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Repressive regulation of potassium channel genes by Polycomb group (PcG) proteins contributes to PcG protein-mediated neuroprotection against neuronal ischemic injury, as seen in an ischemic stroke. Here we asked the question whether Trithorax group (TrxG) proteins, the antagonistic partners of PcG proteins (i.e, epigenetic activators targeting the same genes) may also regulate potassium channels. Results of patch-clamp studies on cultured neuronal cells showed that inhibition of TrxG protein MLL-1 led to an increase in potassium channel activity, an unexpected effect for a presumed gene activator. In contrast, decreased sodium currents were observed with MLL-1 inhibition. Increased or decreased levels of potassium channel protein Kv2.1 or sodium channel protein Nav1.2, respectively, were seen with MLL-1 inhibition, as determined by immunocytochemistry. These results, for the first time, demonstrate an involvement of TrxG protein MLL-1 in regulating neuronal ion channels, potentially repressing potassium channel genes.

Background: Delirium is an acute syndrome of organ dysfunction with long-term consequences which commonly occurs in the Intensive Care Unit (ICU). The incidence of delirium ranges from 30% - 50% in low severity ICU patients and up to 80% in mechanically ventilated patients. This condition is frequently under-recognized and daily routine screening is a key strategy to early intervention. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) are the most recommended assessment tools for detecting delirium in the critical ill patient. Objective: The main objective of this study is to educate ICU staff about delirium. In addition, nurses were trained to use the CAM-ICU as a standard screening tool. The intervention was evaluated through a survey aimed at ICU staff. Methods: An educational intervention was started in 2014 in our ICU. An educational package for ICU staff consisted of a didactic brochure and explanatory videos. One-on-one teaching, case based scenarios and didactic teaching were strategies used in the implementation process. The entire intervention was evaluated by means of a survey directed to the professionals. Results: The structure of the didactic brochure was simple in order to have an easy understanding of the CAM-ICU tool. We also created 10-minute videos. According to the results of the satisfaction survey (N=62), disorganized thinking was the most difficult feature of CAM-ICU to interpret. When in doubt, consultation between co-workers was the primary resource selected by unit staff. Conclusion: This initiative achieved the objective of training health care professionals in the application of the CAM-ICU tool with a good level of satisfaction from them. Therefore, ICU staff consider delirium management in the broader picture of critically ill patient care as a major activity of daily practice.

Assessment of the microbial load of the operating environment during daily pre-, intra-, and post-operative procedures in a surgical department of a military emergency hospital in Bucharest showed the bacterial contamination of intra-operative air by increasing the number of bacteria above the allowed maximum level and the detection of a strain of Escherichia coli (E. coli).

Familial dysautonomia is a rare autosomal recessive neurodegenerative disease affecting cells of the autonomic nervous system. Patients with this disease are insensitive to pain but their autonomic nervous system is still activated with noxious stimuli. This report details a case of a patient with familial dysautonomia who underwent right ankle open reduction and internal fixation for a bimalleolar right ankle fracture. The patients preoperative and intraoperative course were uneventful but shortly after handoff to the intensive care unit, the patient experienced an autonomic crisis. Management of these patients is complex, requiring maintenance of physiologic homeostasis as well as preventing hemodynamic instability caused by noxious stimuli. Any deviations from baseline may cause an autonomic crisis, as happened in our patient. Herein, we detail the perioperative management of a patient with familial dysautonomia in further detail.

Cadmium is one of the transition metals, known by the scientific name Cd. One of its main characteristics is the high toxicity, even in very little amounts. Cadmium is often released through industrial effluents, pesticides, chemical fertilizers, and the burning of fossil fuels. Since the presence of cadmium ions in the living organisms’ body, especially humans, can cause serious damage to the liver and pancreas, and also because its role in causing cancer has been proven, measuring very low amounts of this metal is of high importance. In the first step, this study has reviewed and analyzed common laboratory methods for measuring small amounts of cadmium. Then, according to economic, environmental, feasibility, speed, and accuracy factors, all available methods were evaluated using the ELECTRE technique. The results showed that the extraction methods using Dowex Optipore V-493 resin and extraction system in Triton X-114 surfactant, placed in the first and second positions.

Cadmium is naturally present in the mineral cadmium sulfide which is a rare form of this element and the highest amount of cadmium is obtained from the extraction process of other minerals such as lead, copper and zinc. The release of this metal into the environment leads to widespread epidemiological effects. Therefore, measuring small amounts of this metal is also of particular importance. Small amount measuring methods of this metal are such as,preconcentration using solid phase extraction system using adsorbents. The main part of the preconcentration process is achieved by adsorption processes. In this study, the behavior of Freundlich and Langmuir adsorption isotherms for the capacity of TMON and IMNM adsorbents in cadmium adsorption has been evaluated by Power and Rational statistical distributions. At the end of the study, the constant coefficients of the Freundlich and Langmuir models were compared in both linear and non-linear modes. The results showed; the linearization method for the Kf coefficient of the Freundlich isotherm can cause errors equal to 41.6% in TMON adsorbent and 39.3% in IMNM adsorbent. Also, in parameter b, errors of 66.66% are obtained in TMON adsorbent and 32.45% in IMNM adsorbent.

Since snow load is one of the loads of designing the industrial shed roof, this research presents a new system to reduce the industrial sheds roof design. In this system, sensitive units of moisture and temperature, which can be adjusted with different areas, are installed on the shed’s roof. The mechanism of system is that the sensors in the units detect the presence of snow on the shed roof and send an order to connect electricity to the elements; therefore, the snow on the roof melts by the heat generated. In this system, solar panels are used to supply electricity. As with the help of this mechanism, snow does not remain on the roof, it is possible to eliminate the snow load in the calculations of the shed and apply at least the live load of the sixth regulation (Due to having a one-story shed, minimum live load applied and it used only for the foundation design of the structure.), this issue will create an economic plan in shed designing. According to the study conducted in this research, it is shown that the dimensions of the sheet beam used in the shed are reduced, which will significantly reduce the cost of construction and installation to some extent. In the following, two samples of sheds with a span of 20 meters in the presence of snow and the absence of snow in the software were modelled, and the results were compared with each other.

The introduction of a new class of drugs known as direct acting antiviral (DAA) agents represents a revolution in the treatment of hepatitis C virus (HCV) in the general population, as these regimens are associated with higher sustained virological response (SVR) rates and fewer side effects. However, for patients with advanced chronic kidney disease suffering from HVC infection, treatment options including DAA remain limited. The aim of this study is to report our experience on Sofosbuvir (SOF) based regimen in the treatment of HCV in hemodialysis patients.In this observational study, we included all patients with chronic HCV infection on hemodialysis who were treated with SOF in our Hospital between April 2016 and March 2018. All patients were treated with a combination of 400 mg of SOF three times a week after hemodialysis and of 60 mg of Daclatasvir daily for a total of 12 to 24 weeks.A total of 20 hemodialysis patients were included in this study. 12 were females and the mean age was 52.1 ± 15.5 years. 11 patients were infected with HCV genotypes 1b. All patients achieved SVR. Clinical and biological tolerance was very good for all patients and none of them had to discontinue treatment because of side effects or developed hepatobiliary and cardiac toxicity. Two patients reported fatigue and another patient reported headaches. However, these symptoms were spontaneously resolved after the end of the treatment.In Morocco, despite the absence of new DAA combination treatment regimens which are not renally eliminated, our study concludes that SOF based treatment without Ribavirin or Peginterferon was effective and safe with minimal side effects. However, larger studies are still needed in order to validate these results.

Flow cytometry (FCM) is a unique technique that allows rapid quantitative measurement of multiple parameters on a large number of cells at the individual level. FCM is based on immunolabelling with fluorochrome-conjugated antibodies, leading to high sensitivity and precision while time effective sample preparation. FCM can be performed on tissue following enzymatic or mechanical dissociation. The expression of epithelial antigens and cytokeratin isoforms help in distinguishing tumor cells from adjacent epithelial cells and from tumor infiltrating leukocytes. Tumor phenotypes can be characterized on expression intensity, aberrancies and presence of tumor-associated antigens as well as their cell proliferation rate and eventual heteroploidy. FCM can measure quantitative expression of hormone or growth factor receptors, immunoregulatory proteins to guide adjuvant therapy. Expression of adhesion molecules tells on tumor’s capacity for tissue invasion and metastasis seeding. Tumor heterogeneity can be explored quantitatively and rare, potentially emerging, clones with poor prognosis can be detected. FCM is easily applicable on fine needle aspiration and in any tumor related biological fluids. FCM can also be used to detect circulating tumor cells (CTC) to assess metastatic potential at diagnosis or during treatment. Detecting CTC could allow early detection of tumors before they are clinically expressed although some difficulties still need to be solved. It thus appears that FCM should be in the pathologist tool box to improve cancer diagnosis, classification and prognosis evaluation as well as in orientating personalized adjuvant therapy and immunotherapy. More developments are still required to better known tumor phenotypes and their potential invasiveness

We report a case of a right gluteal mass from the sacroiliac joint to the knee of an infant girl. Biopsy showed histopathological features similar to infantile fibrosarcoma (IFS). However, unlike most IFS, no ETV6-NTRK3 fusion gene abnormality was detected. Molecular analysis with TruSight RNA Pan-Cancer Panel detected the presence of KIAA1549-BRAF translocation and an oncogenic NF2p.Q459* SNV with potential clinical significance. A review revealed that the combination of this patient’s tumor site with the presence of a KIAA1549-BRAF translocation abnormality and an accompanying single nucleotide variant has not been previously described. The detection of this translocation abnormality raises the possibility that the spindle cell tumors in infants with an absence of the ETV6-NTRK3 fusion gene abnormality might have a distinct pathogenetic mechanism different from the previously known IFS and congenital mesoblastic nephroma. Furthermore, the discovery of BRAF translocation and its aberrant signaling of the mitogen-activated protein kinase (MAPK) pathway in this tumor contributes to the promise of clinical benefit of using the MEKi trametinib for the treatment of progressive disease that is refractory to conventional chemotherapy. 

According to raising teenage parents though their abusing and neglecting children at a rural community with the ethnographic qualitative research method was surveyed. All children have protected on violence, abuse, neglect and exploitation from their teenage parents. To investigate and emphasize the consequences of violence ranged from immediate to the impact of their development on physical injury, learning ability, and local child care performance to long-term harm that caregivers carry into adult life is affected for raising children. Administration to the 89-households’ families and household memberships, 10 house stakeholders, 8 community leaders, 36 children, 65 caregivers, teenage parents and grandparents, and 3 mentors. Using the ethnographic qualitative research participatory with observation, natural conversation and in-depth interviews were randomized in rural Northeastern Region, Thailand. There are 52% of children being sexually, physically, or psychologically abused, neglected per day. Most of the teenagers’ education is poor learning skills, low academic learning achievements, and independent freedom of their sexual behaviors. These sexual intercourses between their groups are normal. Adding gambling habits among friends and adult groups are amputated without parents to dissuade. Either lifestyles as freely with sexually and gambling and the basic education are stopped, experiences’ living skills are poorly. Teenage women are changed to pregnant and young mothers. The teenage men must be searched for the job without a lack of worker’s skills to look for children with whom they are conflicted family relationships to take care.

To investigate the variables correlation analysis research method for assessing the caregivers’ perceptions in two groups including dependent and independent variables to correlate the measuring of early childhoods. Typically, in correlated data, for jointly normally distributed data with relevant outliers that can use a correlation as a measure of a monotonic association. Designing the 65-paired samples for the Thai Model of early detection and intervention of children as the health care system guidelines from 26-CUPs have compared. Using the DSPM divided into 65-appropriate and 65-inappropriate development early childhoods for every 13 CUPS that depends on talented children. Selecting the Receptive Language (RL) skills identified in contributing growth relative factors with four research instruments: the EPRLS, PRLF, CNRLF, and CMRLF are valid and reliable significantly. Comparisons of the appropriate and inappropriate early childhoods are differences ( < .05), the intercorrelation circumflex nature analysis (p < .05), positively. The R2 values show that 26% and 55% of the variance in training caregivers’ factor skills on the PRLF, CNRLF, and CMRLF to the EPRLS in inappropriate and appropriate early childhoods, respectively. Developmentally Appropriate Practice is a perspective in a child’s development: social, emotional, physical, and cognitive-based on the child’s cultural background: community, family history, and family structure.

To investigate the associated an inappropriate development of the 9-month-old-baby with the Matched Case-Control Study on five categories and three factors including predisposing, contributing, and complementary through the babies’ malfunction development with the Analysis Research Method was analyzed. The babies’ developing crisis was enhanced as the guidelines for promoting healthy babies’ development via the DSPM in the future of Thailand. Creative the Interview Factor Questionnaire analyzed the 130-child caregivers’ parenting matching 65-pairs-case-control group into 5 parts: the Predisposing Factor Questionnaire, the Positive Interview Form; the Baby-Self-Efficacy Form; the Inappropriate Contributing Interview Form; the Inappropriate Development Interview Form for assessing the motor skills, self-efficacy, predisposing, contributing, and complementary factors of the 9-month-old-baby, respectively. Highest, Middle, and Lowest means levels are indicated. The child caregivers’ are presenting responses, overall on the Predisposing Factor Questionnaire on five categories’ motor skills, and the Inappropriate Development Interview Form showed off at the Middle Levels. The Positive Interview Form, the Baby-Self-Efficacy Form, and the Inappropriate Contributing Interview Form comprised at the Highest Levels for the predisposing, self-efficacy, and contributing factors for developing the 9-month-old-baby, respectively. To help professionals assess the factors affecting a child’s development into environmental factors, biological factors, interpersonal relationships, and early environments and experiences that identified in contributing to growth, brain, emotional, social developments at early childhood are the GM, FM, RL, EL, and PS motor skills practices with the DSPM for Thai’s children are also more likely to have health problems all child ages with the knowledge and skills.

The global identities of parents’ popularity in rural communities to make-decision effects of their attitudes to transfer their Early Childhood from Child Development Centres and Local Primary School for moving study into the schooling cities that looks like children’ asylum of their educational conditions, problems, administration’ school directors, teachers, and schools’ environments to protect that described. The involving CDCs’ perceptions got using the 25-item My CDC Identity Inventory (MCDCII) in five scales, three options. Teacher and Caregiver-Early Childhood interactions have assessed with the 30-item Questionnaires on Teacher Identity Interaction (QTII) in five scales on five options. The 10-item Local Identity-Related Attitude (LIRA) has been associated with a sample of 300 children’s parents, teachers, and caregivers. The determination of efficient predictive value (R2) shows that 30% of accepted the identities on cohesiveness, competitiveness, physical indoor and outdoor environmental development, satisfaction, and strong-sense identity. 74% of their CDCs can protect the educational asylum of early childhoods from rural communities. The R2 value shows 49% of the variance in children’s parents’ perceptions was because of the MCDCII have associated. Despite Thailand’s success in expanding educational access, new empirical evidence suggests that much more needs to be done to maximize the potential of its students. The performance gaps among schools have disadvantaged and poorer-performing students have concentrated in small rural village schools. The Thai pre-primary school system is dramatically lacking in qualified the CDCs’ learning environments and achievements, and teachers. It allocated small rural schools teachers with lower qualifications and teaching experience.

This study aims to assess parents’ perceptions of their responses to the perceived awareness programme competency abilities and expectations for enhancing parents on weight control of their pre-school children in preventing with Obesity. It has defined self-efficacy as one’s belief in one’s ability to succeed in specific situations and accomplish a task with the theoretical framework of Bandura’s Model by quasi-experimental research in 16 weeks. To promote the self-efficacy and expectations, the 10-item Questionnaire on Self-Efficacy Program, the 22-item Questionnaire on Parents’ Efficacy Interaction, and the 46-item Questionnaire on Parental Expectations assessed parents’ perceptions. A sample size consisted of 14-pre-school children whose age ranged 2-5 years old at the Child Development Demonstration Centre, Khon Kaen University was selected. Providing knowledge, teaching, demonstration, experimentation, and organized activities were organized. Parents’ perceptions of their abilities for controlling children’s weight and height with pre- and post-experimental programmes differentiated, significantly. Parents’ responses to the post performances are over than pre-experiment for the QSEP, the QPEA, and the QPE, differently. They answered and followed up on child management with parents online for 16 weeks, continuously. The obese early childhood at the CDC Demonstration Centre, Faculty of Nursing used the food programme to self-efficacy with their parents taking part and cooperating well in specifying research objectives. There are 2,958,441 children in rural areas are lacking attention, because of food and health problems in the 19,171-Child Development Centres none yet have food programmes to prevent health and hygiene problems. Although Thailand took the next leap forward for its investment in Early Childhood Development through legislation, improved quality services, and social transfer grants for families with young children since 2018.

Development of genetic profiles from the biological mixtures has remained challenging, although modern-day technologies may help forensic scientists to attain a reliable genetic profile in the identification of the accused. In the case of rape, vaginal swab exhibits usually contain epithelial cells of victims and sperm cells of accused, such samples are more challenging when there is more than one contributor. In such cases, separation of distinct cells from a mixture that includes blood cells, epithelial cells and sperm cells for their single genetic profile is important. In the last ten decades several new techniques were developed and invented for the separation of single cell from the biological mixture that includes differential lysis, laser micro-dissection, cell sorting (FACS), sieve-based filtration, (vi) micro-fluidic devices or immunomagnetic beads cell separation of fresh samples, and the magnetic activated cell sorting (MACS). Out of them, some techniques have been commonly applied for cell separation in forensic biology. Each technique has its own limitation. Some recent studies showed, magnetic activated cell sorting (MACS), laser capture microdissection (LCM), DEPArray technology and fluorescence activated cell sorting (FACS) has proved to be effective in separation of single cell from cell mixtures. Therefore, in this review we have evaluated these four alternative methods and their potential application in the modern-day over the others for the separation of a single cell from the mixture. In this review we also discuss the advantage of these methods and their modern–day applicability and acceptance in the forensic world.

Introduction: The tendency to impulsive behaviors and/or violence is exacerbated after alcohol consumption. Still, the relation between alcohol/violent deaths reported in the literature is not accurate, and in general, alcohol is only seen as a trigger to aggressive actions. The relationship of the victims with their blood alcohol is less studied. They were especially concerned about the role of alcohol as a risk factor for victims of unnatural death. Thus, our goal is to check the influence of alcohol in victims of violent deaths as homicides, suicides, and accidents. Materials and methods: Retrospectively the medical records of 805 autopsies performed at the Institute of Forensic Medicine (IML) of Franco da Rocha, in the period 2001 to 2017 were reviewed. The variables studied were sex, age, types of violent death rates, and alcohol - these were considered positive when above 0.3 mg/ml. The dosage of blood alcohol concentration (BAC) was performed using samples of 10 ml of blood collected at necropsy, is preferably taken from the cardiac chambers or of the right femoral vein. Dosages of alcohol in blood samples were done in the Forensic Toxicology Center of the IML by gas chromatography, using the technique of separation “headspace” and double column. Results: Drug testing for alcohol was available for 488 (79.1%) of 617 necropsies. Of the 617 subjects studied, 532 (85.7%) were male, and 85 (13.8%) were females (with high rates of adolescents). The vast majority (n = 230) were killed, and 40.5% of victims had BAC above 0.3 mg/ml of blood. Traffic accidents came next, accounting for 181 deaths, with 41% of victims presenting positive BAC. Discussion: High blood alcohol levels of the victims were associated mainly with the genesis of accidents (drowning, falls, traffic, aspiration/ smothering) and murder (with impaired ability to resist or by causing the release of impulses to engage in violent situations), about 40% of cases. Conclusion: Our results indicate that alcohol abuse is a risk factor for victims of violent death. In these cases, alcohol has two types of action. Direct: contributes to accidents of various kinds - from traffic by decreasing powers of concentration, attention, and loss of reflexes, to other types of accidents such as drowning, falls, swallowing disorders causing airway obstruction, and mechanical asphyxia. And they were indirect, making it easier for individuals to engage in conflict (and thus become victims of crimes).

Background: In developing countries, manual small incision cataract surgery is a better alternative and less expensive in comparison to phacoemulsification and thus the incision is an important factor causing high rates of postoperative astigmatism resulting into poor visual outcome. Thus, modifications to the site of the incision is needed to reduce the pre-existing astigmatism and also to prevent postoperative astigmatism. Modification to superotemporal incision relieves pre-existing astigmatism majorly due to its characteristic of neutralizing against-the-rule astigmatism, which is more prevalent among elderly population and thus improves the visual outcome.Aims: To study the incidence, amount and type of surgically induced astigmatism in superior and superotemporal scleral incision in manual SICS.Methodology: It is a randomized, comparative clinical study done on 100 patients attending the OPD of Ophthalmology at a tertiary care hospital, with senile cataract within a period of one year and underwent manual SICS. 50 of them chosen randomly for superior incision and rest 50 with superotemporal incision. MSICS with PCIOL implantation were performed through unsutured 6.5 mm scleral incision in all. Patients were examined post-operatively on 1st day, 7th day, 2nd week and 4th week and astigmatism was evaluated and compared in both groups.Results: It is seen that on postoperative follow up on 4th week, 77.78% of the patients with ATR astigmatism who underwent superior incision had increased astigmatism whereas, only 13.63% of the patients with ATR astigmatism who underwent supero-temporal incision, had increased astigmatism but 81.82% had decreased ATR astigmatism. However, 77.78% of the patients with preoperative WTR astigmatism who underwent supero-temporal incision, had increased astigmatism, whereas 44.45% of the patients with WTR astigmatism preoperatively, had increased astigmatism in contrast to 50% had decreased amount of astigmatism. It is also seen that the supero-temporal incision group had more number of patients (78%) with visual acuity better than 6/9 at 4th postoperative week than superior incision group (42%).Conclusion: This study concludes that superior incision cause more ATR astigmatism postoperatively whereas superotemporal incision causes lower magnitude of WTR astigmatism, which is advantageous for the elderly. Besides superotemporal incision provides better and early visual acuity postoperatively.

Solid tumor oncology treatments are primarily performed in the outpatient setting. However, hospitalizations are inevitable due to complications of cancer and treatment-related toxicities. With rising health care spending, the length of hospital stay (LOS) is increasingly considered a proxy for healthcare costs. There are several ongoing efforts to abbreviate the inpatient LOS and ensure a safe and timely discharge to the outpatient setting. In addition to the acute illness and the associated comorbidities, various factors affect the LOS: social determinants of health (SDOH), nutritional status in cancer patients, and end-of-life issues. Furthermore, it is unclear how the institutional policies on social distancing and visitation during the current coronavirus disease (COVID-19) pandemic may impact the LOS. The purpose of this article is to review various factors and barriers that lead to longer LOS for solid tumor patients during the COVID-19 pandemic, and identify the critical areas of quality improvement.

Introduction: Cancer treatment and prognosis depend heavily on early detection. Survival in the early stages is excellent for almost all types of cancer. Unfortunately, in Saudi Arabia, a large number of cancer patients present with advanced disease, resulting in a poor prognosis. There are three levels of delay in the management of cancer patients. The first level is the time between the first cancer-related symptoms and the presentation to the health facility, the second level is from the presentation to the diagnosis, and the third level is between the diagnosis and the treatment. This study aims to determine if there is a delay, at what level and to study the factors causing such delays.Materials and methods: Two hundred cancer patients who presented to the Armed Forces Hospital Southern Region, Oncology Department, were interviewed from January 1st to June 30th, 2018. The interviews were conducted by trained physicians familiar with the questionnaire’s contents. The questionnaire consisted of four sections: a demographic section and three more sections to identify factors causing the delay at the three levels from the patients’ perspectives. All data were analyzed using the SPSS version 20.0.Results: The mean patient age was 63 years. A total of 112 patients were female and 88 were male. The most common cancer type was breast cancer (27.5%). Among the patients, 61% were illiterate and 25.5% had elementary school degrees, 86% expressed little or no general medical knowledge about cancer. More women than men paid attention to cancer symptoms (70% vs. 54%). 75% of the patients presented to the first health facility after 2 months from the first appearance of symptoms (level 1 delay). Only 2% of the patients presented within one week. 50% of the patients received a diagnosis after visiting two health facilities. All patients were diagnosed at hospitals. 40% of patients used alternative medicines, 70% of whom thought this was the cause of their delayed presentations. 67% had their diagnosis confirmed within one month (level 2 delay), and 66% started their definitive treatment within one month (level 3 delay). 75% of the patients blame themselves for the delay. Educational level (p = 0.03), knowledge about cancer (p < 0.01), and the use of complementary and alternative medicines (CAM) (p = 0.01) were significantly associated with delayed presentation of patients to the health facility. Conclusion: There is a delay in the presentation of cancer patients (level 1) in the southern part of Saudi Arabia. Educational level, knowledge of cancer symptoms, and use of complementary and alternative medicines are the main causes. There were no delays in diagnosis and start of treatment (level 2,3).