The utility of menstrual cycle length as an indicator of cumulative hormonal exposure.

Context: Associations between menstrual cycle length and chronic diseases are hypothesized to be due to differences in underlying hormonal patterns.

Objective: The aim of the study was to evaluate the association between menstrual cycle length and the hormonal profile and anovulation.

Design And Setting: We conducted a prospective cohort study at the University at Buffalo from 2005 to 2007.

Transcriptional regulation of the 5-HT1A receptor: implications for mental illness.

The serotonin-1A (5-HT(1A)) receptor is an abundant post-synaptic 5-HT receptor (heteroreceptor) implicated in regulation of mood, emotion and stress responses and is the major somatodendritic autoreceptor that negatively regulates 5-HT neuronal activity. Based on animal models, an integrated model for opposing roles of pre- and post-synaptic 5-HT(1A) receptors in anxiety and depression phenotypes and response to antidepressants is proposed. Understanding differential transcriptional regulation of pre- versus post-synaptic 5-HT(1A) receptors could provide better tools for their selective regulation.

The neurobiology of depression--revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms.

The serotonin (5-HT) hypothesis of depression dates from the 1960s. It originally postulated that a deficit in brain serotonin, corrected by antidepressant drugs, was the origin of the illness. Nowadays, it is generally accepted that recurring mood disorders are brain diseases resulting from the combination, to various degrees, of genetic and other biological as well as environmental factors, evolving through the lifespan.

Volcanic ash layers illuminate the resilience of Neanderthals and early modern humans to natural hazards.

Marked changes in human dispersal and development during the Middle to Upper Paleolithic transition have been attributed to massive volcanic eruption and/or severe climatic deterioration. We test this concept using records of volcanic ash layers of the Campanian Ignimbrite eruption dated to ca. 40,000 y ago (40 ka B.

The antioxidant tempol reduces carcinogenesis and enhances survival in mice when administered after nonlethal total body radiation.

There is significant interest in the development of agents that can ameliorate radiation damage after exposure to radiation has occurred. Here we report that chronic supplementation of the antioxidant Tempol in the diet of mice can reduce body weight without toxicity, decrease cancer, and extend survival when administered after nonlethal total body radiation (TBI). These effects were apparent in two different strains of mice (C3H, CBA) exposed to TBI (3 Gy).

The impact of random-effect misspecification on percentile estimation for longitudinal growth data.

Identifying unusual growth-related measurements or longitudinal patterns in growth is often the focus in fetal and pediatric medicine. For example, the goal of the ongoing National Fetal Growth Study is to develop both cross-sectional and longitudinal reference curves for ultrasound fetal growth measurements that can be used for this purpose. Current methodology for estimating cross-sectional and longitudinal reference curves relies mainly on the linear mixed model.

Bronchodilator responsiveness as a phenotypic characteristic of established chronic obstructive pulmonary disease.

Background: Bronchodilator responsiveness is a potential phenotypic characteristic of chronic obstructive pulmonary disease (COPD). We studied whether change in lung function after a bronchodilator is abnormal in COPD, whether stable responder subgroups can be identified, and whether these subgroups experience different clinical outcomes.

Methods: 1831 patients with COPD, 285 smoking (SC) and 228 non-smoking (NSC) controls from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort.

Mechanistic role for a novel glucocorticoid-KLF11 (TIEG2) protein pathway in stress-induced monoamine oxidase A expression.

Chronic stress is a risk factor for psychiatric illnesses, including depressive disorders, and is characterized by increased blood glucocorticoids and brain monoamine oxidase A (MAO A, which degrades monoamine neurotransmitters). This study elucidates the relationship between stress-induced MAO A and the transcription factor Kruppel-like factor 11 (KLF11, also called TIEG2, a member of the Sp/KLF- family), which inhibits cell growth. We report that 1) a glucocorticoid (dexamethasone) increases KLF11 mRNA and protein levels in cultured neuronal cells; 2) overexpressing KLF11 increases levels of MAO A mRNA and enzymatic activity, which is further enhanced by glucocorticoids; in contrast, siRNA-mediated KLF11 knockdown reduces glucocorticoid-induced MAO A expression in cultured neurons; 3) induction of KLF11 and translocation of KLF11 from the cytoplasm to the nucleus are key regulatory mechanisms leading to increased MAO A catalytic activity and mRNA levels because of direct activation of the MAO A promoter via Sp/KLF-binding sites; 4) KLF11 knockout mice show reduced MAO A mRNA and catalytic activity in the brain cortex compared with wild-type mice; and 5) exposure to chronic social defeat stress induces blood glucocorticoids and activates the KLF11 pathway in the rat brain, which results in increased MAO A mRNA and enzymatic activity.

Candidate measures of whole plant food intake are related to biomarkers of nutrition and health in the US population (National Health and Nutrition Examination Survey 1999-2002).

Indices of overall dietary patterns are used in epidemiologic research to examine the relationship between nutrition and health. The objective of this study was to develop and validate an interpretable summary measure of dietary intake of whole plant foods (WPF; whole grains, vegetables, whole fruit, legumes, nuts, seeds) because of their similar nutritional characteristics and health effects. Six candidate WPF measures were calculated using data from subjects (age ≥ 6 years) participating in the 1999-2000 and 2001-2002 National Health and Nutrition Examination Survey.

Summer activity patterns among teenage girls: harmonic shape invariant modeling to estimate circadian cycles.

Background: Physical activity as measured by activity counts over short time intervals across a 24 h period are often used to assess circadian variation. We are interested in characterizing circadian patterns in activity among adolescents and examining how these patterns vary by obesity status. New statistical approaches are needed to examine how factors affect different features of the circadian pattern and to make appropriate covariate adjustments when the outcomes are longitudinal count data.

Predicting large fetuses at birth: do multiple ultrasound examinations and longitudinal statistical modelling improve prediction?

Predicting large fetuses at birth has long been a challenge in obstetric practice. We examined whether ultrasound examinations at multiple times during pregnancy improve the accuracy of prediction using repeated, longitudinal statistical modelling, and whether adding maternal characteristics improves the accuracy of prediction. We used data from a previous study conducted in Norway and Sweden from 1986 to 1989 in which each pregnant woman had four ultrasound examinations at around 17, 25, 33 and 37 weeks of gestation.

Marginal Analysis of Longitudinal Count Data in Long Sequences: Methods and Applications to A Driving Study.

Most of the available methods for longitudinal data analysis are designed and validated for the situation where the number of subjects is large and the number of observations per subject is relatively small. Motivated by the Naturalistic Teenage Driving Study (NTDS), which represents the exact opposite situation, we examine standard and propose new methodology for marginal analysis of longitudinal count data in a small number of very long sequences. We consider standard methods based on generalized estimating equations, under working independence or an appropriate correlation structure, and find them unsatisfactory for dealing with time-dependent covariates when the counts are low.

17β-estradiol-induced regulation of the novel 5-HT1A-related transcription factors NUDR and Freud-1 in SH SY5Y cells.

Nuclear deformed epidermal autoregulatory factor-1 (NUDR/Deaf-1) and five prime repressor element under dual repression (Freud-1) are novel transcriptional regulators of the 5-HT(1A) receptor, a receptor that has been implicated in the pathophysiology of various psychiatric illnesses. The antidepressant effect of 17β-Estradiol (17βE(2)) is purported to involve the downregulation of this receptor. We investigated the possible role of NUDR and Freud-1 in 17βE(2)-induced downregulation of the 5-HT(1A) receptor in the neuroblastoma cell line SH SY5Y.

Do elevated gravitational-force events while driving predict crashes and near crashes?

The purpose of this research was to determine the extent to which elevated gravitational-force event rates predict crashes and near crashes. Accelerometers, global positioning systems, cameras, and other technology were installed in vehicles driven by 42 newly licensed Virginia teenage drivers for a period of 18 months between 2006 and 2009. Elevated gravitational force and crash and near-crash events were identified, and rates per miles driven were calculated.

Increased serotonin-1A (5-HT1A) autoreceptor expression and reduced raphe serotonin levels in deformed epidermal autoregulatory factor-1 (Deaf-1) gene knock-out mice.

Altered regulation of the serotonin-1A (5-HT1A) receptor gene is implicated in major depression and mood disorders. The functional human 5-HT1A C(-1019)G promoter polymorphism (rs6295), which prevents the binding of Deaf-1/NUDR leading to dysregulation of the receptor, has been associated with major depression. In cell models Deaf-1 displays dual activity, repressing 5-HT1A autoreceptor expression in serotonergic raphe cells while enhancing postsynaptic 5-HT1A heteroreceptor expression in nonserotonergic neurons.

Pre-Clinical Assessment of Lu-Labeled Trastuzumab Targeting HER2 for Treatment and Management of Cancer Patients with Disseminated Intraperitoneal Disease.

Studies from this laboratory have demonstrated the potential of targeting HER2 for therapeutic and imaging applications with medically relevant radionuclides. To expand the repertoire of trastuzumab as a radioimmunoconjugate (RIC) vector, use of (177)Lu was investigated. The combination of a 6.

Ser/ Thr residues at α3/β5 loop of Gαs are important in morphine-induced adenylyl cyclase sensitization but not mitogen-activated protein kinase phosphorylation.

The signaling switch of β2-adrenergic and μ(1) -opioid receptors from stimulatory G-protein (G(αs) ) to inhibitory G-protein (G(αi) ) (and vice versa) influences adenylyl cyclase (AC) and extracellular-regulated kinase (ERK)1/2 activation. Post-translational modifications, including dephosphorylation of G(αs) , enhance opioid receptor coupling to G(αs) . In the present study, we substituted the Ser/Thr residues of G(αs) at the α3/β5 and α4/β6 loops aiming to study the role of G(αs) lacking Ser/Thr phosphorylation with respect to AC sensitization and mitogen-activated protein kinase activation.

Serum macrophage inhibitory cytokine-1 (MIC-1/GDF15): a potential screening tool for the prevention of colon cancer?

Background: Macrophage inhibitory cytokine-1 (MIC-1/GDF15) mediates nonsteroidal anti-inflammatory drug (NSAID) protection from colonic polyps in mice and is linked to the development of colorectal carcinoma in humans. Therefore, changes in serum MIC-1/GDF15 levels could predict the presence of premalignant colonic polyposis and assist in population screening strategies.

Methods: Serum MIC-1/GDF15 levels were measured in subjects in the Polyp Prevention Trial, in which NSAID use and colon cancer risk factors were defined.

Physical activity monitoring in COPD: compliance and associations with clinical characteristics in a multicenter study.

Background: Little is known about COPD patients' compliance with physical activity monitoring and how activity relates to disease characteristics in a multi-center setting.

Methods: In a prospective study at three Northern European sites physical activity and clinical disease characteristics were measured in 134 COPD patients (GOLD-stage II-IV; BODE index 0-9) and 46 controls. Wearing time, steps per day, and the physical activity level (PAL) were measured by a multisensory armband over a period of 6 consecutive days (in total, 144 h).

The effect of passengers and risk-taking friends on risky driving and crashes/near crashes among novice teenagers.

Purpose: The high crash rates of novice teenage drivers are thought to be caused by inexperience and risky driving behavior, exacerbated by passengers, driving at night, and other complex driving conditions. This study examined factors associated with crash/near crash and risky driving rates among novice teenagers, including driving at night versus day, passenger presence and characteristics, and driver psychosocial factors.

Method: The vehicles of 42 newly licensed teenage drivers were equipped with recording systems that collected data on driving performance and occupant characteristics during their first 18 months of licensure.

Synthetic human parathyroid hormone 1-34 replacement therapy: a randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism.

Context: Vitamin D therapy for hypoparathyroidism does not restore PTH-dependent renal calcium reabsorption, which can lead to renal damage. An alternative approach, PTH 1-34 administered twice daily, provides acceptable long-term treatment but is associated with nonphysiological serum calcium fluctuation.

Objective: Our objective was to compare continuous PTH 1-34 delivery, by insulin pump, with twice-daily delivery.

An evaluation of the natural history of bacterial vaginosis using transition models.

Background: The natural history of bacterial vaginosis (BV) is complex given the variability across and within women over time. This article considers 3 different transition models for analyzing longitudinal BV data.

Methods: Data from the Longitudinal Study of Vaginal Flora were used to evaluate 3 transition modeling strategies: (1) a Markov regression, (2) a Markov regression with random effects, and (3) a mover-stayer model.

A linear mixed model for predicting a binary event from longitudinal data under random effects misspecification.

The use of longitudinal data for predicting a subsequent binary event is often the focus of diagnostic studies. This is particularly important in obstetrics, where ultrasound measurements taken during fetal development may be useful for predicting various poor pregnancy outcomes. We propose a modeling framework for predicting a binary event from longitudinal measurements where a shared random effect links the two processes together.

Crash and risky driving involvement among novice adolescent drivers and their parents.

Objectives: We compared rates of risky driving among novice adolescent and adult drivers over the first 18 months of adolescents' licensure.

Methods: Data-recording systems installed in participants' vehicles provided information on driving performance of 42 newly licensed adolescent drivers and their parents. We analyzed crashes and near crashes and elevated g-force event rates by Poisson regression with random effects.