Global Proteinuria Guidelines: Are We Nearly There Yet?

Assessment of albumin and/or protein excretion in the urine is a key step in the early detection and appropriate management of chronic kidney disease. The approach to testing for albuminuria/proteinuria in the community is variable and often suboptimal. It is hampered by: variation in laboratory measurement; lack of standard reference materials and testing procedures; variable definitions and units of reporting; conflicting recommendations and practices regarding who to test; and uncertainty over when and how testing is most appropriately done. This review discusses the current status of proteinuria guidelines around the world and the key clinical issues that need to be addressed before a unifying global guideline can be developed.     

Global Epidemiology of Mental Disorders: What Are We Missing?

Background

Population-based studies provide the understanding of health-need required for effective public health policy and service-planning. Mental disorders are an important but, until recently, neglected agenda in global health. This paper reviews the coverage and limitations in global epidemiological data for mental disorders and suggests strategies to strengthen the data.

Methods

Systematic reviews were conducted for population-based epidemiological studies in mental disorders to inform new estimates for the global burden of disease study. Estimates of population coverage were calculated, adjusted for study parameters (age, gender and sampling frames) to quantify regional coverage.

Results

Of the 77,000 data sources identified, fewer than 1% could be used for deriving national estimates of prevalence, incidence, remission, and mortality in mental disorders. The two major limitations were (1) highly variable regional coverage, and (2) important methodological issues that prevented synthesis across studies, including the use of varying case definitions, the selection of samples not allowing generalization, lack of standardized indicators, and incomplete reporting. North America and Australasia had the most complete prevalence data for mental disorders while coverage was highly variable across Europe, Latin America, and Asia Pacific, and poor in other regions of Asia and Africa. Nationally-representative data for incidence, remission, and mortality were sparse across most of the world.

Discussion

Recent calls to action for global mental health were predicated on the high prevalence and disability of mental disorders. However, the global picture of disorders is inadequate for planning. Global data coverage is not commensurate with other important health problems, and for most of the world''s population, mental disorders are invisible and remain a low priority.     

Is the Distribution of α-Tocopherol in Membranes Consistent with Its Putative Functions?

Vitamin E acts as an antioxidant and stabilizer of membranes. Other functions of vitamin E unrelated to its effects on membranes are emerging. Vitamin E partitions into the lipid bilayer matrix of membranes. It orients perpendicularly to the plane of the membrane with the hydroxyl group pointing to the lipid-water interface. The vitamin is not randomly distributed in the plane of the membrane but tends to form clusters. These clusters appear to be composed of vitamin E and phosphatidylcholine in a stoichiometry of about one vitamin E per 10 phospholipid molecules. Vitamin E partitions into domains of phosphatidylcholine in model membranes formed from mixtures of phosphatidylcholine and phosphatidylethanolamine irrespective of whether the phosphatidylcholine is in the fluid or gel phase. The creation of domains enriched in vitamin E in membranes is not consistent with an antioxidant function and effects on membrane structure and stability indicate other roles of the vitamin.     

A Direct Coupling between Global and Internal Motions in a Single Domain Protein? MD Investigation of Extreme Scenarios

Proteins are not rigid molecules, but exhibit internal motions on timescales ranging from femto- to milliseconds and beyond. In solution, proteins also experience global translational and rotational motions, sometimes on timescales comparable to those of the internal fluctuations. The possibility that internal and global motions may be directly coupled has intriguing implications, given that enzymes and cell signaling proteins typically associate with binding partners and cellular scaffolds. Such processes alter their global motion and may affect protein function. Here, we present molecular dynamics simulations of extreme case scenarios to examine whether a possible relationship exists. In our model protein, a ubiquitin-like RhoGTPase binding domain of plexin-B1, we removed either internal or global motions. Comparisons with unrestrained simulations show that internal and global motions are not appreciably coupled in this single-domain protein. This lack of coupling is consistent with the observation that the dynamics of water around the protein, which is thought to permit, if not stimulate, internal dynamics, is also largely independent of global motion. We discuss implications of these results for the structure and function of proteins.     

Are most samples of animals systematically biased? Consistent individual trait differences bias samples despite random sampling

Sampling animals from the wild for study is something nearly every biologist has done, but despite our best efforts to obtain random samples of animals, ‘hidden’ trait biases may still exist. For example, consistent behavioral traits can affect trappability/catchability, independent of obvious factors such as size and gender, and these traits are often correlated with other repeatable physiological and/or life history traits. If so, systematic sampling bias may exist for any of these traits. The extent to which this is a problem, of course, depends on the magnitude of bias, which is presently unknown because the underlying trait distributions in populations are usually unknown, or unknowable. Indeed, our present knowledge about sampling bias comes from samples (not complete population censuses), which can possess bias to begin with. I had the unique opportunity to create naturalized populations of fish by seeding each of four small fishless lakes with equal densities of slow-, intermediate-, and fast-growing fish. Using sampling methods that are not size-selective, I observed that fast-growing fish were up to two-times more likely to be sampled than slower-growing fish. This indicates substantial and systematic bias with respect to an important life history trait (growth rate). If correlations between behavioral, physiological and life-history traits are as widespread as the literature suggests, then many animal samples may be systematically biased with respect to these traits (e.g., when collecting animals for laboratory use), and affect our inferences about population structure and abundance. I conclude with a discussion on ways to minimize sampling bias for particular physiological/behavioral/life-history types within animal populations.     

Continuum Gating Current Models Computed with Consistent Interactions

The action potential of nerve and muscle is produced by voltage-sensitive channels that include a specialized device to sense voltage. The voltage sensor depends on the movement of charges in the changing electric field as suggested by Hodgkin and Huxley. Gating currents of the voltage sensor are now known to depend on the movements of positively charged arginines through the hydrophobic plug of a voltage sensor domain. Transient movements of these permanently charged arginines, caused by the change of transmembrane potential V, further drag the S4 segment and induce opening/closing of the ion conduction pore by moving the S4-S5 linker. This moving permanent charge induces capacitive current flow everywhere. Everything interacts with everything else in the voltage sensor and protein, and so it must also happen in its mathematical model. A Poisson-Nernst-Planck (PNP)-steric model of arginines and a mechanical model for the S4 segment are combined using energy variational methods in which all densities and movements of charge satisfy conservation laws, which are expressed as partial differential equations in space and time. The model computes gating current flowing in the baths produced by arginines moving in the voltage sensor. The model also captures the capacitive pile up of ions in the vestibules that link the bulk solution to the hydrophobic plug. Our model reproduces the signature properties of gating current: 1) equality of ON and OFF charge Q in integrals of gating current, 2) saturating voltage dependence in the Q(charge)-voltage curve, and 3) many (but not all) details of the shape of gating current as a function of voltage. Our results agree qualitatively with experiments and can be improved by adding more details of the structure and its correlated movements. The proposed continuum model is a promising tool to explore the dynamics and mechanism of the voltage sensor.     

Global Warming： Can Existing Reserves Really Preserve Current Levels of Biological Diversity？

Peleoecologlcel evidence end peleoclimatlc records indicate that there wee e plant polewerd migration in latitude and an upward shift In elevation with increased temperatures after the last glaciation. Recent studies have shown that global warming over the past 100 years has been having a noticeable effect on living systems. Current global warming Is causing a poleward and upward shift In the range of many plants and animals. Climate change, In connection with other global changes, is threatening the survival of a wide range of plant and animal species. This raises the question： can existing reserves really preserve current levels of biological diversity In the long term given the present rapid pace of climate change？ The present paper deals with this question In the context of the responses of plants and animals to global climate change, based on a literature review. Consequently, we recommend expanding reserves towards the poles and/or towards higher altitudes, to permit species to shift their ranges to keep pace with global warming.     

Are patients with non-ST elevation myocardial infarction undertreated?

Background

We have previously documented significant differences in orthogonal P wave morphology between patients with and without paroxysmal atrial fibrillation (PAF). However, there exists little data concerning normal P wave morphology. This study was aimed at exploring orthogonal P wave morphology and its variations in healthy subjects.

Methods

120 healthy volunteers were included, evenly distributed in decades from 20–80 years of age; 60 men (age 50+/-17) and 60 women (50+/-16). Six-minute long 12-lead ECG registrations were acquired and transformed into orthogonal leads. Using a previously described P wave triggered P wave signal averaging method we were able to compare similarities and differences in P wave morphologies.

Results

Orthogonal P wave morphology in healthy individuals was predominately positive in Leads X and Y. In Lead Z, one third had negative morphology and two-thirds a biphasic one with a transition from negative to positive. The latter P wave morphology type was significantly more common after the age of 50 (P < 0.01). P wave duration (PWD) increased with age being slightly longer in subjects older than 50 (121+/-13 ms vs. 128+/-12 ms, P < 0.005). Minimal intraindividual variation of P wave morphology was observed.

Conclusion

Changes of signal averaged orthogonal P wave morphology (biphasic signal in Lead Z), earlier reported in PAF patients, are common in healthy subjects and appear predominantly after the age of 50. Subtle age-related prolongation of PWD is unlikely to be sufficient as a sole explanation of this finding that is thought to represent interatrial conduction disturbances. To serve as future reference, P wave morphology parameters of the healthy subjects are provided.     

Are low cholesterol values associated with excess mortality?

The relation between cholesterol concentration and mortality was studied prospectively over 17 years in 630 New Zealand Maoris aged 25-74. The dead or alive state of each person was determined in 1981. The causes of death were divided into three categories: cancer, cardiovascular disease, and "other." Using univariate and both linear and non-linear multivariate methods of analysis for survivorship data, significant inverse relations with serum cholesterol were found for total mortality in women, for mortality from cancer in men and women, and for other causes of mortality in both men and women. The inverse and non-linear association with total mortality in women remained significant when deaths in the first five years of follow up were excluded. This suggests that the association was not explained by undetected illness causing low cholesterol concentrations at the time of initial examination.     

Are seals frequently infected with avian influenza viruses?

Influenza A virus isolates of the H4N5 subtype (which has previously been detected only in birds) were recovered from harbor seals dying of viral pneumonia on the New England coast from June 1982 through March 1983. When these isolates were compared with other mammalian and avian viruses in serological assays and RNA-RNA competitive hybridization, it was found that the seal viruses were most closely related antigenically and genetically to recent avian virus strains and were readily distinguishable from mammalian viruses, including H7N7 isolates recovered from seals in 1980. Unlike any previous isolates from mammals, these recent seal viruses replicate in the intestinal tracts of ducks, a characteristic of avian viruses. The association of avian viruses with influenza outbreaks in seals suggests that transmission of avian viruses to seals is occurring in nature. Potentially, this may be an example of the adaptation of avian viruses to mammals, which would represent an intermediate step in the evolution of new mammalian strains.     

Reference Valence Effects of Affective S–R Compatibility: Are Visual and Auditory Results Consistent?

Humans may be faster to avoid negative words than to approach negative words, and faster to approach positive words than to avoid positive words. That is an example of affective stimulus–response (S–R) compatibility. The present study identified the reference valence effects of affective stimulus–response (S–R) compatibility when auditory stimulus materials are used. The researchers explored the reference valence effects of affective S–R compatibility using a mixed-design experiment based on visual words, visual pictures and audition. The study computed the average compatibility effect size. A t-test based on visual pictures showed that the compatibility effect size was significantly different from zero, t (22) = 2.43, p<.05 (M = 485 ms). Smaller compatibility effects existed when switching the presentation mode from visual stimuli to auditory stimuli. This study serves as an important reference for the auditory reference valence effects of affective S–R compatibility.     

Are Trade-Offs Among Species’ Ecological Interactions Scale Dependent? A Test Using Pitcher-Plant Inquiline Species

Trade-offs among species' ecological interactions is a pervasive explanation for species coexistence. The traits associated with trade-offs are typically measured to mechanistically explain species coexistence at a single spatial scale. However, species potentially interact at multiple scales and this may be reflected in the traits among coexisting species. I quantified species' ecological traits associated with the trade-offs expected at both local (competitive ability and predator tolerance) and regional (competitive ability and colonization rate) community scales. The most common species (four protozoa and a rotifer) from the middle trophic level of a pitcher plant (Sarracenia purpurea) inquiline community were used to link species traits to previously observed patterns of species diversity and abundance. Traits associated with trade-offs (competitive ability, predator tolerance, and colonization rate) and other ecological traits (size, growth rate, and carrying capacity) were measured for each of the focal species. Traits were correlated with one another with a negative relationship indicative of a trade-off. Protozoan and rotifer species exhibited a negative relationship between competitive ability and predator tolerance, indicative of coexistence at the local community scale. There was no relationship between competitive ability and colonization rate. Size, growth rate, and carrying capacity were correlated with each other and the trade-off traits: Size was related to both competitive ability and predator tolerance, but growth rate and carrying capacity were correlated with predator tolerance. When partial correlations were conducted controlling for size, growth rate and carrying capacity, the trade-offs largely disappeared. These results imply that body size is the trait that provides the basis for ecological interactions and trade-offs. Altogether, this study showed that the examination of species' traits in the context of coexistence at different scales can contribute to our understanding of the mechanisms underlying community structure.     

Are antibodies important in mice infected with Plasmodium yoelii?

It is unwise to extrapolate results, even from one mouse strain to another, when attempting to define the mechanisms that control and effect anti-malaria immunity. It is important to better characterize the broad range o f possible responses that are likely to occur when individuals in an outbred population are infected. Here, Peter Sayles and Donald Wossom discuss briefly their views on the role of antibody in murine and human malaria infections, based on their work on mice infected with Plasmodium yoelii.