A longitudinal, observational study of women who persisted in smoking in successive pregnancies.

BACKGROUND: This longitudinal study examined the profile and pregnancy-related behaviours of women who reported smoking in two successive pregnancies when they presented for prenatal care in a large maternity hospital. METHODS: Using the hospital electronic medical records, women who delivered two successive singleton pregnancies during the years 2011-15 were analyzed. Standardized data were computerized by a midwife at the first prenatal visit, following delivery and before discharge. RESULTS: Over the 5 years, 6647 women delivered twice. Overall 5754 (86.6%) were persistent non-smokers in both pregnancies, 609 (9.2%) were persistent smokers in both pregnancies and between pregnancies 202 (3.0%) quit and 82 (1.2%) started smoking. Compared with persistent non-smokers, persistent smokers had higher rates of reported illicit drug use, alcohol consumption and psychological problems and lower rates of planned pregnancy, folic acid supplementation and breastfeeding in both pregnancies (all P < 0.001). In persistent smokers, folic acid supplementation practices deteriorated and illicit drug use increased in the subsequent pregnancy. CONCLUSIONS: We found that approximately one in 10 women smoked in two consecutive pregnancies. Furthermore, compared with non-smokers, persistent smokers were more likely to report other health behaviours associated with adverse pregnancy outcomes and may require additional multidisciplinary support.

A web-based dietary intervention in early pregnancy and neonatal outcomes: a randomized controlled trial.

BACKGROUND: Maternal nutrition is a determinant of pregnancy outcomes. Few studies have evaluated the potential of online nutrition resources to modify behaviour. This randomized controlled trial aimed to determine whether access to a customized evidence-based nutrition website in pregnancy improved neonatal outcomes. METHODS: Women <18 weeks gestation were recruited at their convenience. The control group received standard care. In addition to standard care, the intervention group received access to an evidence-based nutrition website, customized to the preferences of pregnant women. RESULTS: Of the 250 women, there were no differences in characteristics between the two groups. Of the women, 91.0% reported they make a conscious effort currently to eat a healthy diet. However, only 19.6% met dietary requirements for calcium, 13.2% for iron, 2.7% for folate and 2.3% for iodine. The most popular website section was pregnancy nutrition advice but engagement was not sustained. Access to the website was not associated with any improvement in clinical outcomes (P > 0.05). CONCLUSIONS: We found that provision of a customized website providing nutrition information, did not improve neonatal outcomes. Future studies should explore whether redesign with website interactivity or embedding information on popular digital platforms sustains women's engagement and modifies dietary behaviour.

Maternal anaemia and folate intake in early pregnancy.

Background: The World Health Organization recommends that women take 400 µg of folate supplementation daily throughout pregnancy. We examined the relationship between total folate intake from the diet and supplements at the first prenatal visit and haematological indices at this visit and subsequently. Methods: Women were recruited at their convenience and in addition to clinical and sociodemographic details, detailed questionnaires on dietary intakes and supplementation consumption were completed under supervision. A full blood count and serum and red blood cell (RBC) folate levels were taken. Results: Of the 502 women studied, 97.5% had inadequate total dietary folate intake at the first visit, but, 98.2% were taking folic acid (FA) supplementation. Only 1.8% (n = 9) had anaemia at their first visit (with no case of macrocytosis). Subsequently, 212 women had a further Hb sample in the third trimester and 8.5% (n = 18) were anaemic and 43.4% (89/205) were anaemic postnatally. There was a relationship between the development of anaemia postnatally and lower RBC folate levels at the first visit (P = 0.02). Conclusions: In a country where FA food fortification remains voluntary, these findings support the recommendation that women should start FA supplementation before pregnancy and continue FA after the first trimester.

Screening For Gestational Diabetes Mellitus Selectively in a University Maternity Hospital

Aims Screening for gestational diabetes mellitus (GDM) may be universal or selective based on risk factors. We audited selective screening with an Oral Glucose Tolerance Test (OGTT). Methods Clinical and laboratory details of the first 200 women who delivered a baby in 2017 were analysed. Results Based on national recommendations, 46.5% (n=93) had maternal risk factors (RF) and an additional 6.5% (n=13) had fetal RF. Nine women with RF, for unexplained reasons did not have their OGTT. Of the 95 who had their OGTT, the diagnosis of GDM was made in 27.4% (n=26). The diagnosis of GDM was made in an additional 8 women outside selective screening giving an overall incidence of 17.0%. Discussion More than half of the women needed to be screened selectively for GDM. Compliance with the national recommendations was incomplete and thus the diagnosis of GDM may be missed even in an academic setting.

The accuracy of breast MRI radiomic methodologies in predicting pathological complete response to neoadjuvant chemotherapy: A systematic review and network meta-analysis.

BACKGROUND: Achieving pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) improves survival outcomes for breast cancer patients. Currently, conventional histopathological biomarkers predicting such responses are inconsistent. Studies investigating radiomic texture analysis from breast magnetic resonance imaging (MRI) to predict pCR have varied radiomic protocols introducing heterogeneity between results. Thus, the efficacy of radiomic profiles compared to conventional strategies to predict pCR are inconclusive. PURPOSE: Comparing the predictive accuracy of different breast MRI radiomic protocols to identify the optimal strategy in predicting pCR to NAC. MATERIAL AND METHODS: A systematic review and network meta-analysis was performed according to PRISMA guidelines. Four databases were searched up to October 4th, 2021. Nine predictive strategies were compared, including conventional biomarker parameters, MRI radiomic analysis conducted before, during, or after NAC, combination strategies and nomographic methodology. RESULTS: 14 studies included radiomic data from 2,722 breast cancers, of which 994 were used in validation cohorts. All MRI derived radiomic features improved predictive accuracy when compared to biomarkers, except for pre-NAC MRI radiomics (odds ratio [OR]: 0.00; 95 % CI: -0.07-0.08). During-NAC and post-NAC MRI improved predictive accuracy compared to Pre-NAC MRI (OR: 0.14, 95 % CI: 0.02-0.26) and (OR: 0.26, 95 % CI: 0.07-0.45) respectively. Combining multiple MRIs did not improve predictive performance compared to Mid- or Post-NAC MRIs individually. CONCLUSION: Radiomic analysis of breast MRIs improve identification of patients likely to achieve a pCR to NAC. Post-NAC MRI are the most accurate imaging method to extrapolate radiomic data to predict pCR.

The diagnosis of gestational diabetes mellitus (GDM) using a 75 g oral glucose tolerance test: A prospective observational study.

AIMS: Screening for Gestational Diabetes Mellitus (GDM) is controversial. This prospectivestudy compared different sets of diagnostic cut-off points for plasma glucose measurements following a 75 g Oral Glucose Tolerance Test (OGTT). METHODS: Women who had maternal risk factors for GDM were recruited at their convenience attheir first prenatal visit and consented to a one-step OGTT at 26-28 weeks gestation.All women fulfilling the World Health Organization (WHO) 2013 diagnostic criteriareceived standard care for GDM. RESULTS: Of the 202 women, 139 (69%) had one risk factor for GDM and 63 (31%) had > 1.Using the WHO criteria, 53% (n = 108) had GDM compared with 35% (n = 71) usingCanadian criteria and 18% (n=36) using National Institute for Health Care Excellencecriteria (NICE) criteria (both p<0.001). Of the 108 women, 50% (n = 54) requiredpharmacological treatment to control hyperglycaemia. If the Canadian criteria wereapplied, 11/54 (20.4%) women would not have received hypoglycaemics. If the NICEcriteria were applied, 36/54 (66.7%) women would not have received hypoglycaemics.Maternal insulin, HOMA-IR and C-peptide measured at the time of the OGTT showed evidence of increased insulin resistance in women who had GDM based on the WHOcriteria but who had a normal OGTT based on the Canadian or NICE criteria. CONCLUSIONS: Under stringent research conditions, our study suggeststhat the Canadian and, in particular, the NICE criteria are not identifying women who may benefit fromimproved glycaemic control. These findings support the need for the planned review of the NICE guidelines on GDM in 2020.

Pro-contractile effects of perivascular fat in health and disease.

Perivascular adipose tissue (PVAT) is now recognized as an active player in vascular homeostasis. The expansion of PVAT in obesity and its possible role in vascular dysfunction have attracted much interest. In terms of the regulation of vascular tone and blood pressure, PVAT has been shown to release vasoactive mediators, for instance, angiotensin peptides, reactive oxygen species, chemokines and cytokines. The secretory profile of PVAT is altered by obesity, hypertension and other cardiovascular diseases, leading to an imbalance between its pro-contractile and anti-contractile effects. PVAT adipocytes represent an important source of the mediators, but infiltrating immune cells may become more important under conditions of hypoxia and inflammation. This review describes recent advances in the effects of PVAT on the regulation of vascular tone, highlighting the evidence for a pro-contractile action in health and disease. The role of the endothelium, vascular smooth muscle, immune cells and probably perivascular nerves in PVAT function is also discussed. LINKED ARTICLES: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.

Obesity-related chronic lymphoedema-like swelling and physical function.

BACKGROUND: People with severe obesity (body mass index [BMI] > 40 kg/m(2)) have an 85% higher mortality than people with a healthy BMI. Poor physical function may contribute to this excess mortality. Lymphoedema-like swelling can affect the legs of severely obese people with normal lymphoscintigraphy. AIM: We sought to determine the relationship between the presence of lymphoedema-like swelling and physical function in the severely obese. DESIGN AND METHODS: In people with severe obesity, we ascertained whether lower leg lymphoedema-like swelling was present and determined the circumference of the lower leg, time taken to ascend and descend a 17-cm step 50 times and time taken to walk 500 m. RESULTS: The 330 participants, 33% of whom were male, were aged 43.4 ± 12.7 years (mean ± standard deviation) and had a BMI of 51.7 ± 8.4 kg/m(2). Lymphoedema-like swelling was present in approximately one-third (n = 108) in whom a prior history of cellulitis and venous thromboembolism was more common (relative risks 6.16 and 3.86, respectively) than in those without lymphoedema-like swelling. Participants with lymphoedema-like swelling, compared with non-affected counterparts, had a higher lower leg circumference (35.0 ± 7.1 vs. 32.4 ± 4.8 cm), a slower step speed (0.40 ± 0.12 vs. 0.43 ± 0.10 steps/s) and a slower walking speed (0.97 ± 0.37 vs. 1.08 ± 0.30 m/s, P < 0.05 for all comparisons). CONCLUSIONS: In this cross-sectional study, 33% of our severely obese participants had lymphoedema-like swelling. Participants with lymphoedema-like swelling had worse physical function than those without. This association was independent of BMI. The presence of obesity-related chronic lymphoedema-like swelling should lead to interventions that improve physical function.

The utility of topographic EEG mapping in obstructive sleep apnea syndrome.

A study was undertaken to determine whether topographic brain mapping of standard EEG and cognitive evoked potentials would provide additional information for the detection of subtle brain abnormalities associated with obstructive sleep apnea. During nocturnal sleep, significant brain activity was detected in frontal regions not usually monitored with standard sleep recordings. Moreover, preliminary results suggest that total brain activity decreased in association with apneic events and depth of O2 desaturation. Also, component asymmetry in the P300 waveform observed in brain areas not typically recorded improved with treatment. We conclude that the use of topographic mapping adds important information to the study of brain function during sleep and sleep apnea.

Sleep habits of Long Island Rail Road commuters.

STUDY OBJECTIVES: We addressed the issue of how commuting affects sleep habits, and its association with general health and potential sleep disorders in individuals on a large, U.S. commuter rail system. DESIGN: Postage-paid mail back questionnaires were distributed to commuters over 6 consecutive weekdays. The questionnaire incorporated previously validated questions regarding sleep habits. SETTING: Questionnaires were dispensed at 15 different rail stations. PARTICIPANTS: 21,000 commuters accepted the questionnaire. MEASUREMENTS AND RESULTS: Data was analyzed by total group and length of commute. A total of 4715 (22%) questionnaires were returned. Over 50% of the sample reported difficulty with sleep and wakefulness while only 3% sought professional help. Sleep apnea was suspected in 4.2% of male and 1% of female respondents and was associated with increased reports of excessive daytime sleepiness, and history of hypertension, diabetes and obesity. Total nocturnal sleep time was significantly less in those subjects with long commutes. Seventy percent of respondents reported napping during the commute. Length of commute was associated with hypertension. CONCLUSION: Commuting long distances negatively impacts one's ability to capture adequate sleep. Data suggests that there may be significant numbers of respondents with unrecognized sleep disorders which further impact on general health.

Mesencephalic type I astrocytes mediate the survival of substantia nigra dopaminergic neurons in culture.

We previously demonstrated that substantia nigra (SN) support cells selectively increase SN dopamine (DA) neuron survival in dissociated primary culture. Increased survival was elicited specifically by nigral support cells; glia from other brain regions exerted lesser effects. We now report that Type I astrocytes, the principal component of SN support cell monolayers, mediate the enhanced DA cell survival. Initially, the predominant glial subtypes in SN support cell cultures were identified. Postnatal day 1 rat SN was dissociated and cells were grown to confluence (7-9 days in vitro; DIV). Monolayers were immunostained with antibodies against glial fibrillary acidic protein (GFAP; an astrocyte-specific marker), myelin basic protein (MBP; an oligodendrocyte marker), or A2B5 (recognizes 0-2A progenitors and Type II astrocytes). The number of GFAP+ cells far exceeded MBP+ and A2B5+ cells, suggesting that astrocytes constituted the predominant subpopulation. Further, direct comparison of GFAP+ (Type I and Type II astrocytes) and A2B5+ (Type II astrocytes) cells indicated that the vast majority were Type I astrocytes. Greater than 98% of cells reacted with glial antibodies. To definitively characterize the cellular subtype that augments survival of DA neurons, glial subcultures were established. At 2 DIV, enriched populations of Type I or Type II astrocytes, or oligodendrocytes, were tested for the ability to elicit DA neuron survival. Embryonic day 16 rat SN dissociates were added and DA cell number was assessed with antibody against tyrosine hydroxylase (TH), the DA biosynthetic enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Nigral type I astrocytes release a soluble factor that increases dopaminergic neuron survival through mechanisms distinct from basic fibroblast growth factor.

Our studies have been directed to the identification of local, naturally-occurring molecules that support substantia nigra (SN) dopaminergic (DA) neuron survival. We have previously demonstrated that local Type I astrocytes selectively increase the dopaminergic population [30,31]. However, the mechanism of action remains to be defined. To determine whether survival is elicited through diffusible agents, Type I astrocyte conditioned medium (CM) was tested on SN dissociates. After 7 days of exposure to CM, DA neuronal integrity was monitored immunocytochemically with antibody to tyrosine hydroxylase (TH), the DA biosynthetic enzyme, or by TH catalytic assay. CM increased TH+ cell number greater than 2-fold, suggesting that a soluble factor(s) promoted neuron survival. Neurons cultured in serum free medium (SFM) are known to contain few, but detectable numbers of glia [34]. To examine whether CM affected neurons directly, or indirectly through glia, glial populations were stained with antibody against the glial marker, glial fibrillary acidic protein (GFAP). We employed several approaches to define the potential role of glia. Initially, CM was compared to basic fibroblast growth factor (bFGF), a glial mitogen that reportedly enhances nigral DA neuron survival. bFGF enhanced TH activity in our system, as well, but the effect was blocked by the mitotic inhibitor 5-fluorodeoxyuridine (FDUR), which kills dividing glia. In parallel studies CM increased enzyme activity and TH cell number in cultures exhibiting GFAP+ cells. To define the role of these glial cells in the CM effect, we completely eliminated astrocytes in CM-treated cultures employing alpha-aminoadipic acid (AA; 10-30 microM), a specific gliotoxin. At a concentration of AA that eliminated detectable GFAP+ cells, CM continued to elicit a significant increase in TH cell number. These data suggest that, in contrast to effects of bFGF, the DA neurotrophic activity in CM acts directly on nigral neurons to enhance survival.

Relationship of familial prominent corneal nerves and lesions of the tongue resembling neuromas to multiple endocrine neoplasia type 2B.

PURPOSE: We studied a two-generation family with an inherited syndrome of prominent corneal nerves and lesions of the tongue resembling neuromas without the characteristic neoplasms of the multiple endocrine neoplasia type 2B syndrome. Several different point mutations in the RET proto-oncogene on chromosome 10 have been associated with the multiple endocrine neoplasia type 2 syndromes. Molecular genetic studies of families with partial phenotypic expression of these syndromes may aid in further understanding the origin of the variety of clinical manifestations observed in multiple endocrine neoplasia type 2. METHODS: A family consisting of an 8-year-old male proband, his 10-year-old sister, and 40-year-old mother was identified as having prominent corneal nerves and lesions of the tongue resembling neuromas. Pentagastrin-stimulated serum calcitonin levels were measured in the mother and sister. Molecular genetic studies were performed on all three affected members, to look for the specific point mutation seen in over 95% of patients with multiple endocrine neoplasia type 2B. RESULTS: Serum calcitonin levels were normal, indicating no C-cell hyperplasia or medullary thyroid carcinoma. Molecular genetic studies on these individuals did not disclose the specific point mutation seen in multiple endocrine neoplasia type 2B. CONCLUSIONS: This family demonstrates some of the phenotypic features of the multiple endocrine neoplasia type 2B syndrome without the characteristic neoplasms or the mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B. Their physical findings may be caused by genetic alterations within the RET proto-oncogene on chromosome 10 at yet undetermined sites.

To tunnel or not to tunnel catheters for parenteral nutrition.

The effect of subcutaneous catheter tunnelling on the incidence of catheter sepsis and on catheter life span in the absence of a nutrition team was determined in a prospective controlled clinical trial. Eighty one patients who received 92 courses of parenteral nutrition had 110 catheters inserted. Alternate catheters were tunnelled. Four patients who received parentheral nutrition for less than 48 hours were excluded from the study. Catheter related sepsis occurred in one tunnelled (1.8%) and 4 non-tunnelled catheters (7.6%) (P greater than 0.05 NS). Mean life span of tunnelled catheters was 21 days (range 5-37 days) compared to 12.6 days for non-tunnelled (range 3-19 days) (P less than 0.05). Six non-tunnelled catheters became displaced, a complication which did not occur with tunnelled catheters (P less than 0.01). In conclusion subcutaneous tunnelling of silicone catheters prolongs catheter life span but does not significantly influence catheter sepsis.

The role of CT in the management of carcinoma of the oesophagus and cardia.

The role of computed tomography in assessing tumour spread and tumour resectability was evaluated in 50 patients with oesophageal carcinoma (17 middle third, 33 lower third). CT accurately identified all patients with tumour confined to the oesophagus (Stage I or II) but was limited in its ability to assess direct organ invasion (Stage III) with an overall accuracy for evaluating middle third lesions of 82% (aorta 70%, tracheobronchial tree 94%, other mediastinal structures 82%) compared to an overall accuracy for lower third lesions of 97% (aorta 97%, pancreas 100%, diaphragm 97%). Tumours deemed resectable on CT were always resectable at operation but two of seven middle third tumours and one of twelve lower third lesions deemed unresectable underwent curative resection. Preoperative CT evaluation of oesophageal tumours is useful in that it may reliably identify tumour lesions confined to the oesophagus and reliably identify distant metastases. Because of its limitations however in the assessment of organ invasion, particularly by middle third lesions, this study suggests that patients with oesophageal tumours with no evidence of distant metastases, who are otherwise fit to undergo tumour resection, should not be denied surgery on the sole basis of positive organ invasion on CT particularly if that organ is the aorta.

The management of advanced rhabdomyosarcoma of the upper eyelid.

An advanced case of rhabdomyosarcoma of the upper eyelid is used to demonstrate and discuss the principles of diagnosis and proper management of this most malignant extra-ocular neoplasm in the orbital region.

Gastric heterotopia in a gall bladder.

A case of extensive gastric heterotopia involving the gall bladder in a girl aged 17 is reported. This was associated with peptic ulceration in the heterotopic gastric mucosa. The extent of the change was greater than in the 7 other cases already reported, only one of which showed peptic ulceration.

Association between vitamin D status and physical function in the severely obese.

CONTEXT: Mortality is 85% higher in severely obese subjects (body mass index [BMI] > 40 kg/m(2)) than in subjects with a healthy BMI; poor physical function may be contributory. Hypovitaminosis D is common in obese subjects and is associated with physical dysfunction in the elderly. OBJECTIVE: We determined the relationship between vitamin D status and physical function in severely obese subjects. DESIGN, SETTING, AND PATIENTS: We conducted a clinic-based, cross-sectional study of severely obese subjects. Participants were stratified into three groups according to the Institute of Medicine (IOM) vitamin D status categorization. MAIN OUTCOME MEASURES: We compared levels of self-reported activity and times taken to walk 500 m and to ascend and descend a 17-cm step 50 times. RESULTS: We recruited 252 subjects (age, 43.7 ± 11.2 y; BMI, 50.7 ± 9.7 kg/m(2)); 25-hydroxyvitamin D (25OHD) concentrations were less than 30 nmol/L in 109 participants. Participants with a 25OHD > 50 nmol/L, compared to those with a 25OHD < 30 nmol/L, had the highest activity levels (3.1 ± 3.4 h/wk versus 1.5 ± 2.5 h/wk; P = .015) and the shortest 500-m walk times (6.2 ± 1.1 min versus 7.4 ± 1.5 min; P = .003). Serum 25OHD concentrations had a weakly positive association with activity level (r = 0.19; P = .008) and a moderately negative association with 500-m walk time (r = -0.343; P < .001). CONCLUSIONS: Vitamin D status had a significant relationship with physical activity and physical function in this cohort of severely obese subjects. Low activity levels are likely to perpetuate the problem of hypovitaminosis D due to less time spent outdoors. Studies exploring the effects of vitamin D supplementation in this population are warranted.