Previous studies found larger lung volumes at school-age in formerly breastfed children, with some studies suggesting an effect modification by maternal asthma. We wanted to explore this further in children who had undergone extensive lung function testing. The current study aimed to assess whether breastfeeding was associated with larger lung volumes and, if so, whether all compartments were affected. We also assessed association of breastfeeding with apparent diffusion coefficient (ADC), which measures freedom of gas diffusion in alveolar-acinar compartments and is a surrogate of alveolar dimensions. Additionally, we assessed whether these effects were modified by maternal asthma.
We analysed data from 111 children and young adults aged 11–21 years, who had participated in detailed lung function testing, including spirometry, plethysmography and measurement of ADC of 3Helium (3He) by MR. Information on breastfeeding came from questionnaires applied in early childhood (age 1–4 years). We determined the association between breastfeeding and these measurements using linear regression, controlling for potential confounders.
We did not find significant evidence for an association between duration of breastfeeding and lung volumes or alveolar dimensions in the entire sample. In breastfed children of mothers with asthma, we observed larger lung volumes and larger average alveolar size than in non-breastfed children, but the differences did not reach significance levels.
Confirmation of effects of breastfeeding on lung volumes would have important implications for public health. Further investigations with larger sample sizes are warranted.
To prevent mother-to-child transmission (MTCT) of HIV in developing countries, new World Health Organization (WHO) guidelines recommend maternal combination antiretroviral therapy (cART) during pregnancy, throughout breastfeeding for 1 year and then cessation of breastfeeding (COB). The efficacy of this approach during the first six months of exclusive breastfeeding has been demonstrated, but the efficacy of this approach beyond six months is not well documented.
A prospective observational cohort study of 279 HIV-positive mothers was started on zidovudine/3TC and lopinavir/ritonavir tablets between 14 and 30 weeks gestation and continued indefinitely thereafter. Women were encouraged to exclusively breastfeed for six months, complementary feed for the next six months and then cease breastfeeding between 12 and 13 months. Infants were followed for transmission to 18 months and for survival to 24 months. Text message reminders and stipends for food and transport were utilized to encourage adherence and follow-up.
Total MTCT was 9 of 219 live born infants (4.1%; confidence interval (CI) 2.2–7.6%). All breastfeeding transmissions that could be timed (5/5) occurred after six months of age. All mothers who transmitted after six months had a six-month plasma viral load >1,000 copies/ml (p<0.001). Poor adherence to cART as noted by missed dispensary visits was associated with transmission (p=0.04). Infant mortality was lower after six months of age than during the first six months of life (p=0.02). The cumulative rate of infant HIV infection or death at 18 months was 29/226 (12.8% 95 CI: 7.5–20.8%).
Maternal cART may limit MTCT of HIV to the UNAIDS target of <5% for eradication of paediatric HIV within the context of a clinical study, but poor adherence to cART and follow-up can limit the benefit. Continued breastfeeding can prevent the rise in infant mortality after six months seen in previous studies, which encouraged early COB.
breastfeeding transmission of HIV; vertical transmission; option B+; infant survival; efficacy of WHO guidelines; perinatal transmission of HIV
Intracellular Ca2+ dysregulation and transport disruption precede cell death in Alzheimer's disease. Mechanisms of AβO-induced Ca2+ elevation are identified that regulate the onset, severity, and spatiotemporal progression of BDNF transport defects. The results challenge dogmatic views on mechanisms of AβO toxicity and subcellular sites of action.
Disruption of fast axonal transport (FAT) and intracellular Ca2+ dysregulation are early pathological events in Alzheimer's disease (AD). Amyloid-β oligomers (AβOs), a causative agent of AD, impair transport of BDNF independent of tau by nonexcitotoxic activation of calcineurin (CaN). Ca2+-dependent mechanisms that regulate the onset, severity, and spatiotemporal progression of BDNF transport defects from dendritic and axonal AβO binding sites are unknown. Here we show that BDNF transport defects in dendrites and axons are induced simultaneously but exhibit different rates of decline. The spatiotemporal progression of FAT impairment correlates with Ca2+ elevation and CaN activation first in dendrites and subsequently in axons. Although many axonal pathologies have been described in AD, studies have primarily focused only on the dendritic effects of AβOs despite compelling reports of presynaptic AβOs in AD models and patients. Indeed, we observe that dendritic CaN activation converges on Ca2+ influx through axonal voltage-gated Ca2+ channels to impair FAT. Finally, FAT defects are prevented by dantrolene, a clinical compound that reduces Ca2+ release from the ER. This work establishes a novel role for Ca2+ dysregulation in BDNF transport disruption and tau-independent Aβ toxicity in early AD.
Aspirin for the primary prevention of coronary heart disease (CHD) is only recommended for individuals at high risk for CHD although the majority of CHD events occur in individuals who are low to intermediate risk.
Methods and Results
To estimate the potential of coronary artery calcium (CAC) scoring to guide aspirin use for primary prevention of CHD, we studied 4229 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were not on aspirin at baseline and were free of diabetes. Using data from median 7.6-year follow-up, five-year number-needed-to-treat (NNT5) estimations were calculated by applying an 18% relative CHD reduction to the observed event rates. This was contrasted to 5-year number-needed-to-harm (NNH5) estimations based on the risk of major bleeding reported in an aspirin meta-analysis. Results were stratified by a 10% 10-year CHD Framingham Risk Score (FRS). Individuals with CAC ≥ 100 had an estimated net benefit with aspirin regardless of their traditional risk status (estimated NNT5 of 173 for individuals <10% FRS and 92 for individuals ≥ 10% FRS, estimated NNH5 of 442 for a major bleed). Conversely, individuals with zero CAC had unfavorable estimations (estimated NNT5 of 2,036 for individuals <10% FRS and 808 for individuals ≥ 10% FRS, estimated NNH5 of 442 for a major bleed). Gender specific and age-stratified analyses showed similar results.
For the primary prevention of CHD, MESA participants with CAC ≥ 100 had favorable risk/benefit estimations for aspirin use while participants with zero CAC were estimated to receive net harm from aspirin.
Aspirin; imaging; prevention; coronary disease
We sought to evaluate the impact of coronary artery calcium (CAC) burden and regional distribution on the need for and type of future coronary revascularization (percutaneous [PCI] vs. surgical [CABG]) among asymptomatic individuals.
The need for coronary revascularization and the chosen mode of revascularization are thought to be a function of disease burden and anatomic distribution. The association between the baseline burden and regional distribution of CAC and the risk and type of future coronary revascularization remains unknown.
6,540 MESA participants (individuals aged 45-84 years, free of known baseline cardiovascular disease) with vessel-specific CAC measurement were followed for median 8.5 (7.7 – 8.6) years. Annualized rates and multivariable adjusted hazard ratios for revascularization and revascularization type were analyzed according to CAC score category, number of vessels with CAC (0-4, including the left main), and by involvement of individual coronary arteries.
A total of 265 revascularizations (4.2%) occurred during follow-up, and 206 (78% of total) were preceded by adjudicated symptoms. Revascularization was uncommon when CAC=0 (0.6%), with graded increase over both rising CAC burden and increasingly diffuse CAC distribution. The revascularization rate per 1,000 person-years for CAC 1-100, 101-400, and >400 was 4.9, 11.7 and 25.4; for 1, 2, 3, and 4 vessels with CAC the rates were 3.0, 8.0, 16.1, and 24.8. In multivariable models adjusting for CAC score, number of vessels with CAC remained predictive of mode of revascularization. Independent predictors of CABG vs. PCI included 3 or 4 vessel CAC, higher CAC burden, and involvement of the left main. Risk for CABG was extremely low with <3 vessel baseline CAC. Results were similar when considering only symptom-driven revascularizations.
In this multi-ethnic cohort of asymptomatic individuals, baseline CAC was highly predictive of future coronary revascularization procedures, with measures of CAC burden and distribution each independently predicting need for PCI vs. CABG over 8.5 year follow-up.
cardiac CT; coronary artery calcium; coronary artery disease; revacularization
The development and exacerbation of many psychiatric and neurologic conditions are associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis as measured by aberrant levels of cortisol secretion. Here we report on the relationship between the amplitude of diurnal cortisol secretion, measured across 3 typical days in 18 healthy individuals, and blood oxygen level dependant (BOLD) response in limbic fear/stress circuits, elicited by in-scanner presentation of emotionally negative stimuli, specifically, images of the World Trade Center (WTC) attack. Results indicate that subjects who secrete a greater amplitude of cortisol diurnally demonstrate less brain activation in limbic regions, including the amygdala and hippocampus/parahippocampus, and hypothalamus during exposure to traumatic WTC-related images. Such initial findings can begin to link our understanding, in humans, of the relationship between the diurnal amplitude of a hormone integral to the stress response, and those neuroanatomical regions that are implicated as both modulating and being modulated by that response.
Amygdala; Medial prefrontal cortex; Hippocampus; Cortisol; Neuroimaging; Stress
Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer’s disease (AD). Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. It remains unknown, however, if O-GlcNAc can influence the formation of amyloid plaques in the presence of tau pathology.
We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques.
This study indicates that increased O-GlcNAc can influence β-amyloid pathology in the presence of tau pathology. The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease.
tau; Amyloid precursor protein; O-GlcNAc; Thiamet-G
Background. Protease inhibitor (PI)–based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels.
Methods. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women.
Results. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile.
Conclusions. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes.
progesterone; protease inhibitors; lopinavir; small for gestational age; low birth weight; HIV; pregnancy
Most functional neuroimaging studies of panic disorder (PD) have focused on the resting state, and have explored PD in relation to healthy controls rather than in relation to other anxiety disorders. Here, PD patients, Posttraumatic stress disorder (PTSD) patients, and healthy control subjects were studied with functional magnetic resonance imaging utilizing an instructed fear conditioning paradigm incorporating both Threat and Safe conditions. Relative to PTSD and control subjects, PD patients demonstrated significantly less activation to the Threat condition and increased activity to the Safe condition in the subgenual cingulate, ventral striatum and extended amygdala, as well as in midbrain periaquaeductal grey, suggesting abnormal reactivity in this key region for fear expression. PTSD subjects failed to show the temporal pattern of activity decrease found in control subjects.
anxiety disorders; panic disorder; posttraumatic stress disorder; subgenual cingulate cortex; ventral striatum; extended amygdala; brainstem; neuroimaging
Obesity demonstrates a direct relation with cardiovascular risk and all-cause mortality, while cardiorespiratory fitness demonstrates an inverse relation. In clinical practice, several cardiometabolic (“CM”) risk factors are commonly measured to gauge cardiovascular risk yet the interaction between fitness and obesity with regard CM risk has not been fully explored. We studied 2,634 Brazilian adults referred for an employer-sponsored heath exam. Obesity was defined as BMI >30 kg/m2 or waist circumference > 102cm (men) or >88cm (women) when BMI 25–30kg/m2. Fitness was quantified by stage achieved on an Ellestad treadmill stress test, with those completing stage 4 considered fit. Hepatic steatosis was determined by ultrasound. We compared CM risk factors after stratifying patients into 4 groups: fit/normal weight, fit/obese, unfit/normal weight & unfit/obese. Approximately 22% of patients were obese; 12% were unfit. Fitness and obesity were moderately correlated (ρ=0.38–50). 6.5% of the sample was unfit/normal weight, and 16% fit/obese. In overweight and obese patients, fitness was negatively associated with CM risk (p<0.01 for all values). In fit patients, increasing BMI was positively associated with CM risk (p<0.01 for all values). In instances of discordance between fitness and obesity, obesity was the stronger determinant of CM risk. Fitness and obesity are independently associated with CM risk. The effects of fitness and obesity are additive but obesity is more strongly associated with CM risk when fitness and obesity are discordant. These findings underscore the need for weight loss in obese individuals and suggest an unmeasured benefit of fitness.
fitness; obesity; metabolic syndrome; liver fat; inflammation
Zimbabwe underwent a socioeconomic crisis and resultant increase in food insecurity in 2008–9. The impact of the crisis on Tuberculosis (TB) incidence is unknown.
Prospective databases from two mission hospitals, which were geographically widely separated, and remained open during the crisis, were reviewed.
At the Howard Hospital (HH) in northern Zimbabwe, TB incidence increased 35% in 2008 from baseline rates in 2003–2007 (p<0.01) and remained at that level in 2009. Murambinda Hospital (MH) in Eastern Zimbabwe also demonstrated a 29% rise in TB incidence from 2007 to 2008 (p<0.01) and remained at that level in 2009. Data collected post-crisis at HH showed a decrease of 33% in TB incidence between 2009 to 2010 (p<0.001) and 2010/2011 TB incidence remained below that of the crisis years of 2008/2009 (p<0.01). Antenatal clinic HIV seroprevalence at HH decreased between 2001(23%) to 2011(11%) (p<0.001). Seasonality of TB incidence was analyzed at both MH and HH. There was a higher TB incidence in the dry season when food is least available (September-November) compared to post harvest (April-June) (p<0.001).
This study suggests that an epidemic of TB mirrored socioeconomic collapse and recovery in Zimbabwe. The seasonal data suggests that food security may have been associated with TB incidence both annually and during the crisis in this high HIV prevalence country.
The A3 adenosine receptor (A3AR) is overexpressed in the tumor and in the peripheral blood mononuclear cells of patients with hepatocellular carcinoma (HCC). The orally active drug candidate CF102, an A3AR agonist, induces apoptosis of HCC cells via deregulation of the Wnt signaling pathway. In this open label phase I/II trial, the safety and clinical effects of CF102 were assessed in patients with advanced unresectable HCC.
The primary objectives of this trial were to examine the safety and pharmacokinetic (PK) behavior of CF102 given orally (1, 5, and 25 mg BID) in 28-day cycles. Evaluation of anti-tumor effects and the utilization of A3AR as a biological predictive marker of response to CF102 were the secondary objectives.
Eighteen patients received CF102—six at each dose level. No serious drug-related adverse events or dose-limiting toxicities were observed. CF102 demonstrated good oral bioavailability and linear PK behavior. Median overall survival in the study population, 67% of whom had received prior sorafenib, was 7.8 months, and for Child Pugh B patients (28%) it was 8.1 months. Stable disease by RECIST was observed in four patients for at least 4 months. CF102 maintained liver function over a 6-month period. A correlation between receptor overexpression levels at baseline and patients' overall survival was found. One of the patients who presented with skin nodules that were biopsy-proven to be HCC metastases prior to the trial showed complete metastasis regression during three months of treatment with CF102.
CF102 is safe and well-tolerated, showing favorable PK characteristics in Child Pugh A and B HCC patients, justifying further clinical development.
Increased uric acid (UA) is strongly linked to cardiovascular disease. However, the independent role of UA is still debated because it is associated with several cardiovascular risk factors including obesity and metabolic syndrome. This study assessed the association of UA with increased high-sensitivity C-reactive protein (hs-CRP), increased ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL), sonographically detected hepatic steatosis, and their clustering in the presence and absence of obesity and metabolic syndrome. We evaluated 3,518 employed subjects without clinical cardiovascular disease from November 2008 through July 2010. Prevalence of hs-CRP ≥3 mg/L was 19%, that of TG/HDL ≥3 was 44%, and that of hepatic steatosis was 43%. In multivariable logistic regression after adjusting for traditional cardiovascular risk factors and confounders, highest versus lowest UA quartile was associated with hs-CRP ≥3 mg/L (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.01 to 2.28, p = 0.04), TG/HDL ≥3 (OR 3.29, 95% CI 2.36 to 4.60, p <0.001), and hepatic steatosis (OR 3.10, 95% CI 2.22 to 4.32, p <0.001) independently of obesity and metabolic syndrome. Association of UA with hs-CRP ≥3 mg/L became nonsignificant in analyses stratified by obesity. Ascending UA quartiles compared to the lowest UA quartile demonstrated a graded increase in the odds of having 2 or 3 of these risk conditions and a successive decrease in the odds of having none. In conclusion, high UA levels were associated with increased TG/HDL and hepatic steatosis independently of metabolic syndrome and obesity and with increased hs-CRP independently of metabolic syndrome.
Rationale: Histologic data from fatal cases suggest that extreme prematurity results in persisting alveolar damage. However, there is new evidence that human alveolarization might continue throughout childhood and could contribute to alveolar repair.
Objectives: To examine whether alveolar damage in extreme-preterm survivors persists into late childhood, we compared alveolar dimensions between schoolchildren born term and preterm, using hyperpolarized helium-3 magnetic resonance.
Methods: We recruited schoolchildren aged 10–14 years stratified by gestational age at birth (weeks) to four groups: (1) term-born (37–42 wk; n = 61); (2) mild preterm (32–36 wk; n = 21); (3) extreme preterm (<32 wk, not oxygen dependent at 4 wk; n = 19); and (4) extreme preterm with chronic lung disease (<32 wk and oxygen dependent beyond 4 wk; n = 18). We measured lung function using spirometry and plethysmography. Apparent diffusion coefficient, a surrogate for average alveolar dimensions, was measured by helium-3 magnetic resonance.
Measurements and Main Results: The two extreme preterm groups had a lower FEV1 (P = 0.017) compared with term-born and mild preterm children. Apparent diffusion coefficient was 0.092 cm2/second (95% confidence interval, 0.089–0.095) in the term group. Corresponding values were 0.096 (0.091–0.101), 0.090 (0085–0.095), and 0.089 (0.083–0.094) in the mild preterm and two extreme preterm groups, respectively, implying comparable alveolar dimensions across all groups. Results did not change after controlling for anthropometric variables and potential confounders.
Conclusions: Alveolar size at school age was similar in survivors of extreme prematurity and term-born children. Because extreme preterm birth is associated with deranged alveolar structure in infancy, the most likely explanation for our finding is catch-up alveolarization.
alveolar structure; lung acinus; bronchopulmonary dysplasia; neonatal chronic lung disease
The role of tau in axonal transport disruption during early-stage Alzheimer disease is controversial. The amyloid-β oligomers markedly impair BDNF transport in primary wild-type and tau-knockout neurons. This occurs by nonexcitotoxic activation of calcineurin, and inhibition of calcineurin rescues transport defects independent of tau.
Disruption of fast axonal transport (FAT) is an early pathological event in Alzheimer's disease (AD). Soluble amyloid-β oligomers (AβOs), increasingly recognized as proximal neurotoxins in AD, impair organelle transport in cultured neurons and transgenic mouse models. AβOs also stimulate hyperphosphorylation of the axonal microtubule-associated protein, tau. However, the role of tau in FAT disruption is controversial. Here we show that AβOs reduce vesicular transport of brain-derived neurotrophic factor (BDNF) in hippocampal neurons from both wild-type and tau-knockout mice, indicating that tau is not required for transport disruption. FAT inhibition is not accompanied by microtubule destabilization or neuronal death. Significantly, inhibition of calcineurin (CaN), a calcium-dependent phosphatase implicated in AD pathogenesis, rescues BDNF transport. Moreover, inhibition of protein phosphatase 1 and glycogen synthase kinase 3β, downstream targets of CaN, prevents BDNF transport defects induced by AβOs. We further show that AβOs induce CaN activation through nonexcitotoxic calcium signaling. Results implicate CaN in FAT regulation and demonstrate that tau is not required for AβO-induced BDNF transport disruption.
To test whether dexamethasone (DEX) treatment of pregnancies at risk for congenital adrenal hyperplasia (CAH) impairs cognitive functioning in the offspring.
Observational follow-up of prenatally DEX-exposed offspring and controls.
Study 1 included 140 children age 5-12 years: 67 DEX-exposed (long-term: 8 CAH girls) and 73 unexposed (with 15 CAH girls). Study 2 included 20 participants age 11-24 years: 7 DEX-exposed (long-term: 1 CAH woman) and 13 unexposed (with 4 CAH women). Neuropsychological testing was done in hospital settings or patients' homes. Data analysis aimed at maximizing detection of effects of DEX exposure.
The vast majority of group comparisons were not marginally or conventionally significant. The few significant findings on short-term prenatal DEX exposure suggested more positive than adverse outcomes. By contrast, the few significant findings in females with CAH and long-term DEX exposure indicated slower mental processing than in controls on several neuropsychological variables, although partial correlations of DEX-exposure duration with cognitive outcome did not corroborate this association.
Our studies do not replicate a previously reported adverse effect of short-term prenatal DEX exposure on working memory, while our findings on cognitive function in CAH girls with long-term DEX exposure contribute to concerns about potentially adverse cognitive aftereffects of such exposure. Yet, our studies are not definitive, and replications in larger samples are required.
To explore the safety and efficacy of CF101, an A3 adenosine receptor agonist, in patients with moderate-to-severe dry eye syndrome
Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study.
68 patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group.
Patients were orally treated with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week post-treatment observation.
Main Outcome Measures
an improvement of >25% over baseline at week 12 in one of the following parameters: (a) tear break-up time (BUT); (b) superficial punctate keratitis assessed by fluorescein staining (FS); (c) Schirmer tear test 1 (ST1).
clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements and monitoring of adverse events.
A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group.
CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate-to-severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry eye syndrome.
It is unclear whether coronary artery calcium (CAC) is effective for risk stratifying patients with diabetes in whom treatment decisions are uncertain.
RESEARCH DESIGN AND METHODS
Of 44,052 asymptomatic individuals referred for CAC testing, we studied 2,384 individuals with diabetes. Subjects were followed for a mean of 5.6 ± 2.6 years for the end point of all-cause mortality.
There were 162 deaths (6.8%) in the population. CAC was a strong predictor of mortality across age-groups (age <50, 50–59, ≥60), sex, and risk factor burden (0 vs. ≥1 additional risk factor). In individuals without a clear indication for aspirin per current guidelines, CAC stratified risk, identifying patients above and below the 10% risk threshold of presumed aspirin benefit.
CAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention.
A short prodrome in children is associated with more severe disease and increased risk for death.
Encephalitis; arbovirus; Eastern equine encephalitis; Eastern equine encephalitis virus; pediatric; Massachusetts; New Hampshire; children; viruses
Fecal microbiome transplantation by low-volume enema is an effective, safe, and inexpensive alternative to antibiotic therapy for patients with chronic relapsing Clostridium difficile infection (CDI). We explored the microbial diversity of pre- and posttransplant stool specimens from CDI patients (n = 6) using deep sequencing of the 16S rRNA gene. While interindividual variability in microbiota change occurs with fecal transplantation and vancomycin exposure, in this pilot study we note that clinical cure of CDI is associated with an increase in diversity and richness. Genus- and species-level analysis may reveal a cocktail of microorganisms or products thereof that will ultimately be used as a probiotic to treat CDI.
Antibiotic-associated diarrhea (AAD) due to Clostridium difficile is a widespread phenomenon in hospitals today. Despite the use of antibiotics, up to 30% of patients are unable to clear the infection and suffer recurrent bouts of diarrheal disease. As a result, clinicians have resorted to fecal microbiome transplantation (FT). Donor stool for this type of therapy is typically obtained from a spouse or close relative and thoroughly tested for various pathogenic microorganisms prior to infusion. Anecdotal reports suggest a very high success rate of FT in patients who fail antibiotic treatment (>90%). We used deep-sequencing technology to explore the human microbial diversity in patients with Clostridium difficile infection (CDI) disease after FT. Genus- and species-level analysis revealed a cocktail of microorganisms in the Bacteroidetes and Firmicutes phyla that may ultimately be used as a probiotic to treat CDI.
Rationale: The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals.
Objectives: We reexamined the current hypothesis using helium-3 (3He) magnetic resonance (MR) to assess alveolar size noninvasively between 7 and 21 years, during which lung volume nearly quadruples. If new alveolarization does not occur, alveolar size should increase to the same extent.
Methods: Lung volumes were measured by spirometry and plethysmography in 109 healthy subjects aged 7–21 years. Using 3HeMR we determined two independent measures of peripheral airspace dimensions: apparent diffusion coefficient (ADC) of 3He at FRC (n = 109), and average diffusion distance of helium (Xrms¯) by q-space analysis (n = 46). We compared the change in these parameters with lung growth against a model of lung expansion with no new alveolarization.
Measurements and Main Results: ADC increased by 0.19% for every 1% increment in FRC (95% confidence interval [CI], 0.13–0.25), whereas the expected change in the absence of neoalveolarization is 0.41% (95% CI, 0.31–0.52). Similarly, increase of (Xrms¯) with FRC was significantly less than the predicted increase in the absence of neoalveolarization. The number of alveoli is estimated to increase 1.94-fold (95% CI, 1.64–2.30) across the age range studied.
Conclusions: Our observations are best explained by postulating that the lungs grow partly by neoalveolarization throughout childhood and adolescence. This has important implications: developing lungs have the potential to recover from early life insults and respond to emerging alveolar therapies. Conversely, drugs, diseases, or environmental exposures could adversely affect alveolarization throughout childhood.
growth and development; lung development; alveolarization
The purpose of this study is to describe the patterns of hospitalization for depression in the year following delivery in relation to social, demographic, and behavioral characteristics.
Data on fetal deliveries were linked to hospitalizations for depression over the subsequent year in order to describe the frequency and patterns of hospitalized postpartum depression among 2,355,886 deliveries in New York State from 1995 – 2004. We identified “definite postpartum depression” based on ICD codes indicative of “mental disorders specific to pregnancy,” and “possible postpartum depression” by ICD codes for hospitalization with any depressive disorders.
In New York State, we identified 1,363 women (5.8 per 10,000) who were hospitalized with definite postpartum depression, and 6,041 women (25.6 per 10,000) with possible postpartum depression, with lower risks in the New York City area. Postpartum depression was more common in later years and among mothers who were older, Black, smokers, lacking private insurance, and with multiple gestations, and was rarer among Asians. For possible postpartum depression, socioeconomic gradients were enhanced.
Risk of hospitalized postpartum depression is strongly associated with socioeconomic deprivation and varies markedly by ethnicity, with direct implications for screening and health services, also providing suggestions for etiologic studies.
postpartum depression; pregnancy; ethnicity