Search

BACKGROUND OBJECTIVES: Human milk (HM) is better tolerated than formula in preterm infants. Insulin, which is naturally present in HM but not in formula, has been suggested as a key factor for feeding tolerance, as it appears to stimulate intestinal maturation. Its precise concentrations during the early postnatal period, however, remains unknown. The objective of this study was to assess the natural timecourse of the HM insulin concentration during the first ten days postpartum. The effect of preterm delivery, maternal obesity, and diurnal rhythm were also assessed. METHOD: HM was collected from 31 non-diabetic mothers (21 preterm [gestational age (GA)

Introduction Disability in RA is associated with loss of workdays, greater use of health resources and a higher prevalence of depression. The purpose of this study was to determine the prevalence of functional disability and the factors associated with it. Methods A cross-sectional study was carried out during January-June 2019 at a rheumatology clinic in the city of Guayaquil. Patients with pre-established RA were included. Functional disability was measured using the HAQ-DI. Data were analyzed using the statistical program SPSS v22. We compared characteristics between patients with and without disability using Student's t-test and chi-square. A multiple logistic regression model for functional disability was made. Results We included 395 patients, 87.8% female and 12.2% male with a mean age of 51.4±12 years and mean duration of disease 13.8±7 years. Most patients had extra-articular manifestations (80.8%) and comorbidities (81.3%). The mean HAQ-DI was 0.8±0.9, with a prevalence of disability of 26.6%. We found a statistically significant relationship between disability and female sex (p=0.018), age (p=0.020), presence of extra-articular manifestations (p=0.008), myalgia (p

In the development of cancer therapeutics, no suitable replacements for the use of animals that are capable of modeling such complex disease processes are currently available. In orthotopic models, surgery is often required to access the target organ for tumor cell inoculation. Historically analgesics have been withheld in such models in light of potential effects on tumor development. The current study evaluated the effect of the opioid buprenorphine on tumor growth of a human ovarian cancer cell line (OVCAR5 OT luc2 mCherry). Female CB17 SCID mice (n = 150) underwent surgery for orthotopic inoculation and were assigned to 1 of 3 treatment groups: vehicle control, 1 dose of buprenorphine, or 2 doses of buprenorphine administered perioperatively. Bioluminescence imaging revealed no significant difference on tumor engraftment rate or growth between control and analgesia-treated groups. These data demonstrate that acute, perioperative analgesia with buprenorphine did not alter tumor growth. Although further research is needed to evaluate potential effects of buprenorphine in other cell lines and mouse strains, the justification for withholding analgesia and the potential influence of pain and stress due to insufficient analgesia in these models should be considered thoroughly.

Summary Background Few large projects have evaluated the factors that influence the HIV RNA concentrations (viral load) in cerebrospinal fluid (CSF) during antiretroviral therapy (ART) over time. We aimed to determine the correlates of HIV RNA in CSF in a large cohort. Methods We analysed longitudinal data from adults living with HIV in the US CHARTER cohort. Participants in the CHARTER study were recruited from six US academic medical centres—in Baltimore (MD), Galveston (TX), New York (NY), St Louis (MO), San Diego (C92A), and Seattle (WA). Participants in this study had been assessed at least three times between Sept 4, 2003, and Sept 14, 2010, and were taking ART and underwent venous and lumbar puncture with measurement of HIV RNA concentration at all assessments. The lower limit of quantification of the HIV RNA assays was 50 copies per mL. Data were analysed with longitudinal mixed effects logistic regression to identify correlates of HIV RNA concentration (as a binary [detectable or not] and as a continuous variable) in CSF over time. We tested demographic characteristics, plasma HIV RNA, nadir and current CD4 cell count in blood, current CD8 cell count in blood, estimated duration of HIV infection, AIDS diagnosis, duration of ART, adherence to ART, ART characteristics, and CSF characteristics as potential correlates. Findings At the time of analysis, 2207 assessments from 401 participants met the criteria for inclusion in this study. Mean duration of observation was 33·7 months (range 12–84). HIV RNA concentrations in 710 (32·2%) plasma specimens and in 255 (11·6%) CSF specimens were greater than the lower limit of quantification. The best multivariate model of HIV RNA concentration in CSF greater than the lower limit of quantification over time included increased plasma HIV RNA concentration (odds ratio 18·0 per 1 log10 copy per mL, 95% CI 11·3 to 28·8; p Interpretation The identified correlates of HIV RNA concentration in CSF during ART could strengthen clinical prediction of risk for failure to achieve or maintain HIV RNA suppression in CSF. Because most participants in this analysis were ART-experienced and were taking a three-drug regimen that did not include an integrase inhibitor, future research should focus on participants who are taking their first ART regimens or regimens that include integrase inhibitors or two drugs. Funding The work was supported by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.

Hay fever patients can be helped in managing their symptoms by predicting the severity of the upcoming grass pollen seasons., Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season’s severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season.

Objectives Drugs with anticholinergic properties are associated with an increased prevalence of delirium, especially in older persons. The aim of this study was to evaluate the association between the use of this class of drugs in nursing home (NH) patients and prevalence of delirium, particularly in people with dementia. Design Cross-sectional multicenter study. Setting and participants 3924 nursing home patients of 57 nursing homes in 7 European countries participating in the Services and Health for Elderly in Long TERmcare (SHELTER) project. Methods Descriptive statistics, calculation of percentage, and multivariable logistic analysis were applied to describe the relationship between anticholinergic drug use and prevalence of delirium in NH patients. The Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB) were used to calculate the anticholinergic load. Results 54% of patients with dementia and 60% without dementia received at least 1 anticholinergic drug according to the ACB. The prevalence of delirium was higher in the dementia group (21%) compared with the nondementia group (11%). Overall, anticholinergic burden according to the ACB and ARS was associated with delirium both in patients with and without dementia, with odds ratios ranging from 1.07 [95% confidence interval (CI) 0.94-1.21] to 1.26 (95% CI 1.11-1.44). These associations reached statistical significance only in the group of patients with dementia. Among patients with dementia, delirium prevalence increased only modestly with increasing anticholinergic burden according to the ACB, from 20% (with none or minimal anticholinergic burden) to 25% (with moderate burden) and 27% delirium (with strong burden scores). Conclusions and Implications The ACB scale is relatively capable to detect anticholinergic side effects, which are positively associated with prevalence of delirium in NH patients. Given the modest nature of this association, strong recommendations are currently not warranted, and more longitudinal studies are needed.

Delirium is a common serious complication in dementia that is associated with poor prognosis and a high burden on caregivers and healthcare professionals. Appropriate care is therefore important at an early stage for patients with delirium superimposed on dementia To gain insight into the care of six patients with delirium superimposed on dementia, 19 semi-structured interviews were conducted focused on the experiences of caregivers and professionals. The interviews revealed four themes that appeared to play a role: 1. experiences with and views on behavioral problems of these patients, 2. recognition and diagnosis of delirium in dementia, 3. views on good care and 4. organizational aspects. Knowledge gaps about delirium in dementia, as well as ethical considerations, play an important role in organizing timely and adequate care for patients with delirium superimposed on dementia.

Summary Background & aims Experimental (nutritional) interventions in preterm infants frequently focus on intestinal maturation, as improving tolerance to enteral nutrition is a major goal. Intestinal permeability and lactase activity serve as markers for intestinal maturation. We aimed to develop a protocol for the simultaneous assessment of both markers in human-milk-fed preterm infants by a sugar absorption test. In addition, we developed a new gas chromatography-mass spectrometry (GC–MS) method for the analysis of lactulose, lactose, and mannitol in urine and milk collected during the sugar absorption test. Methods The sugar absorption test was performed on days 4, 7, and 14 postpartum in 12 preterm infants (gestational age of 26–32 weeks). Human milk was collected, pooled, and divided into equal portions to provide a stable lactose intake for 24 h. Urine was collected in the last 6 h of this 24 h period, after administration of a bolus test sugar solution. Samples were analyzed by GC–MS after derivatization by oxime formation combined with acetylation. Results The GC–MS method was validated and used for the accurate measurement of lactulose, lactose, and mannitol concentrations. The urinary lactulose/mannitol ratio declined with time, suggesting a decreased intestinal permeability. The urine-to-milk-lactulose/lactose ratio increased as a result of increased lactase activity with time. Conclusions The developed protocol for simultaneous assessment of intestinal permeability and lactase activity can be used to monitor the effect of experimental (nutritional) interventions in human-milk-fed preterm infants. Urine and milk samples obtained during the sugar absorption test can be accurately analyzed by GC–MS.

Objectives To determine whether ultrasound (US) imaging of obese pregnant women in early gestation improves fetal cardiac visualization. Methods We report a prospective longitudinal trial comparing late first- and early second-trimester US to traditional second-trimester US for fetal cardiac screening in maternal obesity. All study participants received US for fetal cardiac screening at a gestational age of 13 weeks to 15 weeks 6 days using a transvaginal or transabdominal approach (UST1). All patients also underwent a traditional transabdominal examination at 20 to 22 weeks (UST2). If UST2 failed to complete the cardiac visualization, a follow up examination (second UST2) was performed 2 to 4 weeks later. Imaging was considered complete if the visceral situs, 4 chambers, outflow tracts, and 3 vessels were visualized. The completion rates between UST1 and UST2 were the primary outcomes. A power analysis (85%) and sample size calculation (n = 145) were performed. Results A total of 152 pregnancies met study criteria. Completion rates of cardiac screening were 77% for UST1 and 70% for UST2 (P = .143). This comparison reached statistical significance in patients with a body mass index of greater than 40 kg/m2 (UST1 [69%] versus UST2 [38%]; P = .001). Sixty-two percent of patients with a body mass index of greater than 40 kg/m2 required second UST2. The highest fetal cardiac screening completion rate was achieved when UST1 was combined with UST2 (96.1%). In 1 fetus, congenital heart disease was detected at UST1 and later confirmed. Conclusions This study represents the largest prospective trial assessing early-gestation US for fetal cardiac screening in the setting of maternal obesity. In obese pregnancies, the addition of early-gestation US to the 20- to 22-week US substantially improves the visualization of fetal cardiac anatomy.

Background: Chagas disease is a major neglected vector-borne disease. In this study, we investigated the safety and efficacy of three oral E1224 (a water-soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult chronic indeterminate Chagas disease. Method: In this proof-of-concept, double-blind, randomised phase 2 clinical trial, we recruited adults (18–50 years) with confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in Bolivia. Patients were randomised with a computer-generated randomisation list, which was stratified by centre and used a block size of ten. Patients were randomly assigned (1:1:1:1:1) to five oral treatment groups: high-dose E1224 (duration 8 weeks, total dose 4000 mg), low-dose E1224 (8 weeks, 2000 mg), short-dose E1224 (4 weeks + 4 weeks placebo, 2400 mg), benznidazole (60 days, 5 mg/kg per day), or placebo (8 weeks, E1224-matched tablets). Double-blinding was limited to the E1224 and placebo arms, and assessors were masked to all treatment allocations. The primary efficacy endpoint was parasitological response to E1224 at the end of treatment, assessed by PCR. The secondary efficacy endpoints were parasitological response to benznidazole at end of treatment, assessed by PCR; sustainability of parasitological response until 12 months; parasite clearance and changes in parasite load; incidence of conversion to negative response in conventional and non-conventional (antigen trypomastigote chemiluminescent ELISA [AT CL-ELISA]) serological response; changes in levels of biomarkers; and complete response. The primary analysis population consisted of all randomised patients by their assigned treatment arms. This trial is registered with ClinicalTrials.gov, number NCT01489228. Findings: Between July 19, 2011, and July 26, 2012, we screened 560 participants with confirmed Chagas disease, of whom 231 were enrolled and assigned to high-dose E1224 (n=45), low-dose E1224 (n=48), short-dose E1224 (n=46), benznidazole (n=45), or placebo (n=47). Parasite clearance was observed with E1224 during the treatment phase, but no sustained response was seen with low-dose and short-dose regimens, whereas 13 patients (29%, 95% CI 16·4–44·3) had sustained response with the high-dose regimen compared with four (9%, 2·4–20·4) in the placebo group (p

Objectives The 2012 Eunice Kennedy Shriver National Institute of Child Health fetal imaging consensus suggested that fetal anatomy ultrasound in obese pregnancies be performed at 20 to 22 weeks, with follow-up in 2 to 4 weeks if anatomy is incomplete. It was postulated that imaging in early gestation may improve visualization, although no prospective trials had been done to date. Methods We performed a prospective longitudinal blinded trial comparing an early gestation ultrasound (13 + 0 to 15 + 6 weeks) with the traditional second-trimester ultrasound for completion of the fetal anatomy survey in obese patients. Inclusion criteria included singleton gestation, body mass index (BMI) more than 30, less than 16 + 0 weeks' gestation, and no karyotype abnormality; exclusion criteria included age younger than 18 years, more than 16 weeks' gestation at time of consent, and BMI less than 30. Participants received a transvaginal and/or transabdominal sonogram for fetal anatomic survey at 13 + 0 to 15 + 6 weeks' gestation (US1). Images from US1 were blinded to physicians and sonographers performing subsequent examinations. All participants underwent the traditional transabdominal sonogram at 18 to 24 weeks (US2). If US2 failed to complete the anatomic survey, a repeat transabdominal sonogram (2-US2) was performed 2 to 4 weeks later. Results A total of 152 pregnancies met the criteria. Anatomy completion rate was 57.2% for US1 and 62.5% for US2, which was not statistically significant, even when stratified by BMI. Excluding the philtrum, the US1 performed better than US2 for class III obesity (65.5% versus 45.5% [P = .035]). Combination of US1 + US2 yielded a higher completion rate than US2 + 2-US2 (94.1% versus 83.6% [P = .0023]). Conclusions In the setting of maternal obesity, the addition of an ultrasound in early gestation may be of highest benefit for patients with class III obesity (BMI > 40 kg/m2).

Allergic rhinitis caused by pollen exposure is one of the most common allergic diseases. Therefore monitoring pollen levels in ambient air is an important tool in research and health care. Most European monitoring stations collect airborne pollen at rooftop levels for measurements in the larger surrounding of the sampling station, and not in the direct environment of sensitized subjects. Here we present the development and evaluation of a por table pollen sampler, called "Pollensniffer", that was designed to collect pollen in the immediate environment of allergic subjects. Validation of the Pollensniffer against the standard volumetric pollen sampler showed for most pollen types high correlations between the number of pollen collected by those two devices (Spearman's Correlation Coefficient > 0.8); the Pollensniffer appeared to collect on average 5.8 times more pollen per hour than the static sampler. Pollen monitoring was performed using this Pollensniffer at street level at 3 different locations in the city of Leiden during 22 weeks in 2017 and 21 weeks in 2018, during three 15-min periods a day and at one day in the week. The results showed that the pollen levels for birch and grass pollen can significantly differ from location to location and per time of day. Furthermore, the Pollensniffer measurements at street level showed that birch and grass pollen grains were detected 1 1/2 and 2-3 weeks, respectively, before detection at rooftop level. The street measurements show that allergic subjects can encounter varying pollen levels throughout the city and that they can be exposed to grass and birch pollen and may experience hay fever symptoms, even before the sampler at rooftop level registers these pollen. (C) 2020 The Authors. Published by Elsevier B.V

Background Premenstrual dysphoric disorder (PMDD) is an understudied, debilitating disorder of women. Given evidence for prefrontal cortical and limbic dysfunction in PMDD, we compared intrinsic connectivity of the executive control network (ECN), default mode network (DMN), and amygdala in women with PMDD vs. controls. Methods Thirty-six women (18 PMDD, 18 control) participated in fMRI during the follicular and luteal phases of the menstrual cycle. At each time, resting-state functional connectivity was evaluated both before and after participants performed an emotion regulation task. The ECN was identified using independent components analysis, and connectivity of left and right amygdala seeds was also evaluated. Results Nonparametric permutation testing identified a cluster in the left middle temporal gyrus (MTG) with significantly stronger connectivity to the left ECN in women with PMDD vs. controls in all four fMRI sessions. Women with PMDD exhibited no difference in functional connectivity between menstrual cycle phases. Amygdala connectivity did not differ between the groups but differed significantly with menstrual phase, with left amygdala connectivity to cingulate cortex being significantly stronger during the follicular vs. luteal phase. Right amygdala connectivity to the middle frontal gyrus was also stronger during the follicular vs. luteal phase, with no group differences. These findings suggest that women with PMDD have different intrinsic network dynamics in the left executive control network compared to healthy controls.

Objective This study aims to compare completion rates and reproducibility of myocardial performance index (MPI) using conventional spectral Doppler versus tissue Doppler in an unselected high-risk third trimester population.Study Design This was a prospective cross-sectional study of high-risk pregnancies at ≥28 + 0 weeks’ gestation. Conventional spectral and tissue Doppler MPI of the left ventricle (LV) and right ventricle (RV) was attempted on all patients.Results Seventy-nine pregnancies were evaluated. LV tissue Doppler MPI was completed more frequently than LV conventional spectral Doppler MPI (63/79, 79.7% vs. 45/79, 55.7%), p-value Conclusion Tissue Doppler had statistically higher completion rates than conventional spectral Doppler, including the obese subgroup, with evidence of strong reproducibility in the third trimester.

Background The aim of this retrospective study was to examine the longitudinal association between disease activity and radiographic damage in a cohort of patients with early RA (symptom onset Methods Baseline to 3-year follow-up data were used from patients included in the DREAM remission induction cohort. Patients received protocolized T2T treatment, aimed at 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) remission. Disease activity (DAS28-ESR and C-reactive protein, CRP) were assessed at least every 3 months; X-rays of the hand and feet at inclusion, 6 months, and 1, 2, and 3 years were scored using modified Sharp/van der Heijde scoring (SHS). Between and within-person associations between time-integrated disease activity and radiographic progression over time were examined. Results A subset of 229 out of 534 included patients were available for analysis. At the between-patient level, time-integrated DAS28-ESR scores were not significantly correlated with progression at the 6 month and 2-year follow-up and only weakly at the 1-year (Pearson’s correlation coefficient r = 0.17, P r = 0.21, P r between 0.39 and 0.59; P values Conclusions In early RA patients treated according to T2T, radiographic progression appears to be an individually determined disease process, driven by factors other than consistent high disease activity. For individual patients, the intra-patient relation between disease activity and cumulative radiographic damage during the first 6 months is a good indicator for this relation in later years. Trial registration Netherlands Trial Register NTR578, 12 January 2006.

BACKGROUND: Because of the prevalence and impact of sleep disorders in Parkinson's disease (PD), valid instruments for their evaluation and monitoring are necessary. However, some nocturnal sleep disorders may go unnoticed by patients themselves. OBJECTIVES: To validate a pan‐Spanish version of the Parkinson's Disease Sleep Scale Version 2 (PDSS‐2) and to test the relationships between the PDSS‐2 and a PDSS‐2 roommate version. METHODS: PD patients (n = 399) from seven Spanish‐speaking countries were included. In addition to the tested PDSS‐2 scales, valid measures for sleep disorders and both motor and nonmotor manifestations were applied. Acceptability, dimensionality, reliability, precision, and construct validity were explored, as well as discrepancies and agreement between the PDSS‐2 and the roommate version. RESULTS: PDSS‐2 showed negligible floor and ceiling effects. Four factors (57% of the variance) were identified. Reliability parameters were satisfactory: alpha = 0.84; item homogeneity coefficient = 0.27; corrected item total correlation = 0.28 to 0.61; and test‐retest reliability (average kappa = 0.70; intraclass correlation coefficient [ICC] = 0.83). The standard error of measurement was 5.84, and correlations with other scales assessing nocturnal sleep were high (r(S) = 0.62–0.56). In comparison to the patient‐based total score, the by proxy total score showed no significant difference, high correlation (r(S) = 0.70), and acceptable agreement (ICC = 0.69), but there were discrepancies in two or more points in 18% of item scores. CONCLUSIONS: The Spanish version of the PDSS‐2 has shown satisfactory clinimetric attributes. Acceptability and precision data are presented for the first time. The PDSS‐2 roommate version could be useful to complement the patient‐based evaluation, but additional studies are needed.

With aging of HIV populations, there is concern that Alzheimer’s disease (AD) may become prevalent and difficult to distinguish from HIV-associated neurocognitive disorders. To date, there are no reports documenting histologically verified Alzheimer’s neuropathology in individuals with HIV and dementia. Herein, we report two antiretroviral-treated, virally suppressed, HIV-infected individuals autopsied by the Manhattan HIV Brain Bank. Subject A presented to study at 52 years, already dependent in instrumental activities of daily living (ADLs), with severe cognitive impairment inclusive of learning and memory dysfunction. Her history was significant for educational disability and head trauma. She had rapid cognitive decline and, by death at age 59 years, was bed-bound, incontinent, and non-communicative. At autopsy, she exhibited severe AD neuropathologic change (NIA-AA score A3B3C3) and age-related tau astrogliopathy (ARTAG). She was homozygous for APOE e3/e3. No HIV DNA was detected in frontal lobe by nested polymerase chain reaction. Subject B was a community dwelling 81-year-old woman who experienced sudden death by pulmonary embolus. Prior to death, she was fully functional, living independently, and managing all ADLs. At autopsy, she displayed moderate amyloid and severe tau AD neuropathologic changes (A2B3C2), ARTAG, and cerebral congophilic angiopathy. She was an APOE e3/e4 heterozygote, and HIV DNA, but not RNA, was detected in frontal lobe, despite 20 years of therapy-induced viral suppression. We conclude that in the setting of HIV, AD neuropathology may occur with or without symptomatic cognitive dysfunction; as with seronegative individuals, there are likely to be complex factors in the generation of clinically relevant impairments.

Item does not contain fulltext IMPORTANCE: Infections and necrotizing enterocolitis, major causes of mortality and morbidity in preterm infants, are reduced in infants fed their own mother's milk when compared with formula. When own mother's milk is not available, human donor milk is considered a good alternative, albeit an expensive one. However, most infants at modern neonatal intensive care units are predominantly fed with own mother's milk. The benefits of add-on donor milk over formula are not clear. OBJECTIVE: To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection, necrotizing enterocolitis, and mortality. DESIGN, SETTINGS, AND PARTICIPANTS: The Early Nutrition Study was a multicenter, double-blind randomized clinical trial in very low-birth-weight infants (birth weight

Objectives To investigate changes in the cardiac axis (CAx) within the cardiac cycle of normal fetuses and fetuses with congenital heart defects (CHD). Methods This was a retrospective case–control study in which stored videoclips of four-chamber views from 527 prenatal ultrasound examinations performed at 18 + 0 to 36 + 6 weeks of gestation were reviewed. Among the ultrasound scans included, 287 were of normal fetuses (controls) and 240 were of fetuses with CHD. In each case, the CAx was measured at end systole (just before the atrioventricular (AV) valve opened) and at end diastole (just before the AV valve closed). CAx measurements of fetuses with CHD were compared to those of controls. Results The mean CAx in the control group was 45.9 ± 8.5° at end systole and 38.3 ± 8.4° at end diastole (P

Cystic echinococcosis (CE) is an important helminthic zoonotic disease that commonly affects the liver and lungs. Imaging methods and serology establish the diagnosis in most cases. Chest x-ray can diagnose uncomplicated pulmonary hydatid cysts, whereas superinfection and/or rupture of the hydatid cyst (complicated cysts) may change the radiographic appearance and lead to delayed diagnosis and treatment. We report the case of a patient with hemoptysis and chest pain, where computer tomography scan of the lung suggested a large, ruptured hydatid cyst. However, serological tests with indirect hemagglutination (IHA)for Echinococcus granulosus antibodies were negative, and there was massive growth of Streptococcus pneumoniae in sputum. Based on this, we concluded that the patient had a bacterial lung abscess. The diagnosis of CE was only made after surgical removal of the cyst followed by microscopy and polymerase chain reaction.

BackgroundDifficulties in regulating emotions are linked to the core symptoms of premenstrual dysphoric disorder (PMDD). We therefore investigated the neural substrates of emotion-regulation problems in women with PMDD.MethodsOn the basis of self-evaluations over 2 months on the Daily Record of Severity of Problems, eligible participants were assigned to two groups: PMDD and control (18 per group). Functional magnetic resonance imaging (fMRI) and a well-validated task were used to assess brain function during emotion regulation. Participants were tested twice, once during the follicular (asymptomatic) and once in the late luteal (symptomatic) phase of the menstrual cycle.ResultsWomen with PMDD gave higher ratings of negative affect in the luteal phase than in the follicular phase, and compared with healthy control participants during the luteal phase. A region-of-interest fMRI analysis indicated that during the late luteal phase, women with PMDD had hypoactivation in right dorsolateral prefrontal cortex (dlPFC) during all conditions of the emotion-regulation task, not only in the contrast that isolated emotion regulation. An exploratory whole-brain, voxel-wise analysis showed that women with PMDD had less activation in the precentral gyrus during the luteal phase than the follicular phase, and less activation in the postcentral gyrus compared with control participants.ConclusionsDuring the luteal phase of the menstrual cycle, women with PMDD experience difficulty regulating emotions. Hypoactivation in the right dlPFC may contribute to this problem, but may be related more generally to other affective symptoms of PMDD. Hypofunction in the right pre- and postcentral gyri warrants additional study.

Controversy exists as to whether effects of HIV infection can be detected in the cognitive profiles of substance users, with methodological differences in degree of control for confounding factors a major contributor to empirical discrepancies. To address this shortcoming, we conducted a small but well-controlled study aimed at isolating HIV neurocognitive (NC) effects in a group of chronic substance users. Thirty HIV-negative substance users were individually matched to 30 HIV-positive substance users on relevant medical and demographic factors, including reading level and methadone therapy status. Results revealed that reading level, methadone maintenance therapy, and positive urine toxicology each exerted significant influence on NC function, and that HIV status was a significant predictor of learning and speeded processing after these control factors were considered. The HIV-positive group also displayed significantly more neurologically assessed motor impairment (p < .05), which was specifically related to impaired cognition in this group and independent of degree of immunocompromise. These data demonstrate the need for increased attention to clinical/demographic characteristics of groups under study. They also show that with applied methodological rigor, the deleterious effects of HIV on cognition can be parsed from substance use, even in small samples with chronic and active use histories. (JINS, 2013, 19, 1–11)

The use of preclinical models to study tumor biology and response to treatment is central to cancer research. Long-established human cell lines, and many transgenic mouse models, often fail to recapitulate the key aspects of human malignancies. Thus, alternative models that better represent the heterogeneity of patients' tumors and their metastases are being developed. Patient-derived xenograft (PDX) models in which surgically resected tumor samples are engrafted into immunocompromised mice have become an attractive alternative as they can be transplanted through multiple generations,and more efficiently reflect tumor heterogeneity than xenografts derived from human cancer cell lines. A limitation to the use of PDXs is that they are difficult to transfect or transduce to introduce traceable reporters or to manipulate gene expression. The current protocol describes methods to transduce dissociated tumor cells from PDXs with high transduction efficiency, and the use of labeled PDXs for experimental models of breast cancer metastases. The protocol also demonstrates the use of labeled PDXs in experimental metastasis models to study the organ-colonization process of the metastatic cascade. Metastases to different organs can be easily visualized and quantified using bioluminescent imaging in live animals, or GFP expression during dissection and in excised organs. These methods provide a powerful tool to extend the use of multiple types of PDXs to metastasis research.

This study assessed the effectiveness of a Teaching Interaction procedure for four social skills across three participants diagnosed with autism. All social skills fell into four broad domains (i.e., social-communication, play, emotion skills, and choice/selection skills). In addition, a teaching package was used to increase communication between the three participants and three selected target peers. The teaching package consisted of the Teaching Interaction procedure, reinforcement, and priming of participants to demonstrate social skills and to engage with their target peers. Prior to intervention, participants displayed near zero levels of the four social skills that were targeted; after intervention, all three participants were able to demonstrate these skills. Prior to intervention, participants did not communicate or play with their selected target peer; after intervention, participants were able to increase the amount of play and communication. A multiple baseline design showed that the teaching package was effective in teaching both the targeted social skills and in increasing the development of initial associations that could lead to friendships for three children diagnosed with autism.

Premenstrual dysphoric disorder (PMDD) is a psychiatric disorder that causes serious impairments in the functioning and quality of life of affected women. Until recently, research efforts were somewhat hampered by the lack of formal diagnostic criteria, which have now been codified as a category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Better characterization of deficits in socioemotional functioning caused by PMDD may aid in improving treatment efforts. In this investigation, prospective symptom ratings, based on DSM-5 criteria, were used to measure PMDD symptoms in 36 women (18 with PMDD and 18 healthy controls). Two self-report inventories, the Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, were used to measure ability to regulate emotions, and socioemotional functioning was measured by inventories of social connectedness, perceived stress, and affect. Potential relationships between ability to regulate emotion and PMDD symptom severity, as well as other measures of socioemotional functioning and affective state, were tested. Women with PMDD reported significantly more behavioral impulsivity and greater difficulties in regulating emotion and in socioemotional functioning. Cognitive or behavioral strategies to improve these problems may benefit women with PMDD and help to alleviate distress caused by this disorder.

Introduction: On average 23% of the European population suffers from allergic rhinitis of which pollen is a major cause. Hay fever symptom forecasts can help these patients to adapt their behaviour and to take their medication in time. We developed the LUMC hay fever forecast for grass pollen allergic patients based on local weather parameters (de Weger et al. Int J Biometeorol 2013). In this study we analysed to what extent symptom scores collected by the citizen science platform www.Allergieradar.nl (de Weger et al. Allergy 2014) are correctly predicted by the LUMC hay fever forecast. Methods: The Netherlands was divided into five regions based on similar weather conditions in order to construct region-specific hay fever forecasts. During the grass pollen season of 2014 daily symptom scores were registered by participants of Allergieradar and were grouped per region. Using multiple regression analysis, we assessed to what extent the forecasted symptom scores were related to the number of daily entries, the mean symptom scores and the interaction between the latter two. Results: The number of daily entries and registered symptom severity submitted per day via Allergieradar.nl were positively correlated with the forecasted symptom scores. The full model, including the interaction of the number of daily entries and the mean registered symptom score, explained variance of 76%. Conclusion: The LUMC hay fever forecast is for 76% in line with the symptom scores combined with the number of entries from the citizen science based internet platform Allergieradar. Therefore, hay fever symptoms experienced in allergic rhinitis patients are well predicted by the LUMC hay fever forecast.

Objectives To report changes in the use of the combined first-trimester screen (FTS) in patients classified as high and low risk for fetal aneuploidy, including after introduction of noninvasive prenatal testing (NIPT). Methods A prospectively collected database was reviewed to investigate changes in FTS use before and after American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 77 (Obstet Gynecol 2007; 109:217-227), which recommended that all patients be offered aneuploidy screening, and after NIPT introduction. High-risk patients were classified as 35 years or older at the estimated time of delivery or those with an abnormal prior screen, abnormal ultrasound findings, or family history of aneuploidy. Data were normalized per 100 morphologic ultrasound examinations to account for changes in patient number over time. Statistical significance was defined as P Results A total of 10,125 FTSs were recorded during the 88-month study period, including 2962 in high-risk patients and 7163 in low-risk patients. The total number of FTSs performed per 100 morphologic ultrasound examinations significantly increased after ACOG Practice Bulletin No. 77 and significantly decreased after NIPT introduction. In high-risk patients, the total number of FTSs performed per 100 morphologic ultrasound examinations significantly increased after ACOG Practice Bulletin No. 77 but significantly decreased after NIPT introduction. In contrast, in low-risk patients, the total number of FTSs performed per 100 morphologic ultrasound examinations significantly increased after ACOG Practice Bulletin No.77 but was not statistically different after NIPT introduction. Conclusions American College of Obstetricians and Gynecologists Practice Bulletin No. 77 significantly increased patient use of FTS. The introduction of NIPT significantly decreased FTS use in the high-risk population but not in the low-risk population.

Serological data on myxoma virus, rabbit haemorrhagic disease (RHD) virus and RHD-like viruses in juvenile rabbits (Oryctolagus cuniculus) trapped in 1995, 1996 and 1997 in two areas of France were analysed. For each disease, the effects of bodyweight, year, month and seropositivity for the other disease were modelled by using logistic regressions. In one area, a model including RHD seropositivity was selected to explain the myxoma virus seropositivity. Models including myxoma virus seropositivity were selected to explain the RHD seropositivity in both areas, and the odds of a rabbit being seropositive to both viruses were 5.1 and 8.4 times higher than the odds of a rabbit being seronegative to myxoma virus and seropositive to RHD. The year and bodyweight had significant effects for myxomatosis in one area and for RHD in both areas.

Background/Aims: Although delirium is generally regarded as a transient syndrome, persistence of delirium in patients with cognitive impairment - even with fatal outcome - has been reported as well. This study aims to describe the clinical features and neuropathological correlates of this type of delirium. Methods: Inclusion criteria for this case series were: (1) severe persistent delirium until death, (2) history of cognitive decline and (3) consent for brain autopsy. Medical records were examined in combination with collected clinical data and neuropathological findings. Result: In 15 patients, all living at home before admission, episodes with delirium lasted for 4.2 months on average. No distinct medical causes of persistent delirium could be identified. Pathological diagnoses included Alzheimer's disease and dementia with Lewy bodies as well as single cases of Creutzfeldt-Jakob disease and progressive supranuclear palsy. Conclusion: Severe, persistent and fatal delirium in patients with cognitive impairment can occur relatively early in the disease trajectory and is associated with diverse neuropathologies.

The Control of Allergic Rhinitis and Asthma Test (CARAT) monitors control of asthma and allergic rhinitis. To determine the CARAT’s minimal clinically important difference (MCID) and to evaluate the psychometric properties of the Dutch CARAT. CARAT was applied in three measurements at 1-month intervals. Patients diagnosed with asthma and/or rhinitis were approached. MCID was evaluated using Global Rating of Change (GRC) and standard error of measurement (s.e.m.). Cronbach’s alpha was used to evaluate internal consistency. Spearman’s correlation coefficients were calculated between CARAT, the Asthma Control Questionnaire (ACQ5) and the Visual Analog Scale (VAS) on airway symptoms to determine construct and longitudinal validity. Test–retest reliability was evaluated with intra-class correlation coefficient (ICC). Changes in pollen counts were compared with delta CARAT and ACQ5 scores. A total of 92 patients were included. The MCID of the CARAT was 3.50 based on GRC scores; the s.e.m. was 2.83. Cronbach’s alpha was 0.82. Correlation coefficients between CARAT and ACQ5 and VAS questions ranged from 0.64 to 0.76 (P

Counseling and therapy have traditionally been known as "talking cures," used to relieve the symptoms of emotional distress and the problems in living encountered by clients as they progress through life. Consistent with the mind-body duality that had its origins in the teachings of Aristotle and Plato, whatever the theoretical underpinnings of the various theorists, and irrespective of the psychological or somatic nature of clients' concerns, these talking cures have all had as their goal facilitating changes in clients' thoughts, feelings, behaviors, and perceptions. Noticeably absent in most traditional approaches, however, has been attention to the body--to the embodied aspects of clients' psychosocial experiencing (Simonds, 1994). Even when clients have experienced significant physical trauma, as in the case of physical or sexual abuse or various health crises (e.g., mastectomy, hysterectomy, spinal cord injury, stroke), direct attention is rarely paid to the clients' relationships with and experiences of living in their bodies. Yet, each individual's history is etched in their body and is reflected in their breathing, in the lines on their faces, in their eyes, and in the way they walk in the world (P. L. Bernstein, 1986; Levy, 1988; Siegel, 1995). As Alice Miller (1981/1984) aptly stated in relation to traumatic childhood experiences, The truth about our childhood is stored up in our body, and although we can repress it, we can never alter it. Our intellect can be deceived, our feelings manipulated, our perceptions confused, and our body tricked with medication. But someday the body will present its bill. (p. 316) Vigier (1994) also speaks of the power of the "voice of the body"--a "voice inside the flesh" that is beyond interpretation, "that is simply the body speaking" (p. 236). She underscores the importance of finding ways to give voice to this "place of subtle and silent speech" (p. 236), in particular through dance. In virtually all known cultures, dance has existed as a form of communication, ritual, and celebration (Schmais & White, 1986). However, it was not until the 1930s that dance was formally adapted for therapeutic purposes (Levy, 1988), to provide individuals with mental illness or disabilities with a means of communication. Since then, it has been used in the treatment of anxiety disorders (Leste & Rust, 1990), eating disorders (Wise, 1984), Parkinson's disease (Westbrook & McKibben, 1989), addictions (Murray-Lane, 1995; Rose, 1995), head injuries (Berrol & Katz, 1985), multiple personality disorder (Baum, 1995), abused children (Goodill, 1987), battered women (Chang, 1995), older persons (Sandel & Hollander, 1995), people who are blind (Fried, 1995), people with learning difficulties (MacDonald, 1992), individuals with physical disabilities (Levy, 1988), and survivors of sexual abuse (B. Bernstein, 1995). B. Bernstein uses numerous case examples and anecdotal material to illustrate how dance therapy can be used to work through and resolve various issues that commonly arise in therapeutic work with sexual abuse survivors. These include shame, guilt, dissociation, sexuality, boundaries, intimacy, and personal power. Commonly referred to in the literature as "dance therapy" or "dance-movement therapy" (Payne, 1992), this approach to facilitating therapeutic change uses psychomotor expression as its major mode of intervention. On its Web page (http://www.adta.org), the American Dance Therapy Association defined dance therapy as "the psychotherapeutic use of movement as a process which furthers the emotional, cognitive and physical integration of the individual." Conducted individually and in groups, dance therapy is aimed broadly at facilitating personal mind, body, and emotional integration; emotional growth (P. L. Bernstein, 1986); and clearer self-definition (Payne, 1992) The movement component of dance therapy can include rhythmic dance, spontaneous and creative movements, thematic movement improvisations, unconscious symbolic body movement, group dance, and range of movement and relaxation exercises (P. …

Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16–72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.

One-third of the Dutch population suffers from allergic rhinitis, including hay fever. In this study, a 5-day-ahead hay fever forecast was developed and validated for grass pollen allergic patients in the Netherlands. Using multiple regression analysis, a two-step pollen and hay fever symptom prediction model was developed using actual and forecasted weather parameters, grass pollen data and patient symptom diaries. Therefore, 80 patients with a grass pollen allergy rated the severity of their hay fever symptoms during the grass pollen season in 2007 and 2008. First, a grass pollen forecast model was developed using the following predictors: (1) daily means of grass pollen counts of the previous 10 years; (2) grass pollen counts of the previous 2-week period of the current year; and (3) maximum, minimum and mean temperature (R 2 = 0.76). The second modeling step concerned the forecasting of hay fever symptom severity and included the following predictors: (1) forecasted grass pollen counts; (2) day number of the year; (3) moving average of the grass pollen counts of the previous 2 week-periods; and (4) maximum and mean temperatures (R 2 = 0.81). Since the daily hay fever forecast is reported in three categories (low-, medium- and high symptom risk), we assessed the agreement between the observed and the 1- to 5-day-ahead predicted risk categories by kappa, which ranged from 65 % to 77 %. These results indicate that a model based on forecasted temperature and grass pollen counts performs well in predicting symptoms of hay fever up to 5 days ahead.

The Viral Activation Transfusion Study (VATS) was a randomized trial that compared leukocyte-reduced transfusions with unfiltered red blood cell transfusions in HIV and cytomegalovirus (CMV) antibody-positive patients with anemia who were undergoing their first blood transfusion. The relations of the baseline qualitative and quantitative polymerase chain reaction (PCR) measures of plasma CMV viremia, HIV RNA, CD4 + cell counts, and quality of life in these study subjects were examined. The 511 study subjects had a median CD4 + cell count equal to 15 cells/mm 3 , and 110 (21.5%) had CMV viremia by qualitative assay. In multivariate models, frequency of positive qualitative CMV increased with decreasing CD4 + cell counts (p =.04 trend), higher HIV RNA (p

OBJECTIVES: To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis.METHODS: Historical cohort study in a population of infants born at RESULTS: Of 1362 patients, 55 suffered from GNS and 29 suffered from NCS; cumulative incidence 4.2% and 2.2%, respectively. During the follow-up period the mortality rate was 34% for both GNS and NCS and 5% for UC. The adjusted Odds Ratio (OR) [95% CI] for adverse outcome in the GNS group compared to the NCS group was 1.4 [0.4-4.9]. The adjusted ORs [95% CI] for adverse outcome in the GNS and NCS groups compared to the UC group were 4.8 [1.5-15.9] and 3.2 [0.7-14.7], respectively.CONCLUSIONS: We found no statistically significant difference in outcome at the corrected age of 24 months between neonatal GNS and NCS cases. Suffering from either gram-negative or Candida sepsis increased the odds for adverse outcome compared with an uncomplicated neonatal period.

LEENDERS, M., L. B. VERDIJK, L. VAN DER HOEVEN, J. VAN KRANENBURG, R. NILWIK, W. K. W. H. WODZIG, J. M. G. SENDEN, H. A. KEIZER, and L. J. C. VAN LOON. Protien Supplementation during Resistance-Type Exercise Training in the Elderly. Med. Sci. Sports Exerc., Vol. 45, No. 3, pp. 542–552, 2013. Introduction: Resistance training has been well established as an effective treatment strategy to increase skeletal muscle mass and strength in the elderly. We assessed whether dietary protein supplementation can further augment the adaptive response to prolonged resistance-type exercise training in healthy elderly men and women. Methods: Healthy elderly men (n = 31, 70 T 1 yr) and women (n = 29, 70 T 1 yr) were randomly assigned to a progressive, 24-wk resistance-type exercise training program with or without additional protein supplementation (15 gIdj1 ). Muscle hypertrophy was assessed on a wholebody Dual-energy X-ray absorptiometry (DXA), limb (computed tomography), and muscle fiber (biopsy) level. Strength was assessed regularly by 1-repetition maximum (RM) strength testing. Functional capacity was assessed with a sit-to-stand and handgrip test. Results: One-RM strength increased by 45% T 6% versus 40% T 3% (women) and 41% T 4% versus 44% T 3% (men) in the placebo versus protein group, respectively (P G 0.001), with no differences between groups. Leg muscle mass (women, 4% T 1% vs 3% T 1%; men, 3% T 1% vs 3% T 1%) and quadriceps cross-sectional area (women, 9% T 1% vs 9% T 1%; men, 9% T 1% vs 10% T 1%) increased similarly in the placebo versus protein groups (P G 0.001). Type II muscle fiber size increased over time in both placebo and protein groups (25% T 13% vs 30% T 9% and 23% T 12% vs 22% T 10% in the women and men, respectively). Sit-to-stand improved by 18% T 2% and 19% T 2% in women and men, respectively (P G 0.001). Conclusion: Prolonged resistance-type exercise training increases skeletal muscle mass and strength, augments functional capacity, improves glycemia and lipidemia, and reduces blood pressure in healthy elderly men and women. Additional protein supplementation (15 gIdj1 ) does not further increase muscle mass, strength, and/or functional capacity

Background The loss of muscle mass with aging reduces muscle strength, impairs functional capacity, and increases the risk of developing chronic metabolic disease. It has been suggested that the development of type 2 diabetes results in a more rapid decline in muscle mass, strength, and functional capacity. Objective To investigate the impact of type 2 diabetes on muscle mass, strength, and functional capacity in an older population. Methods Muscle mass (DXA and muscle biopsies), strength (1-repetition maximum), functional capacity (sit-to-stand test and handgrip strength), and reaction time performance (computer task) were compared between 60 older men with type 2 diabetes (71 ± 1 years) and 32 age-matched normoglycemic controls (70 ± 1 years). Data were analyzed using ANCOVA to adjust for several potential confounders. Results Leg lean mass and appendicular skeletal muscle mass were significantly lower in older men with type 2 diabetes (19.1 ± 0.3 and 25.9 ± 0.4 kg, respectively) compared with normoglycemic controls (19.7 ± 0.3 and 26.7 ± 0.5 kg, respectively). Additionally, leg extension strength was significantly lower in the group with type 2 diabetes (84 ± 2 vs 91 ± 2 kg, respectively). In agreement, functional performance was impaired in the men with type 2 diabetes, with longer sit-to-stand time (9.1 ± 0.4 vs 7.8 ± 0.3 seconds) and lower handgrip strength (39.5 ± 5.8 vs 44.6 ± 6.1 kg) when compared with normoglycemic controls. However, muscle fiber size and reaction time performance did not differ between groups. Conclusion Older patients with type 2 diabetes show an accelerated decline in leg lean mass, muscle strength, and functional capacity when compared with normoglycemic controls. Exercise intervention programs should be individualized to specifically target muscle mass, strength, and functional capacity in the older population with type 2 diabetes.

The impact of pollen on human health is primarily evident in allergic diseases. Sensitized patients can respond to pollen by symptoms of nose, eyes and bronchi. Pollen threshold levels for sensitization are unknown; instead most studies focus on the prevalence of sensitization for different pollen species. The pollen thresholds for symptom development vary among the different studies. Factors that influence the threshold level of a pollen species for symptom development are discussed. (i) Differences in response are observed among individual patients, but also among (ii) ethnic populations, (iii) changes in response to pollen concentrations during the pollen season occur, (iv) the amount of allergens carried by the pollen grains can differ in per region, from day to day and from year to year, and finally (v) threshold levels are affected by environmental factors, like weather conditions (temperature, pressure and storms), and air pollutants.The diversity of factors that influence the health impact of pollen has hampered the definition of a straight forward relationship between pollen and the severity of symptoms. However, within the public, the policymakers and the pharmaceutical industry there is a need for a definition of threshold pollen levels. A first approach to meet this need could be to define preliminary threshold values for different regions, followed by a validation of these preliminary threshold levels with patient symptom scores that can be collected by using new information and communication technology (ICT).

A Fall Committee was developed in response to an increase in the rate of falls by patients at a primarily behavioral health, urban teaching hospital in the mid-Atlantic region of the United States. The Fall Committee identified interventions to potentially lessen the number of patient falls and areas where documentation could be improved to better describe an incident in the medical record. The Fall Committee developed paperwork to be completed after each patient fall and made changes to the low fall risk and high fall risk treatment plans. This article describes the recommendations submitted by the Fall Committee and its subsequent implementation. Although not causational, the fall rate decreased after the recommendations of the Fall Committee were implemented; however, a recent rise in the fall rate was noted and attributed to higher patient acuity on the unit. The committee investigation into this issue highlighted the paucity of research in this field and the need for a streamlined, easy-to-use, behavioral health fall scale to more accurately judge the fall risk of patients in this specialized subset.

A progressive global increase in the burden of allergic diseases has affected the industrialized world over the last half century and has been reported in the literature. The clinical evidence reveals a general increase in both incidence and prevalence of respiratory diseases, such as allergic rhinitis (common hay fever) and asthma. Such phenomena may be related not only to air pollution and changes in lifestyle, but also to an actual increase in airborne quantities of allergenic pollen. Experimental enhancements of carbon dioxide (CO2) have demonstrated changes in pollen amount and allergenicity, but this has rarely been shown in the wider environment. The present analysis of a continental-scale pollen data set reveals an increasing trend in the yearly amount of airborne pollen for many taxa in Europe, which is more pronounced in urban than semi-rural/rural areas. Climate change may contribute to these changes, however increased temperatures do not appear to be a major influencing factor. Instead, we suggest the anthropogenic rise of atmospheric CO2 levels may be influential

Reduced expression of miR-129 has been reported in multiple tumor cell lines and in primary tumors including medulloblastoma, undifferentiated gastric cancers, lung adenocarcinoma, endometrial cancer and colorectal carcinoma. There is also recent evidence of an anti-proliferative activity of miR-129 in tumor cell lines. Still, little is known about how miR-129 regulates cell proliferation. Here we found that lentiviral-mediated overexpression of miR-129 in mouse lung epithelial cells (E10 cells) results in significant G(1) phase arrest that eventually leads to cell death. miR-129 induce G(1) phase arrest in multiple human lung adenocarcinoma cell lines, suggesting miR-129 targeting of G(1)/S phase-specific regulators. Interestingly, we show that Cdk6, a kinase involved in G(1)-S transition, is a direct target of miR-129. We also found the downregulation of three other cell cycle-related novel targets of miR-129, including Erk1, Erk2 and protein kinase C epsilon (Prkce). We further show that among these targets, only Cdk6 is functionally relevant. Restoring expression of Cdk6, but not Prkce partially rescues the cell growth arrest and cell death phenotype that results from miR-129 overexpression. Together, our data indicate that miR-129 plays an important role in regulating cell proliferation by downregulation of Cdk6.

Restocking is now a common practice in management of European rabbit Oryctolagus cuniculus in France, Portugal and Spain, following the decline of this species that occurred during the second half of the 20th century. This population decline was mainly due to the global change in the countryside caused by intensification of agriculture in temperate regions and conversely decline in Mediterranean regions, and to the appearance of new epizootics, myxomatosis in the 1950s (Ross and Tittensor 1986), and rabbit hemorrhagic disease in the 1980s (Marchandeau et al. 2000a). In addition, there has often been unsustainable hunting management of European rabbits. The extent of the population decline is shown by the French national bag records survey: 13.5 million rabbits in 1974/75, 6.4 million rabbits in 1983/84 and 3.2 million rabbits in 1998/99 (Arthur and Guenezan 1986; Marchandeau 2000). The European rabbit is not actually endangered, but many of its populations are still declining and cannot support sustained harvesting, which is problematic for hunting and for the conservation of rabbit-specialist predators such as the Iberian lynx (Lynx pardinus), the Imperial eagle (Aquila adalberti), or even the Bonelli’s eagle (Hieraaetus fasciatus). Therefore, hunters and wildlife managers have promoted rabbit restocking so that in south-western Europe, around half a million rabbits are translocated each year from large natural populations or breeding centres. However, the success of rabbit restocking is known to be generally low (Arthur 1989; Mauvy et al. 1991; Calvete et al. 1997; Letty et al. 2002a).

Inhalation medication is essential in the treatment of asthma and chronic obstructive pulmonary disease (COPD) patients. Incorrect inhalation technique reduces the effects of medication and has been reported to range from 22% to 95% from optimal. The objective of this study was to determine inter- and intraobserver reliability in inhalation technique assessment. For interobserver reliability three observers scored after three times viewing a total of 49 video recorded inhalation demonstrations using device-specific checklists and mutually agreed scoring rules. Intraobserver reliability was assessed for two observers after 8 months by scoring inhalation demonstrations a second time. Both inter- and intraobserver reliability were expressed by mean percent agreement and mean Kappa scores. All inhaler devices revealed a high mean percent agreement and a substantial or almost perfect Kappa scoring for both inter- and intraobserver reliability. Only one item, "exhale to residual volume," showed poor intraobserver reliability. Assessment of video recorded inhalation technique using device-specific checklists, triple viewing, and mutual agreed scoring rules is reliable. This method enables blind observation of inhalation technique.