Machine-learned modeling of PM2.5 exposures in rural Lao PDR.

This study presents a machine-learning-enhanced method of modeling PM2.5 personal exposures in a data-scarce, rural, solid fuel use context. Data collected during a cookstove (Africa Clean Energy (ACE)-1 solar-battery-powered stove) intervention program in rural Lao PDR are presented and leveraged to explore advanced techniques for predicting personal exposures to particulate matter with aerodynamic diameter smaller than 2.5 µm (PM2.5). Mean 48-h PM2.5 exposure concentrations for female cooks were measured for the pre- and post-intervention periods (the "Before" and "After" periods, respectively) as 123 µg/m3 and 81 µg/m3. Mean 48-h PM2.5 kitchen air pollution ("KAP") concentrations were measured at 462 µg/m3 Before and 124 µg/m3 After. Application of machine learning and ensemble modeling demonstrated cross-validated personal exposure predictions that were modest at the individual level but reasonably strong at the group level, with the best models producing an observed vs. predicted r2 between 0.26 and 0.31 (r2 = 0.49 when using a smaller, un-imputed dataset) and mean Before estimates of 119-120 µg/m3 and After estimates of 86-88 µg/m3. This offered improvement over one typical method of predicting exposure - using a kitchen exposure factor (the ratio of exposure to KAP)- which demonstrated an r2 ~ 0.03 and poorly estimated group average values. The results of these analyses highlight areas of methodological improvement for future exposure assessments of household air pollution and provide evidence for researchers to explore the advantages of further incorporating machine learning methods into similar research across wider geographic and cultural contexts.

Connective tissue and related disorders and preterm birth: clues to genes contributing to prematurity.

To identify candidate genes contributing to preterm birth, we examined the existing literature on the association between known disorders of connective tissue synthesis and metabolism and related diseases and prematurity. Our hypothesis was that abnormal matrix metabolism contributes to prematurity by increasing risk of preterm premature rupture of membranes (PPROM) and cervical incompetence. Based on this review, we identified gene mutations inherited by the fetus that could predispose to preterm birth as a result of PPROM. The responsible genes include COL5A1, COL5A2, COL3A1, COL1A1, COL1A2, TNXB, PLOD1, ADAMTS2, CRTAP, LEPRE1 and ZMPSTE24. Marfan syndrome, caused by FBN1 mutations, and polymorphisms in the COL1A1 and TGFB1 genes have been associated with cervical incompetence. We speculate that an analysis of sequence variation at the loci noted above will reveal polymorphisms that may contribute to susceptibility to PPROM and cervical incompetence in the general population.

Practice trends in outpatient obstetrics and gynecology: findings of the Collaborative Ambulatory Research Network, 1995--2000.

UNLABELLED: Historically, obstetrics and gynecology has been a medical/surgical specialty focusing on women's health and reproductive concerns during the childbearing years. Newer responsibilities-for example, in primary care, gerontology, and genetics-require Ob-Gyns to draw upon a base of medical knowledge that traditionally was not considered germane to their practices. Ob-Gyns are increasingly providing more primary care services to their patients; consequently, the field has expanded considerably. The Collaborative Ambulatory Research Network (CARN) was created in 1990 as a vehicle for investigating issues pertinent to women's health and to the practice of obstetrics and gynecology in the outpatient setting. This article summarizes the findings of CARN studies from 1995 to 2000, covering a range of topics related to women's health across the life cycle, including, but not limited to perinatal care. Topics include nutrition, infectious disease, hormone replacement therapy, psychosocial issues, and genetic testing in obstetric and gynecologic practice. Each study produced a picture of current practice patterns and knowledge of the physicians surveyed. Findings on knowledge, attitudes, and practices varied widely. Overall, Ob-Gyns were knowledgeable and consistent in more traditional areas of practice. Conversely, inconsistencies were observed in newer areas. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to define what the Collaborative Ambulatory Research Network (CARN) involves, describe how CARN obtains its data, and summarize some of the findings of CARN from the years 1995 to 2000.

Obstetrician-gynecologists' attitudes towards premenstrual dysphoric disorder and major depressive disorder.

Nine hundred ninety-seven fellows of the American College of Obstetricians and Gynecologists were surveyed by mailed questionnaire regarding their attitudes toward the conceptualization, diagnosis and treatment of premenstrual dysphoric disorder (PMDD) and major depressive disorder (MDD). Hypothesized differences in attitudes based on age, gender and professional identity as a primary care provider versus non-primary care provider were examined. Comparisons between attitudes toward PMDD and MDD were also investigated. Approximately 36% of the questionnaires were completed and returned. Overall attitudes toward PMDD versus MDD were found to be significantly different. Roughly one in three respondents disagreed with statements indicating responsibility for and confidence in their ability to treat MDD, but not PMDD. When significant differences were found for age, gender and professional identity, younger physicians, women physicians and those who self-identified as primary care providers reported attitudes that may be more likely to be associated with diagnosis and treatment of MDD and PMDD in gynecologic practice. For example, about 41% of self-identified non-primary care providers and 14.8% of primary care providers disagreed with the statement 'treating depression is my responsibility as a gynecologist'. Differences in gynecologists' attitudes toward MDD versus PMDD may be associated with under-treatment of MDD in gynecologic practice.

Childhood sexual abuse and preterm labor in adulthood: an endocrinological hypothesis.

Anecdotal reports link adverse pregnancy outcomes, such as preterm delivery, to women with histories of childhood sexual abuse. Although little research has been conducted on this subject, we provide an overview of known health effects of violence against women and posit a biological explanation for adverse pregnancy outcomes among this population. Specifically, we hypothesize that early traumatic experiences of childhood sexual abuse may activate corticotropin releasing hormone (CRH) gene expression in the brain, and a vulnerability to elevated CRH gene expression in the placenta. Those traumatized by early abuse may be more susceptible to stress vís a vís CRH dysregulation during a major psychosocial stressor, such as pregnancy. Elevated CRH has been associated with preterm labor.

Gynecologists' training, knowledge, and experiences in genetics: a survey.

OBJECTIVE: To explore gynecologists' knowledge, training, and practice experience with genetic screening and DNA-based testing. METHODS: A questionnaire survey was sent to 1,248 ACOG Fellows, of whom 564 (45%) responded. One hundred thirty-four respondents (24%) reported that they do not order DNA-based tests or take family histories to screen for heritable diseases or disorders. Results from the 428 respondents who provide genetic screening services are reported. RESULTS: Most physicians (90%) knew that genetic tests are most informative when used in conjunction with family histories. Gynecologists gave more correct responses regarding genetic testing for breast and ovarian cancers than for colon cancer and other adult-onset diseases. Sixty-five percent of the respondents had not received formal training in DNA-based testing in gynecologic practice. Older physicians were less likely to have had training. Younger physicians generally gave more correct responses on the knowledge portion of the survey (r = -.165, P < .01). Physicians who had formal training in genetics gave more correct answers. Physicians who order DNA-based tests scored higher than those who do not and had no formal training, but not higher than those who had formal training and do not order DNA-based tests. CONCLUSION: Gynecologists were more knowledgeable about genetic issues pertaining to breast and ovarian cancer than to other cancers or certain adult-onset disorders. Training appeared to increase knowledge. Increased training and affiliation with genetic specialists and others could improve gynecologists' ability to use genetic screening in clinical practice.

Open repair of hiatus hernia: abdominal approach.

Open hiatus hernia repair can be accomplished with very low mortality and excellent long-term results. The vast majority of hiatus hernias, including those with peptic structure, can be repaired transabdominally. The Hill repair, the Nissen, and the Collis-Nissen are well-established techniques for repairing a hiatus hernia that have stood the test of time and are associated with good long-term results. The technical aspects of these repairs are discussed in detail within this article.

Laparoscopic Hill repair in patients with abnormal motility.

BACKGROUND: Gastroesophageal reflux is frequently associated with abnormal motility in the body of the esophagus. Concern for dysphagia has led surgeons to perform less competent procedures in this group, or to avoid surgery altogether. The current study was undertaken to evaluate our experience with the laparoscopic Hill repair in patients with reflux-associated abnormal motility. METHODS: A retrospective review of 338 laparoscopic Hill repairs was performed; 253 patients had adequate information for analysis, and 8 patients were excluded because of hypertensive motility. The remaining 245 patients were divided into group I (175) with normal esophageal body peristalsis, group IIA (37) with moderate dysmotility, and group IIB (33) with severe dysmotility. All patients underwent standard laparoscopic Hill repair. Follow-up included postoperative manometry and 24-hour pH studies and interview by an independent physician. Dilation for dysphagia was performed when necessary. Statistical analysis was performed using the F test. RESULTS: Mean follow-up was 11.0 months (range 1 to 41). Early dysphagia (<3 months) occurred in 4.0% of group I patients and 12.9% of group II patients. Late dysphagia (>3 months) occurred in 1.1% of group I patients and 1.4% of group II patients. Postoperative motility returned to normal in 43% of group IIB patients studied. Twenty-four hour pH evaluation showed fractional pH <4 an average of 4.8% in group I (median 2.1%) and 6.4% in group II (median 4.0%; P = 0.57). Patient rating of results was good to excellent in 91.0% with no statistical difference between the two groups. No patient required reoperation for dysphagia. CONCLUSION: The laparoscopic Hill repair can be safely performed in patients with reflux-associated dysmotility, with excellent results. Even severely disordered motility will return to normal in a high percentage of cases. Manometric control of the repair and secure distal fixation of the gastroesophageal junction are advantages. Abnormal motility may be an indication for, rather than a contraindication to, laparoscopic Hill repair.

The gastroesophageal flap valve: in vitro and in vivo observations.

BACKGROUND: This study was performed to confirm the presence and significance of a gastroesophageal flap valve. METHODS: The pressure gradient needed to induce reflux across the gastroesophageal junction and the level of a high-pressure zone were determined in 13 cadavers. On inspection in the cadavers, a mucosal flap valve at the entrance of the esophagus into the stomach was seen through a gastrostomy. This valve was deficient or absent in cadavers with a hiatal hernia. The valve was inspected in controls and in patients with reflux with a retroflexed endoscope. RESULTS: In cadavers with no hiatal hernia, a gradient across the gastroesophageal junction was present in nearly all cadavers. The gradient could be increased by surgically accentuating the valve without a concomitant rise in pressure in the high-pressure zone. Reduction of the hiatal hernia in the cadaver and anchoring of the gastroesophageal junction to the normal attachment to the preaortic fascia restored the valve and the gradient as seen through a gastrostomy. Control subjects had a prominent fold of tissue that extended 3 to 4 cm along the lesser curve of the stomach and tightly grasped the shaft of the endoscope. This was diminished or absent in reflux patients. Inspection of the valve in control subjects and subjects with reflux allowed for a grading system with Grades I through IV. This grading system was applied to a cohort of patients with and without reflux. The appearance of the flap valve was a better predictor of the presence or absence of reflux than was lower esophageal sphincter pressure. Endoscopic viewing of the valve during surgery can confirm that a competent valve has been reconstructed. CONCLUSIONS: Grading of the gastroesophageal valve is simple, reproducible, and offers useful information in the evaluation of patients with suspected reflux undergoing endoscopy.

Early results with the laparoscopic Hill repair.

The open Hill repair is established as a highly effective and durable antireflux procedure. At the present time, we have multi-institutional experience with over 140 laparoscopic Hill repairs. Detailed follow-up on the first 40 patients at our institution is described. All patients had well-documented reflux or esophagitis preoperatively, 7 patients had evidence of peptic stricture or Schatzki's ring, 11 had large hiatal hernia, and 10 weighed more than 200 lb. There were no serious complications and no reoperations. There was 1 death during the follow-up period that was not attributable to the repair. Hospital stay averaged 2.8 days with return to normal activity in 7 to 14 days. Postoperative manometry has been obtained in 24 of the 39 patients available for follow-up (62%) and 24-hour pH studies in 23 of the 39 (59%). Thirty-nine patients were evaluable at a mean follow-up of 10 months and a median follow-up of 8 months (range: 4 to 20 months), with 36 (92%) subjectively rating results as good or excellent. Only one of the three remaining patients has objective evidence of reflux, yielding 97% clinical control of reflux. Mean lower esophageal sphincter pressure (LESP) was raised from 10.7 mm Hg, preoperatively, to 25 mm Hg, postoperatively. Postoperatively, 33 of the 39 patients (85%) are now free of medications referable to the esophagus or upper gastrointestinal tract. This early follow-up experience with the laparoscopic Hill repair leads us to conclude that it is safe, widely applicable, and highly effective as an antireflux operation. Its special features give it certain advantages over the laparoscopic Nissen repair, and we recommend it as the procedure of choice.

Laparoscopic Hill repair.

Gastroesophageal reflux disease, with its attendant symptoms and complications of heartburn, esophagitis, dysphagia, and upper gastrointestinal bleeding, is the most common disorder of the upper gastrointestinal tract. The open Hill repair, which has been utilized in more than 2000 patients, is best defined as restoration of the anti-reflux barrier. The anti-reflux barrier includes the gastroesophageal valve, lower esophageal sphincter, and diaphragm. The Hill repair has now been done laparoscopically in 17 patients (10 men and 7 women) who have been entered into a detailed protocol, including pre-operative evaluation, intra-operative monitoring, and post-operative evaluation. Results have been excellent, with correction of reflux in all patients. Duration of follow-up ranges from 1 to 18 months, with a mean of 10.5 months. No mortality or serious complications have occurred. Extensive post-operative testing in 13 patients, including complete symptom evaluation, standard acid reflux testing, and 24-hour pH monitoring, has shown no recurrence of reflux; lower esophageal sphincter pressure has been restored to a mean of 28 mm Hg, and gastroesophageal valve status to grade 1. Because the laparoscopic procedure is similar to the open Hill repair, expectations for good long-term results are very high.

Effect of interleukin-4 on the synthesis of the third component of complement by pulmonary epithelial cells.

Complement activation in the lung is important in a variety of physiological and pathological conditions. The third component of complement, C3, is the pivotal constituent of the complement cascade. C3 is produced in the lung by several cell types including pulmonary epithelial cells. Because pulmonary epithelial cells and T lymphocytes may interact within the lung to regulate local immune responses, we examined the effect of a T lymphocyte-derived cytokine, interleukin-4 (IL-4) on C3 production by A549 human pulmonary epithelial cells. Treatment of A549 cells with IL-4 increased C3 production in a time- and dose-dependent fashion. Concentrations of IL-4 > or = 0.1 ng/ml significantly increased C3 production. Maximal increase in C3 synthesis occurred after stimulation of A549 cells with IL-4 (10 ng/ml) for 3 days. Preincubation of IL-4 with a neutralizing anti-human IL-4 antibody inhibited IL-4's effect on C3 production. The relative abundance of C3 messenger RNA levels in A549 cells increased following IL-4 treatment, indicating that IL-4's effects on C3 production were pretranslational. Intercellular communication between T lymphocytes and pulmonary epithelial cells via cytokines such as IL-4 may be important in the local regulation of C3 gene expression during the inflammatory response.

Effect of steroids on the synthesis of complement C3 in a human alveolar epithelial cell line.

The third component of complement, C3, is produced in the lung by several cell types, including alveolar epithelial cells. Steroid hormones are important in gene regulation in alveolar epithelial cells. The effects of steroids on C3 production were examined using A549 human pulmonary alveolar epithelial cells. Treatment of A549 cells with the glucocorticoids dexamethasone, hydrocortisone, corticosterone, and 11-deoxycortisol increased C3 production, as measured by ELISA. The glucocorticoid receptor antagonist RU486 inhibited C3 synthesis by dexamethasone- and hydrocortisone-stimulated cells. Because the glucocorticoid receptor is a member of a superfamily of receptors, the effects of steroid members of the superfamily on C3 production were examined. The mineralocorticoid, aldosterone, increased C3 production. RU486 completely inhibited aldosterone's stimulatory effects on C3 production, whereas the mineralocorticoid receptor antagonist spironolactone partially inhibited aldosterone's effects. In contrast, testosterone, progesterone 17 alpha-hydroxyprogesterone, and estradiol did not alter C3 production by A549 cells. Northern analysis showed that C3 mRNA abundance in A549 cells increased following stimulation with dexamethasone, hydrocortisone, corticosterone, and aldosterone. Testosterone, progesterone, 17 alpha-hydroxyprogesterone, and estradiol did not alter C3 mRNA levels. Therefore, among the steroids tested, only glucocorticoids and aldosterone altered C3 production by A549 cells suggesting that these steroids may play a role in the regulation of C3 in the lung.

Transdiaphragmatic approach to the posterior mediastinum and thoracic esophagus.

OBJECTIVE: Complex operations involving the lower esophagus and posterior mediastinum are frequently compromised by poor exposure, thereby requiring combined thoracic and abdominal incisions. We describe our technique and report our experience with a transdiaphragmatic approach to the posterior mediastinum that improves exposure and eliminates the need for thoracotomies. PATIENTS: The lower thoracic esophagus and posterior mediastinum were exposed through a semicircular incision in the central tendon of the diaphragm. The indications for operation in 14 patients were benign conditions of the lower esophagus (reflux esophagitis, lye stricture, scleroderma, and achalasia) (n = 8), malignant neoplasm of the lower esophagus (n = 3), and revagotomy (n = 3). RESULTS: All indicated procedures, resections, and esophagogastric, esophagojejunal, or esophagocolonic anastomoses were completed through abdominal and/or cervical incisions. There were no thoracotomies performed. CONCLUSIONS: We believe this transdiaphragmatic approach greatly improves exposure to the lower and middle esophagus and posterior mediastinum compared with transhiatal approaches; preserves the integrity of the gastroesophageal junction; allows easy access to the vagus nerves without risking esophageal injury in patients who had undergone surgery previously; shortens operative time; and lessens pulmonary morbidity and decreases patients' pain and recovery time when compared with thoracotomy.

C3 synthesis by A549 alveolar epithelial cells is increased by interferon-gamma and dexamethasone.

The third component of complement, C3, is produced in the lung by several cell types including alveolar epithelial cells. Since interferon-gamma (IFN-gamma) and dexamethasone regulate C3 gene expression in non-pulmonary cells, and because IFN-gamma and dexamethasone interact to regulate the functional activity of alveolar epithelial cells, we investigated the effects of IFN-gamma and dexamethasone on C3 production by A549 human alveolar epithelial cells. Treatment of A549 cells with IFN-gamma alone increased C3 production in a time-and dose-dependent manner. Maximal increase in C3 production occurred after stimulation of A549 cells with 500 IU/ml IFN-gamma for 3 days and was 3.4-fold greater than control. Dexamethasone (0.1 microM) stimulation of A549 cells increased C3 production 6.7-fold over controls on day 3. Treatment of A549 cells with IFN-gamma plus dexamethasone resulted in an 11-to 13-fold increase in C3 synthesis. C3 mRNA levels were increased in A549 cells treated with IFN-gamma and dexamethasone individually and in combination suggesting that IFN-gamma and dexamethasone increase C3 synthesis by a pre-translational mechanism. IFN-gamma and dexamethasone did not alter the two-chain structure of the C3 molecule produced by A549 cells, as assessed by Western blotting. We speculate that IFN-gamma and glucocorticoids may be important in the local regulation of C3 synthesis in the lung.

Effect of glucocorticoids on C3 gene expression by the A549 human pulmonary epithelial cell line.

The third component of C, C3, is the key opsonin of the C cascade and is produced locally within the lung by pulmonary epithelial cells, macrophages, and fibroblasts. Because glucocorticoids regulate the maturation and expression of several physiologically important genes in pulmonary epithelial cells, we examined the effects of glucocorticoids on C3 mRNA expression and C3 synthesis by the human pulmonary epithelial cell line, A549. Treatment with dexamethasone enhanced C3 production in a time- and dose-dependent fashion such that concentrations of dexamethasone greater than or equal to 0.001 microM significantly increased C3 production on day 3 of culture. Natural glucocorticoids, corticosterone, cortisol, and 11-deoxycortisol also increased C3 concentrations in A549 supernatants. Both cycloheximide and the glucocorticoid receptor antagonist, RU486, individually inhibited the effect of dexamethasone on C3 production. Northern analysis demonstrated that the steady state 5.2-kb C3 message increased in A549 cells within 10 h of treatment with dexamethasone. RU486 inhibited the effect of dexamethasone on C3 mRNA expression. The integrity of the C3 thiolester bond, as measured by [3H]iodoacetic acid titration and hemolytic assay, was not disrupted by dexamethasone. We conclude that glucocorticoids such as dexamethasone enhance the expression of C3 mRNA and increase the production of functionally active C3 by A549 cells by a mechanism that is mediated by the intracellular glucocorticoid receptor.

Does modern technology belong in gastro-intestinal surgery? A step from subjective perception to objective information.

The intra-operative measurement of lower esophageal sphincter (LES) pressure can aid the surgeon in primary repair of the gastroesophageal junction. We evaluated 1,000 patients undergoing primary repairs; 540 patients underwent surgery before the introduction of LES pressure measurements and 460 patients after LES pressure measurement. The incidence of continued reflux was lower in the group having intraoperative LES pressure measurement (4.5% vs. 1.5%). The incidence of continued reflux in this group has been less than 1%. The measurement of intra-operative LES pressure brings objective technology to our patients and improves their quality of life.

Use of purified streptokinase in empyema and hemothorax.

Enzymatic debridement of the pleural cavity for retained hemothorax or empyema is a frequently overlooked option. Thirteen of fourteen patients (93%) with retained pleural collections underwent successful enzymatic debridement and tube drainage with purified streptokinase injections. The average increase in chest tube output following streptokinase injections was 158%. No significant adverse reactions occurred. One patient required thoracotomy when streptokinase therapy failed. Two others had successful resolution of their pleural collections but required thoracotomy for other indications. There were two deaths (14%), which were unrelated to the use of streptokinase or residual empyema. Intrapleural streptokinase is a safe, effective means of removing retained proteinaceous collections in the pleural space. It is a useful adjunct to chest tube drainage and may obviate the need for more invasive procedures.

Antireflux surgery. A surgeon's look.

With a reassessment of the antireflux barrier, we are gaining a better appreciation of the components of the barrier and their importance in preventing reflux. The GE valve in particular appears to play a key role in preventing reflux. With better understanding of the anatomy and function of the GE barrier, we should do a better job, both medically and surgically. The knowledge and new technology that are available should allow the surgeon to perform antireflux surgery with 95% good to excellent results with a minimum of morbidity. As our 15 to 20 year follow-up with a mean of 17.8 years shows, these good results will last over the long term. These observations should give the gastroenterologist confidence that antireflux surgery is highly effective for those patients who fail medical management.