Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids

In vertebrates, the entire central nervous system is derived from the neural tube, which is formed through a conserved early developmental morphogenetic process called neurulation. Although the perturbations in neurulation caused by genetic or environmental factors lead to neural tube defects (NTDs), the most common congenital malformation and the precise molecular pathological cascades mediating NTDs are not well understood. Recently, we have developed human spinal cord organoids (hSCOs) that recapitulate some aspects of human neurulation and observed that valproic acid (VPA) could cause neurulation defects in an organoid model. In this study, we identified and verified the significant changes in cell–cell junctional genes/proteins in VPA-treated organoids using transcriptomic and immunostaining analysis. Furthermore, VPA-treated mouse embryos exhibited impaired gene expression and NTD phenotypes, similar to those observed in the hSCO model. Collectively, our data demonstrate that hSCOs provide a valuable biological resource for dissecting the molecular pathways underlying the currently unknown human neurulation process using destructive biological analysis tools.

Embryonal Neuromesodermal Progenitors for Caudal Central Nervous System and Tissue Development

Neuromesodermal progenitors (NMPs) constitute a bipotent cell population that generates a wide variety of trunk cell and tissue types during embryonic development. Derivatives of NMPs include both mesodermal lineage cells such as muscles and vertebral bones, and neural lineage cells such as neural crests and central nervous system neurons. Such diverse lineage potential combined with a limited capacity for self-renewal, which persists during axial elongation, demonstrates that NMPs are a major source of trunk tissues. This review describes the identification and characterization of NMPs across multiple species. We also discuss key cellular and molecular steps for generating neural and mesodermal cells for building up the elongating trunk tissue.

Embryonal Neuromesodermal Progenitors for Caudal Central Nervous System and Tissue Development

Neuromesodermal progenitors (NMPs) constitute a bipotent cell population that generates a wide variety of trunk cell and tissue types during embryonic development. Derivatives of NMPs include both mesodermal lineage cells such as muscles and vertebral bones, and neural lineage cells such as neural crests and central nervous system neurons. Such diverse lineage potential combined with a limited capacity for self-renewal, which persists during axial elongation, demonstrates that NMPs are a major source of trunk tissues. This review describes the identification and characterization of NMPs across multiple species. We also discuss key cellular and molecular steps for generating neural and mesodermal cells for building up the elongating trunk tissue.

Anesthesia for the patient with a recently diagnosed concussion: think about the brain! / 대한마취과학회지

Some patients require emergent, urgent, or elective surgery in the time period immediately following diagnosis of concussion. However, changes in brain homeostatic mechanisms following a concussion and concern for secondary brain injury can complicate the decision as to whether or not a surgery should proceed or be postponed. Given the paucity of available evidence, further evaluation of the use of anesthesia in a patient with concussion is warranted. This article summarizes what is currently known about the relevant pathophysiology of concussion, intraoperative anesthesia considerations, and effects of anesthesia on concussion outcomes in an attempt to help providers understand the risks that may accompany surgery and anesthesia in this patient population. While most contraindications to the use of anesthesia in concussed patients are relative, there are nonetheless pathophysiologic changes associated with a concussion that can increase risk of its use. Understanding these changes and anesthetic implications can help providers optimize outcomes in this patient population.

A study on prescribing errors in in-patients of a corporate tertiary care hospital in North India

Background: Prescribing errors are a subset of medication errors which have a potential for grave harm to the patient. Identification and acknowledgement of such errors can ameliorate much of this danger. Studies of prescribing errors are sparse in India. Such studies, whatever have been conducted, mainly focus on the out-patients or the patients on discharge. Hence, this study was undertaken to study the prescribing errors in prescriptions generated for patients admitted in wards of a corporate hospital in North India.Methods: The prescriptions for in-patients admitted in wards were analyzed for different types of prescribing errors in individual drug orders and prescription as a whole.Results: The prescribing error rate was found to be 3.3% in this study. Of all errors, errors leading to delays in patient care (i.e. Errors of prescription writing) (54.54%) and erroneous copying of the prescription to the drug chart by junior/ resident doctors (Transcription errors) (31.31%) were found to be the major causes of prescribing errors in this study. Of the former category, prescribing a wrong strength (24.24%) and illegible drug orders (12.12%) were the most numerous error subtypes. Errors leading to sub-optimal patient care (i.e. Errors of decision making) were least identified of which Therapeutic duplication (12.12%) was the most common subtype.Conclusions: The error rate found in this study is comparable to the data available from developed countries. However, there are significant differences in the occurrences of error subtypes found in this study as compared to the studies of the west.

Evaluation of the prevalence of waterpipe tobacco smoking and its related factors in Tehran, Islamic Republic of Iran

This study is designed to evaluate the prevalence of waterpipe tobacco smoking and its related factors among Iranian adults. This is a cross-sectional study carried out during 2013/14 in Tehran, Islamic Republic of Iran, among 1830 citizens aged over 15 years. Sampling was through Stratified multistage cluster sampling with proportional allocation within strata. Global Adult Tobacco Survey [GATS] questionnaire for waterpipe consumption was used for data gathering. Data were statistically analyzed by SPSS software. The prevalence of current waterpipe tobacco smoking was 17.6% .Waterpipe use prevalence in men was significantly more than women [24.2% vs. 11.3%]. Multivariate analysis showed that age, sex, cigarette consumption, waterpipe consumption at home and ignorance of safety issues significantly influenced current waterpipe smoking [P = 0.001]. Thus, prevalence of waterpipe smoking in Iranian adults is high and significant. Tackling waterpipe smoking should be considered in tobacco control programmes. However, further studies in this field are needed

Intra-operative assessment of sentinel lymph nodes in breast cancer

Lymph node status remains an important prognostic indicator for survival in breast cancer. Sentinel lymph node biopsy has become the standard method of assessment of clinically node negative breast cancers. Economic implications as well as patient related factors have lead to the development a number of intra-operative techniques. Review of the emerging trends in the last 4 years show that although routine histological examination remains the gold standard in most centres intra-operative assessment remains the most favourable, timely and cost-effective option to analyse sentinel nodes. Molecular techniques appear to be far more superior to other histological tests such as Frozen Section or Touch Imprint Cytology. Emerging research suggests that molecular techniques can be used to predict the presence of non sentinel node metastasis

Combination of opioid agonist and agonist-antagonist admixtures for postoperative pain relieve after upper abdominal surgery

Nalbuphine, a mixed agonist-antagonist opioid, has a potential to attenuate the mu-opoid effects and to enhance the kappa-opioid effects. However, when morphine and nalbuphine are mixed together, the clinical interactions in different combining ratios on analgesic effect and adverse events are unknown. This study was designed to evaluate the interaction of combining different ratios of morphine and nalbuphine in i. v boluses for postoperative pain relieve in upper abdominal surgery and their effects on pulmonary function. This study enrolled 75 patients aged between 18 and 65 yr with an ASA physical status I and II underwent upper abdominal surgery under general anesthesia Patients were allocated randomly into one of five groups: In group I, 10 mg morphine were added into normal saline to a total of 10 ml [concentration of [morphine] [nalbuphine] =1/0 mg/ ml; pure morphine]. In group II, 7.5 mg morphine and 2.5 mg nalbuphine morphine: nalbuphine=3:1]. In group III, 5 mg morphine and 5 mg nalbuphine ratio of morphine: nalbuphine=1: 1]. In group IV, 2.5 mg morphine and 7.5 mg nalbuphine were added morphine: nalbuphine=1:3,]. In group V 10 mg nalbuphine were added into normal saline to a total of 10 ml morphine: nalhuphine=0: 1 mg /ml; pure nalbuphine]. Patients received standard general anesthetic technique without premedication, Postoperative analgesia was commenced with a loading dose of 3 ml solution i. v. immediately after patient recovery. The boluses of the drug were given on the patient request 1 ml/bolus. Pain intensity was evaluated with a 0-10 VAS at rest [1 hour after loading dose then at 2, 4, 12 and 24 hours] and upon movement [during coughing or changing body position from supine to lateral on bed]. FVC, FEV1 and /FEVI /FVC were measured by spirometry [SPIRO 601] preoperatively, immediately postoperatively [1h after loading dose] and 24 h postoperatively [on discharge]. Arterial pH, PaCO2 and PaO2 were measured preoperatively, immediately postoperatively and 24 hours postoperatively [on discharge]. Nausea, vomiting and pruritus were recorded by incidence. Sedation was reported using the Ramsay sedation score. Treatment failures were considered to be: Insufficient analgesia was de fined as VAS >4 at rest during 4-24 h after operation. Adjunctive analgesic with i.v. meperidine 50 mg or ketorolac 30 mg was given for insufficient analgesia. Intolerable nausea and vomiting were defined as persistent nausea or vomiting episodes that required more than three administrations of antiemetic [metoelopromide]. Intolerable Pruritus was defined as persistent Pruritus that required more than three administrations of antipruritics [diphenhydramine] Twenty-four hour analgesic requirements were similar among the five studied groups. Verbal analogue scores far pain were statistically similar among the five groups. The incidences of pruritus, nausea, and vomiting were higher in Group I than in other groups. There were no significant differences between the five groups as regards the incidences and severity of sedation. Pulmonary function tests [FVC and FEVI] were decreased significantly from the preoperative base line value to the immediately postoperative value and values after 24 hours in the five groups, while FEVI/FVC ratios increased significantly in the two postoperative times intervals compared to the baseline value. There were no significant differences in between the five groups. The effects of adding morphine and nalbuphine in admixture on analgesia far upper abdominal surgery is additive. Combinations of morphine and nalbuphine decreased the incidence of pruritus, nausea and vomiting. This may provide a novel combination strategy of opioid agonist and agonist-antagonist for postoperative pain management

Knowledge and practice of jordanian women towards breast cancer and breast self-examination: a cross-sectional study in 2006

To determine the knowledge of Breast cancer and practices of Breast Self-Examination among Jordanian women aged 20 years and above. A descriptive cross-sectional study was conducted to determine the Jordanian women's knowledge and practices about Breast Cancer and Breast-Self Examination. A sample of 5,230 women aged 20 years and above was recruited in proportion to size of the population in the different governorates. Systematic sampling method was used to select the subjects from the attendees to the Comprehensive Health Centers during the period from September 1st and November 30th 2006. A specially designed questionnaire was used to obtain sociodemographic data and knowledge about Breast Cancer and Breast-Self Examination. The interviewers were trained for consistent data collection during the interviews. The questionnaire was tested on a pilot sample of 150 women, who were excluded from the study. Data analysis was carried out using SPSS version 13. Simple descriptive statistics: frequencies, means, and percentages were used to describe the study findings. Of 5230 women, 87% knew that breast cancer was the most prevalent cancer among women, 71% knew what a Breast-Self Examination is. About 48% were practicing Breast-Self Examination and 58% had got the information about Breast-Self Examination from the media. There is a need for developing health education programs about symptoms and early signs of breast cancer with emphasis on the importance of early breast cancer detection. Breast-self examination should be encouraged. Additionally, the role of the media regarding awareness about prevention and early detection of Breast Cancer needs to be increased. The health education programs and mass media education should be targeted towards females in the age group between 20 years and above, ideally those 35 years of age and above. Further research regarding knowledge and practice of Jordanian women towards breast cancer is recommended

Primary health care physicians' knowledge, use, and attitude towards online continuous medical education in Saudi Arabia

To determine the knowledge, attitude, and use of primary health care [PHC] physicians of online continuous medical education [OCME] in the regions of Riyadh, Kingdom of Saudi Arabia. This is a cross-sectional analysis using a self administered questionnaire. The physician sample was selected to cover all Riyadh regions [city of Riyadh, and all accessible clinics in the villages, and cities outside of Riyadh]. The study was conducted from April until May 2007. The data were analyzed using the Statistical Package for Social Sciences software version 12. Out of the 613 questionnaires distributed, 483 was completed and returned. Approximately two-thirds of the participants are aware of OCME. Almost all were interested to learn more regarding OCME. Although 80% of the participants are currently using the internet to obtain medical knowledge, only one-third are using OCME. Ninety percent of those who are using OCME think that it will improve their patient's care. The use of OCME is significantly related to the level of computer skills the physicians have. There was no statistical significant difference on the use of OCME on one hand, and age, gender, level of education, years of experience, and location on the other hand. The PHC physicians have favorable attitude towards OCME, however, their use is quite minimal. More effort is needed to encourage our physicians to utilize this promising method of continuous education, and to understand the challenges and obstacles against using it

Endocarditis caused by Abiotrophia defectiva

A 35-year-old man with pre-existing rheumatic heart disease and aortic regurgitation [AR] presented with intermittent fever, ankle swelling and clinical evidence of endocarditis. Transoesophageal echocardiogram [TEE] revealed vegetations and destruction of the aortic valve [AV]. Blood cultures grew a gram positive coccobacillus which was phenotypically identified as Abiotrophia defectvia [A.defectiva]. A diagnosis of infective endocarditis [IE] due to A.defectiva was made. Treatment, with penicillin and gentamicin, was administered for 4 weeks. Mechanical valve replacement was required few days after starting the antibiotic therapy. The patient had a favorable outcome on follow up. Although A.defectiva is an uncommon cause of endocarditis, early and correct identification of this pathogen is important to improve the outcome and the prognosis of patients with IE due to this organism

Metabolic syndrome in Saudi Arabia

Metabolic syndrome [MS] is a well-established risk factor for the development of coronary artery disease [CAD]. We designed this study to obtain the prevalence of MS and each of its components in Saudi Arabia. This study is part of Coronary Artery Disease in Saudi Study [CADISS]. We conducted this community-based national epidemiological health survey by examining Saudi subjects in the age group of 30-70 years of selected households over a 5-year period between 1995 and 2000 in Saudi Arabia. We interviewed all subjects, examined and took measurements of their blood pressure, weight, height, waist circumference, as well as fasting samples of plasma glucose, triglycerides, and high-density lipoprotein [HDL] cholesterol. We obtained the prevalence of MS based on the presence of at least 3 of the following: abdominal obesity [waist circumference >102 cm [40 inch] in male and >88 cm [35 inch] in female], triglycerides >=150 mg/dl [1.69 mmol/L], HDL cholesterol <40 mg/dl [1.03 mmol/L] in male and <50 mg/dl [1.29 mmol/L] in female, blood pressure >=130/85 mm Hg, fasting glucose >=110 mg/dl [6.1 mmol/L] as defined by the Adult Treatment Panel [ATP] III in 2001. We included 17,293 subjects in this survey during the study period. The overall age-adjusted prevalence of MS in Saudi Arabia obtained from this study is 39.3%. Age adjusted prevalence in males is 37.2% and crude prevalence is 40.9% [95% confidence interval [CI] 39.8-42], while females have a higher prevalence of 42% and crude prevalence of 41.9% [95% CI 40.9-42.9]. Saudi subjects from urban areas have significantly higher prevalence of 44.1% [95% CI 43.2-45] compared to those living in rural areas of 35.6% [95% CI 34.3-36.7] [p<0.0001]. Low HDL affects 81.8% of females and 74.8% of males with MS leading all other factors, and it continued to be consistent in all different age groups. Metabolic syndrome is a risk factor for CAD, as the prevalence of CAD was higher among patients with MS [6.7%] compared to subjects without MS [4.6%] [p<0.0001]. The prevalence of MS is high in Saudi Arabia. Low HDL cholesterol plays a major role in the contribution to the MS in Saudi Arabia. Therefore, we recommend routine assessment for the components of MS in patients with CAD, furthermore, we encourage aggressive management of the MS for primary prevention of CAD, particularly, measures to increase HDL cholesterol

Comparison of the immediate and long-term outcomes of Percutaneous balloon mitral valvuloplasty for severe mitral stenosis and predictors of restenosis

To study the immediate and long-term results of percutaneous balloon mitral valvuloplasty [PBMV] in patients with severe mitral stenosis and to determine the predictors of restenosis. Consecutive patients presented to King Khalid University Hospital, Riyadh, Saudi Arabia during the period from 1999 to 2003. Two hundred fifteen patients with severe symptomatic mitral stenosis submitted to PBMV using the Inoue technique. The morphological features of the mitral valve were graded using Wilkin's echocardiography score. Clinical and echocardiography data were available on follow-up on 195 patients [90.6%], 46 male and 149 females. Mean age was 32 +/- 10.9 years with a mean follow-up 96 +/- 28 months [11 month to 11 year]. Result: The procedure was successful [i.e. MVA >/= 1.5 cm[2] and mitral regurgitation [MR] < 3] in 205 patients [95%], without mortality. MVA increased from 0.98 +/- 0.27 cm[2] to 2.02 +/- 0.29 cm[2] [P<0.0001]. Acute complication occurred in 5 patients, 3 had cardiac tamponade [1.4%] and 2 had severe MR [0.9%]. There were no cases of cerebral embolism. Fifteen patients [7%] had mild worsening of MR and 19 patients [8.8%] has insignificant interatrial shunt. The restenosis rate on follow-up was 16.4%. The predictors of restenosis were the echo score and immediate mitral valve area. Our data showed that PBMV is a safe procedure with good immediate and long-term outcome.sbeta The restenosis predictors were the morphological features of the mitral valve and the area achieved at dilatation

Diabetes mellitus in Saudi Arabia

Diabetes mellitus [DM] is a major public health problem worldwide, and it is a known risk factor for coronary artery disease [CAD]. New recommendations for the diagnosis of diabetes have changed the epidemiology of DM. Therefore, we designed this study with the objective to determine the prevalence of DM among Saudis of both sexes, between the ages of 30-70-years in rural as well as urban communities. This work is part of a major national project: Coronary Artery Disease in Saudis study [CADISS] that is designed to look at CAD and its risk factors in Saudi population. This study is a community-based national epidemiological health survey, conducted by examining Saudi subjects in the age group of 30-70-years of selected households over a 5-year period between 1995 and 2000. Data were obtained from history, fasting plasma glucose levels, and body mass index. The data were analyzed to classify individuals as diabetic, impaired fasting glucose and normal, using 1997 American Diabetes Association [ADA] criteria, which was adopted by the World Health Organization [WHO] in 1998, to provide prevalence of DM in the Kingdom of Saudi Arabia [KSA]. A total of 17232 Saudi subjects were selected in the study, and 16917 participated [98.2% response rate]. Four thousand and four subjects [23.7%], out of 16917 were diagnosed to have DM. Thus, the overall prevalence of DM obtained from this study is 23.7% in KSA. The prevalence in males and females were 26.2% and 21.5% [p<0.00001]. The calculated age-adjusted prevalence for Saudi population for the year 2000 is 21.9%. Diabetes mellitus was more prevalent among Saudis living in urban areas of 25.5% compared to rural Saudis of 19.5% [p<0.00001]. Despite the readily available access to healthcare facilities in KSA, a large number of diabetics 1116 [27.9%] were unaware of having DM. The overall prevalence of DM in adults in KSA is 23.7%. A national prevention program at community level targeting high risk groups should be implemented sooner to prevent DM. We further recommend a longitudinal study to demonstrate the importance of modifying risk factors for the development of DM and reducing its prevalence in KSA

Coronary artery disease in Suadi Arabia

Coronary artery disease [CAD] is a major public health problem worldwide. To our knowledge, there is no national data available from community based studies on prevalence of CAD in the Kingdom of Saudi Arabia [KSA]. Therefore, we designed this study with the objective to determine the prevalence of CAD among Saudis of both sexes, between the ages of 30-70-years in rural as well as urban communities. Further, to determine the prevalence and clinical pattern of the major modifiable risk factors for CAD among the same population. This work is part of a major national study on CAD in Saudis Study [CADISS]. This is a community based study conducted by examining subjects in the age group of 30-70-years of selected households during 5-year period between 1995 and 2000 in KSA. Data were obtained from history using a validated questionnaire, and electrocardiography. The data were analyzed to provide prevalence of CAD and risk assessment model. Nine hundred and forty-four subjects, out of 17232 were diagnosed to have CAD. Thus, the overall prevalence of CAD obtained from this study is 5.5% in KSA. The prevalence in males and females were 6.6% and 4.4% [P<0.0001]. Urban Saudis have a higher prevalence of 6.2% compared to rural Saudis of 4% [P<0.0001]. The following variables are found to be statistically significant risk factors in KSA: age, male gender, body mass index [BMI], hypertension, current smoking, fasting blood glucose, fasting cholesterol and triglycerides. The overall prevalence of CAD in KSA is 5.5%. A national prevention program at community level as well as high risk groups should be implemented sooner to prevent the expected epidemic of CAD that we are seeing, beginning. Measures are needed to change lifestyle and to address the management of the metabolic syndrome, to reduce modifiable risk factors for CAD. A longitudinal study is needed to demonstrate the importance of reducing modifiable risk factors for CAD in KSA

Benefits versus side effects of inhaled and oral steroids in patients with chronic obstructive pulmonary disease

Tying to evaluate benefits and side effects of inhaled and oral steroids in patients with chronic obstructive pulmonary disease [COPD], this study was conducted on 70 patients with COPD. They were selected from patients in A-Hussein University Hospital from January 2002 to January 2003. Patients were divided into 5 groups:-Group [1]: included 20 patients receiving oral prednisolone 20 mg single morning dose, Group [2]: included 20 patients receiving inhaled steroids, [750 mirco g BDP/day], Group [3]: included 20 patients receiving inhaled steroids [1500 mirco BDP/day], Group [4]: included 5 patients receiving oral placebo and Group [5]: included 5 patients receiving inhaled placebo. Pulmonary function tests, morning serum cortisol level and bone mineral density [BMD] were measured. Results obtained showed: It was found that both oral and inhaled corticosteroids [Cs] caused significant improvement in pulmonary functions in a minority of patients [20% in oral Cs and 10% inhaled Cs]. The improvement with oral was higher than that with inhaled [Cs] and was achieved in the 1st month and continuing the treatment for 3 months kept the improvement but did not increase it significantly. The improvement with low dose inhaled and high dose inhaled CS was nearly similar. Oral CS decreased BMD while inhaled Cs showed no change in BMD during the treatment period. Also oral CS caused adrenal suppression in 70% of patients. Inhalation of high dose of CS caused adrenal suppression in 30% of patients, while low dose did not affect HPA axis. Thus the effect of inhaled CS on HPA axis was dose dependent

medicolegal study of firearm injuries in El-Menofia governorate

Gunshot injuries are of major pathological interest in that they can be interpreted with considerable objectivity; the pathologist can often give opinions that are very well based and that are very well based and that are particularly valuable both to the policed and to the lawer. The work was a medicolegal and sociodemograhic study of firearm injuries in El-Menofia Governorate during the year 2000. The study was carried out on thirty-five cases with firearm injuries. The included 25 homicidal injuries [71.0%] and 10 accidental injuries [29.0%]. No suicidal cases were recorded in the present work and the majority of victims were males 31 [88.6%]. The maximum number of injuries was in the age group 20-30 years, and no cases were detected in the age group 0-10 years and above 60 years. A relatively large number of victims [4%] were rural which was related to the total number of population distributed in El-Menofia Governorate. The study revealed that home-made non-rifled weapons either firing shots or bullets [68.5%] were the most frequent weapons used. Extremities and trunk were the most common vulnerable sites for injuries 42.8% and 20.0% respectively. Although complete healing without infirmity was the most common outcome of firearm injuries [71.43%], permanent infirmity was the end results in 5 cases [14.29%]. Limb disabilities were the commonest type [80.0%], followed by eye affection or loss [20.0%] by air pistol gun. Fatal firing was recorded in five cases only [14.3%], of the total 35 victims of firearm injuries which can be explained by the predominance of home-made firearm weapons. Also most injuries were sited in the extremities which are generally less life-threatening