Maternal prepregnancy weight as an independent risk factor for congenital heart defect: systematic review and meta-analysis stratified by subtype and severity of defect.

OBJECTIVE: To assess the association between increased maternal prepregnancy body mass index (BMI) and the risk of congenital heart defect (CHD) in offspring. METHODS: This systematic review and meta-analysis searched PubMed/MEDLINE, Web of Science and Scopus from inception to 20 April 2023. Risk estimates were abstracted or calculated for increased BMI categories (overweight, obesity, moderate obesity and severe obesity) compared with normal weight (reference). Fixed-effects or random-effects models were used to combine individual study risk estimates based on the degree of heterogeneity. Sensitivity analyses were conducted to weight pooled estimates for relevant moderators, particularly diabetes before and during pregnancy. Subgroup analyses for specific CHD subtypes were conducted if there were at least two studies with available data. Findings were presented for groups of defects, categorized using severity and topographic-functional criteria, and for individual defects. The certainty of the evidence for each effect estimate was evaluated according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: Overall, 31 studies comprising 4 861 693 patients and 86 136 CHD cases were included. The risk of CHD increased progressively from moderate to severe obesity (pooled odds ratio (OR), 1.15 (95% CI, 1.11-1.20) and 1.39 (95% CI, 1.27-1.53), respectively). Sensitivity analysis indicated that this effect persisted independently of maternal diabetes status before or during pregnancy. In the subgroup analysis, obesity was associated with up to a 1.5-fold increase in the risk of severe CHD (pooled OR, 1.48 (95% CI, 1.03-2.13)). Severe obesity was associated with an even higher risk, with 1.8-times higher odds compared with the reference group for specific CHD subtypes, including tetralogy of Fallot (pooled OR, 1.72 (95% CI, 1.38-2.16)), pulmonary valve stenosis (pooled OR, 1.79 (95% CI, 1.39-2.30)) and atrial septal defect (pooled OR, 1.71 (95% CI, 1.48-1.97)). CONCLUSIONS: Maternal weight is a crucial modifiable risk factor for CHD, particularly for severe forms of defect. Further research is needed to investigate whether weight management before pregnancy might serve as a preventive measure against CHD. In pregnant women with obesity, fetal echocardiography should be a routine diagnostic procedure. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prokaryotic assemblages in the maritime Antarctic Lake Limnopolar (Byers Peninsula, South Shetland Islands).

The potentially metabolically active components within the prokaryotic assemblages inhabiting the Antarctic Lake Limnopolar (Byers Peninsula, Maritime Antarctica) were investigated by a polyphasic approach which included culture-dependent and culture-independent methods (based on RNA molecules). Results support previous observations on the Proteobacteria and Bacteroidetes dominance, followed by Actinobacteria, in Antarctic lakes. In particular, Alpha-, Betaproteobacteria and Bacteroidetes were mainly detected by CARD-FISH and cDNA cloning, whereas Gammaproteobacteria and Actinobacteria dominated within the cultivable fraction. Overall, this study demonstrates the survival potential and physiological heterogeneity of the prokaryotic community in the Lake Limnopolar. The microbial community composition in the lake is affected by external influences (such as marine environment by sea spray and seabird dropping, and microbial mats and mosses of the catchment). However, most external bacteria would be inactive, whereas typical polar taxa dominate the potentially active fraction and are subsidized by external nutrient sources, thus assuming the main biogeochemical roles within the lake.

A possible unique ecosystem in the endoglacial hypersaline brines in Antarctica.

Here, we present the results related to a new unique terrestrial ecosystem found in an englacial hypersaline brine found in Northern Victoria Land (Antarctica). Both the geochemistry and microbial (prokaryotic and fungal) diversity revealed an unicity with respect to all the other known Antarctic brines and suggested a probable ancient origin mainly due a progressive cryoconcentration of seawater. The prokaryotic community presented some peculiarities, such as the occurrence of sequences of Patescibacteria (which can thrive in nutrient-limited water environments) or few Spirochaeta, and the presence of archaeal sequences of Methanomicrobia closely related to Methanoculleus, a methanogen commonly detected in marine and estuarine environments. The high percentage (35%) of unassigned fungal taxa suggested the presence of a high degree of undiscovered diversity within a structured fungal community (including both yeast and filamentous life forms) and reinforce the hypothesis of a high degree of biological uniqueness of the habitat under study.

Identification and characterization of a tumor cell receptor for CSVTCG, a thrombospondin adhesive domain.

We have previously shown that peptides derived from the thrombospondin sequence, CSVTCG, promoted tumor cell adhesion. To further investigate this observation, the CSVTCG-tumor cell adhesion receptor from A549 human lung adenocarcinoma cells was isolated and characterized. A single protein peak was isolated by CSVTCG affinity chromatography which also analyzed as a single peak by anion exchange chromatography. The purified protein had a pI of 4.7 and analyzed on SDS-gels as a single band of M(r) = 50,000 under nonreducing conditions and as two protein bands of M(r) = 50,000, and 60,000 under reducing conditions. Purified CSVTCG binding protein (CBP) bound either CSVTCG- or TSP-Sepharose but showed little interaction with either VCTGSC- or BSA-Sepharose. CBP was cell surface exposed. CSVTCG derivatized with [125I] Bolton-Hunter reagent was taken up by cells in a dose-dependent manner and the cell association was inhibited with a monospecific polyclonal anti-CBP antibody. Examination of the cell proteins crosslinked to labeled CSVTCG by SDS-gel electrophoresis revealed one band that comigrated with purified CPB. Using an in vitro binding assay, purified CBP bound mannose, galactose, and glucosamine-specific lectins. CBP bound TSP saturably and reversibly. The binding was Ca+2/Mg+2 ion dependent and inhibited with fluid phase TSP and anti-CBP. Little or no binding was observed on BSA, fibronectin, GRGES, and GRGDS. Heparin, but not lactose, inhibited binding. Anti-CBP IgG and anti-CSVTCG peptide IgG inhibited A549 cell spreading and adhesion on TSP but not on fibronectin and laminin. These results indicate that CBP and the CSVTCG peptide domain of TSP can mediate TSP-promoted tumor cell adhesion.

[Proteomics and the kidney: an innovative approach to the study of renal disease]. / Proteomica e rene: un approccio innovativo allo studio delle malattie renali.

In the post human genome era, several ''omics'' fields are emerging. Proteomics has experienced a rapid growth in the recent past and has great potential for the future. Proteomic technologies are used with increasing frequency also in nephrology. The aim of this review is to examine the recent application of emerging proteomic technologies to the study of renal physiology and pathophysiology. We highlight the use in renal research of a number of available techniques including 2-dimensional gel electrophoresis, liquid chromatography/mass spectrometry, surface-enhanced laser desorption/ionization, and capillary electrophoresis/mass spectrometry. We examine the role, efficacy and diagnostic potential of the different proteomic approaches, focusing on current difficulties and potential solutions. The integrating role of bioinformatics and the need for standardized procedures for sample preservation and analysis and reporting of results are also discussed. Although the field is still in an embryonic stage, the knowledge gained up to now is important not only for a better understanding of renal physiology and pathophysiology, but also for the identification of disease markers and the development and follow-up of new therapies. This review gives an overview of proteomics, providing background information, outlining the scopes, highlighting the applications in nephrology, and reporting advantages and limitations.

Age-related changes of the noradrenergic innervation of rat tracheo-bronchial tree and pulmonary vasculature.

Age-related changes of the noradrenergic innervation of the tracheo-bronchial tree and of pulmonary vasculature were investigated in male Wistar rats of 3 months (young), 12 months (adult) and 24 months (old/aged), using catecholamine histofluorescence techniques associated with image analysis and by high pressure liquid chromagraphy with electrochemical detection. In young rats, blue-green fluorescent nerve fibres supply tracheo-bronchial smooth muscle and tracheal and bronchial glands, which are innervated by a delicate network of nerve fibres rich in varicosities. Pulmonary artery and vein are sparsely innervated. They are supplied with nerve fibres distributed in the vasa vasorum or the adventitia and the outer tunica media. The higher noradrenaline concentrations were found in the trachea and extraparenchymal bronchi, followed by pulmonary vein and pulmonary artery. The density and pattern of noradrenergic innervation of the tracheo-bronchial tree, or of the pulmonary vasculature, were similar in young and adult rats. In aged rats, a loss of noradrenergic innervation involving primarily the supply to the smooth muscle of the tracheo-bronchial tree was observed. Histofluorescence techniques demonstrated a higher sensitivity than noradrenaline assay in detecting changes of the sympathetic innervation of the tracheo-bronchial tree and of the pulmonary vasculature. The possible significance of reduced noradrenergic innervation of the tracheo-bronchial tree in aged rats is discussed.

The effect of thrombospondin on invasion of fibrin gels by human A549 lung carcinoma.

Thrombospondin (TSP) was evaluated for its effect on the capacity of human A549 lung adenocarcinoma cells to invade and degrade fibrin gels. Cells suspended in DMEM containing 0.01 units/mL plasminogen were added to a 2.5 mm diameter well in a 2 mm thick fibrin gel. Various concentrations of TSP were added either to the cells or to the gel. After 18 hours, the number of spread and gel-adherent cells were counted and the diameter of the well was measured to determine the extent of tumor-induced fibrinolysis. In the absence of TSP, the tumor cells were non-adherent but catalyzed the rapid degradation of the fibrin gel, causing the application well to increase in diameter several-fold. In contrast, addition of either TSP to the gel or to the cell suspension inhibited fibrinolysis in a dose-dependent manner and promoted attachment and spreading of cells in the fibrin matrix. In contrast, fibronectin had no effect. The effect of TSP on both tumor cell-associated fibrinolysis and cell adhesion was inhibited with an anti-TSP monoclonal antibody. The cell adhesive peptides CSVTCG, derived from the type 1 repeats of TSP, and GRGDS also had no effect on tumor cell-associated fibrinolysis. TSP inhibited fibrinolysis by inhibiting tumor cell-secreted urokinase activity, but had no effect on total urokinase secreted-antigen. In contrast, cell-associated urokinase activity was protected from inhibition by TSP. These results suggest that TSP may promote tumor cell metastasis not only by promoting cell-attachment but also by protecting tumor cell-fibrin emboli from degradation by tumor secreted- and host fibrinolytic enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in monocyte phagocyting activity after multi-agent chemotherapy in non-small cell lung cancer.

Changes in monocyte functions have been described in several human malignancies. The monocyte/macrophage system is known to play a crucial role in the rejection of tumor cells and phagocytosis represents an important defense mechanism used by these cells. This paper reports the adherence power and phagocyting ability (latex beads) of circulating monocytes in 20 patients with unresectable non-small cell lung cancer (NSCLC), stage IIIB or stage IV, before and after multiagent chemotherapy (carboplatin + etoposide + ifosfamide or cisplatinum + etoposide). We demonstrated that both monocyte adherence and phagocytosis were not affected in lung cancer patients before chemotherapy in comparison with healthy controls. After chemotherapy, a statistically significant decrease in monocyte count on day 4 (p < 0.05) and in their phagocyting ability on day 4 and 15 (p < 0.001 and p < 0.05 respectively) was showed. In addition, a statistically reduced monocyte adherence was found on day 4 (p < 0.05). The described impairment was prolonged but reversible. These changes in monocyte functions after chemotherapy could be due to a direct effect of the chemotherapy on these cells or to functionally immature cells circulating after myelodepression. The in vitro assessment of monocyte functions may be useful to better clarify mechanisms by which anti-neoplastic agents may act on immune functions and prevent adverse side effects.

Delayed pubertal growth spurt and normal adult height attainment in boys receiving long-term alternate-day prednisone therapy.

Statural growth to age > or = 20 years was studied in 10 boys with glomerulonephritis who received alternate-day prednisone (mean 1.2 mg/kg) for at least 2 consecutive years during pubertal age. Peak growth velocity was delayed after age 15 years in six patients and it was less than 7 cm/year in five. However, after age 16, growth velocity was significantly (p = 0.02) higher than expected and allowed patients to ultimately reach their genetic height potential.

Impact of Italian legislation regulating assisted reproduction techniques on ICSI outcomes in severe male factor infertility: a multicentric survey.

BACKGROUND: In 2004, a law regulating assisted reproduction techniques (ART) was passed in Italy. The new rules allow for the formation and transfer of a maximum of three embryos at one time, whereas embryo selection and embryo storage are prohibited. The aim of this study is to evaluate the impact of these restrictions on ICSI outcome in couples affected by severe male factor infertility. METHODS: Thirteen Italian ART Units were involved in this study. Data were collected on ICSI cycles performed during 2 years before (control group) and 2 years after (study group) the enforcement of the law. Only cases of obstructive azoospermia (OA), non-obstructive azoospermia (NOA) and severe oligoastenoteratozoospermia (OAT) (sperm count

The impact of lifestyle health risk on the bottom line: a case study.

As the Lifestyle Advantage study continues, HPS expects to follow the utilization trends for a consistent group of participants and nonparticipants, maintaining full confidentiality. Several key issues will be addressed in the process: As the participation rate increases, will the claims payment gap between participants and nonparticipants be reduced? Can a company hope to see a return on an investment in a health promotion program? If so, over what period of time? Finding answers to these questions will contribute to the larger issues of long-term health care cost containment and health care reform.

Assessment of the relevance of zona pellucida antibodies in follicular fluid of in-vitro fertilization (IVF) patients.

The presence of anti-zona pellucida antibodies in the follicular fluid of 11 women who underwent in-vitro fertilization (IVF) and embryo transfer was analysed. Only infertile couples with tubal or unexplained pathologies were included in our study, which was aimed at investigating the relationship between anti-zona pellucida antibodies in follicular fluid and failed fertilization. Whether or not these antibodies were present in some or all follicles in the same patient was also investigated. Out of 55 follicular fluids analysed, 36.3% were positive to the test and no fertilization was observed in oocytes from these follicles, while 63.6% were negative, and the oocyte fertilization rate associated with these was 51.4%. The presence of anti-zona pellucida antibodies was positively correlated with the degree of fertilization failure (P < 0.001 chi 2 test).

Chronic interstitial cystitis and systemic lupus erythematosus in an 8-year-old girl.

An 8-year-old girl with systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis had chronic interstitial cystitis (CIC) early in the course of SLE. The early occurrence of CIC, the lack of intestinal symptoms, the association with vesicoureteric reflux, and the improvement of CIC during therapy with cyclosporin A were the prominent features of the patient reported here.

Pulmonary alveolar microlithiasis: review of Italian reports.

Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown etiology, characterized by the presence of calcific concretions in the alveolar spaces. A familial occurrence is frequently found so that an inherited trait is thought to be involved. The chest X-ray is characterized by a 'sandstrom' picture while the clinical state undergoes to a slow and progressive impairment resulting in respiratory failure at the end stage. We have reviewed the Italian literature of the past 50 years detecting 48 case-reports of PAM (19 males and 29 females). Only 20 out of them were documented in international journals. A familial occurrence of 43.7% was found and 18 patients were under age fifteen. There was a prevalence in the female sex (60.4%) and in the second decade of life. Chest X-ray was the most important tool to diagnose PAM revealing the characteristic picture in all patient. Bronchoalveolar lavage (BAL) and open lung biopsy respectively show the characteristic calcospherites in the recovered fluid (BALF) and in the alveolar spaces. About 300 cases of PAM are reported in the international literature. We believe these data are probably underestimated because many case-reports are not published in international literature.

Catch-up growth in children with vesico-ureteric reflux.

A longitudinal retrospective study of height Z score (HZ score) and weight-for-height index (WHI) was performed on 94 pre-pubertal children with vesico-ureteric reflux (VUR) and normal creatinine clearance followed for 1-6.8 years (mean 3.1 years). Thirty patients had bilateral VUR with scintigraphic signs of renal scarring (B+), 17 had bilateral VUR without renal scarring (B-), 27 had unilateral VUR with (U+) and 20 unilateral VUR without (U-) renal scarring. Thirty-three patients received only antimicrobial medication and 61 underwent successful antireflux operation. The increase in HZ score and WHI during the 1st year of follow-up was significantly (P = 0.001 and 0.00003, respectively) higher than during the 2nd year. At first visit, B+ subjects had an average WHI and HZ score that were significantly (P = 0.02 and 0.04, respectively) lower than the other groups of patients together. At last visit this difference was not significant. In B+ subjects, the WHI and HZ score at last visit were significantly (P = 0.04 for both) higher than at the first visit. B+ patients fully recover their body growth deficit compared with other groups of VUR subjects after medical and/or surgical therapy.

Growth retardation in non-steroid treated juvenile rheumatoid arthritis.

Growth in height was studied in 58 patients with juvenile rheumatoid arthritis (JRA) followed for 4.9 +/- (SD) 2.8 years, who had never received steroids. Height measurements were converted to Height Z Scores. Height Z scores at first and at last visit were respectively 0.7 +/- 1 and 0.7 +/- 0.9 (NS) in pauciarticular, 0 +/- 1.6 and -0.55 +/- 1.6 (p = 0.045) in systemic, 0.29 +/- 0.8 and -0.4 +/- 1 (p = 0.0001) in polyarticular JRA patients. In systemic and polyarticular patients a significant negative relation was found between the duration of disease and the delta Height Z score (p = 0.0008) as well as between the sum of the periods of active disease and the delta Height Z score (p = 0.0001). The patients with functional class = 1 lost 0.01 +/- 0.19 Height Z score per year while those with functional class > or = 2 lost 0.16 +/- 0.13 Height Z score per year (p = 0.005). The loss of Height Z score in systemic and polyarticular subjects observed during pubertal age (-0.71 +/- 0.67 Height Z score) was significantly (p = 0.02) greater than in those observed before puberty (-0.1 +/- 0.72). The longer duration of disease, the higher degree of functional joint involvement, and the age of puberty appear to be risk factors for height growth impairment in systemic and polyarticular JRA.

Body growth in early diagnosed vesicoureteric reflux.

Body growth was studied in 32 subjects with vesicoureteric reflux (VUR), diagnosed following the prenatal finding of urinary tract dilatation, who had normal renal filtration function and who received antibacterial prophylaxis by the first few days of life. They were followed for 1-5 years (mean 2.3 years). Most had persistent VUR during the 1st year of life. Body growth performance was compared with that of 94 subjects with VUR diagnosed and treated by us after the neonatal period. During the follow-up period, none of the patients with prenatally detected VUR had a height Z score below -2, nor a weight-for-height index below 90%, and 1 had variations in height Z score >/=1. The difference in the percentage of patients with prenatally detected VUR (1/32) and those with VUR diagnosed and treated after the neonatal period (20/94) who had variations in height Z score >/=1 was significant (P=0.035). Patients with prenatally detected VUR and normal renal filtration function, given antibacterial prophylaxis by the first few days of life, have normal body growth, although VUR still persists.

Calyceal microlithiasis in children: report on 196 cases.

Recognition of children at greatest risk for urolithiasis may allow early detection or prevention of stone formation. We report clinical data from 196 children aged 0.9-15.9 years in whom renal ultrasound examination revealed hyperechogenic spots in renal calyces less than 3 mm in diameter. We called this finding "calyceal microlithiasis" (CM). There was a history of urolithiasis in 70.4% of patients in at least one first- or second-degree relative. Presenting symptoms were recurrent abdominal pain, dysuria, and hematuria, occurring alone or in combination. Hematuria was the presenting symptom in 41% of patients and was the only urinary finding in more than one-third. Hypercalciuria was present in about one-third and hyperuricuria in one-fifth of the patients. Of 29 patients who were followed for at least 2 years, 9 developed calculi 4-7 mm in diameter. CM possibly represents the first step in calculus formation. The finding of CM might explain a number of symptoms and signs that are often mild and non-specific, thus reducing invasive diagnostic procedures.