The significance of accumulated oropharyngeal secretions and swallowing frequency in predicting aspiration

This study retrospectively investigated the value of both endoscopically visible oropharyngeal secretions in the hypopharynx and swallowing frequency in the prediction of aspiration of food and liquid. Fiberoptic endoscopic evaluation of swallowing (FEES) was performed on a total of 69 individuals that included hospitalized elderly, nonhospitalized elderly, and young normal subjects. A four-level rating scale for determining the severity of accumulated orpharyngeal secretions was developed and employed to rate subjects prior to the presentation of food or liquid during the FEES. Spontaneous dry swallows were also counted during the observation period of the FEES. It was found that the accumulation of endoscopically visible oropharyngeal secretions located within the laryngeal vestibule was highly predictive of aspiration of food or liquid. There were significantly fewer spontaneous swallows in hospitalized subjects when compared with nonhospitalized subjects. There was also a significant decrease in the frequency of spontaneous swallows in aspirating hospitalized subjects when compared with nonaspirating hospitalized subjects. Results are discussed in terms of integrating this information with clinical bedside examination techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41360/1/455_2004_Article_BF00417898.pd

Individual tree and stand-level carbon and nutrient contents across one rotation of loblolly pine plantations on a reclaimed surface mine

While reclaimed loblolly pine (Pinus taeda L.) plantations in east Texas, USA have demonstrated similar aboveground productivity levels relative to unmined forests, there is interest in assessing carbon (C) and nutrients in aboveground components of reclaimed trees. Numerous studies have previously documented aboveground biomass, C, and nutrient contents in loblolly pine plantations; however, similar data have not been collected on mined lands. We investigated C, N, P, K, Ca, and Mg aboveground contents for first-rotation loblolly pine growing on reclaimed mined lands in the Gulf Coastal Plain over a 32-year chronosequence and correlated elemental rates to stand age, stem growth, and similar data for unmined lands. At the individual tree level, we evaluated elemental contents in aboveground biomass components using tree size, age, and site index as predictor variables. At the stand-level, we then scaled individual tree C and nutrients and fit a model to determine the sensitivity of aboveground elemental contents to stand age and site index. Our data suggest that aboveground C and nutrients in loblolly pine on mined lands exceed or follow similar trends to data for unmined pine plantations derived from the literature. Diameter and height were the best predictors of individual tree stem C and nutrient contents (R ≥ 0.9473 and 0.9280, respectively) followed by stand age (R ≥ 0.8660). Foliage produced weaker relationships across all predictor variables compared to stem, though still significant (P ≤ 0.05). The model for estimating stand-level C and nutrients using stand age provided a good fit, indicating that contents aggrade over time predictably. Results of this study show successful modelling of reclaimed loblolly pine aboveground C and nutrients, and suggest elemental cycling is comparable to unmined lands, thus providing applicability of our model to related systems

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients

Adult Circadian Behavior in Drosophila Requires Developmental Expression of cycle, But Not period

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex

Sonographic assessment of abdominal fat distribution in infancy

There is growing evidence that not only the total amount of fat, but also the distribution of body fat determines risks for metabolic and cardiovascular disease. Developmental studies on factors influencing body fat distribution have been hampered by a lack of appropriate techniques for measuring intraabdominal fat in early life. Sonography, which is an established method for assessing abdominal fat distribution in adults, has not yet been evaluated in infants. To adapt the sonographic measurement of abdominal fat distribution to infants and study its reliability. The Generation R study, a population-based prospective cohort study. We included 212 one- and 227 two-year old Dutch infants in the present analysis. Sixty-two infants underwent replicate measurements to assess reproducibility. We developed a standardized protocol to measure the thickness of (1) subcutaneous and (2) preperitoneal fat in the upper abdomen of infants. To this end we defined infancy specific measurement areas to quantify fat thickness. Reproducibility of fat measurements was good to excellent with intraclass correlation coefficients of 0.93–0.97 for intra-observer agreement and of 0.89–0.95 for inter-observer agreement. We observed a pronounced increase in preperitoneal fat thickness in the second year of life while subcutaneous fat thickness increased only slightly, resulting in an altered body fat distribution. Gender did not significantly influence fat distribution in the first two years of life. Our age specific protocol for the sonographic measurement of central subcutaneous and preperitoneal fat is a reproducible method that can be instrumental for investigating fat distribution in early life

The Antimicrobial Peptide Histatin-5 Causes a Spatially Restricted Disruption on the Candida albicans Surface, Allowing Rapid Entry of the Peptide into the Cytoplasm

Antimicrobial peptides play an important role in host defense against microbial pathogens. Their high cationic charge and strong amphipathic structure allow them to bind to the anionic microbial cell membrane and disrupt the membrane bilayer by forming pores or channels. In contrast to the classical pore-forming peptides, studies on histatin-5 (Hst-5) have suggested that the peptide is transported into the cytoplasm of Candida albicans in a non-lytic manner, and cytoplasmic Hst-5 exerts its candicidal activities on various intracellular targets, consistent with its weak amphipathic structure. To understand how Hst-5 is internalized, we investigated the localization of FITC-conjugated Hst-5. We find that Hst-5 is internalized into the vacuole through receptor-mediated endocytosis at low extracellular Hst-5 concentrations, whereas under higher physiological concentrations, Hst-5 is translocated into the cytoplasm through a mechanism that requires a high cationic charge on Hst-5. At intermediate concentrations, two cell populations with distinct Hst-5 localizations were observed. By cell sorting, we show that cells with vacuolar localization of Hst-5 survived, while none of the cells with cytoplasmic Hst-5 formed colonies. Surprisingly, extracellular Hst-5, upon cell surface binding, induces a perturbation on the cell surface, as visualized by an immediate and rapid internalization of Hst-5 and propidium iodide or rhodamine B into the cytoplasm from the site using time-lapse microscopy, and a concurrent rapid expansion of the vacuole. Thus, the formation of a spatially restricted site in the plasma membrane causes the initial injury to C. albicans and offers a mechanism for its internalization into the cytoplasm. Our study suggests that, unlike classical channel-forming antimicrobial peptides, action of Hst-5 requires an energized membrane and causes localized disruptions on the plasma membrane of the yeast. This mechanism of cell membrane disruption may provide species-specific killing with minimal damage to microflora and the host and may be used by many other antimicrobial peptides

Adult Circadian Behavior in Drosophila Requires Developmental Expression of cycle, But Not period

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex

The biogeography of abundant and rare bacterioplankton in the lakes and reservoirs of China.

Bacteria play key roles in the ecology of both aquatic and terrestrial ecosystems; however, little is known about their diversity and biogeography, especially in the rare microbial biosphere of inland freshwater ecosystems. Here we investigated aspects of the community ecology and geographical distribution of abundant and rare bacterioplankton using high-throughput sequencing and examined the relative influence of local environmental variables and regional (spatial) factors on their geographical distribution patterns in 42 lakes and reservoirs across China. Our results showed that the geographical patterns of abundant and rare bacterial subcommunities were generally similar, and both of them showed a significant distance-decay relationship. This suggests that the rare bacterial biosphere is not a random assembly, as some authors have assumed, and that its distribution is most likely subject to the same ecological processes that control abundant taxa. However, we identified some differences between the abundant and rare groups as both groups of bacteria showed a significant positive relationship between sites occupancy and abundance, but the abundant bacteria exhibited a weaker distance-decay relationship than the rare bacteria. Our results implied that rare subcommunities were mostly governed by local environmental variables, whereas the abundant subcommunities were mainly affected by regional factors. In addition, both local and regional variables that were significantly related to the spatial variation of abundant bacterial community composition were different to those of rare ones, suggesting that abundant and rare bacteria may have discrepant ecological niches and may play different roles in natural ecosystems

Body Mass Index and Diabetes in Asia: A Cross-Sectional Pooled Analysis of 900,000 Individuals in the Asia Cohort Consortium

10.1371/journal.pone.0019930PLoS ONE66

Effectiveness of individualized physiotherapy on pain and functioning compared to a standard exercise protocol in patients presenting with clinical signs of subacromial impingement syndrome. A randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Shoulder impingement syndrome is a common musculoskeletal complaint leading to significant reduction of health and disability. Physiotherapy is often the first choice of treatment although its effectiveness is still under debate. Systematic reviews in this field highlight the need for more high quality trials to investigate the effectiveness of physiotherapy interventions in patients with subacromial impingement syndrome.</p> <p>Methods/Design</p> <p>This randomized controlled trial will investigate the effectiveness of individualized physiotherapy in patients presenting with clinical signs and symptoms of subacromial impingement, involving 90 participants aged 18-75. Participants are recruited from outpatient physiotherapy clinics, general practitioners, and orthopaedic surgeons in Germany. Eligible participants will be randomly allocated to either individualized physiotherapy or to a standard exercise protocol using central randomization.</p> <p>The control group will perform the standard exercise protocol aiming to restore muscular deficits in strength, mobility, and coordination of the rotator cuff and the shoulder girdle muscles to unload the subacromial space during active movements. Participants of the intervention group will perform the standard exercise protocol as a home program, and will additionally be treated with individualized physiotherapy based on clinical examination results, and guided by a decision tree. After the intervention phase both groups will continue their home program for another 7 weeks.</p> <p>Outcome will be measured at 5 weeks and at 3 and 12 months after inclusion using the shoulder pain and disability index and patients' global impression of change, the generic patient-specific scale, the average weekly pain score, and patient satisfaction with treatment. Additionally, the fear avoidance beliefs questionnaire, the pain catastrophizing scale, and patients' expectancies of treatment effect are assessed. Participants' adherence to the protocol, use of additional treatments for the shoulder, direct and indirect costs, and sick leave due to shoulder complaints will be recorded in a shoulder log-book.</p> <p>Discussion</p> <p>To our knowledge this is the first trial comparing individualized physiotherapy based on a defined decision making process to a standardized exercise protocol. Using high-quality methodologies, this trial will add evidence to the limited body of knowledge about the effect of physiotherapy in patients with SIS.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN86900354</p