Topical treatment of peripheral neuropathic pain: applying the evidence

Patients with peripheral neuropathic pain (NP) may only achieve partial pain relief with currently recommended first-line oral treatments, which are also associated with systemic adverse events. Topical treatments are currently considered second- or third-line options, but a recent pharmacologic treatment algorithm has called for broader first-line use of these agents. This has highlighted a need to communicate the benefits associated with topical agents, in particular around the efficacy, targeted local action, and limited systemic availability resulting in minimal systemic adverse events and drug-drug interactions

Feasibility, Architecture and Cost Considerations of Using TVWS for Rural Internet Access in 5G

The cellular technology is mostly an urban technology that has been unable to serve rural areas well. This is because the traditional cellular models are not economical for areas with low user density and lesser revenues. In 5G cellular networks, the coverage dilemma is likely to remain the same, thus widening the rural-urban digital divide further. It is about time to identify the root cause that has hindered the rural technology growth and analyse the possible options in 5G architecture to address this issue. We advocate that it can only be accomplished in two phases by sequentially addressing economic viability followed by performance progression. We deliberate how various works in literature focus on the later stage of this ‘two-phase’ problem and are not feasible to implement in the first place. We propose the concept of TV band white space (TVWS) dovetailed with 5G infrastructure for rural coverage and show that it can yield cost-effectiveness from a service provider’s perspective

Leveraging Random Assignment to Impute Missing Covariates in Causal Studies

Baseline covariates in randomized experiments are often used in the estimation of treatment effects, for example, when estimating treatment effects within covariate-defined subgroups. In practice, however, covariate values may be missing for some data subjects. To handle missing values, analysts can use imputation methods to create completed datasets, from which they can estimate treatment effects. Common imputation methods include mean imputation, single imputation via regression, and multiple imputation. For each of these methods, we investigate the benefits of leveraging randomized treatment assignment in the imputation routines, that is, making use of the fact that the true covariate distributions are the same across treatment arms. We do so using simulation studies that compare the quality of inferences when we respect or disregard the randomization. We consider this question for imputation routines implemented using covariates only, and imputation routines implemented using the outcome variable. In either case, accounting for randomization offers only small gains in accuracy for our simulation scenarios. Our results also shed light on the performances of these different procedures for imputing missing covariates in randomized experiments when one seeks to estimate heterogeneous treatment effects

Insulin-like growth factor I (IGF-I)-induced chronic gliosis and retinal stress lead to neurodegeneration in a mouse model of retinopathy

Insulin-like growth factor I (IGF-I) exerts multiple effects on different retinal cell types in both physiological and pathological conditions. Despite the growth factor's extensively described neuroprotective actions, transgenic mice with increased intraocular levels of IGF-I showed progressive impairment of electroretinographic amplitudes up to complete loss of response, with loss of photoreceptors and bipolar, ganglion, and amacrine neurons. Neurodegeneration was preceded by the overexpression of genes related to retinal stress, acute-phase response, and gliosis, suggesting that IGF-I altered normal retinal homeostasis. Indeed, gliosis and microgliosis were present from an early age in transgenic mice, before other alterations occurred, and were accompanied by signs of oxidative stress and impaired glutamate recycling. Older mice also showed overproduction of pro-inflammatory cytokines. Our results suggest that, when chronically increased, intraocular IGF-I is responsible for the induction of deleterious cellular processes that can lead to neurodegeneration, and they highlight the importance that this growth factor may have in the pathogenesis of conditions such as ischemic or diabetic retinopathy

Insulin-like growth factor 2 overexpression induces β-Cell dysfunction and increases beta-cell susceptibility to damage

The human insulin-like growth factor 2 (IGF2) and insulin genes are located within the same genomic region. Although human genomic studies have demonstrated associations between diabetes and the insulin/IGF2 locus or the IGF2 mRNA-binding protein 2 (IGF2BP2), the role of IGF2 in diabetes pathogenesis is not fully understood. We previously described that transgenic mice overexpressing IGF2 specifically in β-cells (Tg-IGF2) develop a pre-diabetic state. Here, we characterized the effects of IGF2 on β-cell functionality. Overexpression of IGF2 led to β-cell dedifferentiation and endoplasmic reticulum stress causing islet dysfunction in vivo. Both adenovirus-mediated overexpression of IGF2 and treatment of adult wild-type islets with recombinant IGF2 in vitro further confirmed the direct implication of IGF2 on β-cell dysfunction. Treatment of Tg-IGF2 mice with subdiabetogenic doses of streptozotocin or crossing these mice with a transgenic model of islet lymphocytic infiltration promoted the development of overt diabetes, suggesting that IGF2 makes islets more susceptible to β-cell damage and immune attack. These results indicate that increased local levels of IGF2 in pancreatic islets may predispose to the onset of diabetes. This study unravels an unprecedented role of IGF2 on β-cells function

Prevalence, antimicrobial resistance and genetic diversity of Campylobacter coli and Campylobacter jejuni in Ecuadorian broilers at slaughter age

Thermotolerant Campylobacter spp. are a major cause of foodborne gastrointestinal infections worldwide. The linkage of human campylobacteriosis and poultry has been widely described. In this study we aimed to investigate the prevalence, antimicrobial resistance and genetic diversity of C. coli and C. jejuni in broilers from Ecuador. Caecal content from 379 randomly selected broiler batches originating from 115 farms were collected from 6 slaughterhouses located in the province of Pichincha during 1 year. Microbiological isolation was performed by direct plating on mCCDA agar. Identification of Campylobacter species was done by PCR. Minimum inhibitory concentration (MIC) values for gentamicin, ciprofloxacin, nalidixic acid, tetracycline, streptomycin, and erythromycin were obtained. Genetic variation was assessed by RFLP-flaA typing and Multilocus Sequence Typing (MLST) of selected isolates. Prevalence at batch level was 64.1%. Of the positive batches 68.7% were positive for C. coli, 18.9% for C. jejuni, and 12.4% for C. coli and C. jejuni. Resistance rates above 67% were shown for tetracycline, ciprofloxacin, and nalidixic acid. The resistance pattern tetracycline, ciprofloxin, and nalidixic acid was the dominant one in both Campylobacter species. RFLP-flaA typing analysis showed that C. coli and C. jejuni strains belonged to 38 and 26 profiles respectively. On the other hand MLST typing revealed that C. coli except one strain belonged to CC-828, while C. jejuni except 2 strains belonged to 12 assigned clonal complexes (CCs). Furthermore 4 new sequence types (STs) for both species were described, whereby 2 new STs for C. coli were based on new allele sequences. Further research is necessary to estimate the impact of the slaughter of Campylobacter positive broiler batches on the contamination level of carcasses in slaughterhouses and at retail in Ecuador