A window of opportunity: improving cardiovascular health in women

From our daily lives we know that men and women differ considerably. Men buy cars and women shoes, men ruin the white laundry and women destroy acceleration gears, and we eagerly read the books describing that men are from Mars and women from Venus. These stereotypes do reflect the constant debate on gender differences in society. Similarly, it is increasingly accepted within cardiovascular health care that male and female patients might need another approach.     

A window of opportunity: Subdominant predators can use suboptimal prey

Introduced species have been linked to declines of native species through mechanisms including intraguild predation and exploitative competition. However, coexistence among species may be promoted by niche partitioning if native species can use resources that the invasive species cannot. Previous research has shown that some strains of the aphid Aphis craccivora are toxic to a competitively dominant invasive lady beetle, Harmonia axyridis. Our objective was to investigate whether these aphids might be an exploitable resource for other, subdominant, lady beetle species. We compared larval development rate, survival, and adult weight of five lady beetle species in no‐choice experiments with two different strains of A. craccivora, one of which is toxic to H. axyridis and one that is nontoxic. Two lady beetle species, Cycloneda munda and Coleomegilla maculata, were able to complete larval development when feeding on the aphid strain that is toxic to H. axyridis, experiencing only slight developmental delays relative to beetles feeding on the other aphid strain. One species, Coccinella septempunctata, also was able to complete larval development, but experienced a slight reduction in adult weight. The other two lady beetle species, Hippodamia convergens and Anatis labiculata, demonstrated generally low survivorship when consuming A. craccivora, regardless of aphid strain. All five species showed increased survival and/or development relative to H. axyridis on the “toxic” aphid strain. Our results suggest that this toxic trait may act as a narrow‐spectrum defense for the aphids, providing protection against only some lady beetle enemies. For other less‐susceptible lady beetles, these aphids have the potential to provide competitive release from the otherwise dominant H. axyridis.     

Eye movements: viewing the window of opportunity

When searching with our eyes, parallel programming of successive eye movements ensures that visual information arriving too late to alter the direction of one eye movement can still influence the direction of the next. Paradoxically, we can use random noise to probe the time period over which visual information influences where next to direct our gaze.     

Pediatric Post-Discharge Mortality in Resource Poor Countries: A Systematic Review

Objectives

Mortality following hospital discharge is an important and under-recognized contributor to overall child mortality in developing countries. The primary objective of this systematic review was to identify all studies reporting post-discharge mortality in children, estimate likelihood of death, and determine the most important risk factors for death.

Search Strategy

MEDLINE and EMBASE were systematically searched using MeSH terms and keywords from the inception date to October, 2012. Key word searches using Google Scholar™ and hand searching of references of retrieved articles was also performed. Studies from developing countries reporting mortality following hospital discharge among a pediatric population were considered for inclusion.

Results

Thirteen studies that reported mortality rates following discharge were identified. Studies varied significantly according to design, underlying characteristics of study population and duration of follow-up. Mortality rates following discharge varied significantly between studies (1%–18%). When reported, post-discharge mortality rates often exceeded in-hospital mortality rates. The most important baseline variables associated with post-discharge mortality were young age, malnutrition, multiple previous hospitalizations, HIV infection and pneumonia. Most post-discharge deaths occurred early during the post-discharge period. Follow-up care was examined in only one study examining malaria prophylaxis in children discharged following an admission secondary to malaria, which showed no significant benefit on post-discharge mortality.

Conclusions

The months following hospital discharge carry significant risk for morbidity and mortality. While several characteristics are strongly associated with post-discharge mortality, no validated tools are available to aid health workers or policy makers in the systematic identification of children at high risk of post-discharge mortality. Future research must focus on both the creation of tools to aid in defining groups of children most likely to benefit from post-discharge interventions, and formal assessment of the effectiveness of such interventions in reducing morbidity and mortality in the first few months following hospital discharge.     

Fenestration: a window of opportunity for carnivorous plants

A long-standing but controversial hypothesis assumes that carnivorous plants employ aggressive mimicry to increase their prey capture success. A possible mechanism is that pitcher plants use aggressive mimicry to deceive prey about the location of the pitcher''s exit. Specifically, species from unrelated families sport fenestration, i.e. transparent windows on the upper surfaces of pitchers which might function to mimic the exit of the pitcher. This hypothesis has not been evaluated against alternative hypotheses predicting that fenestration functions to attract insects from afar. By manipulating fenestration, we show that it does not increase the number of Drosophila flies or of two ant species entering pitchers in Sarracenia minor nor their retention time or a pitcher''s capture success. However, fenestration increased the number of Drosophila flies alighting on the pitcher compared with pitchers of the same plant without fenestration. We thus suggest that fenestration in S. minor is not an example of aggressive mimicry but rather functions in long-range attraction of prey. We highlight the need to evaluate aggressive mimicry relative to alternative concepts of plant–animal communication.     

Cotranslational control of DNA transposition: a window of opportunity

Transposable elements are important in genome dynamics and evolution. Bacterial insertion sequences (IS) constitute a major group in number and impact. Understanding their role in shaping genomes requires knowledge of how their transposition activity is regulated and interfaced with the host cell. One IS regulatory phenomenon is a preference of their transposases (Tpases) for action on the element from which they are expressed (cis) rather than on other copies of the same element (trans). Using IS911, we show in vivo that activity in cis was ~200 fold higher than in trans. We also demonstrate that a translational frameshifting pause signal influences cis preference presumably by facilitating sequential folding and cotranslational binding of the Tpase. In vitro, IS911 Tpase bound IS ends during translation but not after complete translation. Cotranslational binding of nascent Tpase permits tight control of IS proliferation providing a mechanistic explanation for cis regulation of transposition involving an unexpected partner, the ribosome.     

Probiotics tailored to the infant: a window of opportunity

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A window of opportunity: timing protein degradation by trimming of sugars and ubiquitins

Of the many post-translational modifications of proteins, ubiquitination and N-glycosylation stand out because they are polymeric additions. In contrast to single-unit modifications, the fate of the modified protein is determined by the dynamic equilibrium of polymerization versus depolymerization, rather than by the initial addition itself. Notably, it is the trimming of sugar chains and elongation of polyubiquitin that target the protein to degradation. Recent research suggests that, for each process, special receptors recognize chains that reach an appropriate length and commit the conjugated substrate for proteasomal disposal. We propose that the 'magic numbers' are loss of at least three mannose residues from the initial chain, or extension to at least four ubiquitins. Although these processes are compartmentalized to either side of the endoplasmic reticulum (ER) membrane, some proteins are sequentially subjected to both because they transverse this membrane for ER-associated degradation.     

The Spread of Multi Drug Resistant Infections Is Leading to an Increase in the Empirical Antibiotic Treatment Failure in Cirrhosis: A Prospective Survey

BackgroundThe spread of multi-resistant infections represents a continuously growing problem in cirrhosis, particularly in patients in contact with the healthcare environment.AimOur prospective study aimed to analyze epidemiology, prevalence and risk factors of multi-resistant infections, as well as the rate of failure of empirical antibiotic therapy in cirrhotic patients.MethodsAll consecutive cirrhotic patients hospitalized between 2008 and 2013 with a microbiologically-documented infection (MDI) were enrolled. Infections were classified as Community-Acquired (CA), Hospital-Acquired (HA) and Healthcare-Associated (HCA). Bacteria were classified as Multidrug-Resistant (MDR) if resistant to at least three antimicrobial classes, Extensively-Drug-Resistant (XDR) if only sensitive to one/two classes and Pandrug-Resistant (PDR) if resistant to all classes.ResultsOne-hundred-twenty-four infections (15% CA, 52% HA, 33% HCA) were observed in 111 patients. Urinary tract infections, pneumonia and spontaneous bacterial peritonitis were the more frequent. Forty-seven percent of infections were caused by Gram-negative bacteria. Fifty-one percent of the isolates were multi-resistant to antibiotic therapy (76% MDR, 21% XDR, 3% PDR): the use of antibiotic prophylaxis (OR = 8.4; 95%CI = 1.03-76; P = 0,05) and current/recent contact with the healthcare-system (OR = 3.7; 95%CI = 1.05-13; P = 0.04) were selected as independent predictors. The failure of the empirical antibiotic therapy was progressively more frequent according to the degree of resistance. The therapy was inappropriate in the majority of HA and HCA infections.ConclusionsMulti-resistant infections are increasing in hospitalized cirrhotic patients. A better knowledge of the epidemiological characteristics is important to improve the efficacy of empirical antibiotic therapy. The use of preventive measures aimed at reducing the spread of multi-resistant bacteria is also essential.     

The window of opportunity: a relevant concept for axial spondyloarthritis

The window of opportunity is a concept critical to rheumatoid arthritis treatment. Early treatment changes the outcome of rheumatoid arthritis treatment, in that response rates are higher with earlier disease-modifying anti-rheumatic drug treatment and damage is substantially reduced. Axial spondyloarthritis is an inflammatory axial disease encompassing both nonradiographic axial spondyloarthritis and established ankylosing spondylitis. In axial spondyloarthritis, studies of magnetic resonance imaging as well as tumor necrosis factor inhibitor treatment and withdrawal studies all suggest that early effective suppression of inflammation has the potential to reduce radiographic damage. This potential would suggest that the concept of a window of opportunity is relevant not only to rheumatoid arthritis but also to axial spondyloarthritis. The challenge now remains to identify high-risk patients early and to commence treatment without delay. Developments in risk stratification include new classification criteria, identification of clinical risk factors, biomarkers, genetic associations, potential antibody associations and an ankylosing spondylitis-specific microbiome signature. Further research needs to focus on the evidence for early intervention and the early identification of high-risk individuals.     

我国葡萄球菌的耐药性

本报告是利用纸片法对来自我国20个省市百余家医院1091株临床分离的金黄色葡萄球菌对12种常用的抗菌药物敏感性的调查报告,其结果表明99.7%的菌株对RIFAMPICINUM极度敏感,99.8%的菌株对CHLORAMPHENICOLUM和FURAZOLIDONUM高度敏感;29.6%的菌株对CARBENICILLNUM,21.1%的菌株对ERYTHROMYCINUM,18.1%的菌株对KANAMYCINUM,13.7%的菌株对PENICILLINUM NATRICUM耐药.调查结果表明,分布在我国南北方不同纬度的葡萄球菌对12种常用抗菌药物的敏感性基本相同,无明显的地域性差异.     

The phenological window of opportunity for early-season birch sawflies

Abstract 1. The phenological window of opportunity hypothesis posits that an insect herbivore cannot survive outside a specific leaf age interval of its host plant.
2. Previous studies have shown that mountain birch displays extensive seasonal changes in leaf biochemical characteristics. Young, expanding leaves are full of water and amino acids but they also contain large amounts of protein-precipitating gallotannins as well as flavonoid-glycosides. Concentrations of these compounds decline during leaf growth whereas concentrations of sugars and proanthocyanidins and leaf toughness increase.
3. Adult birch sawflies hatch in early summer and oviposit on growing leaves, which compels larvae to feed on leaves that are already well developed. The purpose of this study was to test whether leaves that were younger and biochemically different from the leaves available under natural conditions are within the phenological window of opportunity for the larvae of two early-season birch sawfly species, Amauronematus amplus Konow and Pristiphora alpestris (Konow).
4. Amauronematus amplus larvae survived better and developed faster, and P. alpestris larvae developed faster and became bigger, on atypically young leaves compared with larvae reared on leaves encountered normally. Therefore, these species can exploit the putative nutritional superiority of very young leaves, which probably outweighs the potential impact of the new set of secondary metabolites offered to them. In conclusion, young leaves that are consumed rarely by sawfly larvae are within their phenological window of opportunity, even though the timing of sawfly life cycles constrains their utilisation.     

An extended window of opportunity for G-CSF treatment in cerebral ischemia

Background  

Granulocyte-colony stimulating factor (G-CSF) is known as a powerful regulator of white blood cell proliferation and differentiation in mammals. We, and others, have shown that G-CSF is effective in treating cerebral ischemia in rodents, both relating to infarct size as well as functional recovery. G-CSF and its receptor are expressed by neurons, and G-CSF regulates apoptosis and neurogenesis, providing a rational basis for its beneficial short- and long-term actions in ischemia. In addition, G-CSF may contribute to re-endothelialisation and arteriogenesis in the vasculature of the ischemic penumbra. In addition to these trophic effects, G-CSF is a potent neuroprotective factor reliably reducing infarct size in different stroke models.     

Bedaquiline: Fallible Hope Against Drug Resistant Tuberculosis

Tuberculosis (TB) is a deadly bacterial infectious disease caused by intra-cellular pathogen Mycobacterium tuberculosis (Mtb). There were an estimated 1.4 million TB deaths in 2015 and an additional 0.4 million deaths resulting from TB among individuals with HIV. Drug-discovery for its cure is very slow in comparison with the causative organism’s fast pace of mutations conferring drug resistance. Moreover, the field of drug-discovery of anti-TB drugs is constantly being challenged by the drug resistant strains of Mtb. Several molecules/inhibitors are being tested across the pharmaceutical industry and research centres for their suitability as drug candidate. It takes immense effort, high costs and a whole lot of screening to bring a single molecule to the clinics for patient cure. In last 60 years, hundreds of molecules have been patented for their probable use to develop drug for treatment of TB. However, only one drug has been successfully approved that is bedaquiline (1-(6-bromo-2 -methoxy-quinolin-3-yl)-4-dimethylamino-2-naphtalen-1-yl-1-phenyl-butan-2-ol). This is a brief review about bedaquiline (BDQ), the only drug in last 45 years approved for curing drug-resistant pulmonary TB, its development, action mechanism and development of resistance against it.     

DDTRP: Database of Drug Targets for Resistant Pathogens

Emergence of drug resistance is a major threat to public health. Many pathogens have developed resistance to most of the existing antibiotics, and multidrug-resistant and extensively drug resistant strains are extremely difficult to treat. This has resulted in an urgent need for novel drugs. We describe a database called 'Database of Drug Targets for Resistant Pathogens' (DDTRP). The database contains information on drugs with reported resistance, their respective targets, metabolic pathways involving these targets, and a list of potential alternate targets for seven pathogens. The database can be accessed freely at http://bmi.icmr.org.in/DDTRP.     

Neonate human remains: a window of opportunity to the molecular study of ancient syphilis

Ancient DNA (aDNA) analysis can be a useful tool in bacterial disease diagnosis in human remains. However, while the recovery of Mycobacterium spp. has been widely successful, several authors report unsuccessful results regarding ancient treponemal DNA, casting doubts on the usefulness of this technique for the diagnosis of ancient syphilis. Here, we present results from an analysis of four newborn specimens recovered from the crypt of "La Ermita de la Soledad" (XVI-XVII centuries), located in the province of Huelva in the southwest of Spain. We extracted and analyzed aDNA in three independent laboratories, following specific procedures generally practiced in the aDNA field, including cloning of the amplified DNA fragments and sequencing of several clones. This is the most ancient case, reported to date, from which detection of DNA from T. pallidum subspecies pallidum has been successful in more than one individual, and we put forward a hypothesis to explain this result, taking into account the course of the disease in neonate individuals.