Identification and Prediction of Diabetic Sensorimotor Polyneuropathy Using Individual and Simple Combinations of Nerve Conduction Study Parameters

Objective

Evaluation of diabetic sensorimotor polyneuropathy (DSP) is hindered by the need for complex nerve conduction study (NCS) protocols and lack of predictive biomarkers. We aimed to determine the performance of single and simple combinations of NCS parameters for identification and future prediction of DSP.

Materials and Methods

406 participants (61 with type 1 diabetes and 345 with type 2 diabetes) with a broad spectrum of neuropathy, from none to severe, underwent NCS to determine presence or absence of DSP for cross-sectional (concurrent validity) analysis. The 109 participants without baseline DSP were re-evaluated for its future onset (predictive validity). Performance of NCS parameters was compared by area under the receiver operating characteristic curve (AROC).

Results

At baseline there were 246 (60%) Prevalent Cases. After 3.9 years mean follow-up, 25 (23%) of the 109 Prevalent Controls that were followed became Incident DSP Cases. Threshold values for peroneal conduction velocity and sural amplitude potential best identified Prevalent Cases (AROC 0.90 and 0.83, sensitivity 80 and 83%, specificity 89 and 72%, respectively). Baseline tibial F-wave latency, peroneal conduction velocity and the sum of three lower limb nerve conduction velocities (sural, peroneal, and tibial) best predicted 4-year incidence (AROC 0.79, 0.79, and 0.85; sensitivity 79, 70, and 81%; specificity 63, 74 and 77%, respectively).

Discussion

Individual NCS parameters or their simple combinations are valid measures for identification and future prediction of DSP. Further research into the predictive roles of tibial F-wave latencies, peroneal conduction velocity, and sum of conduction velocities as markers of incipient nerve injury is needed to risk-stratify individuals for clinical and research protocols.     

A framework for estimating the sensitivity of eDNA surveys

Imperfect sensitivity, or imperfect detection, is a feature of all survey methods that needs to be accounted for when interpreting survey results. Detection of environmental DNA (eDNA) is increasingly being used to infer species distributions, yet the sensitivity of the technique has not been fully evaluated. Sensitivity, or the probability of detecting target DNA given it is present at a site, will depend on both the survey method and the concentration and dispersion of target DNA molecules at a site. We present a model to estimate target DNA concentration and dispersion at survey sites and to estimate the sensitivity of an eDNA survey method. We fitted this model to data from a species‐specific eDNA survey for Oriental weatherloach, Misgurnus anguillicaudatus, at three sites sampled in both autumn and spring. The concentration of target DNA molecules was similar at all three sites in autumn but much higher at two sites in spring. Our analysis showed the survey method had ≥95% sensitivity at sites where target DNA concentrations were ≥11 molecules per litre. We show how these data can be used to compare sampling schemes that differ in the number of field samples collected per site and number of PCR replicates per sample to achieve ≥95% sensitivity at a given target DNA concentration. These models allow researchers to quantify the sensitivity of eDNA survey methods to optimize the probability of detecting target species, and to compare DNA concentrations spatially and temporarily.     

Overcoming challenges on using native seeds for restoration of megadiverse resource‐poor environments: a reply to Madsen et al.

Madsen et al. (2016) reviewed several major limiting factors to establishment of seedlings in nonforest ecosystems (NFE), and proposed seed enhancement technologies to overcome these restoration barriers. However, biodiverse nutrient‐poor NFE present additional hurdles that preclude landscape‐scale seed‐based restoration and were not mentioned in their review. Here, we discuss issues related to native seed availability and provenance, and shortfalls in knowledge on seed quality testing and dormancy release that severely hamper restoration of degraded nutrient‐impoverished NFE. We present alternatives for overcoming these challenges and highlight the need for investments to find more practical and cost‐effective options for broad‐scale restoration.     

Restricted Hematopoietic Progenitors and Erythropoiesis Require SCF from Leptin Receptor+ Niche Cells in the Bone Marrow

1. Download high-res image (228KB)
2. Download full-size image

     

Comparative proteome profiling and functional analysis of chronic myelogenous leukemia cell lines

The aim of the present study was the molecular profiling of different Ph+ chronic myelogenous leukemia (CML) cell lines (LAMA84, K562, and KCL22) by a proteomic approach. By employing two-dimensional gel electrophoresis combined with mass spectrometry analysis, we have identified 191 protein spots corresponding to 142 different proteins. Among these, 63% were cancer-related proteins and 74% were described for the first time in leukemia cells. Multivariate analysis highlighted significant differences in the global proteomic profile of the three CML cell lines. In particular, the detailed analysis of 35 differentially expressed proteins revealed that LAMA84 cells preferentially expressed proteins associated with an invasive behavior, while K562 and KCL22 cells preferentially expressed proteins involved in drug resistance. These data demonstrate that these CML cell lines, although representing the same pathological phenotype, show characteristics in their protein expression profile that suggest different phenotypic leukemia subclasses. These data contribute a new potential characterization of the CML phenotype and may help to understand interpatient variability in the progression of disease and in the efficacy of a treatment.     

Tuning of the enzyme ratio in a neutral redox convergent cascade: A key approach for an efficient one-pot/two-step biocatalytic whole-cell system

The efficiency of a versatile in vivo cascade involving a promiscuous alcohol dehydrogenase, obtained from a biodiversity search, and a Baeyer–Villiger monooxygenase was enhanced by the independent control of the production level of each enzyme to produce ε-caprolactone and 3,4-dihydrocoumarin. This goal was achieved by adjusting the copy number per cell of Escherichia coli plasmids. We started from the observation that this number generally correlates with the amount of produced enzyme and demonstrated that an in vivo multi-enzymatic system can be improved by the judicious choice of plasmid, the lower activity of the enzyme that drives the limiting step being counter-balanced by a higher concentration. Using a preconception-free approach to the choice of the plasmid type, we observed positive and negative synergetic effects, sometimes unexpected and depending on the enzyme and plasmid combinations. Experimental optimization of the culture conditions allowed us to obtain the complete conversion of cyclohexanol (16 mM) and 1-indanol (7.5 mM) at a 0.5-L scale. The yield for the conversion of cyclohexanol was 80% (0.7 g ε-caprolactone, for the productivity of 244 mg·L ⁻¹·h ⁻¹) and that for 1-indanol 60% (0.3 g 3,4-dihydrocoumarin, for the productivity of 140 mg·L ⁻¹·h ⁻¹).     

Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data

BackgroundIn 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates.Methods and findingsWe conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK “lockdown”. Data were obtained for Scotland from the Public Health Scotland “COVID19 wider impacts on the health care system” dashboard and for England from ImmForm.Five vaccinations delivered at different ages were evaluated; 3 doses of “6-in-1” diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age.We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels.In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86– to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83).The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake.ConclusionsIn this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.

Fiona McQuaid and colleagues assess the uptake of infant and pre-school immunisations in Scotland and England during the COVID-19 pandemic.     

Experimental evolution of a pheromone signal

Sexual signals are important in speciation, but understanding their evolution is complex as these signals are often composed of multiple, genetically interdependent components. To understand how signals evolve, we thus need to consider selection responses in multiple components and account for the genetic correlations among components. One intriguing possibility is that selection changes the genetic covariance structure of a multicomponent signal in a way that facilitates a response to selection. However, this hypothesis remains largely untested empirically. In this study, we investigate the evolutionary response of the multicomponent female sex pheromone blend of the moth Heliothis subflexa to 10 generations of artificial selection. We observed a selection response of about three‐quarters of a phenotypic standard deviation in the components under selection. Interestingly, other pheromone components that are biochemically and genetically linked to the components under selection did not change. We also found that after the onset of selection, the genetic covariance structure diverged, resulting in the disassociation of components under selection and components not under selection across the first two genetic principle components. Our findings provide rare empirical support for an intriguing mechanism by which a sexual signal can respond to selection without possible constraints from indirect selection responses.