Accelerated brain aging predicts impulsivity and symptom severity in depression

Multiple structural and functional neuroimaging measures vary over the course of the lifespan and can be used to predict chronological age. Accelerated brain aging, as quantified by deviations in the MRI-based predicted age with respect to chronological age, is associated with risk for neurodegenerative conditions, bipolar disorder, and mortality. Whether age-related changes in resting-state functional connectivity are accelerated in major depressive disorder (MDD) is unknown, and, if so, it is unclear if these changes contribute to specific cognitive weaknesses that often occur in MDD. Here, we delineated age-related functional connectivity changes in a large sample of normal control subjects and tested whether brain aging is accelerated in MDD. Furthermore, we tested whether accelerated brain aging predicts individual differences in cognitive function. We trained a support vector regression model predicting age using resting-state functional connectivity in 710 healthy adults aged 18–89. We applied this model trained on normal aging subjects to a sample of actively depressed MDD participants (n = 109). The difference between predicted brain age and chronological age was 2.11 years greater (p = 0.015) in MDD patients compared to control participants. An older MDD brain age was significantly associated with increased impulsivity and, in males, increased depressive severity. Unexpectedly, accelerated brain aging was also associated with increased placebo response in a sham-controlled trial of high-frequency repetitive transcranial magnetic stimulation targeting the dorsomedial prefrontal cortex. Our results indicate that MDD is associated with accelerated brain aging, and that accelerated aging is selectively associated with greater impulsivity and depression severity.Subject terms: Depression, Cognitive ageing     

Cerebrovascular responses to somatomotor stimulation in Parkinson’s disease: A multivariate analysis

Parkinson’s disease (PD) is a common neurodegenerative disorder, yet little is known about cerebral haemodynamics in this patient population. Previous studies assessing dynamic cerebral autoregulation (dCA), neurovascular coupling (NVC) and vasomotor reactivity (VMR) have yielded conflicting findings. By using multi-variate modelling, we aimed to determine whether cerebral blood flow (CBF) regulation is impaired in PD patients.55 healthy controls (HC) and 49 PD patients were recruited. PD subjects underwent a second recording following a period of abstinence from their anti-Parkinsonian medication. Continuous bilateral transcranial Doppler in the middle cerebral arteries, beat-to-beat mean arterial blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO₂ (EtCO₂; capnography) were measured. After a 5-min baseline period, a passive motor paradigm comprising 60 s of elbow flexion was performed. Multi-variate modelling quantified the contributions of MAP, ETCO₂ and neural stimulation to changes in CBF velocity (CBFV). dCA, VMR and NVC were quantified to assess the integrity of CBF regulation.Neural stimulation was the dominant input. dCA, NVC and VMR were all found to be impaired in the PD population relative to HC (p < 0.01, p = 0.04, p < 0.01, respectively). Our data suggest PD may be associated with depressed CBF regulation. This warrants further assessment using different neural stimuli.     

Characteristics and Sonophotocatalytic Activity of Natural Sphalerite under Ultrasonic (1.7 MHz) and UVA LED (365 nm) Irradiation

Naturally occurring sono- and photoactive minerals, which are abundant on Earth, represent an attractive alternative to the synthesized sonophotocatalysts as cost-effective materials for water and wastewater treatment. This study focuses on characterizing and evaluating the sonophotocatalytic activity of natural sphalerite (NatS) from Dovatka deposit (Siberia) under high-frequency ultrasonic (US, 1.7 MHz) and ultraviolet light-emitting diodes (UVA LED, 365 nm) irradiation towards degradation of 4-chlorophenol as a model organic pollutant. Since raw natural sphalerite did not exhibit a measurable photocatalytic activity, it was calcined at 500, 900 and 1200 °C. The natural sphalerite after calcination at 900 °C (NatS*) was found to be the most effective for sonophotocatalytic degradation of 4-chlorophenol, attaining the highest efficiency (55%, 1 h exposure) in the following row: UV < US ≈ UV/US ≈ US/NatS* < UV/NatS* < UV/US/NatS*. Addition of 1 mM H₂O₂ increased the removal to 74% by UV/US/NatS*/H₂O₂ process. An additive effect between UV/NatS* and US/NatS* processes was observed in the sonophotocatalytic system as well as in the H₂O₂-assisted system. We assume that the sonophotocatalytic hybrid process, which is based on the simultaneous use of high-frequency ultrasound, UVA light, calcined natural sphalerite and H₂O₂, could provide a basis of an environmentally safe and cost-effective method of elimination of organic pollutants from aqueous media.     

Female sexual function and pelvic floor disorders

OBJECTIVE: To investigate the hypothesis that pelvic floor disorders are associated with female sexual problems, independently of other related factors. METHODS: The study population included 301 adult women seeking outpatient gynecologic and urogynecologic care. Pelvic floor disorders were assessed with the Pelvic Floor Disorders Inventory-20 (PFDI-20) and the pelvic organ prolapse quantification examination. Sexual function was assessed with the Personal Experiences Questionnaire. Using ordinal regression analysis, we identified characteristics and conditions associated with decreased libido, infrequent orgasm, decreased arousal, and dyspareunia. RESULTS: Sexual function was poorer among 78 women (26%) without a current sexual partner than among 223 with a partner (P<.01). Among the 223 with a current partner, women with a high Pelvic Floor Disorders Inventory score were significantly more likely to report decreased arousal (P<.01), infrequent orgasm (P<.01), and increased dyspareunia (P<.01). A similar pattern was observed for the urinary, colorectal-anal, and prolapse scales of the Pelvic Floor Disorders Inventory, although some associations were marginally significant. Stage III-IV prolapse was significantly associated with infrequent orgasm (P=.02), but other sexual complaints were not more common with increasing prolapse stage. CONCLUSION: Pelvic floor symptoms are significantly associated with reduced sexual arousal, infrequent orgasm, and dyspareunia. We conclude that sexual function is worse in women with symptomatic prolapse but not in women with asymptomatic prolapse. LEVEL OF EVIDENCE: II.     

Single nucleotide polymorphisms in the human progesterone receptor gene and spontaneous preterm birth

Progesterone supplementation can prevent preterm birth in some high-risk women. Progesterone binds to progesterone receptor (PR) and modulates the expression of target genes. This study investigates the association between single nucleotide polymorphisms (SNPs) in the PR gene and spontaneous preterm birth. DNA was extracted from consecutive patients with preterm birth (n = 78) and term controls (n = 415), and genotyping was performed for 3 PR SNPs (+331[G>A], + 770[C>T], +660[G>T]) using Sequenom matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Data were analyzed by chi(2) test and logistic regression analysis. Multivariate analysis showed no association between maternal carriage of minor + 331T, +770T, and/or +660T alleles and preterm birth when controlled for maternal age, ethnicity, gravidity, parity, prior preterm birth, route of delivery, or neonatal outcome. Carriage of +770T and +660T (but not +331T) was associated with preterm birth in women with a body mass index <18.5 kg/m(2) (relative risk, 10.8; 95% confidence interval, 1.4-82.6; P = .02). Maternal carriage of minor alleles of +331(G>A), +770(C>T), and +660(G> T) SNPs in the PR gene is not associated with spontaneous preterm birth.     

Seroprevalence and risk factors associated with herpes simplex virus infection among pregnant women

OBJECTIVES: To estimate the type-specific seroprevalence and identify the risk factors associated with herpes simplex virus (HSV)-2 infection in pregnant women in Bucharest, Romania. METHODS: A prospective survey was conducted in 452 subjects, aged 15-39 years, at the Elias Hospital, during the years 2004-2005. We evaluated serum IgG anti-bodies to HSV-1 and HSV-2 using the HerpeSelect ELISA test. All subjects completed an epidemiological questionnaire. RESULTS: Seroprevalence was 87.3% and 15.1% for HSV-1 and HSV-2, respectively. The risk factors for HSV-2 infection were lower level of education and a greater number of sexual partners. Elementary school and high-school graduates were 6.28 and 2.26 times more exposed than University graduates. Having 2-3 partners and more than three partners was associated with 2.43 and 4.26 times the risk of acquiring HSV-2, compared with having one partner. CONCLUSIONS: In pregnant women, HSV-1 seroprevalence was higher than in Western Europe but similar to that in Eastern Europe. HSV-2 seroprevalence was within European ranges. Both were lower than in the USA. Risk factors for HSV-2 infection may lead to prevention programs.     

Induction of apoptosis and inhibition of telomerase activity by arsenic trioxide (As2O3) in endometrial carcinoma cells

OBJECTIVES: To examine the effects of arsenic trioxide (As2O3) on human endometrial carcinoma cell lines with respect to cytotoxicity and the induction of apoptosis and telomerase expression in vitro. METHODS: Four endometrial carcinoma cell lines (Ishikawa, ECC-1, RL-95-2 and Hec-1B) were treated with increasing concentrations of As2O3. RESULTS: As2O3 inhibited proliferation of all cell lines in a concentration and time-dependent manner (IC50 range of 3-7 microM). Coincident with the inhibition of growth, As2O3 also induced apoptosis in all cell lines as measured by the time-dependent increase in M30 antibody fluorescence (binds a caspase-cleaved epitope of cytokeratin 18) detected by flow cytometry, and reduced telomerase activity by decreasing the hTERT mRNA expression. CONCLUSION: As2O3 may exert anti-tumor effects through the induction of the apoptosis pathway and telomerase and hTERT may play an important role in the anti-apoptotic effects which are observed when endometrial cancer cells are treated in vitro with As2O3.