDA-MB-231 cells is demonstrated.

CuO/WO3 nanoparticles decorated graphene oxide nanosheets with enhanced peroxidase-like activity for electrochemical cancer cell detection and targeted therapeutics.

The novel method was developed for electrochemical cancer cell detection using CuO/WO3 nanoparticle decorated graphene oxide nanosheet (CuO/WO3-GO) with enhanced peroxidase like-activity, based on catalytic reaction of H2O2 with o-Phenylenediamine (OPD). The prepared nanocomposite conjugated with folic acid (FA), as a cancer cell-targeting ligand, and a miniaturized electrochemical cell for cancer cell detection was designed. In this strategy OPD could oxidize in the presence of H2O2 on the surface of working electrode, which produced an electrochemical signal. However, the redox response signal changed by interaction of cells with FA/CuO/WO3-GO. During interaction between cells and CuO/WO3-GO, some amount of H2O2-OPD system participated in chemical reaction and removed from the electrode, resulting in a decrease in the response signal. As a consequence, cancer cells detected in wide detection range of 50 to 105 cells/mL and a detection limit of 18 cells/mL. Furthermore, the nanocomposite shows therapeutic cancer treatment through superior peroxidase activity. This work unveils an effective method for simple, sensitive and selective monitoring of cancer cells and also has the potential for efficient cancer therapy, which will open an avenue of nanozymes toward biological applications.

Generation of Fam83h knockout mice by CRISPR/Cas9-mediated gene engineering.

Family with sequence similarity 83 member H (FAM83H) protein-coding geneplay an essential role in the structural organization, calcification of developing enamel, and keratin cytoskeleton disassembly by recruiting Casein kinase 1 alpha (CSNK1A1) to keratin filaments. In this study, we have applied CRISPR Cas9 nickase (D10A) to knockout (KO) the Fam83h gene in NMRI outbred mice. We generated homozygous Fam83h KO mice ( Fam83h Ko/Ko ) through a premature termination codon, which was validated by Sanger sequencing in F0 generation. Next, we also bred the FAM83H KO for two generations. Reverse-transcription polymerase chain reaction and Western blot analysis approved the Fam83h KO mice. The Fam83h KO mice had evidence of normal morphology at the cervical loops, secretory and maturation stages, and mandibular molars. In comparison with the normal wild-type mice ( Fam83h W/W ), the F2 homozygous KO ( Fam83h Ko/Ko ) had sparse, scruffy coats with small body size and decreased general activity. Also, they had the natural reproductive ability and natural lifespan. In addition, delay in opening the eyes and dry eyes among infant mice were seen. The F1 heterozygous mice looked comparable to the normal wild-type mice ( Fam83h W/W ), which showed autosomal recessive inheritance of these phenotypes. The KO of FAM83H had controversial effects on the development of teeth and the formation of enamel. The phenotype defect in dental development and the enamel formation were seen in three mice among four generations. It can be concluded that null FAM83H in outbred mice not only showed the reported phenotypes in null inbred mouse but also showed normal lifespan and reproductive ability; dental deficiency in three homozygous mice; and the symptoms that were similar to the symptoms of dry eye syndrome and curly coat dog syndrome in all four evaluated KO generations.

Effects of cigarette smoke condensate on proliferation and pluripotency gene expression in mouse embryonic stem cells.

BACKGROUND: Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of blastocysts. They can be used as valuable experimental models to test the effects of drugs, chemicals, and environmental contaminants such as cigarette smoke condensate (CSC) on preimplantation embryo development. The aim of this study was to evaluate the effect of CSC on ESCs derived from mice with different genetic backgrounds and maternal ages. METHODS: The study groups consisted of mouse ESCs (mESCs) obtained from three sources: blastocysts developed from fertilized oocytes of two-month-old (2-C57) and six-month-old (6-C57) C57BL/6 inbred mice and those developed from fertilized oocytes of two-month-old (2-NMRI) NMRI outbred mice. The groups of mESCs were exposed to 0.04, 4, and 40 µg/mL CSC. After exposure, we measured cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and real-time polymerase chain reaction for changes in expressions of Oct4, Sox2, Nanog, Ahr, Bax, Bcl2, TFAM, and POLG. The cell doubling time (DT) of these populations was also determined. RESULTS: We observed that CSC changed proliferation and DT in the 2-C57 and 6-C57 cells. There was no change in 2-NMRI cells. Exposure to CSC caused changes in the gene expressions and induced apoptosis in all three cell lines. CONCLUSION: Based on the results of the study, it can be concluded that CSC has an effect on the viability, DT and gene expression patterns in mouse ESCs and its effects vary based on the genetic background and maternal age of isolated mouse ESCs.

Increasing maternal age of blastocyst affects on efficient derivation and behavior of mouse embryonic stem cells.

Mouse embryonic stem cells (mESCs) have the capability to undergo unlimited cell division and differentiate into derivatives of all three embryonic germ layers. These fundamental features enable mESCs to potentially be appropriate, efficient models for biological and medical research. Therefore, it is essential to produce high-performance mESCs. In the current study, we have produced mESCs from blastocysts that developed from fertilized oocytes of 2 (2-C57)-, 4 (4-C57)-, and 6 (6-C57)-month-old C57BL/6 mice. A comparison of isolated stem cells was done from the viewpoint of the efficiency of mESC derivation, self-renewal, and their differentiation capacity. All generated mESCs showed a similar expression of the molecular markers protein of pluripotency and AP activity. In the 3i medium, there was a significant decrease in undifferentiated marker genes expression in the 2-C57 cells compared with the other two groups ( P < 0.05) but developmental genes significantly increased in the 4-C57 and 6-C57 cells compared with the 2-C57 cells ( P < 0.05). The differentiation capacity into three germ layers through the embryoid body formation and percentage of cell lines with normal numbers of chromosomes reduced with increased maternal age. The highest DT and highest percentage of cells in the S phase belonged to 2-C57 cells. These data demonstrated that blastocysts which developed from fertilized oocytes of 2-, 4-, and 6-month-old C57BL/6 mice can generate pluripotent stem cells, and suggested that both the efficiency of mESC isolation and the behavior of these isolated mESCs including pluripotency, self-renewal, cell cycle, and DT changed with increasing maternal age.

Ni-hemin metal-organic framework with highly efficient peroxidase catalytic activity: toward colorimetric cancer cell detection and targeted therapeutics.

BACKGROUND: Given the great benefits of artificial enzymes, a simple approach is proposed via assembling of Ni2+ with hemin for synthesis of Ni-hemin metal-organic-frameworks (Ni-hemin MOFs) mimic enzyme. The formation of the Ni-hemin MOFs was verified by scanning electron microscopy, Transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, Energy-dispersive X-ray spectroscopy and UV-vis absorption spectroscopy. This novel nanocomposite exhibited surprising peroxidase like activity monitored by catalytic oxidation of a typical peroxidase substrate, 3,3,5,5'-tetramethylbenzidine, in the presence of H2O2. By using folic acid conjugated MOF nanocomposite as a recognition element, we develop a colorimetric assay for the direct detection of cancer cells. RESULTS: The proposed sensor presented high sensitivity and selectivity for the detection of human breast cancer cells (MCF-7) and Human Caucasian gastric adenocarcinoma. By measuring UV-vis absorbance response, a wide detection range from 50 to 105 cells/mL with a detection limit as low as 10 cells/mLwas reached for MCF-7 cells. We further discuss therapeutics efficiency of Ni-hemin MOFs in the presence of H2O2 and ascorbic acid. Peroxidase-mimic Ni-hemin MOFs as reactive oxygen species which could damage MCF-7 cancer cells, however for normal cells (human embryonic kidney HEK 293 cells) killing effect was negligible. CONCLUSIONS: Based on these behaviors, the developed method offers a fast, easy and cheap assay for the interest in future diagnostic and treatment application.

A FRET immunosensor for sensitive detection of CA 15-3 tumor marker in human serum sample and breast cancer cells using antibody functionalized luminescent carbon-dots and AuNPs-dendrimer aptamer as donor-acceptor pair.

We proposed a FRET immunosensing for detection of CA15-3 tumor marker by highly biospecific interactions between CA 15-3 antigen and the corresponding antibody and aptamer. In this sandwich type immunoassay, CA15-3 antibody-functionalized carbon dots and AuNPs labeled PAMAM-Dendrimer/aptamer were used as donor/acceptor, respectively. When CA 15-3 Ag was added to homogenous immunoassay, the strong complex interaction between CA15-3 Ab-CA15-3 Ag- aptamer caused in more coming closer carbon dot and AuNPs and more decreasing fluorescence signal. The decreased fluorescence intensity was linear at three ranges including in concentration range 1.1 µUmL-1 to 16 µU mL-1 with regression of R2 = 0.9879, at the concentration range 16 µU mL-1 to 0.163 mU mL-1 with regression of R2 = 0.9944 and at the concentration range 0.163 mU mL-1 to 5.0 mU mL-1 with regression of R2 = 0.9805. The detection limit of the FRET immunoassay was 0.9 µU mL-1. This assay revealed good sensitivity and specificity with MDA-MB-231 breast cancer cells concentrations from 1000 to 40000 cells/mL with correlation coefficient of 0.9955 and detection limit of 300 cells/mL (3 cells in 10 µL of injected sample). In addition, this FRET immunosensing is applicable in diluted human serum. The recovery values were in the range of 95.86-96.97% for CA 15-3 Ag in spiked serum sample with RSD lower than 7.3%. The proposed immunoassay could be a valid model for establishing other immunoassays for detection of different cancer tumor markers with relevant antigens and antibodies.

Up-Regulation of FOXC2 and FOXQ1 Is Associated with The Progression of Gastric-Type Adenocarcinoma.

OBJECTIVE: Forkhead box (FOX) proteins are important regulators of the epithelial-to-mesenchymal transition (EMT), which is the main mechanism of cancer metastasis. Different studies have shown their potential involvement in progression of cancer in different tissues such as breast, ovary and colorectum. In this study, we aimed to analyze the expression of genes encoding two FOX proteins in gastric adenocarcinoma. MATERIALS AND METHODS: In this experimental case-control study, the expression of FOXC2 and FOXQ1 was examined in 31 gastric adenocarcinoma tumors and 31 normal adjacent gastric tissues by reverse transcription polymerase chain reaction (PCR). RESULTS: The expression of both genes was significantly up-regulated in gastric adenocarcinoma tumors compared with the normal tissues (P<0.05). The differential expression of these two genes was also correlated with the grade of tumors (P<0.01). CONCLUSION: We show that up-regulation of FOXC2 and FOXQ1 are likely to be involved in the progression of gastric adenocarcinoma.

Disrupting incrementalism in health care innovation.

OBJECTIVE: To build enabling innovation frameworks for health care entrepreneurs to better identify, evaluate, and pursue entrepreneurial opportunities. BACKGROUND: Powerful frameworks have been developed to enable entrepreneurs and investors identify which opportunity areas are worth pursuing and which start-up ideas have the potential to succeed. These frameworks, however, have not been clearly defined and interpreted for innovations in health care. Having a better understanding of the process of innovation in health care allows physician entrepreneurs to innovate more successfully. METHODS: A review of academic literature was conducted. Concepts and frameworks related to technology innovation were analyzed. A new set of health care specific frameworks was developed. These frameworks were then applied to innovations in various health care subsectors. RESULTS: Health care entrepreneurs would greatly benefit from distinguishing between incremental and disruptive innovations. The US regulatory and reimbursement systems favor incrementalism with a greater chance of success for established players. Small companies and individual groups, however, are more likely to thrive if they adopt a disruptive strategy. Disruption in health care occurs through various mechanisms as detailed in this article. While the main mechanism of disruption might vary across different health care subsectors, it is shown that disruptive innovations consistently require a component of contrarian interpretation to guarantee considerable payoff. CONCLUSIONS: If health care entrepreneurs choose to adopt an incrementalist approach, they need to build the risk of disruption into their models and also ascertain that they have a very strong intellectual property (IP) position to weather competition from established players. On the contrary, if they choose to pursue disruption in the market, albeit the competition will be less severe, they need to recognize that the regulatory and reimbursement hurdles are going to be very high. Thus, they would benefit from seeking market opportunities that are large enough to warrant greater regulatory and reimbursement risks.

Physician entrepreneur: lessons learned in raising capital for biomedical innovation.

PURPOSE OF REVIEW: The funding landscape for medical devices is becoming increasingly difficult and complex. The purpose of this article is to provide the physician entrepreneur with a review of the main sources of capital available to fund the development and commercialization of biomedical innovations, and to highlight some of the important nuances of these funding sources that the physician entrepreneur should consider. RECENT FINDINGS: The article examines the benefits and drawbacks of funding from venture capital firms, grants, friends and family, angel investors, incubators and industry partners from the perspective of the physician entrepreneur, and provides some key points to consider when selecting and working with an investor. The article's recommendations include: in selecting an investor, seek those whose investment thesis, areas of expertise and desired company stage (early vs. late) match the technology and the objectives of the company. In negotiating with an investor, an effective way to increase the company's valuation is to bring multiple bidders to the table. In working with an investor, respect junior staff members as much as senior partners and be wary of conflicts of interest with venture capital entrepreneurs-in-residence. SUMMARY: There are both advantages and disadvantages to each of the funding sources examined here, and the choice of a funding partner depends significantly on the stage of development (in both corporate and technology) of the physician entrepreneur's venture and the role that the physician entrepreneur desires to play in it.

Learning from mistakes in New Zealand hospitals: what else do we need besides "no-fault"?

AIM: to obtain a more in-depth understanding of some of the key factors influencing medical error reporting behaviours of doctors in New Zealand. METHODS: A cross-sectional anonymous survey of 292 doctors in North Island was conducted over a period of 4 months. RESULTS: 128 doctors completed the survey (45% response rate). The results of the study suggest that (overall) most doctors feel they should report the occurrence of medical errors to both the patient and the hospital when they are anticipating major adverse events (long term/serious complications or mortality). However, when they are anticipating minor complications, not every doctor feels that they should report the error(s). This study also shows that doctors feel more comfortable to report errors to the patient than to report to the hospital (79% vs 21%). Furthermore, doctors selected the fear of losing patient's trust and the threat of public outcry most frequently as the most important reasons for their reluctance to report. Lastly, 86% of surveyed doctors felt that reporting the occurrence of errors to patients will decrease the likelihood of complaints being filed against them. CONCLUSIONS: The study suggests that to learn from most of the mistakes, we need to have a system that not only facilitates the reporting of major errors but also encourages the reporting of minor ones. To mitigate the effects of key factors that prevent error reporting, we may benefit from making changes to how doctors are trained and how media reacts to the occurrence of errors in New Zealand hospitals.