A pregnancy lifestyle intervention to prevent gestational diabetes risk factors in overweight Hispanic women: a feasibility randomized controlled trial.

AIMS: To pilot the feasibility of a prenatal lifestyle intervention to modify physical activity and diet among pregnant overweight and obese Hispanic women, with the aim of reducing risk factors for gestational diabetes mellitus. METHODS: Women were randomized either to a lifestyle intervention (n = 33, 48.5%), consisting of a culturally and linguistically modified, motivationally targeted, individually tailored 6-month prenatal programme, or to standard care (n = 35, 51.5%). Bilingual and bicultural health educators encouraged women to achieve guidelines for physical activity, decrease saturated fat and increase dietary fibre. Outcomes included gestational weight gain, infant birth weight and biomarkers associated with insulin resistance. RESULTS: Patient retention up to delivery was 97% in both study groups. The lifestyle intervention attenuated the pregnancy-associated decline in moderate-intensity physical activity, but differences between groups were not significant (mean ± se -23.4 ± 16.6 vs -27.0 ± 16.2 metabolic equivalent of task h/week; P = 0.88). Vigorous-intensity activity increased during the course of pregnancy in the lifestyle intervention group (mean ± se 1.6 ± 0.8 metabolic equivalent of task h/week) and declined in the standard care group (-0.8 ± 0.8 metabolic equivalent of task h/week; P = 0.04). The lifestyle intervention group also had slightly lower gestational weight gain and infant birth weights compared with the standard care group; however, these differences were not statistically significant. There were no statistically significant differences in biomarkers of insulin resistance between groups. CONCLUSIONS: Findings suggest that a motivationally matched lifestyle intervention is feasible and may help attenuate pregnancy-related decreases in vigorous physical activity in a population of overweight and obese Hispanic women. The intervention protocol can readily be translated into clinical practice in underserved and minority populations.

A cortical folding model incorporating stress-dependent growth explains gyral wavelengths and stress patterns in the developing brain.

In humans and many other mammals, the cortex (the outer layer of the brain) folds during development. The mechanics of folding are not well understood; leading explanations are either incomplete or at odds with physical measurements. We propose a mathematical model in which (i) folding is driven by tangential expansion of the cortex and (ii) deeper layers grow in response to the resulting stress. In this model the wavelength of cortical folds depends predictably on the rate of cortical growth relative to the rate of stress-induced growth. We show analytically and in simulations that faster cortical expansion leads to shorter gyral wavelengths; slower cortical expansion leads to long wavelengths or even smooth (lissencephalic) surfaces. No inner or outer (skull) constraint is needed to produce folding, but initial shape and mechanical heterogeneity influence the final shape. The proposed model predicts patterns of stress in the tissue that are consistent with experimental observations.

The effect of fibre cell remodelling on the power and optical quality of the lens.

Vertebrate eye lenses are uniquely adapted to form a refractive index gradient (GRIN) for improved acuity, and to grow slowly in size despite constant cell proliferation. The mechanisms behind these adaptations remain poorly understood. We hypothesize that cell compaction contributes to both. To test this notion, we examined the relationship between lens size and shape, refractive characteristics and the cross-sectional areas of constituent fibre cells in mice of different ages. We developed a block-face imaging method to visualize cellular cross sections and found that the cross-sectional areas of fibre cells rose and then decreased over time, with the most significant reduction occurring in denucleating cells in the adult lens cortex, followed by cells in the embryonic nucleus. These findings help reconcile differences between the predictions of lens growth models and empirical data. Biomechanical simulations suggested that compressive forces generated from continuous deposition of fibre cells could contribute to cellular compaction. However, optical measurements revealed that the GRIN did not mirror the pattern of cellular compaction, implying that compaction alone cannot account for GRIN formation and that additional mechanisms are likely to be involved.

Perspectives on biological growth and remodeling.

The continuum mechanical treatment of biological growth and remodeling has attracted considerable attention over the past fifteen years. Many aspects of these problems are now well-understood, yet there remain areas in need of significant development from the standpoint of experiments, theory, and computation. In this perspective paper we review the state of the field and highlight open questions, challenges, and avenues for further development.

A walking model to assess the onset of analgesia in osteoarthritis knee pain.

OBJECTIVE: To assess a walking model utilizing a set of standardized treadmill walks to measure acute analgesic response in osteoarthritis (OA) of the knee. DESIGN: Randomized, double-blind, placebo-controlled, multiple dose, three-period crossover study. Patients > or =45 years of age (N=22) with symptomatic knee OA were randomized to naproxen 500 mg bid, tramadol/acetaminophen 37.5 mg/325 mg in forced titration, or placebo in each of three periods. Patients performed multiple 20-minute treadmill walks on Day 1 and Day 3 at a consistent self-selected pace predetermined at screening. Pain intensity (PI) during the walks was assessed on an 11-point numerical rating scale at 0, 3, 6, 9, 12, 15, 18, and 20 min. The primary endpoint was the time-weighted average (TWA) change from baseline PI on Day 3 for the two self-paced walks for the active treatments vs placebo. Time to moderate pain (TTMP) was a key secondary endpoint. RESULTS: Compared with placebo, the TWA change from baseline PI on Day 3 was significantly better with tramadol/acetaminophen (P=0.043) but not with naproxen (P=0.089). TWA change from baseline on Day 1 was also significantly better with both tramadol/acetaminophen (P=0.001) and naproxen (P=0.048) compared with placebo. TTMP was significantly better for tramadol/acetaminophen and naproxen than placebo (P<0.001 to P=0.015) for walks on Day 1 after a single dose and on Day 3. CONCLUSIONS: This novel OA pain model was able to discriminate both tramadol/acetaminophen and naproxen from placebo after single and multiple doses. ClinicalTrials.gov identifier: NCT00772967.

Weight gain in early pregnancy and risk of gestational diabetes mellitus among Latinas.

AIM: To evaluate the association between gestational weight gain (GWG) in early pregnancy and incidence of abnormal glucose tolerance (AGT) and gestational diabetes mellitus (GDM) among Latinas. METHODS: We conducted a retrospective cohort study of 2039 Latinas using pooled data from two medical centres in Massachusetts. Gestational weights were abstracted from medical records and GWG was categorized as low, appropriate and excessive according to 2009 Institute of Medicine Guidelines. Diagnosis of AGT and GDM was confirmed by study obstetricians. RESULTS: A total of 143 women (7.0%) were diagnosed with GDM and 354 (17.4%) with AGT. After adjusting for age and study site, women with low GWG up to the time of GDM screen had a lower odds of GDM (OR: 0.51, 95% CI: 0.29-0.92). Among overweight women, women with excessive first-trimester GWG had 2-fold higher odds of AGT (OR: 1.96, 95% CI: 1.17-3.30) and GDM (OR: 2.07, 95% CI: 1.04-4.12) compared to those with appropriate GWG; however, these findings were not significant among normal weight or obese women. CONCLUSION: Among Latinas, low GWG up to the time of GDM screen was associated with lower odds of AGT and GDM, while excessive GWG among overweight women was associated with higher odds. Findings highlight need for interventions in early pregnancy to help women meet GWG guidelines and to moderate GWG among overweight Latinas.

Moderate intensity sports and exercise is associated with glycaemic control in women with gestational diabetes.

AIM: To assess the association of regular, unsupervised sports and exercise during pregnancy, by intensity level, with glycaemic control in women with gestational diabetes (GDM). METHODS: Prospective cohort study of 971 women who, shortly after being diagnosed with GDM, completed a Pregnancy Physical Activity Questionnaire assessing moderate and vigorous intensity sports and exercise in the past 3 months. Self-monitored capillary glucose values were obtained for the 6-week period following the questionnaire, with optimal glycaemic control defined≥80% values meeting the targets<5.3mmol/L for fasting and <7.8mmol/L 1-hour after meals. Logistic regression estimated the odds of achieving optimal control; linear regression estimated activity level-specific least square mean glucose, as well as between-level mean glucose differences. RESULTS: For volume of moderate intensity sports and exercise ([MET×hours]/week), the highest quartile, compared to the lowest, had significantly increased odds of optimal control (OR=1.82 [95% CI: 1.06-3.14] P=0.03). There were significant trends for decreasing mean 1-hour post breakfast, lunch and dinner glycaemia with increasing quartile of moderate activity (all P<0.05). Any participation in vigorous intensity sports and exercise was associated with decreased mean 1-hour post breakfast and lunch glycaemia (both P<0.05). No associations were observed for fasting. CONCLUSION: Higher volumes of moderate intensity sports and exercise, reported shortly after GDM diagnosis, were significantly associated with increased odds of achieving glycaemic control. Clinicians should be aware that unsupervised moderate intensity sports and exercise performed in mid-pregnancy aids in subsequent glycaemic control among women with GDM.

Molecular cloning and characterization of a human adenocarcinoma/epithelial cell surface antigen complementary DNA.

A human adenocarcinoma-associated antigen (KSA) defined by the monoclonal antibody KS1/4 has become the focus of several site-directed strategies for tumor therapy. KSA, a 40,000 Da cell surface glycoprotein antigen, is found at a high density in all adenocarcinomas examined to date and in corresponding normal epithelial tissues. Here we describe the cloning and sequencing of overlapping complementary DNA clones which encode the entire KSA as expressed in UCLA-P3, a human lung adenocarcinoma cell line. We have deduced the 314-amino acid sequence and have compared it to the N-terminal amino acid sequence data of the affinity-purified antigen. The KSA is synthesized as a 314-residue-long preproprotein that is then processed to a 232-residue-long antigen. KSA appears to have a single transmembrane domain of 23 residues that separates the highly charged 26-residue cytoplasmic domain from the extracellular domain. The N-terminal region of the propeptide is rich in cysteines and contains three potential N-glycosylation sites. Computer-assisted analyses at both the DNA and protein levels have found no significant similarities of this protein to known sequences, but a GC-rich 5' terminus is evident. Northern blot analysis shows that transcription of KSA can be detected in RNA isolated from normal colon but not in RNA isolated from normal lung, prostate, or liver.

Mechanical aspects of cardiac development.

Heart development depends on a dynamic interaction between genetic and epigenetic factors. This paper discusses some of the biomechanical processes that help shape the heart in the embryo. First, an overview is given of some of the critical events that occur during cardiac development. Next, mechanics and modeling strategies are discussed for the morphogenetic processes of cardiac tube formation, cardiac looping, myocardial trabeculation, septation, valve formation, and muscle-fiber alignment. Finally, some considerations for future work in this area are listed.

A prospective study of oral contraceptives and NIDDM among U.S. women.

OBJECTIVE: To examine prospectively the association between modern oral contraceptives with low doses of estrogen and progestin and subsequent incidence of NIDDM. RESEARCH DESIGN AND METHODS: In a prospective cohort study, 98,590 U.S. female nurses aged 25 to 42 and free of diagnosed diabetes, coronary heart disease, stroke, and cancer at baseline in 1989 were followed for 4 years. Endpoint was incidence of confirmed NIDDM. Oral contraceptive use was reported on mailed questionnaires. RESULTS: During 352,067 person-years follow-up, we confirmed 185 incident cases of NIDDM. After adjusting for age, BMI, cigarette smoking, family history of diabetes, parity, physical activity, alcohol intake, ethnicity, history of diagnosis of infertility, elevated cholesterol, and hypertension, women currently using oral contraceptives had a relative risk (RR) of 1.6 (95% CI, 0.9-3.1). For past users, the multivariate RR was 1.2 (95% CI, 0.8-1.8). This association was attenuated after restricting the analysis to symptomatic cases of NIDDM. For current users, RR = 1.3 (95% CI, 0.6-2.8), and for past users, RR = 0.9 (95% CI, 0.6-1.4), suggesting that increased surveillance may explain at least part of any excess risk. CONCLUSIONS: In this large prospective study, we found no appreciable increase in the 4-year risk of NIDDM among current users of oral contraceptives. There was no apparent increase in risk among past users. The small number of cases reflect the low absolute risk of NIDDM in this population of young women.

Herpes zoster-associated encephalitis: clinicopathologic report of 12 cases and review of the literature.

Herpes-zoster associated encephalitis (HZAE) is an uncommon complication of herpes zoster. Over 8 years, we evaluated 12 patients with this clinical diagnosis. The majority of our patients were elderly, immunosuppressed, and found to have disseminated skin lesions prior to the onset of CNS symptoms. All patients had abnormal EEGs, and CSF pleocytosis was found in most. In the seven patients who were tested, specific antibody to the varicella-zoster membrane antigen (FAMA) was detected in spinal fluid during the course of the illness. Although three patients died during the period of active infection, the virus could not be definitively implicated as the cause of death. These HZAE patients could not be distinguished from our other herpes zoster patients on the basis of age, initially involved dermatome, or mortality rate. However, among herpes zoster patients who survived, duration of hospitalization was significantly longer in those with a diagnosis of HZAE. All surviving HZAE patients had a slow but eventual return to their prior cognitive status.

A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women.

BACKGROUND: Oxidation of lens proteins plays a central role in the formation of age-related cataracts, suggesting that dietary antioxidants may play a role in prevention. However, the relation between specific antioxidants and risk of cataract remains uncertain. OBJECTIVE: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in women. METHODS: A prospective cohort of registered female nurses aged 45-71 y and free of diagnosed cancer was followed; in 1980, 50461 were included and others were added as they became 45 y of age for a total of 77466. Information on nutrient intake was assessed by repeated administration of a food-frequency questionnaire during 12 y of follow-up. RESULTS: During 761762 person-years of follow-up, 1471 cataracts were extracted. After age, smoking, and other potential cataract risk factors were controlled for, those with the highest intake of lutein and zeaxanthin had a 22% decreased risk of cataract extraction compared with those in the lowest quintile (relative risk: 0.78; 95% CI: 0.63, 0.95; P for trend = 0.04). Other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin), vitamin A, and retinol were not associated with cataract in multivariate analysis. Increasing frequency of intakes of spinach and kale, foods rich in lutein, was associated with a moderate decrease in risk of cataract. CONCLUSIONS: Lutein and zeaxanthin and foods rich in these carotenoids may decrease the risk of cataracts severe enough to require extraction.

A prospective study of carotenoid intake and risk of cataract extraction in US men.

BACKGROUND: Dietary antioxidants, including carotenoids, are hypothesized to decrease the risk of age-related cataracts by preventing oxidation of proteins or lipids within the lens. However, prospective epidemiologic data concerning this phenomenon are limited. OBJECTIVE: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in men. DESIGN: US male health professionals (n = 36644) who were 45-75 y of age in 1986 were included in this prospective cohort study. Others were subsequently included as they became 45 y of age. A detailed dietary questionnaire was used to assess intake of carotenoids and other nutrients. During 8 y of follow-up, 840 cases of senile cataract extraction were documented. RESULTS: We observed a modestly lower risk of cataract extraction in men with higher intakes of lutein and zeaxanthin but not of other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin) or vitamin A after other potential risk factors, including age and smoking, were controlled for. Men in the highest fifth of lutein and zeaxanthin intake had a 19% lower risk of cataract relative to men in the lowest fifth (relative risk: 0.81; 95% CI: 0.65, 1.01; P for trend = 0.03). Among specific foods high in carotenoids, broccoli and spinach were most consistently associated with a lower risk of cataract. CONCLUSIONS: Lutein and zeaxanthin may decrease the risk of cataracts severe enough to require extraction, although this relation appears modest in magnitude. The present findings add support for recommendations to consume vegetables and fruit high in carotenoids daily.

Herpes simplex encephalitis treated with vidarabine (adenine arabinoside).

Vidarabine, an antiviral chemotherapeutic agent shown to have in vitro activity against the herpes group of viruses, was administered to five patients with brain biopsy-proved herpes simplex virus encephalitis. The mortality in this small number of patients (one of five or 20%) was less than that in most published reports of patients receiving other treatment modalities or no treatment other than supportive measures. No apparent toxicity was found that was attributable to vidarabine. Neuropsychological impairment of varying degree was noted in four surviving patients tested at two months after treatment and again 12 to 21 months later. Progressive improvement had occurred in three.

Prolonged pneumococcal meningitis due to an organism with increased resistance to penicillin.

For more than 30 years, penicillin has been the agent of choice for pneumococcal infections. During this time the majority of strains of Streptococcus pneumoniae have been highly susceptible to penicillin. However, during the last ten years there have been sporadic reports of pneumococci with increased resistance to penicillin. The case report of an 18-month-old white boy with meningitis due to a strain of S. pneumoniae with increased resistance to penicillin is presented. The MIC of the organism to penicillin was 0.2 mug/ml and the MBC 0.39 mug/ml. The patient had normal immunity and no demonstrable sequestered focus of infection but failed to respond to appropriate doses of intravenous penicillin. Treatment with chloramphenicol caused a dramatic bacteriologic and clinical response. This experience reemphasizes the existence of pneumococcal strains of intermediate penicillin sensitivity and the importance of in vitro susceptibility tests.

Nosocomial transmission of group B Streptococci in a newborn nursery.

Group B streptococcal colonization of normal newborn infants increased from 22.5% within 20 hours of birth to 65.4% at the time of hospital discharge (P less than .001). In contrast, colonization in mothers did not change significantly between the time of admission to labor and delivery (27.7%) and the time of discharge (31.1%). Epidemiologic data suggested but did not prove that the mode of nosocomial transmission of group B streptococci among infants was cross colonization via personnel contact.

Breast-feeding and respiratory virus infection.

Thirty-nine breast-fed and 42 bottle-fed infants were followed up from birth over a four-year period. Virus infection was documented by culture and serologic testing, and history and physical examination were recorded for all episodes of respiratory illness. There were no statistically significant differences in rates or distributions of infection with individual viruses or with all viruses over the first three or six months or during the second six months of life in the two groups, nor were there statistically significant differences in rates or distributions of disease of the upper and lower respiratory tract or total respiratory disease, except for decreased disease of the lower respiratory tract in bottle-fed infants in the second six months. There were trends to decreased morbidity in breast-fed infants in the first three and six months and more episodes of pneumonia and bronchiolitis in bottle-fed infants in the first six months (P less than .05) but similar use of medical care by both groups. High cord blood titers to two viruses were not associated with evidence of breast-feeding protection from infection with those two agents. Breast-fed babies do not have fewer respiratory virus infections or illnesses but may experience less severe illness.

A ten-year assessment of methicillin-associated side effects.

The exact incidence and importance of side effects associated with methicillin therapy in children is unknown. During the ten-year period from 1964 to 1974 approximately 3,000 Houston children who received methicillin were observed for side effects. The great majority of these patients received the drug for less than ten days; however, side effects were more common in patients receiving long-term therapy. In order to assess these side effects, experiences with 124 children who received methicillin for ten days or longer were reviewed in depth. The average dose of methicillin was 200 mg/kg/day and the average duration was 22 days. In this highly selected group there were no adverse side effects in 54.8% and only eosinophilia in an additional 13%. Leukopenia occurred in 16%, microscopic hematuria in 8%, gross hematuria in 4%, skin rash in 6%, and "drug fever" in 6%. In many instances several of these side effects occurred within a single patient so that the total number of patients with definite side effects was 39 of 124 (31.5%). The true incidence figure of overall side effects is much lower than 31.5%. Corrected incidence rates based on a conservative figure of 3,000 methicillin-treated children are less than 1.5% for all side effects. In some patients the mechanism producing the adverse reactions seemed to be chemical irritation or toxicity and in others hypersensitivity. In nine of the 39 patients follow-up studies were not optimal. In the other 30 patients all side effects were reversible.

Ribavirin aerosol treatment of bronchiolitis associated with respiratory syncytial virus infection in infants.

In a double-blind study, bronchiolitis associated with respiratory syncytial virus infection in 12 randomly selected patients treated with ribavirin aerosol improved more rapidly than in 14 control patients given saline aerosol (P = .044, Wilcoxon rank sum test, two-tailed). An estimated 10 mg of ribavirin per kilogram of body weight was administered in daily 12-hour treatments over a five-day period. Respiratory syncytial virus disappeared from secretions at about the same rate in treated and control patients. There was no local or systemic intolerance, and there was no evidence of hematologic or other organ toxicity in the ribavirin-treated patients.

Relation of serum antibody to glycoproteins of respiratory syncytial virus with immunity to infection in children.

Immunity in relation to passively transferred maternal and naturally-induced serum antibody to the viral proteins was determined in 34 children who were followed from birth through three years of age for respiratory syncytial virus infection (RSV). Sera were tested by immunoglobulin class-specific enzyme-linked immunosorbent assay using the attachment and fusion proteins of the Long strain. The basis for immunity for maternal antibody in primary infection was assessed by a comparison of the distribution of antibody titers in a) 7 children who had an upper respiratory illness to 12 whose illness was accompanied by lower respiratory disease and of b) 13 children with an RSV-associated illness in the first 6 months of life who were age-matched as to month and approximate day of birth with 11 not infected in the same period. Infection induced immunity was evaluated by a comparison of antibody titers in 19 children who were reinfected with RSV in the year following their primary infection to 15 in whom reinfection was not documented. A statistical analysis of titers revealed that antibody to the fusion protein is an important correlate of immunity. In all three comparisons, the children with less RSV disease had significantly higher IgG anti-F titers prior to infection. No differences were observed between IgA anti-F or IgG and IgA anti-G titers.