Antiretroviral therapy during pregnancy and premature birth: analysis of Swiss data

Background There is an ongoing debate as to whether combined antiretroviral treatment (cART) during pregnancy is an independent risk factor for prematurity in HIV-1-infected women. Objective The aim of the study was to examine (1) crude effects of different ART regimens on prematurity, (2) the association between duration of cART and duration of pregnancy, and (3) the role of possibly confounding risk factors for prematurity. Method We analysed data from 1180 pregnancies prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS). Results Odds ratios for prematurity in women receiving mono/dual therapy and cART were 1.8 [95% confidence interval (CI) 0.85–3.6] and 2.5 (95% CI 1.4–4.3) compared with women not receiving ART during pregnancy (P=0.004). In a subgroup of 365 pregnancies with comprehensive information on maternal clinical, demographic and lifestyle characteristics, there was no indication that maternal viral load, age, ethnicity or history of injecting drug use affected prematurity rates associated with the use of cART. Duration of cART before delivery was also not associated with duration of pregnancy. Conclusion Our study indicates that confounding by maternal risk factors or duration of cART exposure is not a likely explanation for the effects of ART on prematurity in HIV-1-infected women.

EFFECT OF AGING ON MACULAR FEATURES OF X-LINKED RETINOSCHISIS ASSESSED WITH OPTICAL COHERENCE TOMOGRAPHY

X-linked retinoschisis (XLRS) is one of the most common causes of macular degeneration in young men. The purpose of this study was to use optical coherence tomography combined with ophthalmoscopy to study the effects of aging on the morphologic changes associated with XLRS.

Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study

Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care.

Fatal pulmonary embolism in a premature neonate after twin-to-twin transfusion syndrome

Thrombotic events are being increasingly recognized during the neonatal period. An infant girl was born at 29 weeks' gestation after a pregnancy complicated by twin-to-twin transfusion syndrome. After an initial uncomplicated clinical course, her oxygen requirement increased, which was interpreted as an early sign of bronchopulmonary dysplasia. At 3 weeks of age, she suddenly collapsed and died of severe pulmonary hypertension. At autopsy, multiple pulmonary artery emboli and several older renal vein thromboses were found. Results of genetic analyses of the infant and her family were negative for thrombophilia. Although embolism represents a frequent emergency in adults, fatal pulmonary embolism has never, to our knowledge, been described for premature infants. This case suggests that thrombotic events are underdiagnosed and that additional studies are needed to define infants at risk and optimal treatment strategies.

Premature Osteoblast Clustering by Enamel Matrix Proteins Induces Osteoblast Differentiation through Up-Regulation of Connexin 43 and N-Cadherin

In recent years, enamel matrix derivative (EMD) has garnered much interest in the dental field for its apparent bioactivity that stimulates regeneration of periodontal tissues including periodontal ligament, cementum and alveolar bone. Despite its widespread use, the underlying cellular mechanisms remain unclear and an understanding of its biological interactions could identify new strategies for tissue engineering. Previous in vitro research has demonstrated that EMD promotes premature osteoblast clustering at early time points. The aim of the present study was to evaluate the influence of cell clustering on vital osteoblast cell-cell communication and adhesion molecules, connexin 43 (cx43) and N-cadherin (N-cad) as assessed by immunofluorescence imaging, real-time PCR and Western blot analysis. In addition, differentiation markers of osteoblasts were quantified using alkaline phosphatase, osteocalcin and von Kossa staining. EMD significantly increased the expression of connexin 43 and N-cadherin at early time points ranging from 2 to 5 days. Protein expression was localized to cell membranes when compared to control groups. Alkaline phosphatase activity was also significantly increased on EMD-coated samples at 3, 5 and 7 days post seeding. Interestingly, higher activity was localized to cell cluster regions. There was a 3 fold increase in osteocalcin and bone sialoprotein mRNA levels for osteoblasts cultured on EMD-coated culture dishes. Moreover, EMD significantly increased extracellular mineral deposition in cell clusters as assessed through von Kossa staining at 5, 7, 10 and 14 days post seeding. We conclude that EMD up-regulates the expression of vital osteoblast cell-cell communication and adhesion molecules, which enhances the differentiation and mineralization activity of osteoblasts. These findings provide further support for the clinical evidence that EMD increases the speed and quality of new bone formation in vivo.

Osteoporosis and periodontitis in older subjects participating in the Swedish National Survey on Aging and Care (SNAC-Blekinge)

Abstract Objective. We assessed the relationships between (I) ultrasonography calcaneus T-scores (PIXI) and mandibular cortex characteristics on oral panoramic radiographs in older subjects; and (II) osteoporosis and periodontitis. Material and methods. We examined 778 subjects (53% women) aged 59-96 years. Periodontitis was defined by alveolar bone loss assessed from panoramic radiographs. Results. PIXI calcaneus T-values ?-2.5 (osteoporosis) were found in 16.3% of women and in 8.1% of men. PIXI calcaneus T-values <-1.6 (osteoporosis, adjusted) were found in 34.2% of women and in 21.4% of men. The age of the subjects and PIXI T-values were significantly correlated in women (Pearson's r = 0.37, P < 0.001) and men (Pearson's r = 0.19, P < 0.001). Periodontitis was found in 18.7% of subjects defined by alveolar bone level ?5 mm. Subjects with osteoporosis defined by adjusted PIXI T-values had fewer remaining teeth [mean difference 4.1, 95% confidence interval (CI) -1.1 to -6.5, P < 0.001]. The crude odds ratio (OR) of an association between the panoramic assessment of mandibular cortex erosions as a sign of osteoporosis and the adjusted T-value (T-value cut-off <-1.6) was 4.8 (95% CI 3.1-7.2, P < 0.001; Pearson ?(2) = 60.1, P < 0.001). A significant OR between osteoporosis and periodontitis was only found in women for the T-value cut-off ?-2.5 (crude OR 1.8, 95% CI 1.1-3.3, P < 0.03). Conclusions. An association between osteoporosis and periodontitis was only confirmed in women. The likelihood that the mandibular cortex index agrees with adjusted PIXI T-values is significant.

On the traces of XPD: cell cycle matters - untangling the genotype-phenotype relationship of XPD mutations

Abstract Mutations in the human gene coding for XPD lead to segmental progeria - the premature appearance of some of the phenotypes normally associated with aging - which may or may not be accompanied by increased cancer incidence. XPD is required for at least three different critical cellular functions: in addition to participating in the process of nucleotide excision repair (NER), which removes bulky DNA lesions, XPD also regulates transcription as part of the general transcription factor IIH (TFIIH) and controls cell cycle progression through its interaction with CAK, a pivotal activator of cyclin dependent kinases (CDKs). The study of inherited XPD disorders offers the opportunity to gain insights into the coordination of important cellular events and may shed light on the mechanisms that regulate the delicate equilibrium between cell proliferation and functional senescence, which is notably altered during physiological aging and in cancer. The phenotypic manifestations in the different XPD disorders are the sum of disturbances in the vital processes carried out by TFIIH and CAK. In addition, further TFIIH- and CAK-independent cellular activities of XPD may also play a role. This, added to the complex feedback networks that are in place to guarantee the coordination between cell cycle, DNA repair and transcription, complicates the interpretation of clinical observations. While results obtained from patient cell isolates as well as from murine models have been elementary in revealing such complexity, the Drosophila embryo has proven useful to analyze the role of XPD as a cell cycle regulator independently from its other cellular functions. Together with data from the biochemical and structural analysis of XPD and of the TFIIH complex these results combine into a new picture of the XPD activities that provides ground for a better understanding of the patophysiology of XPD diseases and for future development of diagnostic and therapeutic tools.

Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study

Patterns of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals taking antiretroviral therapy are changing as a result of immune reconstitution and improved survival. We studied the influence of aging on the epidemiology of non-AIDS diseases in the Swiss HIV Cohort Study.

Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants

Neonatal sepsis causes high mortality and morbidity in preterm infants, but less is known regarding the long-term outcome after sepsis. This study aimed to determine the impact of sepsis on neurodevelopment at 2 years' corrected age in extremely preterm infants.

Electrophysiological and behavioral correlates of stable automatic semantic retrieval in aging

Previous studies have shown both declining and stable semantic-memory abilities during healthy aging. There is consistent evidence that semantic processes involving controlled mechanisms weaken with age. In contrast, results of aging studies on automatic semantic retrieval are often inconsistent, probably due to methodological limitations and differences. The present study therefore examines age-related alterations in automatic semantic retrieval and memory structure with a novel combination of critical methodological factors, i.e., the selection of subjects, a well-designed paradigm, and electrophysiological methods that result in unambiguous signal markers. Healthy young and elderly participants performed lexical decisions on visually presented word/non-word pairs with a stimulus onset asynchrony (SOA) of 150 ms. Behavioral and electrophysiological data were measured, and the N400-LPC complex, an event-related potential component sensitive to lexical-semantic retrieval, was analyzed by power and topographic distribution of electrical brain activity. Both age groups exhibited semantic priming (SP) and concreteness effects in behavioral reaction time and the electrophysiological N400-LPC complex. Importantly, elderly subjects did not differ significantly from the young in their lexical decision and SP performances as well as in the N400-LPC SP effect. The only difference was an age-related delay measured in the N400-LPC microstate. This could be attributed to existing age effects in controlled functions, as further supported by the replicated age difference in word fluency. The present results add new behavioral and neurophysiological evidence to earlier findings, by showing that automatic semantic retrieval remains stable in global signal strength and topographic distribution during healthy aging.