Non-invasive metabolic biomarkers for early diagnosis of diabetic nephropathy: Meta-analysis of profiling metabolomics studies

AimDiabetic nephropathy (DN) is one of the worst complications of diabetes. Despite a growing number of DN metabolite profiling studies, most studies are suffering from inconsistency in their findings. The main goal of this meta-analysis was to reach to a consensus panel of significantly dysregulated metabolites as potential biomarkers in DN.Data synthesisTo identify the significant dysregulated metabolites, meta-analysis was performed by “vote-counting rank” and “robust rank aggregation” strategies. Bioinformatics analyses were performed to identify the most affected genes and pathways. Among 44 selected studies consisting of 98 metabolite profiles, 17 metabolites (9 up-regulated and 8 down-regulated metabolites), were identified as significant ones by both the meta-analysis strategies (p-value<0.05 and OR>2 or <0.5) and selected as DN metabolite meta-signature. Furthermore, enrichment analyses confirmed the involvement of various effective biological pathways in DN pathogenesis, such as urea cycle, TCA cycle, glycolysis, and amino acid metabolisms. Finally, by performing a meta-analysis over existing time-course studies in DN, the results indicated that lactic acid, hippuric acid, allantoin (in urine), and glutamine (in blood), are the topmost non-invasive early diagnostic biomarkers.ConclusionThe identified metabolites are potentially involved in diabetic nephropathy pathogenesis and could be considered as biomarkers or drug targets in the disease.Prospero registration numberCRD42020197697.     

Feedback and feedforward adaptation to visuomotor delay during reaching and slicing movements

It has been suggested that the brain and in particular the cerebellum and motor cortex adapt to represent the environment during reaching movements under various visuomotor perturbations. It is well known that significant delay is present in neural conductance and processing; however, the possible representation of delay and adaptation to delayed visual feedback has been largely overlooked. Here we investigated the control of reaching movements in human subjects during an imposed visuomotor delay in a virtual reality environment. In the first experiment, when visual feedback was unexpectedly delayed, the hand movement overshot the end‐point target, indicating a vision‐based feedback control. Over the ensuing trials, movements gradually adapted and became accurate. When the delay was removed unexpectedly, movements systematically undershot the target, demonstrating that adaptation occurred within the vision‐based feedback control mechanism. In a second experiment designed to broaden our understanding of the underlying mechanisms, we revealed similar after‐effects for rhythmic reversal (out‐and‐back) movements. We present a computational model accounting for these results based on two adapted forward models, each tuned for a specific modality delay (proprioception or vision), and a third feedforward controller. The computational model, along with the experimental results, refutes delay representation in a pure forward vision‐based predictor and suggests that adaptation occurred in the forward vision‐based predictor, and concurrently in the state‐based feedforward controller. Understanding how the brain compensates for conductance and processing delays is essential for understanding certain impairments concerning these neural delays as well as for the development of brain–machine interfaces.     

Intrahepatic cholangiocarcinoma: current management and emerging therapies

Introduction: Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with an increasing incidence and a high-case fatality. While surgery offers the best hope at long-term survival, only one-third of tumors are amenable to surgical resection at the time of the diagnosis. Unfortunately, conventional chemotherapy offers limited survival benefit in the management of unresectable or metastatic disease. Recent advances in understanding the molecular pathogenesis of iCCA and the use of next-generation sequencing techniques have provided a chance to identify ‘target-able’ molecular aberrations. These novel molecular therapies offer the promise to personalize therapy for patients with iCCA and, in turn, improve the outcomes of patients.

Area covered: We herein review the current management options for iCCA with a focus on defining both established and emerging therapies.

Expert commentary: Surgical resection remains as an only hope for cure in iCCA patients. However, frequently the diagnosis is delayed till advanced stages when surgery cannot be offered; signifying the urge for specific diagnostic tumor biomarkers and targeted therapies. New advances in genomic profiling have contributed to a better understanding of the landscape of molecular alterations in iCCA and offer hope for the development of novel diagnostic biomarkers and targeted therapies.     

Particulate vs. block bone grafts: Three-dimensional changes in graft volume after reconstruction of the atrophic maxilla,a 2-year radiographic follow-up

BackgroundExtensive alveolar bone resorption in the maxilla limits the possibility of successful placement and osseointegration of endosseous implants for future prosthetic rehabilitation. Autogenous bone from the iliac crest may be used as lateral onlays in the atrophic maxilla, both as block and particulate bone. To our knowledge, there is no three-dimensional 2-year follow-up study measuring the volumetric reduction of the augmented areas comparing particulate and block bone grafts.PurposeThe aim of this study was to conduct a radiographic 2-year follow-up study, using computed tomographic (CT) images in order to evaluate and compare the extent of bone graft resorption in the frontal maxillae augmented by particulate (test) and block bone (control).Material and methodsEleven patients treated with iliac bone grafts and oral implants in the maxilla were followed with CT examinations directly post grafting and after 2 years.ResultThe volumetric changes after 6 months were extensive. Additionally, the changes in particulate bone tended to be larger after 2 years compared to block bone, using this protocol. However, the difference was not statistically significant.ConclusionThe present follow-up study showed that there is radiographically complete integration and embedding of implants installed in grafted bone despite extensive initial graft resorption. There was no significant difference in the amount of volumetric reduction between particulate bone and block bone grafts.     

Psychological and Sociocultural Adaptation: Acculturation,Depressive Symptoms,and Life Satisfaction Among Older Iranian Immigrants in Canada

Informed by Ward’s (1996) theory of psychological and sociocultural adaptation, this study identified links between acculturation and the mental health of older Iranian immigrants living in Canada (N = 103). According to Ward and colleagues, both psychological and sociocultural adaptation change at different rates and extend into later life. For this study, participants 50+ years of age and born in Iran completed questionnaires measuring life satisfaction, depressive symptoms, acculturation, and demographic and sociocultural variables (e.g., pre- and post-immigration occupational status). We collected study data anonymously in Persian to obtain responses from long-term residents of Canada as well as more recent immigrants who may not read or write English. We examined both life satisfaction and (the absence of) depressive symptoms as distinct forms of psychological adaptation; these emerged as independent predictors of acculturation. Contrary to theory, acculturation appears to predict life satisfaction, not vice versa; moreover, there seems to be no direct link between depressive symptoms and acculturation. Our findings suggest that integration within Canadian society is associated with higher life satisfaction. In contrast, sociocultural factors are indirectly associated with life satisfaction (except age) and acculturation (except ethnic diversity of social interactions). Involuntary migrants reported higher levels of depression, whereas loss of occupational status is associated with reduced life satisfaction. Implications for future research and health policy are discussed.