Thalamic nuclei changes in early and late onset Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Increasing evidence points to the thalamus as an important hub in the clinical symptomatology of the disease, with the ‘limbic thalamus’ been described as especially vulnerable. In this work, we examined thalamic atrophy in early-onset AD (EOAD) and late-onset AD (LOAD) compared to young and old healthy controls (YHC and OHC, respectively) using a recently developed cutting-edge thalamic nuclei segmentation method. A deep learning variant of Thalamus Optimized Multi Atlas Segmentation (THOMAS) was used to parcellate 11 thalamic nuclei per hemisphere from T1-weighted MRI in 88 biomarker-confirmed AD patients (49 EOAD and 39 LOAD) and 58 healthy controls (41 YHC and 17 OHC) with normal AD biomarkers. Nuclei volumes were compared among groups using MANCOVA. Further, Pearson's correlation coefficient was computed between thalamic nuclear volume and cortical—subcortical regions, CSF tau levels, and neuropsychological scores. The results showed widespread thalamic nuclei atrophy in EOAD and LOAD compared to their respective healthy control groups, with EOAD showing additional atrophy in the centromedian and ventral lateral posterior nuclei compared to YHC. In EOAD, increased thalamic nuclei atrophy was associated with posterior parietal atrophy and worse visuospatial abilities, while LOAD thalamic nuclei atrophy was preferentially associated with medial temporal atrophy and worse episodic memory and executive function. Our findings suggest that thalamic nuclei may be differentially affected in AD according to the age at symptoms onset, associated with specific cortical—subcortical regions, CSF total tau and cognition

Taking care of kidney transplant recipients during the COVID-19 pandemic: experience from a medicalized hotel.

The global overload that health systems are undergoing since the start of the COVID-19 pandemic has forced hospitals to explore sustainable alternatives to treat vulnerable patients that require closer monitoring and higher use of resources, such as Kidney Transplant Recipients (KTRs)1,2 .The use of telemedicine and hospital-like infrastructures represent a valid option for most patients with mild-moderate COVID-19, as well as for patients in the recovery phase who cannot be discharged from hospital

Targeting the Gut Microbiota of Vertically HIV-Infected Children to Decrease Inflammation and Immunoactivation: A Pilot Clinical Trial

Aims: Children with HIV exhibit chronic inflammation and immune dysfunction despite antiretroviral therapy (ART). Strategies targeting persistent inflammation are needed to improve health in people living with HIV. The gut microbiota likely interacts with the immune system, but the clinical implications of modulating the dysbiosis by nutritional supplementation are unclear. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected on ART were randomized to supplementation with a daily mixture of symbiotics, omega-3/6 fatty acids and amino acids, or placebo four weeks, in combination with ART. We analyzed inflammatory markers and T-cell activation changes and their correlations with shifts in fecal microbiota. Results: Twenty-four HIV-infected children were recruited and randomized to receive a symbiotic nutritional supplement or placebo. Mean age was 12 ± 3.9 years, 62.5% were female. All were on ART and had HIV RNA < 50/mL. We did not detect changes in inflammatory (IL-6, IL-7, IP-10), microbial translocation (sCD14), mucosal integrity markers (IFABP, zonulin) or the kynurenine to tryptophan ratio, or changes in markers of the adaptive immune response in relation to the intervention. However, we found correlations between several key bacteria and the assessed inflammatory and immunological parameters, supporting a role of the microbiota in immune modulation in children with HIV. Conclusions: In this exploratory study, a four-week nutritional supplementation had no significant effects in terms of decreasing inflammation, microbial translocation, or T-cell activation in HIV-infected children. However, the correlations found support the interaction between gut microbiota and the immune system

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Did Australia listen to Indigenous people on constitutional recognition? A big data analysis

This paper uses novel electronic tools to identify the degree to which Australia was listening to Indigenous peoples in a ‘national conversation’ about constitutional recognition between 2015 and late 2017. The results show that while there was a superficial overlap in themes, there were important differences of framing. Recognition remained a largely formal, elite and non-Indigenous concern, with First Nations focusing on treaties, sovereignty, listening and respect. Interaction was noticeably aggressive, but not exclusively so. Non-Indigenous people avoided discussing racism, and talked more frequently about history, framing issues in the past tense; First Nations talked about the here and now. And despite more focus on everyday racism, Indigenous peoples were consistently more positive and proud, rejecting ‘plight’ construction

Did Australia listen to Indigenous people on constitutional recognition? A big data analysis

This paper uses novel electronic tools to identify the degree to which Australia was listening to Indigenous peoples in a ‘national conversation’ about constitutional recognition between 2015 and late 2017. The results show that while there was a superficial overlap in themes, there were important differences of framing. Recognition remained a largely formal, elite and non-Indigenous concern, with First Nations focusing on treaties, sovereignty, listening and respect. Interaction was noticeably aggressive, but not exclusively so. Non-Indigenous people avoided discussing racism, and talked more frequently about history, framing issues in the past tense; First Nations talked about the here and now. And despite more focus on everyday racism, Indigenous peoples were consistently more positive and proud, rejecting ‘plight’ construction

Ultrasound Assessment of the Median Nerve Does Not Adequately Discriminate the Carpal Tunnel Syndrome among Patients Diagnosed with Diabetes

Background: Carpal tunnel syndrome is the most prevalent peripheral nerve entrapment condition of the upper limb. Among metabolic risk factors, diabetes is considered the most relevant. Although wrist ultrasound assessment of the median nerve has demonstrated a good correlation with the gold standard for the diagnosis of this syndrome, neurophysiological study, its usefulness in patients with diabetes is questionable because the compressive phenomenon is not the predominant one. Method: We conducted a retrospective study to compare the clinical and median nerve ultrasound features of patients with carpal tunnel syndrome previously diagnosed or not diagnosed with diabetes. Additionally, a linear multivariate regression analysis was performed to determine to what extent the cross-sectional area of the median nerve was dependent on the condition of diabetes by fixing other variables such as sex, age, or time of evolution. Results: We included 303 records of patients (mean age 44.3 ± 11.7 years old, 57.89% female, mean of time of evolution 13.6 ± 8.3 months) from 2012 to 2020. The cross-sectional area of the median nerve was 10.46 ± 1.44 mm2 in non-diabetic patients and 8.92 ± 0.9 mm2 in diabetic patients (p &lt; 0.001). Additionally, diabetic patients had a shorter time of evolution (7.91 ± 8.28 months vs. 14.36 ± 0.526 months, p &lt; 0.001). In the multivariate analysis, the resultant model (fixed R-square = 0.659, p = 0.003) included a constant of the following four variables: the evolution time (Beta coeff. = 0.108, p &lt; 0.001 95% CI 0.091 to 0.126, standardized coeff. = 0.611), the condition of diabetes (Beta coeff. = −0.623, p &lt; 0.001 95% CI −0.907 to −0.339, standardized coeff. = −0.152), the severity (Beta coeff. = 0.359, p = 0.001 95% CI 0.147 to 0.571, standardized coeff. = 0.169), and the masculine sex (Beta coeff. = 0.309, p = 0.003, 95% CI 0.109 to 0.509, standardized coeff. = 0.103). Conclusions: Ultrasound assessment of the median nerve in patients with diabetes is not a useful tool to confirm whether carpal tunnel syndrome should be diagnosed or not diagnosed

Kinetic and dynamic computational model-based characterization of new proteins in mice: application to interferon alpha linked to apolipoprotein a-I

Interferon alpha linked to apolipoprotein A-I has been recently proposed as an improved interferon-based therapy. In the present study, we aimed to develop a computational model to gain further insight into the in vivo behaviour of this new fusion protein. In order to facilitate in vivo evaluation of interferon and the fusion protein without altering their biological properties, green fluorescent protein was incorporated into their structures. Kinetic and dynamic behaviour of both compounds was successfully described after plasmid hydrodynamic administration and in situ synthesis of the studied proteins. Results from the modelling exercise showed that apolipoprotein A-I conferred a modified kinetic behaviour, varying molecule distribution and prolonging half-life without altering liver dynamic performance. However, differences in the gene expression activity were observed at brain level between both compounds. Those differences could be explained by modifications in the dynamic, but also in the biodistribution properties, which would be worth evaluating in future experiments. Therefore, the modelling approach provided a global comprehension of a complex system and allowed us to compare the in vivo behaviour of both compounds and to identify critical aspects that might be important to understand the system better and suggests a need for new model-based experiments

Kinetic and Dynamic Computational Model-Based Characterization of New Proteins in Mice: Application to Interferon Alpha Linked to Apolipoprotein A-I

<div><p>Interferon alpha linked to apolipoprotein A-I has been recently proposed as an improved interferon-based therapy. In the present study, we aimed to develop a computational model to gain further insight into the <em>in vivo</em> behaviour of this new fusion protein. In order to facilitate <em>in vivo</em> evaluation of interferon and the fusion protein without altering their biological properties, green fluorescent protein was incorporated into their structures. Kinetic and dynamic behaviour of both compounds was successfully described after plasmid hydrodynamic administration and <em>in situ</em> synthesis of the studied proteins. Results from the modelling exercise showed that apolipoprotein A-I conferred a modified kinetic behaviour, varying molecule distribution and prolonging half-life without altering liver dynamic performance. However, differences in the gene expression activity were observed at brain level between both compounds. Those differences could be explained by modifications in the dynamic, but also in the biodistribution properties, which would be worth evaluating in future experiments. Therefore, the modelling approach provided a global comprehension of a complex system and allowed us to compare the <em>in vivo</em> behaviour of both compounds and to identify critical aspects that might be important to understand the system better and suggests a need for new model-based experiments.</p> </div

Kinetic parameters.

<p>NA: non applicable.</p>a<p>Parameter estimates are listed together with the corresponding coefficient of variation [CV(%)] calculated as the ratio between the standard error and the estimate of the parameter.</p