The Emerging Role of the Gut-Brain-Microbiota Axis in Neurodevelopmental Disorders.

Autism spectrum disorder (ASD; autism) is a prevalent neurodevelopmental disorder associated with changes in gut-brain axis communication. Gastrointestinal (GI) symptoms are experienced by a large proportion of individuals diagnosed with autism. Several mutations associated with autism modify cellular communication via neuronal synapses. It has been suggested that modifications to the enteric nervous system, an intrinsic nervous system of the GI tract, could contribute to GI dysfunction. Changes in gut motility, permeability, and the mucosal barrier as well as shifts in the large population of microbes inhabiting the GI tract could contribute to GI symptoms. Preclinical research has demonstrated that mice expressing the well-studied R451C missense mutation in Nlgn3 gene, which encodes cell adhesion protein neuroligin-3 at neuronal synapses, exhibit GI dysfunction. Specifically, NL3R451C mice show altered colonic motility and faster small intestinal transit. As well as dysmotility, macrophages located within the gut-associated lymphoid tissue of the NL3R451C mouse caecum show altered morphology, suggesting that neuro-inflammation pathways are modified in this model. Interestingly, NL3R451C mice maintained in a shared environment demonstrate fecal microbial dysbiosis indicating a role for the nervous system in regulating gut microbial populations. To better understand host-microbe interactions, further clarification and comparison of clinical and animal model profiles of dysbiosis should be obtained, which in turn will provide better insights into the efforts taken to design personalized microbial therapies. In addition to changes in neurophysiological measures, the mucosal component of the GI barrier may contribute to GI dysfunction more broadly in individuals diagnosed with a wide range of neurological disorders. As the study of GI dysfunction advances to encompass multiple components of the gut-brain-microbiota axis, findings will help understand future directions such as microbiome engineering and optimisation of the mucosal barrier for health.

Assessment of home care aides' respiratory exposure to total volatile organic compounds and chlorine during simulated bathroom cleaning: An experimental design with conventional and "green" products.

Home care (HC) aide visits to clients' homes often involve cleaning and disinfecting (C&D) bathrooms. Some ingredients in C&D household products are associated with respiratory illness, including sodium hypochlorite (bleach) and quaternary ammonium compounds (quats). "Green" products may be safer for the environment, however there are limited quantitative evaluations of their respiratory risks. This study assessed airborne concentrations and time profiles of total volatile organic compounds (TVOC) and chlorine generated during typical bathroom cleaning performed by aides using conventional and green products. Aides performed cleaning tasks in a simulated residential bathroom constructed in an environmental air sampling laboratory. A balanced experimental design involved each aide coming to the lab for four visits during which she performed two 20-min cleaning sessions using one of three C&D products (bleach-based, 1-5% sodium hypochlorite by weight; quats-based, 0.1-1% by weight quaternary ammonium compounds; and "green," 0.05% by weight thymol, a component of botanical thyme oil) or distilled water as a control. TVOC and chlorine direct reading instruments were attached to aides with sample inlets located in the breathing zone. Ten-second averages of TVOC and chlorine gas concentrations and instantaneous peak concentrations were recorded for the sessions' duration. TVOC concentrations by methods of C&D application (spraying, streaming, wiping) also were evaluated. The study completed 169 air sampling sessions with 22 aides. The quats-based product generated more than twice the average TVOC concentrations (mean = 1,210 ppb) than the bleach-based (mean = 593 ppb) or green (mean = 498 ppb) products. Each product generated TVOC concentrations that rose rapidly within the first few minutes of application. Spraying produced the highest TVOC exposures, wiping the lowest. Thirteen aides (65%) experienced peak chlorine exposures above the OSHA PEL ceiling limit (1 ppm) when using the bleach-based product. HC aides may experience respiratory hazards from use of conventional or green C&D products formulated with bleach or other respiratory irritants and sprayed in small, poorly ventilated spaces typical of bathrooms. Spraying should be avoided.

Temperature-controlled laminar airflow (TLA) device in the treatment of children with severe atopic eczema: Open-label, proof-of-concept study.

BACKGROUND: Children with severe, persistent atopic eczema (AE) have limited treatment options, often requiring systemic immunosuppression. OBJECTIVE: To evaluate the effect of the temperature-controlled laminar airflow (TLA) treatment in children/adolescents with severe AE. METHODS: We recruited 15 children aged 2-16 years with long-standing, severe AE and sensitization to ≥1 perennial inhalant allergen. Run-in period of 6-10 weeks (3 visits) was followed by 12-month treatment with overnight TLA (Airsonett® , Sweden). The primary outcome was eczema severity (SCORAD-Index and Investigator Global Assessment-IGA). Secondary outcomes included child/family dermatology quality of life and family impact questionnaires (CDQLI, FDQLI, DFI), patient-oriented eczema measure (POEM), medication requirements and healthcare contacts. The study is registered as ISRCTN65865773. RESULTS: There was a significant reduction in AE severity ascertained by SCORAD and IGA during the 12-month intervention period (P < .001). SCORAD was reduced from a median of 34.9 [interquartile range 28.75-45.15] at Baseline to 17.2 [12.95-32.3] at the final visit, and IGA improved significantly from 4 [3-4] to 2 [1-3]. We observed a significant improvement in FDQLI (16.0 [12.25-19.0] to 12 [8-18], P = .023) and DFI (P = .011), but not CDQLI or POEM. Compared to 6-month period prior to enrolment, there was a significant reduction at six months after the start of the intervention in potent topical corticosteroids (P = .033). The exploratory cluster analysis revealed two strongly divergent patterns of response, with 9 patients classified as responders, and 6 as non-responders. CONCLUSION AND CLINICAL RELEVANCE: Addition of TLA device to standard pharmacological treatment may be an effective add-on to the management of difficult-to-control AE.

The impact of housing type on low-income asthmatic children receiving multifaceted home interventions.

OBJECTIVES: This study sought to evaluate whether government-assisted vs market-rate housing type influences the frequency of asthma symptoms or the quality of life scores among low-income urban children. In addition, the study sought to evaluate whether housing type influenced the success of in-home environmental and educational interventions in improving children's asthma symptoms or quality of life scores. STUDY DESIGN: This was a before-and-after intervention design. Comprehensive health and environmental assessments and subsequent interventions were completed in 176 low-income households with 257 asthmatic children living in government-assisted housing and market-rate housing in Lowell, Massachusetts. METHODS: We collected environmental and health data with questionnaires at a baseline and a 12-month follow-up visit using the Children's Health Survey for Asthma and a walk-through environmental checklist. Education, tools to remove asthma triggers from the home, and home repairs and remediation were included in the interventions. RESULTS: As in other studies of multifaceted home interventions, there were significant improvements in all asthma symptoms, reductions in healthcare utilization related to asthma, and improvements in quality of life domains for children in both housing types. Environmental indices also improved from the baseline to the final assessment for both housing types. However, the housing type was an important factor in predicting a child's asthma status at the start of the study, with children living in government-assisted housing having significantly better physical health scores (76.8 of 100) and family emotional health scores (74.8 of 100) and fewer overnight hospital stays (mean of 0.02 in the previous 4 weeks) than children living in market-rate housing (67.6, 71.6, and 0.06, respectively). Examination of the change in the health status over the 1-year study period found that children living in market-rate housing had significantly larger reductions in the number of asthma attacks (0.43 in the previous 4 weeks versus 0.24 in assisted housing) and overnight hospital stays (0.06 in the previous 4 weeks versus 0.01 in assisted housing) and larger improvements in physical health quality of life scores (54% improved versus 25.5% in assisted housing). CONCLUSIONS: Public assistance for low-income urban housing is associated with better health among children with asthma, and may influence the impact the in-home interventions have on health outcomes because children in market-rate housing have more prospects for improvement in their asthma-related health.

The effectiveness of three home products in cleaning and disinfection of Staphylococcus aureus and Escherichia coli on home environmental surfaces.

AIMS: The objectives of this study were to investigate three products for: (i) cleaning effectiveness on two common household surfaces, and (ii) disinfection effectiveness against two common bacteria. Products included conventional ('bleach'), environmentally preferable (EP), do-it-yourself (DIY: distilled white vinegar, club soda, tea tree oil), 24-h old DIY, and individual DIY components in dilution. METHODS AND RESULTS: For cleaning ceramic, no product was effective (≥85% removal of Hucker's soil), however, DIY performed better than EP and bleach. On stainless, only DIY failed to meet the standard. For disinfection, bleach and EP achieved ≥5·00 log10 reductions under all conditions. DIY and components were more active against Escherichia coli than Staphylococcus aureus but only fresh DIY and 50% vinegar achieved ≥5·00 log10 reductions. CONCLUSIONS: EP is an effective alternative to bleach. DIY may be an adequate alternative for cleaning ceramic and for household use, where complete elimination of micro-organisms is unnecessary; however, it must be freshly prepared each day. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of performance of purportedly safer alternatives for both cleaning and disinfection for use in home health care. The EP product and DIY are potential alternatives for some household uses.

Effect of a novel temperature-controlled laminar airflow device on personal breathing zone aeroallergen exposure.

Temperature-controlled laminar airflow improves symptoms in atopic asthmatics, but its effects on personal allergen exposure are unknown. We aimed to evaluate its effects on personal cat allergen and particulate exposures in a simulated bedroom environment. Five healthy volunteers lay under an active and an inactive temperature-controlled laminar airflow device for 175 min, in a simulated bedroom containing bedding from a cat owner. Total airborne particles (≥0.5 - ≥10 µm diameter) were quantified with a laser particle counter. Airborne allergen was sampled with Institute of Occupational Medicine filters. Inhaled exposure was sampled with nasal air samplers. Allergen-containing particles were quantified by immunoassay. Treatment reduced total airborne particles (>0.5 µm diameter) by >99% (P < 0.001) and reduced airborne allergen concentration within the breathing zone (ratio of median counts = 30, P = 0.043). Treatment reduced inhaled allergen (ratio of median counts = 7, P = 0.043). Treatment was not associated with a change in airborne allergen concentration outside of the breathing zone (P = 0.160). Temperature-controlled laminar airflow treatment of individuals in an allergen-rich experimental environment results in significant reductions in breathing zone allergenic and non-allergenic particle exposure, and in inhaled cat allergen exposure. These findings may explain the clinical benefits of temperature-controlled laminar airflow.

Developments in the field of allergy in 2013 through the eyes of Clinical and Experimental Allergy.

2013 was another exciting year for allergy in general and Clinical and Experimental Allergy in particular. In the field of asthma and rhinitis, there continued to be a focus on heterogeneity and phenotypes with increasing use of biostatistical techniques to determine clusters of similar populations. Obesity- and aspirin-associated disease are intriguing associations with asthma which were explored in a number of papers. We published a number of excellent papers on mechanisms of airway inflammation and how this relates to physiology, pathology, genetics and biomarkers in both human and experimental model systems. In terms of mechanisms, there is less on individual cell types in allergic disease at the moment, but the immunology of allergic disease continued to fascinate our authors. Another area that was popular both in the mechanisms and in the epidemiology sections was early life events and how these lead to allergic disease, with an increasing focus on the role of the microbiome and how this influences immune tolerance. In the clinical allergy section, oral immunotherapy for food allergy is clearly a major topic of interest at the moment as was in vitro testing to distinguish between sensitization and allergic disease. There was less on inhalant allergy this year, but a good representation from the drug allergy community including some interesting work on non-IgE-mediated mechanisms. In the allergen section, important new allergens continue to be discovered, but the major focus as in the last couple of years was on working out how component-resolved approaches can improve diagnosis and management of food and venom allergy.

University students' notebook computer use: lessons learned using e-diaries to report musculoskeletal discomfort.

The objective of this pilot study was to identify if notebook accessories (ergonomic chair, desktop monitor and notebook riser) combined with a wireless keyboard, mouse and participatory ergonomics training would have the greatest impact on reducing self-reported upper extremity musculoskeletal discomfort in university students. In addition to pre-post computing and health surveys, the Ecological Momentary Assessment was used to capture change in discomfort over time using a personal digital assistant (PDA) as the e-diary. The PDA was programmed with a survey containing 45 questions. Four groups of university students were randomised to either intervention (three external computer accessories) or to control. Participants reported less discomfort with the ergonomic chair and notebook riser based on the pre-post survey data and the e-diary/PDA ANOVA analysis. However, the PDA data, adjusted for the effect of hours per day of computer use, showed no benefit of the chair and limited benefit from the riser. Statement of Relevance:University students' use of notebook computers has increased. This study found evidence of a positive effect of an adjustable chair or notebook riser when combined with ergonomic training on reducing discomfort. Daily notebook computer use of 4 h was confirmed as a risk factor. Without some form of ergonomic intervention, these students are likely to enter the workforce with poor computing habits, which places them on the road to future injuries as technology continues to play a dominant role in their lives.

Altered Processing of Complex Visual Stimuli in Patients with Postconcussive Visual Motion Sensitivity.

BACKGROUND AND PURPOSE: Vestibular symptoms are common after concussion. Vestibular Ocular Motor Screening identifies vestibular impairment, including postconcussive visual motion sensitivity, though the underlying functional brain alterations are not defined. We hypothesized that alterations in multisensory processing are responsible for postconcussive visual motion sensitivity, are detectable on fMRI, and correlate with symptom severity. MATERIALS AND METHODS: Twelve patients with subacute postconcussive visual motion sensitivity and 10 healthy control subjects underwent vestibular testing and a novel fMRI visual-vestibular paradigm including 30-second "neutral" or "provocative" videos. The presence of symptoms/intensity was rated immediately after each video. fMRI group-level analysis was performed for a "provocative-neutral" condition. Z-statistic images were nonparametrically thresholded using clusters determined by Z > 2.3 and a corrected cluster significance threshold of P = .05. Symptoms assessed on Vestibular Ocular Motor Screening were correlated with fMRI mean parameter estimates using Pearson correlation coefficients. RESULTS: Subjects with postconcussive visual motion sensitivity had significantly more Vestibular Ocular Motor Screening abnormalities and increased symptoms while viewing provocative videos. While robust mean activation in the primary and secondary visual areas, the parietal lobe, parietoinsular vestibular cortex, and cingulate gyrus was seen in both groups, selective increased activation was seen in subjects with postconcussive visual motion sensitivity in the primary vestibular/adjacent cortex and inferior frontal gyrus, which are putative multisensory visual-vestibular processing centers. Moderate-to-strong correlations were found between Vestibular Ocular Motor Screening scores and fMRI activation in the left frontal eye field, left middle temporal visual area, and right posterior hippocampus. CONCLUSIONS: Increased fMRI brain activation in visual-vestibular multisensory processing regions is selectively seen in patients with postconcussive visual motion sensitivity and is correlated with Vestibular Ocular Motor Screening symptom severity, suggesting that increased visual input weighting into the vestibular network may underlie postconcussive visual motion sensitivity.

National income, self-reported wheezing and asthma diagnosis from the World Health Survey.

The aims of this study were to quantify and describe the variations in respiratory symptoms and diagnosis prevalence across regions of the world according to national income. In 2002 and 2003, the World Health Organization implemented the World Health Survey (WHS), which used a standardised survey instrument to compile comprehensive baseline information on health and healthcare expenditure. We analysed the WHS data to assess the global patterns of self-reported wheeze and doctor-diagnosed asthma, two commonly reported measures of respiratory health. In total there were 308,218 participants with complete records, from 64 countries. The weighted mean age of the survey population was 43 yrs. Global prevalence of current wheezing symptoms ranged from 2.4% in Vietnam to 24% in Brazil; the prevalence of diagnosed asthma ranged from 1.8% in Vietnam to 32.8% in Australia. Overall, the prevalence of symptoms and diagnosis showed a U-shaped pattern with the largest prevalence reported in low- and high-income countries. The smallest prevalence was consistently found in middle-income countries. These WHS analyses have provided global prevalence estimates of wheeze and doctor-diagnosed asthma using data gathered simultaneously and consistently across six continents. These findings support the need for continued global respiratory illness surveillance for disease prevention, health policy and management.

Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum.

In a study of recombinant proteins that might be useful in developing a vaccine against malaria, synthetic peptides from the circumsporozoite (CS) protein of Plasmodium falciparum were found to be immunogenic for mice and rabbits. Antibody to peptides from the repeating region of the CS protein recognized native CS protein and blocked sporozoite invasion of human hepatoma cells in vitro. Antibodies to peptides from regions I and II had no biologic activity, although antibody to region I recognized processed CS protein by Western blot analysis. These data support the feasibility of developing a vaccine against the sporozoite stage of the malaria parasite by using synthetic peptides of the repeating region of the CS protein conjugated to a carrier protein.

Antibiotic resistant bacteria in wastewater processed by the Metropolitan Water Reclamation District of Greater Chicago system.

The Metropolitan Water Reclamation District of Greater Chicago (District) initiated a research study to determine the total numbers and percentages of antibiotic resistant fecal coliform (FC) bacteria in raw sewage (RS) entering and final effluents (FE) discharged from its seven Water Reclamation Plants (WRPs). The density of FC was determined on m-FC agar containing ampicillin (ampR-16 microg/ml), gentamycin (genR-8 microg/ml), tetracycline (tetR-8 microg/ml), or all three antibiotics. The study was primarily undertaken to determine whether secondary sewage treatment at the District WRPs adequately reduces the numbers and percentages of FC(ampR), FC(tetR), FC(genR), FC(amp/tet/genR) in the FE. The numbers of ampR, tetR, genR, and amp/tet/genR FC observed in RS ranged from 2.0 x 10(5) to 1.1 x 10(7), 9.5 x 10(4) to 2.2 x 10(6), 95 to 1.5 x 10(4) and 90 to 9.5 x 10(3) per 100 mL, respectively. Secondary sewage treatment without disinfection was shown to reduce the number of antibiotic resistant FC by two-three orders of magnitude. The numbers of FC(ampR), FC(tetR), FC(genR), and FC(amp/tet/genR) observed in non-disinfected FE ranged from 2.0 x 10(2) to 6.4 x 10(3), 2.2 x 10(2) to 4.1 x 10(3), 9 to <20 and 9 to <20 per 100 mL, respectively. The relative percentages of antibiotic resistant FC observed in FE followed the same trend observed in RS: FC(ampR) > FC(tetR) > FC(genR) > FC(amp/tet/genR). Only one FC(amp/tet/genR) bacteria was found in this study indicating that multiple-antibiotic resistant FC was virtually eliminated by secondary sewage treatment. The results of multivariate regression analysis showed that the percentages of antibiotic resistant FC in the FE from all seven District WRPs were lower than the percentages of these organisms in RS (p<0.01). These results support the conclusion that secondary sewage treatment in the District effectively reduces the number of antibiotic resistant FC and that the environments of the District's seven WRPs are not conducive to the propagation or survival of antibiotic resistant fecal coliform bacteria.

Dry and wet weather microbial characterization of the Chicago area waterway system.

The Chicago Area Waterway System (CAWS) is a man-made channel, which serves the Chicago area for the drainage of urban storm water and the conveyance of secondary treated effluent from the Metropolitan Water Reclamation District of Greater Chicago's (District) North Side, Stickney and Calumet water reclamation plants (WRPs). A microbial characterization of the CAWS upstream and downstream of the WRPs and from the WRP outfall was initiated by collecting dry and wet weather samples and analyzing for indicators and pathogens. During dry weather, indicator bacteria (fecal coliform [FC], E. coli [EC], enterococci [EN]) were the most abundant microbial species detected in the CAWS compared to pathogens (Salmonella spp [SA], enteric viruses [EV], adenovirus [AV], norovirus [NV] and Giardia and Cryptosporidium). Pseudomonas aeruginosa [PA] levels in the outfall samples were either lower or equivalent to the CAWS. The wet weather samples had a higher frequency of detection of indicator bacteria and pathogens compared to dry weather samples. Overall, the concentrations of pathogens in the CAWS, representing the weather conditions experienced in a recreational year, were relatively low. The study concluded that the presence of pathogens in the CAWS downstream of the WRPs were due to secondary loading of the waterway under wet weather conditions from combined sewer overflows (CSOs) and other discharges.

Hospital injury rates in relation to socioeconomic status and working conditions.

OBJECTIVES: To describe the risk of work injury by socioeconomic status (SES) in hospital workers, and to assess whether SES gradient in injury risk is explained by differences in psychosocial, ergonomic or organisational factors at work. METHODS: Workforce rosters and Occupational Safety and Health Administration injury logs for a 5-year period were obtained from two hospitals in Massachusetts. Job titles were classified into five SES strata on the basis of educational requirements and responsibilities: administrators, professionals, semiprofessionals, skilled and semiskilled workers. 13 selected psychosocial, ergonomic and organisational exposures were assigned to the hospital jobs through the national O*NET database. Rates of injury were analysed as frequency records using the Poisson regression, with job title as the unit of analysis. The risk of injury was modelled using SES alone, each exposure variable alone and then each exposure variable in combination with SES. RESULTS: An overall annual injury rate of 7.2 per 100 full-time workers was estimated for the two hospitals combined. All SES strata except professionals showed a significant excess risk of injury compared with the highest SES category (administrators); the risk was highest among semiskilled workers (RR 5.3, p<0.001), followed by nurses (RR 3.7, p<0.001), semiprofessionals (RR 2.9, p = 0.006) and skilled workers (RR 2.6, p = 0.01). The risk of injury was significantly associated with each exposure considered except pause frequency. When workplace exposures were introduced in the regression model together with SES, four remained significant predictors of the risk of injury (decision latitude, supervisor support, force exertion and temperature extremes), whereas the RR related to SES was strongly reduced in all strata, except professionals. CONCLUSIONS: A strong gradient in the risk of injury by SES was reported in a sample population of hospital workers, which was greatly attenuated by adjusting for psychosocial and ergonomic workplace exposures, indicating that a large proportion of that gradient can be explained by differences in working conditions.

Isolated new onset 'atypical' optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up.

Severe, recurrent or bilateral optic neuritis (ON) often falls within the neuromyelitis optica spectrum disorders (NMOSD), but the diagnosis can be particularly challenging and has important treatment implications. We report the features, course and outcomes of patients presenting with atypical ON when isolated at onset. We retrospectively analyzed 69 sequential patients referred to a single UK NMO center with isolated ON at onset. Aquaporin-4 antibody (AQP4-Ab) assessment was performed in all patients and IgG1 myelin-oligodenrocyte glycoprotein (MOG-Ab) in AQP4-Ab(neg) patients. 37 AQP4-Ab positive (AQP4-Ab(pos)) and 32 AQP4-Ab negative (AQP4-Ab(neg)) patients (8 with MOG-Ab) were identified. The AQP4-Ab(neg) group included heterogeneous diagnoses: multiple sclerosis (MS), NMO, relapsing isolated ON (RION), monophasic isolated ON and relapsing acute disseminated encephalomyelitis (ADEM)-like syndromes. Compared to AQP4-Ab(neg) patients, AQP4-Ab(pos) patients had a worse residual visual outcome from first attack (median VFSS 4 vs. 0, p = 0.010) and at last assessment (median VFSS 5 versus 2, p = 0.005). However, AQP4-Ab(neg) patients with RION also had poor visual outcome. Up to 35% of AQP4-Ab(neg) patients developed a LETM and two developed low positivity for AQP4-Ab over time. Eight AQP4-Ab(neg) patients (25%) were MOG-Ab positive, covering a range of phenotypes excluding MS; the first ON attack was often bilateral and most had relapsing disease with a poor final visual outcome [VFSS 4, range (0-6)]. In conlcusion, AQP4-Ab positivity is confirmed as a predictor of poor visual outcome but AQP4-Ab(neg) RION also had a poor visual outcome. Of those without AQP4-Ab, 25% had MOG-Ab and another 25% developed MS; thus, MOG-Ab is associated with AQP4-Ab(neg) non-MS ON.

Cyclic [beta]-1,6 -1,3 Glucans Are Synthesized by Bradyrhizobium japonicum Bacteroids within Soybean (Glycine max) Root Nodules.

We have previously reported that free-living cultures of Bradyrhizobium species produce novel oligosaccharides that are cyclic, contain between 10 and 13 glucose residues, and are linked by [beta]-1,6 and [beta]-1,3 glycosidic bonds (K.J. Miller, R.S. Gore, R. Johnson, A.J. Benesi, V.N. Reinhold [1990] J Bacteriol 172: 136-142). In the present study, we show that these glucans are also synthesized by bacteroids of Bradyrhizobium japonicum USDA 110 within Glycine max root nodules.

Depressive symptoms and cognitive decline in nondemented elderly women: a prospective study.

BACKGROUND: The association between depressive disorders and subsequent cognitive decline is controversial. We tested the hypothesis that elderly women (aged 65 years and older) without dementia but with depressive symptoms have worse cognitive function and greater cognitive decline than women with few or no symptoms. METHODS: As part of an ongoing prospective study, we evaluated 5781 elderly, mostly white, community-dwelling women. Women completed the Geriatric Depression Scale short form. Three cognitive tests--Trails B, Digit Symbol, and a modified Mini-Mental State Examination--were administered at baseline and approximately 4 years later. Baseline, follow-up, and change scores for the cognitive tests were analyzed by analysis of covariance and Kruskal-Wallis analysis; the odds of cognitive deterioration (> or =3-point decline on the modified Mini-Mental State Examination) were determined by logistic regression. RESULTS: At baseline, 211 (3.6%) of the women had 6 or more depressive symptoms. Only 16 (7.6%) of these women were receiving antidepressant medication. Increasing symptoms of depression were associated with worse performance at baseline and follow-up on all 3 tests of cognitive function (P<.001 for all comparisons). For example, the baseline Digit Symbol score (mean +/- SD) was 45.5 +/- 10.7 among women with 0 to 2 symptoms of depression, 40.3 +/- 10.7 for women with 3 to 5 symptoms, and 39.0 +/- 11.3 for women with 6 or more symptoms. After adjusting for the baseline score, cognitive change scores were also inversely associated with the number of depressive symptoms (P<.001 for all comparisons). Odds ratios for cognitive deterioration using 0 to 2 symptoms as the reference were 1.6 (95% confidence interval, 1.3-2.1) for 3 to 5 symptoms and 2.3 (95% confidence interval, 1.6-3.3) for 6 or more symptoms. Results were similar after being adjusted for education, age, health status, exercise, alcohol use, functional status, and clinic site. CONCLUSIONS: Depressive symptoms in older women are associated with both poor cognitive function and subsequent cognitive decline. Mechanisms underlying the association between these 2 common conditions need further exploration.

Rate of bone loss is associated with mortality in older women: a prospective study.

Older women with low bone density have an increased risk of fracture, cardiovascular disease, and mortality. However, it is not known whether this association is caused by ongoing bone loss or by lower bone mass earlier in life. To determine whether rate of bone loss is associated with total and cause-specific mortality, we prospectively studied 6046 women aged 65 years or older who had serial bone mineral density (BMD) measurements as a part of the Study of Osteoporotic Fractures. Rates (mean +/- SD) of loss of BMD at the heel (for a mean of 5.7 years) and hip (for a mean of 3.5 years) were estimated. Cause-specific mortality was ascertained from death certificates and hospital records. BMD loss at the heel was 5.9 +/- 6.0 mg/cm2 per year (1.5 +/- 1.5%) and BMD loss at the hip was 4.1 +/- 10.2 mg/cm2 per year (0.6 +/- 1.4%). During an average follow-up of 3.2 years after the second measurement of BMD, 371 deaths occurred. Each SD increase in BMD loss at the hip was associated with a 1.3-fold (95% CI, 1.1-1.4) increase in total mortality, adjusted for age, baseline BMD, diabetes, hypertension, incident fractures, smoking, physical activity, health status, weight loss, and calcium use. In particular, hip BMD loss was associated with increased mortality from coronary heart disease (relative hazard [RH] = 1.3 per SD; 95% CI, 1.0-1.8) and pulmonary diseases (RH = 1.6 per SD; 95% CI, 1.1-2.5). The findings were similar for bone loss at the heel, except there was no significant association with pulmonary mortality. These results raise the possibility that bone loss may share common etiologies with coronary and pulmonary diseases.

Once-daily fosinopril in the treatment of hypertension.

This multicenter, dose-ranging study evaluated the antihypertensive effectiveness of once-daily administration of fosinopril sodium in 220 patients with supine diastolic blood pressure of 95-115 mm Hg. After a 4-week placebo period, patients were randomly assigned to double-blind therapy with either placebo or 10, 40, or 80 mg fosinopril once daily for 4 weeks. If treatment goals were not met, chlorthalidone 25 mg/day was added for weeks 5 to 8. Thereafter, patients could enter the long-term, open-label phase and receive 10-80 mg/day fosinopril plus chlorthalidone, if needed. After 4 weeks of monotherapy, the average decreases in supine diastolic blood pressure were 9% (10 mg), 11.5% (40 mg), and 12.5% (80 mg) compared with 6% in the placebo group. After 8 weeks, the average decreases, with or without diuretic therapy, were 12.5-18.2%, compared with 10.8% with placebo. Blood pressure continued to be well controlled, and the patients showed no evidence of tachyphylaxis or tolerance through 12-15 months of treatment. Fosinopril was well tolerated. During the short-term phase, no patient withdrew because of adverse events possibly related to fosinopril; during the long-term phase, nine of 148 patients (6.1%) withdrew for that reason. In patients with mild-to-moderate hypertension, once-daily fosinopril (40 and 80 mg) provided significant antihypertensive effects with or without diuretic therapy. The 10 mg dose was effective in some patients and may be considered a starting dose.

Losulazine, a new antihypertensive.

The efficacy of losulazine was determined in 32 patients with hypertension. Each subject was randomly assigned to receive either losulazine (n = 16) or placebo (n = 16) in a double-blind fashion. Losulazine in the dosage range of 10 to 30 mg b.i.d. effectively lowered the blood pressure. Diastolic blood pressure was lowered to less than or equal to 90 mm Hg in over 70% of the subjects receiving losulazine. There was no evidence of an increase in heart rate; to the contrary, there was a tendency for heart rate to decrease. Six subjects dropped out of the study before completion. Four of these were receiving placebo and dropped out because of lack of efficacy. One subject receiving losulazine dropped out for personal reasons during the first week of the study, and the other subject (also taking losulazine) dropped out when a drug-related pruritus (itchy eyes) developed. This event was readily reversed upon discontinuation of the drug. The drug was well tolerated and side effects were minimal, with no evidence of orthostatic effects or sexual dysfunction. There was a suggestion that nasal stuffiness and conjunctival congestion may be drug related. There were no changes in any laboratory values or body weight.