Auxotab—a Device for Identifying Enteric Bacteria

A multitest system called the Auxotab that uses ten dehydrated reagents on a paper card has been evaluated with 417 known stock cultures of Enterobacteriaceae. In double-blind studies with the Auxotab, 87% of the strains tested were correctly identified. Results of this study indicate that there is a need for modification of the product in regard to ease of handling, time required for use, and accuracy of identification of enteric bacteria.     

Can a Shorter Psychomotor Vigilance Task Be Usedas a Reasonable Substitute for the Ten‐Minute Psychomotor Vigilance Task?

The 10 min psychomotor vigilance task (PVT) is commonly used in laboratory studies to assess the impact of sleep loss, sustained wakefulness, and/or time of day on neurobehavioral performance. In field settings, though, it may be impractical for participants to perform a test of this length. The aim of this study was to identify a performance measure that is sensitive to the effects of fatigue but less burdensome than a 10 min test. Sixteen participants (11 female, 5 male; mean age=21.7 years) slept in the sleep laboratory overnight then remained awake for 28 h from 08:00 h. During every second hour, participants completed three PVTs of differing duration (10 min, 5 min, 90 sec). For the 5 min/10 min comparison, ANOVA indicated that response time was significantly affected by test length (F_1,14=26.9, p<.001) and hours of wakefulness (F_13,182=46.1, p<.001) but not by their interaction (F_13,182=1.7, ns). There was a strong correlation between response time on the 5 and 10 min PVTs (r=.88, p<.001). For the 90 sec/10 min comparison, ANOVA indicated that response time was significantly affected by test length (F_1,14=65.9, p<.001) and hours of wakefulness (F_13,182=29.7, p<.001) as well as by their interaction (F_13,182=6.0, p<.001). There was a strong correlation between response time on the 90 sec and 10 min PVTs (r=.77, p<.001). The effects of hours of wakefulness on neurobehavioral performance were similar for the 5 min and 10 min PVTs. In contrast, performance on the 90 sec PVT was less affected by hours of wakefulness than on the 10 min PVT. In addition, performance on the 10 min PVT was more highly correlated with the 5 min PVT than the 90 sec PVT. These data indicate that the 5 min PVT may provide a reasonable substitute for the 10 min PVT in circumstances where a test shorter than 10 min is required.     

Inhibitory effects of arbutin-β-glycosides synthesized from enzymatic transglycosylation for melanogenesis

To develop a new skin whitening agent, arbutin-β-glycosides were synthesized and evaluated for their melanogenesis inhibitory activities. Three active compounds were synthesized via the transglycosylation reaction of Thermotoga neapolitana β-glucosidase and purified by recycling preparative HPLC. As compared with arbutin (IC₅₀ = 6 mM), the IC₅₀ values of these compounds were 8, 10, and 5 mM for β-d-glucopyranosyl-(1→6)-arbutin, β-d-glucopyranosyl-(1→4)-arbutin, and β-d-glucopyranosyl-(1→3)-arbutin, respectively. β-d-Glucosyl-(1→3)-arbutin also exerted the most profound inhibitory effects on melanin synthesis in B16F10 melanoma cells. Melanin synthesis was inhibited to a significant degree at 5 mM, at which concentration the melanin content was reduced to below 70% of that observed in the untreated cells. Consequently, β-d-glucopyranosyl-(1→3)-arbutin is a more effective depigmentation agent and is also less cytotoxic than the known melanogenesis inhibitor, arbutin.     

What Do We Really Know about Cognitive Inhibition? Task Demands and Inhibitory Effects across a Range of Memory and Behavioural Tasks

Our study explores inhibitory control across a range of widely recognised memory and behavioural tasks. Eighty-seven never-depressed participants completed a series of tasks designed to measure inhibitory control in memory and behaviour. Specifically, a variant of the selective retrieval-practice and the Think/No-Think tasks were employed as measures of memory inhibition. The Stroop-Colour Naming and the Go/No-Go tasks were used as measures of behavioural inhibition. Participants completed all 4 tasks. Task presentation order was counterbalanced across 3 separate testing sessions for each participant. Standard inhibitory forgetting effects emerged on both memory tasks but the extent of forgetting across these tasks was not correlated. Furthermore, there was no relationship between memory inhibition tasks and either of the main behavioural inhibition measures. At a time when cognitive inhibition continues to gain acceptance as an explanatory mechanism, our study raises fundamental questions about what we actually know about inhibition and how it is affected by the processing demands of particular inhibitory tasks.     

Avoidance of roads and selection for recent cutovers by threatened caribou: fitness-rewarding or maladaptive behaviour?

The impact of anthropogenic disturbance on the fitness of prey should depend on the relative effect of human activities on different trophic levels. This verification remains rare, however, especially for large animals. We investigated the functional link between habitat selection of female caribou (Rangifer tarandus) and the survival of their calves, a fitness correlate. This top-down controlled population of the threatened forest-dwelling caribou inhabits a managed forest occupied by wolves (Canis lupus) and black bears (Ursus americanus). Sixty-one per cent of calves died from bear predation within two months following their birth. Variation in habitat selection tactics among mothers resulted in different mortality risks for their calves. When calves occupied areas with few deciduous trees, they were more likely to die from predation if the local road density was high. Although caribou are typically associated with pristine forests, females selected recent cutovers without negative impact on calf survival. This selection became detrimental, however, as regeneration took place in harvested stands owing to increased bear predation. We demonstrate that human disturbance has asymmetrical consequences on the trophic levels of a food web involving multiple large mammals, which resulted in habitat selection tactics with a greater short-term fitness payoff and, therefore, with higher evolutionary opportunity.     

What Happens after Inbreeding Avoidance? Inbreeding by Rejected Relatives and the Inclusive Fitness Benefit of Inbreeding Avoidance

Avoiding inbreeding, and therefore avoiding inbreeding depression in offspring fitness, is widely assumed to be adaptive in systems with biparental reproduction. However, inbreeding can also confer an inclusive fitness benefit stemming from increased relatedness between parents and inbred offspring. Whether or not inbreeding or avoiding inbreeding is adaptive therefore depends on a balance between inbreeding depression and increased parent-offspring relatedness. Existing models of biparental inbreeding predict threshold values of inbreeding depression above which males and females should avoid inbreeding, and predict sexual conflict over inbreeding because these thresholds diverge. However, these models implicitly assume that if a focal individual avoids inbreeding, then both it and its rejected relative will subsequently outbreed. We show that relaxing this assumption of reciprocal outbreeding, and the assumption that focal individuals are themselves outbred, can substantially alter the predicted thresholds for inbreeding avoidance for focal males. Specifically, the magnitude of inbreeding depression below which inbreeding increases a focal male’s inclusive fitness increases with increasing depression in the offspring of a focal female and her alternative mate, and it decreases with increasing relatedness between a focal male and a focal female’s alternative mate, thereby altering the predicted zone of sexual conflict. Furthermore, a focal male’s inclusive fitness gain from avoiding inbreeding is reduced by indirect opportunity costs if his rejected relative breeds with another relative of his. By demonstrating that variation in relatedness and inbreeding can affect intra- and inter-sexual conflict over inbreeding, our models lead to novel predictions for family dynamics. Specifically, parent-offspring conflict over inbreeding might depend on the alternative mates of rejected relatives, and male-male competition over inbreeding might lead to mixed inbreeding strategies. Making testable quantitative predictions regarding inbreeding strategies occurring in nature will therefore require new models that explicitly capture variation in relatedness and inbreeding among interacting population members.     

Site-specific Inhibitory Mechanism for Amyloid β42 Aggregation by Catechol-type Flavonoids Targeting the Lys Residues

The aggregation of the 42-residue amyloid β-protein (Aβ42) is involved in the pathogenesis of Alzheimer disease (AD). Numerous flavonoids exhibit inhibitory activity against Aβ42 aggregation, but their mechanism remains unclear in the molecular level. Here we propose the site-specific inhibitory mechanism of (+)-taxifolin, a catechol-type flavonoid, whose 3′,4′-dihydroxyl groups of the B-ring plays a critical role. Addition of sodium periodate, an oxidant, strengthened suppression of Aβ42 aggregation by (+)-taxifolin, whereas no inhibition was observed under anaerobic conditions, suggesting the inhibition to be associated with the oxidation to form o-quinone. Because formation of the Aβ42-taxifolin adduct was suggested by mass spectrometry, Aβ42 mutants substituted at Arg⁵, Lys¹⁶, and/or Lys²⁸ with norleucine (Nle) were prepared to identify the residues involved in the conjugate formation. (+)-Taxifolin did not suppress the aggregation of Aβ42 mutants at Lys¹⁶ and/or Lys²⁸ except for the mutant at Arg⁵. In addition, the aggregation of Aβ42 was inhibited by other catechol-type flavonoids, whereas that of K16Nle-Aβ42 was not. In contrast, some non-catechol-type flavonoids suppressed the aggregation of K16Nle-Aβ42 as well as Aβ42. Furthermore, interaction of (+)-taxifolin with the β-sheet region in Aβ42 was not observed using solid-state NMR unlike curcumin of the non-catechol-type. These results demonstrate that catechol-type flavonoids could specifically suppress Aβ42 aggregation by targeting Lys residues. Although the anti-AD activity of flavonoids has been ascribed to their antioxidative activity, the mechanism that the o-quinone reacts with Lys residues of Aβ42 might be more intrinsic. The Lys residues could be targets for Alzheimer disease therapy.     

Task Shifting for Non-Communicable Disease Management in Low and Middle Income Countries – A Systematic Review

Background

One potential solution to limited healthcare access in low and middle income countries (LMIC) is task-shifting- the training of non-physician healthcare workers (NPHWs) to perform tasks traditionally undertaken by physicians. The aim of this paper is to conduct a systematic review of studies involving task-shifting for the management of non-communicable disease (NCD) in LMIC.

Methods

A search strategy with the following terms “task-shifting”, “non-physician healthcare workers”, “community healthcare worker”, “hypertension”, “diabetes”, “cardiovascular disease”, “mental health”, “depression”, “chronic obstructive pulmonary disease”, “respiratory disease”, “cancer” was conducted using Medline via Pubmed and the Cochrane library. Two reviewers independently reviewed the databases and extracted the data.

Findings

Our search generated 7176 articles of which 22 were included in the review. Seven studies were randomised controlled trials and 15 were observational studies. Tasks performed by NPHWs included screening for NCDs and providing primary health care. The majority of studies showed improved health outcomes when compared with usual healthcare, including reductions in blood pressure, increased uptake of medications and lower depression scores. Factors such as training of NPHWs, provision of algorithms and protocols for screening, treatment and drug titration were the main enablers of the task-shifting intervention. The main barriers identified were restrictions on prescribing medications and availability of medicines. Only two studies described cost-effective analyses, both of which demonstrated that task-shifting was cost-effective.

Conclusions

Task-shifting from physicians to NPHWs, if accompanied by health system re-structuring is a potentially effective and affordable strategy for improving access to healthcare for NCDs. Since the majority of study designs reviewed were of inadequate quality, future research methods should include robust evaluations of such strategies.     

Avoidance and prohibition of brother–sister sex in humans

Sex between full sibs is unusual in birds, mammals, and humans. These species likely possess an innate avoidance mechanism based on early proximity (i.e., the Westermarck hypothesis), and the rare occurrences may be attributable to error. Alternatively, an inclusive fitness argument shows that a low rate of sib mating may be an adaptation. The widespread occurrence of a prohibition against brother–sister sex in human societies is often invoked as evidence against an innate avoidance mechanism, since if the latter were to exist the former would be superfluous. However, given that punishing violators is costly, a prohibition is more likely to spread through an egalitarian society when the prohibited behavior is already avoided. I describe a model of the cultural dynamics of the sibling incest taboo which we have used to investigate this possibility. The predictions derived from this model are consistent with, and add rigor to, Westermarcks theory of the origin of the incest taboo.     

Differential Diagnosis of Malaria on Truelab Uno?, a Portable,Real-Time,MicroPCR Device for Point-Of-Care Applications

Background

Sensitive and specific detection of malarial parasites is crucial in controlling the significant malaria burden in the developing world. Also important is being able to identify life threatening Plasmodium falciparum malaria quickly and accurately to reduce malaria related mortality. Existing methods such as microscopy and rapid diagnostic tests (RDTs) have major shortcomings. Here, we describe a new real-time PCR-based diagnostic test device at point-of-care service for resource-limited settings.

Methods

Truenat^® Malaria, a chip-based microPCR test, was developed by bigtec Labs, Bangalore, India, for differential identification of Plasmodium falciparum and Plasmodium vivax parasites. The Truenat Malaria tests runs on bigtec’s Truelab Uno^® microPCR device, a handheld, battery operated, and easy-to-use real-time microPCR device. The performance of Truenat^® Malaria was evaluated versus the WHO nested PCR protocol. The Truenat^® Malaria was further evaluated in a triple-blinded study design using a sample panel of 281 specimens created from the clinical samples characterized by expert microscopy and a rapid diagnostic test kit by the National Institute of Malaria Research (NIMR). A comparative evaluation was done on the Truelab Uno^® and a commercial real-time PCR system.

Results

The limit of detection of the Truenat Malaria assay was found to be <5 parasites/μl for both P. falciparum and P. vivax. The Truenat^® Malaria test was found to have sensitivity and specificity of 100% each, compared to the WHO nested PCR protocol based on the evaluation of 100 samples. The sensitivity using expert microscopy as the reference standard was determined to be around 99.3% (95% CI: 95.5–99.9) at the species level. Mixed infections were identified more accurately by Truenat Malaria (32 samples identified as mixed) versus expert microscopy and RDTs which detected 4 and 5 mixed samples, respectively.

Conclusion

The Truenat^® Malaria microPCR test is a valuable diagnostic tool and implementation should be considered not only for malaria diagnosis but also for active surveillance and epidemiological intervention.     

FAD: Fish Aggregating Device or Fish Attracting Device? A new analysis of yellowfin tuna movements around floating objects

Tropical tuna are known to associate with floating objects. Because fish are easier to detect and to catch when around these objects, fishermen have extensively deployed a large number of artificial floating objects in the tropical oceans. Although such objects are referred to as Fish Aggregating Devices (FADs), there is yet no strong evidence that fish do show an aggregative behaviour around them. The high probability of finding tuna around FADs may be the result of an aggregation process (high density of fish because fish stay for a long time around FADs) as well as an attraction process (high flow of fish through FADs). We analysed the movements of 14 yellowfin tuna, Thunnus albacares, in relation to FADs moored in the Indian and Pacific Oceans (corresponding to all the published tracking data) to determine whether the observed movement patterns resulted from an aggregation or an attraction process. Tuna appeared to be attracted by FADs. In general, they did not stay for long close to the FADs reached, and so did not aggregate there. Some FADs may nevertheless act as Fish Aggregating Devices. The possible reasons why tuna associate with floating objects are discussed in the light of these results.     

Is Rumination after Bereavement Linked with Loss Avoidance? Evidence from Eye-Tracking

Rumination is a risk factor in adjustment to bereavement. It is associated with and predicts psychopathology after loss. Yet, the function of rumination in bereavement remains unclear. In the past, researchers often assumed rumination to be a maladaptive confrontation process. However, based on cognitive avoidance theories of worry in generalised anxiety disorder (GAD) and rumination after post-traumatic stress disorder (PTSD), others have suggested that rumination may serve to avoid painful aspects of the loss, thereby contributing to complicated grief. To examine if rumination is linked with loss avoidance, an eye-tracking study was conducted with 54 bereaved individuals (27 high and 27 low ruminators). On 24 trials, participants looked for 10 seconds at a picture of the deceased and a picture of a stranger, randomly combined with negative, neutral or loss-related words. High ruminators were expected to show initial vigilance followed by subsequent disengagement for loss stimuli (i.e., picture deceased with a loss word) in the first 1500 ms. Additionally, we expected high ruminators to avoid these loss stimuli and to show attentional preference for non-loss-related negative stimuli (i.e., picture stranger with a negative word) on longer exposure durations (1500–10000 ms). Contrary to expectations, we found no evidence for an effect of rumination on vigilance and disengagement of loss stimuli in the first 1500 ms. However, in the 1500–10000 ms interval, high ruminators showed shorter gaze times for loss stimuli and longer gaze times for negative (and neutral) non-loss-related stimuli, even when controlling for depression and complicated grief symptom levels. Effects of rumination on average fixation times mirrored these findings. This suggests that rumination and loss avoidance are closely associated. A potential clinical implication is that rumination and grief complications after bereavement may be reduced through the use of exposure and acceptance-based therapeutic techniques.     

Derivation of Inhibitory Peptides to Target the Cardiac Troponin C–I Interaction as Potential Therapeutics for Heart Failure

The Ca²⁺-sensitive cardiac troponin (cTn) is a hetero-trimer complex consisting of three subunits cTnC, cTnI, and cTnT, which has been recognized as an important biomarker and a potential target of cardiovascular diseases. Previously, several small-molecule agents such as levosimendan and pimobendan have been successfully developed to target this protein for the treatment of heart failure. Here, instead of small-molecule chemical drugs, we purposed rational derivation of self-inhibitory peptides as potential biologic disruptors of cTnC–cTnI interaction from the interaction complex interface. In the procedure, the crystal structure of cTn trimer was examined in detail using bioinformatics approach, from which a peptide-mediated interaction between the N-terminal domain of cTnC and the switch region of cTnI was identified. The switch is a 19-mer peptide segment Swt that contains a structured helical core capped by a short N-terminal tripeptide and a disordered C-terminal tail. Structural and energetic analysis revealed that the Swt peptide binds independently to cTnC N-terminal domain, which can be stripped from the intact cTnI subunit to interact effectively with cTnC. Further investigations found that truncation of two N-terminal residues and five C-terminal residues of the full-length Swt peptide, resulting in a shortened version namely Swt-ΔN2ΔC5 peptide, would not cause substantial loss in its binding potency to cTnC. The computational finding was then confirmed by using fluorescence-based affinity assays; the Swt and Swt-ΔN2ΔC5 peptides was experimentally measured to have a moderately high affinity to the recombinant protein of human cTnC N-terminal domain with K _d values at micromolar level. The Swt and Swt-ΔN2ΔC5 are considered as inhibitory peptides that can be further optimized and modified to obtain high-affinity disruptors of cTnI–cTnC interaction.     

Guidelines for Guidelines: Are They Up to the Task? A Comparative Assessment of Clinical Practice Guideline Development Handbooks

Objectives

We conducted a comparative review of clinical practice guideline development handbooks. We aimed to identify the main guideline development tasks, assign weights to the importance of each task using expert opinions and identify the handbooks that provided a comprehensive coverage of the tasks.

Methods

We systematically searched and included handbooks published (in English language) by national, international or professional bodies responsible for evidenced-based guideline development. We reviewed the handbooks to identify the main guideline development tasks and scored each handbook for each task from 0 (the handbook did not mention the task) to 2 (the task suitably addressed and explained), and calculated a weighted score for each handbook. The tasks included in over 75% of the handbooks were considered as ‘necessary’ tasks.

Result

Nineteen guideline development handbooks and twenty seven main tasks were identified. The guideline handbooks’ weighted scores ranged from 100 to 220. Four handbooks scored over 80% of the maximum possible score, developed by the National Institute for Health and Clinical Excellence, Swiss Centre for International Health, Scottish Intercollegiate Guidelines Network and World Health Organization. Necessary tasks were: selecting the guideline topic, determining the guideline scope, identifying relevant existing guidelines, involving the consumers, forming guideline development group,, developing clinical questions, systematic search for evidence, selecting relevant evidence, appraising identifies research evidence, making group decision, grading available evidence, creating recommendations, final stakeholder consultation, guideline implementation strategies, updating recommendations and correcting potential errors.

Discussion

Adequate details for evidence based development of guidelines were still lacking from many handbooks. The tasks relevant to ethical issues and piloting were missing in most handbooks. The findings help decision makers in identifying the necessary tasks for guideline development, provide an updated comparative list of guideline development handbooks, and provide a checklist to assess the comprehensiveness of guideline development processes.