Closing the gap on healthcare quality for equity-deserving groups: a scoping review of equity-focused quality improvement interventions in medicine.

INTRODUCTION: Quality improvement (QI) efforts are critical to promoting health equity and mitigating disparities in healthcare outcomes. Equity-focused QI (EF-QI) interventions address the unique needs of equity-deserving groups and the root causes of disparities. This scoping review aims to identify themes from EF-QI interventions that improve the health of equity-deserving groups, to serve as a resource for researchers embarking on QI. METHODS: In adherence with Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, several healthcare and medical databases were systematically searched from inception to December 2022. Primary studies that report results from EF-QI interventions in healthcare were included. Reviewers conducted screening and data extraction using Covidence. Inductive thematic analysis using NVivo identified key barriers to inform future EF-QI interventions. RESULTS: Of 5,330 titles and abstracts screened, 36 articles were eligible for inclusion. They reported on EF-QI interventions across eight medical disciplines: primary care, obstetrics, psychiatry, paediatrics, oncology, cardiology, neurology and respirology. The most common focus was racialised communities (15/36; 42%). Barriers to EF-QI interventions included those at the provider level (training and supervision, time constraints) and institution level (funding and partnerships, infrastructure). The last theme critical to EF-QI interventions is sustainability. Only six (17%) interventions actively involved patient partners. DISCUSSION: EF-QI interventions can be an effective tool for promoting health equity, but face numerous barriers to success. It is unclear whether the demonstrated barriers are intrinsic to the equity focus of the projects or can be generalised to all QI work. Researchers embarking on EF-QI work should engage patients, in addition to hospital and clinic leadership in the design process to secure funding and institutional support, improving sustainability. To the best of our knowledge, no review has synthesised the results of EF-QI interventions in healthcare. Further studies of EF-QI champions are required to better understand the barriers and how to overcome them.

Phytochemistry and antifatigue activities of Carica papaya leaf from geothermal, coastal and urban areas, Indonesia.

Fatigue, a condition of lack of energy and motivation resulting in the feeling of extreme tiredness or exhaustion, is usually prevented and treated with ergogenic aids, such as in the form of nutritional supplements. Papaya (Carica papaya) may be a potential candidate for ergogenic aids, considering its healthy secondary metabolite properties and number of metabolite compounds that could be affected by the location where the plant growing. The aim of this study was to identify the phytochemicals of papaya leaves from three different locations: geothermal, coastal, and urban areas in Aceh province, Indonesia. Concentrations of papaya leaf with the highest number of secondary metabolite compounds were tested in rats to measure blood lactate acid concentrations after strenuous exercise. The number of chemical compounds identified from the three locations was 24 compounds; 23 compounds and 17 compounds, respectively. The highest concentration of chemical compounds that have antifatigue activity contained in all papaya leaf samples were neophytadiene, linolenic acid, gamma tocopherol, hexadecanoic acid, vitamin E, carpaine, octadecatrienoic acid, nor lean-12-ene, squalene, and phytol. Furthermore, most of the compounds' highest concentrations were found in papaya leaves from the coastal area and, therefore, tested on the animal model. Treatment was provided in 12 male rats with different doses of papaya powder supplements for 15 days. The results showed that lactic acid levels of rats received a dose of 400 mg/kg of papaya leaf extract reduced the lactic acid concentration (p=0.014) compared with the control group. This study highlights that papaya leaves from the coastal area have the most potential activities as ergogenic herbal aid and were able to reduce lactic acid levels in rats after strenuous exercise.

Systems-Based Practice in Graduate Medical Education: Evolving Toward an Ideal Future State.

ABSTRACT: Systems-based practice (SBP) was first introduced as a core competency in graduate medical education (GME) in 2002 by the Accreditation Council for Graduate Medical Education as part of the Outcomes Project. While inclusion of SBP content in GME has become increasingly common, there have also been well-documented stumbling blocks, including perceptions that SBP has eroded the amount of curricular time available for more medically focused competencies, is not relevant for some practice contexts, and is not introduced early enough in training. As a result, SBP learning experiences often feel disconnected from medical trainees' practical reality. In this commentary, the authors provide guidance regarding potential changes that may facilitate the evolution of SBP toward an ideal future state where graduates bring a systems science mindset to all aspects of their work. Specific suggestions include the following: (1) expanding the SBP toolbox to reflect current-day health system needs, (2) evolve the teaching methodology, (3) broadening the scope of relevant SBP content areas, and (4) emphasizing SBP as an integrated responsibility for all health care team members. Levers to enact this transformation exist and must be used to influence change at the learner, faculty, program, and clinical learning environment levels.Physicians operate within an increasingly complex health care system that highlights the intersection of health care with complex social, environmental, and relational contexts. Consequently, the role of SBP in both physician work responsibilities and educational requirements continues to expand. To meet this growing demand, GME must adapt how it supports and trains the next generation of systems thinkers, ensuring they understand how levers in the health care system directly affect health outcomes for their patients, and integrate SBP into the foundation of GME curricula in an inclusive, holistic, and unrestrained way.

Using the relationship between brain tissue regional saturation of oxygen and mean arterial pressure to determine the optimal mean arterial pressure in patients following cardiac arrest: A pilot proof-of-concept study.

INTRODUCTION: Prospectively assess cerebral autoregulation and optimal mean arterial pressure (MAPOPT) using the dynamic relationship between MAP and regional saturation of oxygen (rSO2) using near-infrared spectroscopy. METHODS: Feasibility study of twenty patients admitted to the intensive care unit following a cardiac arrest. All patients underwent continuous rSO2 monitoring using the INVOS(®) cerebral oximeter. ICM+(®) brain monitoring software calculates the cerebral oximetry index (COx) in real-time which is a moving Pearson correlation coefficient between 30 consecutive, 10-s averaged values of MAP and correspond rSO2 signals. When rSO2 increases with increasing MAP (COx ≥0.3), cerebral autoregulation is dysfunctional. Conversely, when rSO2 remains constant or decreases with increasing MAP (COx <0.3), autoregulation is preserved. ICM+(®) fits a U-shaped curve through the COx values plotted vs. MAP. The MAPOPT is nadir of this curve. RESULTS: The median age was 59 years (IQR 54-67) and 7 of 20 were female. The cardiac arrest was caused by myocardial infarction in 12 (60%) patients. Nineteen arrests were witnessed and return of spontaneous circulation occurred in a median of 15.5min (IQR 8-33). Patients underwent a median of 30h (IQR 23-46) of monitoring. COx curves and MAPOPT were generated in all patients. The mean overall MAP and MAPOPT were 76mmHg (SD 10) and 76mmHg (SD 7), respectively. MAP was outside of 5mmHg from MAPOPT in 50% (SD 15) of the time. Out of the 7672 5-min averaged COx measurements, 1182 (15%) were at 0.3 or above, indicating absence of autoregulation. Multivariable polynomial fractional regression demonstrated an increase in COx with increasing temperature (P=0.008). CONCLUSIONS: We demonstrated the feasibility to determine a MAPOPT using cerebral oximetry in patients after cardiac arrest.

Missed Opportunities for HIV Prophylaxis Among Emergency Department Patients With Occupational and Nonoccupational Body Fluid Exposures.

STUDY OBJECTIVE: Exposures to HIV are frequently managed in the emergency department (ED) for assessment and potential initiation of HIV postexposure prophylaxis. Despite established guidelines, it is unclear whether patients with a nonoccupational exposure are managed similarly to patients with an occupational exposure. METHODS: This retrospective study used an administrative database to identify consecutive patients at a single ED with a discharge diagnosis of "blood or body fluid exposure" without sexual assault from April 1, 2007 to June 30, 2013. Patient exposure details and physician management were ascertained according to predefined guidelines. The primary outcome was the proportion of patients with high-risk exposures who were correctly given HIV prophylaxis; the secondary outcome was the proportion of patients with low-risk exposures who were correctly not given HIV prophylaxis. Other outcomes included the proportion of patients who had a baseline HIV test in the ED, the proportion who followed up with an HIV test within 6 months, and the number of seroconversions in this group. All outcomes were compared between nonoccupational and occupational exposure. RESULTS: Of 1,972 encounters, 1,358 patients (68.9%) had an occupational exposure and 614 (31.1%) had a nonoccupational exposure. In the occupational exposure group, 190 patients (14.0%) were deemed high risk, with 160 (84.2%; 95% confidence interval [CI] 78.1% to 88.9%) appropriately given prophylaxis. In the nonoccupational exposure group, 287 patients (46.7%) had a high-risk exposure, with 208 (72.5%; 95% CI 66.8% to 77.5%) given prophylaxis, for a difference of 11.7% (95% CI 3.8% to 19.1%). For low-risk exposures, appropriate management of both occupational and nonoccupational exposure was similar (92.4% versus 93.0%). At the index ED visit, 90.5% of occupational exposure patients and 76.7% of nonoccupational exposure patients received HIV testing, for a difference of 13.8% (95% CI 10.1% to 17.7%). At 6 months, 25.4% of patients with an occupational exposure and 35.0% of patients with a nonoccupational exposure had a follow-up test, for a difference of -9.6% (95% CI -14.2% to -5.1%). Of patients who had follow-up testing within 6 months, 4 of 215 (1.9%) in the nonoccupational exposure group tested newly positive for HIV, whereas 0 of 345 (0%) in the occupational exposure group tested positive. CONCLUSION: For ED patients with blood or body fluid exposures, those with high-risk nonoccupational exposures were not given HIV prophylaxis nearly twice as often as those with high-risk occupational exposure. Although 6-month follow-up testing rates were low, 1.9% of high-risk nonoccupational exposure patients seroconverted.

Association between blood pressure and outcomes in patients after cardiac arrest: A systematic review.

OBJECTIVE: Hypoxic ischaemic brain injury (HIBI) is a major cause of disability after cardiac arrest. HIBI leads to impaired cerebral autoregulation such that adequate cerebral perfusion becomes critically dependent on blood pressure. However, the optimal blood pressure after cardiac arrest remains unclear. Therefore, we conducted a systematic review to investigate the association between blood pressure and neurologic outcome patients after cardiac arrest. METHODS: We systematically searched MEDLINE, EMBASE, conference abstracts and article references to identify randomized and observational studies investigating the relationship between blood pressure and neurologic outcome. We included studies that reported adjusted point estimates for the relationship between blood pressure and neurologic status in adult patients after cardiac arrest. RESULTS: We included 9 studies with a total of 13,150 patients. Three studies included only patients with an out-of-hospital cardiac arrest. There was marked between-study heterogeneity with respect to blood pressure definition (MAP vs. systolic), exposure duration and modelling (dichotomous vs. continuous). All studies examined either mortality or neurological status as an outcome. Seven of nine studies demonstrated that higher blood pressure was associated with improved outcomes either by an association between higher MAP and good neurologic outcome or the presence of hypotension and increased odds of mortality. CONCLUSIONS: The included studies suggest improved neurologic outcomes are associated with higher blood pressures in patients after cardiac arrest. This study highlights a need for further research to define the optimal management of blood pressure in this population.

Building a Generation of Physician Advocates: The Case for Including Mandatory Training in Advocacy in Canadian Medical School Curricula.

There is an increasing focus on the social accountability of physicians as individuals, and of medicine itself. This has led to increasing emphasis on physician advocacy from a wide variety of institutions. The physician advocacy concept is now part of the Health Advocacy competency mandated by the Royal College of Physicians and Surgeons of Canada. Despite its growing prominence, physician advocacy remains poorly integrated into current medical undergraduate curricula. The authors recommend how and why curricular reform should proceed; they focus on Canadian medical education, although they hope their views will be useful in other countries as well.The authors discuss conflicting definitions of physician advocacy, which have previously hampered curriculum development efforts, and suggest a way of reconciling the conflicts. They review current gaps in advocacy-related curricula, suggest that these can be addressed by incorporating practice-based and skills acquisition elements into current didactic teaching, and offer several strategies by which an advocacy curriculum could be implemented, ranging from small modifications to current curriculum to developing new competencies in medical education nationally.The authors present a case for making an advocacy curriculum mandatory for every Canadian medical trainee; they argue that teaching trainees how to fulfill their professional responsibility to advocate may also help them meet the social accountability mandate of medical school education. Finally, the authors explain why making the development and implementation of a mandatory, skill-based curriculum in advocacy should be a priority.

Experimental infection of several fish species with the causative agent of Kuchijirosho (snout ulcer disease) derived from the tiger puffer Takifugu rubripes.

Kuchijirosho (snout ulcer disease) is a fatal epidemic disease which affects the tiger puffer, Takifugu rubripes, a commercial fish species in Japan and Korea. To assess the possibility that non-tiger puffer fish can serve as reservoirs of infection, 5 fish species were challenged by infection with the extracts of Kuchijirosho-affected brains from cultured tiger puffer: grass puffer T. niphobles, fine-patterned puffer T. poecilonotus, panther puffer T. pardalis, red sea bream Pagrus major, and black rockfish Sebastes schlegeli. When slightly irritated, all these species, especially the puffer fish, exhibited typical signs of Kuchijirosho, i.e., erratic swimming, biting together and bellying out (swelling of belly), as generally observed in tiger puffers affected by Kuchijirosho. Although the mortalities of the 2 non-puffer species were lower, injection of the extracts prepared from the brains of both inoculated fish into tiger puffer resulted in death, indicating that the inoculated fish used in this experiment have the potential to be infected with the Kuchijirosho agent. Condensations of nuclei or chromatin in the large nerve cells, which is a major characteristic of Kuchijirosho, were histopathologically observed to some extent in the brains of all kinds of puffer fish species infected. These findings suggest that the virus can spread horizontally among wild and cultured puffers and even among fishes belonging to different orders.

The effect of ultraviolet rays on the prevention of exit-site infections.

The aim of this study was to show that ultraviolet (UV) irradiation to the skin around the catheter exit site (ES) could inhibit its infection. First, bacterial cultures of swabbed fluid from the ES were obtained from 68 continuous ambulatory peritoneal dialysis (CAPD) outpatients six times during the 24-month observation period. Second, the bactericidal effects of UV irradiation on the catheter ES were examined. The results were as follows: (1) In spite of disinfection of the catheter ES by the strict application of povidone-iodine once or twice a day, 23%-45% of the cases were found to be micro-organism positive. The most prevalent micro-organisms from the catheter ES were, in order of highest to lowest prevalence, Staphylococcus epidermidis (SE), Staphylococcus aureus (SA), and Pseudomonas aeruginosa (PA). (2) In the nasal cavity SA was detected in 20%-25% of patients. There was a high incidence of ES infection among the SA nasal carriers. (3) UV irradiation was performed in 18 cases that constantly revealed bacteria on culture at the catheter ES. Ten cases (55%) became culture-negative, 3 cases showed a microbial decrease, and 5 cases remained unchanged. These results suggest that UV irradiation can eliminate bacteria and can be of prophylactic use for ES infections.

Lecithin-cholesterol acyltransferase and lipid transfer protein activities in liver disease.

The activities of lecithin-cholesterol acyltransferase (LCAT) and lipid transfer protein (LTP) were assayed using sensitive radioassay methods in controls (n = 113) and in patients with various liver diseases (n = 72). Plasma LCAT activity decreased with progression of hepatocellular damage. Plasma LTP activity in controls was 216 +/- 68 nmol/mL/h, and there were no significant differences between controls and patients with chronic hepatitis ([CH], 193 +/- 70), compensated liver cirrhosis (LC) with or without hepatocellular carcinoma ([HCC], 197 +/- 48 and 193 +/- 62, respectively), or decompensated liver cirrhosis ([dLC], 182 +/- 65). In acute viral hepatitis, LTP activity decreased significantly; however, the degree of reduction was not as dramatic as that for LCAT. There was no correlation between LCAT and LTP activity both in controls and patients with various liver diseases. LCAT activity was positively correlated with serum albumin (r = .52, P < 0.1) and cholinesterase (r = .37, P < .01) levels, and inversely correlated with serum bilirubin level (r = -.38, P < 0.1); there was no correlation between plasma LTP activity and these parameters of liver function. That plasma LTP activity did not change with hepatocellular damage may indicate that the liver in humans may not be the primary site of LTP production.

Nutritional improvement in elderly CAPD patients with additional high protein foods.

One of the key factors in improving the survival and dropout rate in continuous ambulatory peritoneal dialysis (CAPD) patients is to improve their nutritional status. In this study 18 CAPD patients were encouraged to add 0.1-0.3 g of protein/kilogram/day of high biological value nutrients for more than 6 months in the form of a dessert. Several nutritional parameters, such as serum total protein, albumin, prealbumin, transferrin, plasma total amino acids, the ratio of essential amino acids (EAA) to nonessential amino acids (NEAA), and serum C3, C4, increased significantly. The values of (KT/V) urea increased simultaneously with increases in the protein catabolic rate (PCR) after the administration of nutrients. There was also a significant correlation between the (KT/V) urea and PCR in each patient. These results suggest that supplementary protein nutrients can improve the biochemical and physical nutritional parameters that are related to nutritional status and peritoneal functions.

Regional differences in insulin receptor function in Werner's syndrome.

Werner's syndrome is a genetic disease characterized by premature aging and is often associated with glucose intolerance due to insulin resistance. The clinical manifestations in this syndrome are preferentially expressed in the face and acral regions without apparent involvement of the trunk. We compared insulin receptor binding and amino acid uptake of fibroblasts derived from the forearm that had sclerodermoid features, and from the abdomen that was apparently normal in a patient with Werner's syndrome. In normal controls, specific insulin binding was not different in forearm and abdomen-derived fibroblasts (10.72 +/- 2.11%, 10.40 +/- 1.27%, respectively). In the patient, however, specific insulin binding was reduced in the fibroblasts derived from the forearm compared with those derived from the abdomen (3.55%, 8.16%, respectively). Scatchard analysis revealed that the reduction in insulin binding of the forearm fibroblasts from the patient was due to a reduction in receptor number with no change in receptor affinity. The dose-response curve for insulin of alpha-aminoisobutyric acid (AIB) uptake is shifted to the right in the fibroblasts derived from the acral area. The results show that in a patient with Werner's syndrome, regional differences occur in fibroblast insulin receptor binding and function. This suggests early phenotypic expression of the genetic abnormality of insulin receptor function in these patients.

Key factors to improve survival of elderly patients on CAPD.

The adequacy of dialysis is a primary concern when caring for patients undergoing CAPD. It is also important to analyze the key factors, which will reflect on the prognosis of elderly patients on CAPD. In this study, 60 CAPD patients were examined. The peritoneal and residual renal clearance of these patients were calculated every six months. These patients were divided into three groups (G-1 = poor, G-2 = fairly good, G-3 = good) according to their clinical parameter scores using a s-albumin,Ht,LBW, and s-cholesterol level. This study showed that the values of (KT/V) urea and Curea showed no statistical differences. These results therefore indicate that the major reason for the poor outcome in elderly patients is due to low dietary protein intake.

Effects of cyclosporin A and low dosages of steroid on posttransplantation diabetes in kidney transplant recipients.

OBJECTIVE: To investigate the adverse effects of cyclosporin A (CsA) on pancreatic beta-cell function in kidney transplant recipients. RESEARCH DESIGN AND METHODS: The study consisted of 73 patients without a history of diabetes mellitus who had undergone kidney transplantation in our clinic. RESULTS: We experienced a higher incidence of posttransplantation diabetes mellitus (PTDM) in patients receiving CsA and low dosages of methylprednisolone (6/20, 30%, P less than 0.05) than in patients receiving conventional therapy of azathioprine methylprednisolone (4/53, 7.5%) since the introduction of CsA. In all 6 patients in the CsA-treated group, PTDM occurred within 3 mo after transplantation. The CsA level during the initial 3 mo posttransplant was significantly higher in diabetic than nondiabetic subjects, and the highest CsA level was observed shortly (1 mo) before the development of PTDM. After an average of 71 days of insulin therapy, there was complete remission of PTDM in 5 of 6 diabetic patients, with a corresponding decrease in CsA level. For the patients who were in remission for greater than 1 yr, a significant improvement of glucose intolerance was observed in association with a significantly higher insulin response to oral glucose load; however, their glycemic profile still showed a significantly higher plasma glucose concentration and a prolonged continuous elevation without initial peak of the insulin-response curve in contrast to the normal pattern found in nondiabetic subjects in the CsA-treated group. CONCLUSIONS: This study suggests that CsA in combination with low dosages of steroid may have adverse effects on glucose metabolism, which may lead to effects similar to those in non-insulin-dependent diabetes mellitus.

Effects of hyperglycaemia on sorbitol and myo-inositol contents of cultured embryos: treatment with aldose reductase inhibitor and myo-inositol supplementation.

To demonstrate the myo-inositol depletion hypothesis in hyperglycaemia-induced embryopathy, rat conceptuses of 9.5 days of gestation in the early head-fold stage were grown in vitro during neural tube formation for 48 h with increasing amounts of glucose. The effects of an aldose reductase inhibitor and the myo-inositol supplementation were also investigated. Sorbitol and myo-inositol contents were measured in separated embryos and extra-embryonic membranes including yolk sac and amnion at the end of culture. After addition of 33.3 mmol/l and 66.7 mmol/l glucose to the culture media, the myo-inositol content of the embryos was significantly decreased by 43.1% (p less than 0.05) and 64.6% (p less than 0.01) of the control group, while a marked accumulation of sorbitol was observed (25 and 41 times that of the control). Although the addition of an aldose reductase inhibitor (0.7 mmol/l) to the hyperglycaemic culture media containing an additional 66.7 mmol/l glucose significantly reduced the sorbitol content of embryos to approximately one-eighth, the myo-inositol content of embryos remained decreased and the frequency of neural lesions was unchanged (23.1% vs 23.9%, NS). Supplementation of the myo-inositol (0.28 mmol/l) completely restored the myo-inositol content of the embryos and resulted in a significant decrease in the frequency of neural lesions (7.1% vs 23.9%, p less than 0.01) and a significant increase in crown-rump length and somite numbers. Much less significantly, sorbitol accumulation was also observed in the extra-embryonic membrane in response to hyperglycaemia, neither hyperglycaemia nor the myo-inositol supplementation modified the myo-inositol contents of the extra-embryonic membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma lipid transfer activities in hyper-high-density lipoprotein cholesterolemic and healthy control subjects.

The relationships between plasma lipid transfer protein (LTP) activity and various lipid or lipoprotein concentrations were studied in 14 hyper-high-density lipoprotein (hyper-HDL) cholesterolemic subjects and 152 healthy controls. We measured plasma LTP activity by our sensitive assay method, using radiolabeled proteoliposomes as the lipid donor, low-density lipoprotein (LDL) as the acceptor, and a very small amount of untreated plasma (typically 1 to 2 microliters) as the sample. Control subjects had the mean of LTP activity at 206 +/- 45 nmol/mL/h. The difference of LTP activity between men and women was not statistically significant. In the control subjects, the activity of plasma LTP had a significantly positive correlation with the concentrations of total cholesterol (r = .639, P less than .01) and LDL cholesterol (r = .634, P less than .01), but not with those of HDL cholesterol and total triglyceride, nor with percent ideal body weight. One of 14 patients with hyper-HDL cholesterolemia had no detectable LTP activity, and three others had very low LTP activity. From these data, LTP activity may be one of the important factors to influence plasma LDL concentration, and the lack of LTP activity may be related to a subclass of hyper-HDL cholesterolemias.

Effects of brief exposure to insulin-induced hypoglycemic serum during organogenesis in rat embryo culture.

We have previously shown that long-term exposure to medium containing insulin-induced hypoglycemic serum during the early phase of organogenesis can adversely affect embryonic development in rat embryo culture and that these effects were mediated through the interruption of glycolytic flux that constituted the principal pathway at this embryonic stage. Further experiments were performed to examine whether brief exposure to the hypoglycemic medium during critical developmental periods would have adverse effects on embryogenesis during embryo culture not only in normal but also in high glucose concentrations. Rat embryos in the early head-fold stage (9.5 days gestation) were grown in vitro for 48 h until neural tube closure occurred; dysmorphogenic lesions were not elicited in either the basal culture medium containing 6.6 mM glucose (control medium) or the hyperglycemic medium supplemented with glucose at a concentration of 33.3 mM. Hypoglycemic mediums (2.2-2.5 mM glucose) were prepared from the serum of rats given insulin intraperitoneally. Postimplantation embryos (in early neural tube formation) were briefly exposed (1 h) to hypoglycemic medium on day 10.3 of gestation during the basal culture. After exposure to the hypoglycemic medium for 1 h during culture in the control medium, embryos showed minor growth retardation and dysmorphogenic lesions (7.1% open neural pores). Exposure to the hypoglycemic medium for 1 h during culture in hyperglycemic medium suplemented with a subteratogenic concentration of glucose (33.3 mM) resulted in greater growth retardation and increased occurrence of dysmorphogenic lesions (17.3% open neural pores).(ABSTRACT TRUNCATED AT 250 WORDS)