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Introduction Despite being an occupational hazard, environmental exposure to lead (Pb) has been and will continue to be a major public health concern, because this metal is widely present in [...], BACKGROUND: The role of environmental factors in Alzheimer's disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain [beta]-amyloid (A[beta]) deposition. However, the nature of Pb-induced amyloid deposition and how it contributes to AD development remain unclear. OBJECTIVES: This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model. METHODS: Female APP/PS1 mice at 8 wk of age were administered either 50 mg/kg Pb-acetate (PbAc) (i.e., 27 mg Pb/kg) or an equivalent molar concentration of sodium acetate (NaAc) via oral gavage once daily for 8 wk. Amyloid deposition and vascular amyloid were determined by immuno-staining. In addition, A[beta] perivascular drainage, vascular binding assay, and microglial endocytosis were examined to determine underlying mechanisms. Furthermore, magnetic resonance imaging demyelination imaging was performed in vivo measure the level of demyelination. Finally, Y-maze and Morris water maze tests were assessed to evaluate the cognitive function of mice. RESULTS: APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to A[beta]40, higher A[beta]40/A[beta]42 ratios, strikingly lower A[beta]40 levels in the perivascular drainage, and microglial endocytosis. Importantly, exposure to a specific PAI-1 inhibitor, tiplaxtinin, which previously was reported to lower CAA pathology in mice, resulted in less CAA-related outcomes following PbAc exposure. DISCUSSION: Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. https://doi.org/10.1289/EHP14384

Without careful dissection of the ways in which biases can be encoded into artificial intelligence (AI) health technologies, there is a risk of perpetuating existing health inequalities at scale. One major source of bias is the data that underpins such technologies. The STANDING Together recommendations aim to encourage transparency regarding limitations of health datasets and proactive evaluation of their effect across population groups. Draft recommendation items were informed by a systematic review and stakeholder survey. The recommendations were developed using a Delphi approach, supplemented by a public consultation and international interview study. Overall, more than 350 representatives from 58 countries provided input into this initiative. 194 Delphi participants from 25 countries voted and provided comments on 32 candidate items across three electronic survey rounds and one in-person consensus meeting. The 29 STANDING Together consensus recommendations are presented here in two parts. Recommendations for Documentation of Health Datasets provide guidance for dataset curators to enable transparency around data composition and limitations. Recommendations for Use of Health Datasets aim to enable identification and mitigation of algorithmic biases that might exacerbate health inequalities. These recommendations are intended to prompt proactive inquiry rather than acting as a checklist. We hope to raise awareness that no dataset is free of limitations, so transparent communication of data limitations should be perceived as valuable, and absence of this information as a limitation. We hope that adoption of the STANDING Together recommendations by stakeholders across the AI health technology lifecycle will enable everyone in society to benefit from technologies which are safe and effective. [ABSTRACT FROM AUTHOR]

BACKGROUND: The role of environmental factors in Alzheimer’s disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain β-amyloid (Aβ) deposition. However, the nature of Pb-induced amyloid deposition and how it contributes to AD development remain unclear. OBJECTIVES: This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model. METHODS: Female APP/PS1 mice at 8 wk of age were administered either 50 mg/kg Pb-acetate (PbAc) (i.e., 27 mg Pb/kg) or an equivalent molar concentration of sodium acetate (NaAc) via oral gavage once daily for 8 wk. Amyloid deposition and vascular amyloid were determined by immunostaining. In addition, Aβ perivascular drainage, vascular binding assay, and microglial endocytosis were examined to determine underlying mechanisms. Furthermore, magnetic resonance imaging demyelination imaging was performed in vivo measure the level of demyelination. Finally, Y-maze and Morris water maze tests were assessed to evaluate the cognitive function of mice. RESULTS: APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to Aβ40, higher Aβ40/Aβ42 ratios, strikingly lower Aβ40 levels in the perivascular drainage, and microglial endocytosis. Importantly, exposure to a specific PAI-1 inhibitor, tiplaxtinin, which previously was reported to lower CAA pathology in mice, resulted in less CAA-related outcomes following PbAc exposure. DISCUSSION: Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. [ABSTRACT FROM AUTHOR]

In traditional Data Envelopment Analysis (DEA) approaches, inputs and outputs are usually considered as exact and real values. The relative efficiency of the Decision-Making Units (DMUs) is evaluated and it is known that the factors are inputs and/or outputs. However, there are some conditions under which the efficiency of DMUs should be calculated while the data are integer and ambiguous. Therefore, various integer DEA models have been proposed to determine the performance of DMUs when integer data and fuzzy factors are available. In addition, there are cases where the efficiency of DMUs should be determined when integer data and flexible factors are available. Therefore, some integer DEA methods have been proposed to calculate the performance of DMUs and specify the role of flexible measures when some of the data are integer and flexible factors are available. However, there are some situations where there are integer data, fuzzy integer measures and flexible factors. Therefore, this paper sheds light on the nature of the model to determine the efficiency of DMUs when there are integer inputs and/or outputs, flexible factors and fuzzy integer measures, and determines the role of factors with uncertain inputs or outputs. In fact, slacks are addressed and a slack-based efficiency measure (SBM) is defined to compute the performance of DMUs in the presence of flexible factors, integer data and fuzzy integer measures. The proposed approaches are demonstrated and illustrated using an example. [ABSTRACT FROM AUTHOR]

Summary: Background: Ulceration is a recognized risk factor for surgical site infection (SSI); however, the proportion of patients developing SSI after excision of an ulcerated skin cancer is unknown. Aim: To determine the proportion of participants with SSI after surgical excision of an ulcerated skin cancer. A secondary aim was to assess feasibility outcomes to inform the design of a randomized controlled trial to investigate the benefits and harms of perioperative antibiotics following excision of ulcerated tumours. Methods: This was a multicentre, prospective, observational study of patients undergoing excision of an ulcerated skin cancer between March 2019 and March 2020. Prior to surgical excision, surface swabs of the ulcerated tumours of participants recruited from one centre were undertaken to determine organism growth. At 4 weeks after surgery, all participants were e‐mailed or posted the Wound Healing Questionnaire (WHQ) to determine whether they had developed SSI. Results: In total, 148 participants were recruited 105 (70.9%) males; mean ± SD age 77.1 ± 12.3 years. Primary outcome data were available for 116 (78.4%) participants, of whom 35 (30.2%) were identified as having an SSI using the WHQ with a cutoff score of 8, and 47 (40.5%) were identified with a cutoff score of 6. Using the modified WHQ in participants with wounds left to heal by secondary intention, 33 (28.4%) and 43 (37.1%) were identified to have SSI respectively. Conclusion: This prospective evaluation of SSI identified with the WHQ following excision of ulcerated skin cancers demonstrated a high proportion with SSI. The WHQ was acceptable to patients; however, further evaluation is required to ensure validity in assessing skin wounds. [ABSTRACT FROM AUTHOR]

IntroductionExpressing emotions play a special role in daily communication, and one of the most essential methods in detecting emotions is to detect facial emotional states. Therefore, one of the crucial aspects of the natural human–machine interaction is the recognition of facial expressions and the creation of feedback, according to the perceived emotion.MethodsTo implement each part of this model, two main steps have been introduced. The first step is reading the video and converting it to images and preprocessing on them. The next step is to use the combination of 3D convolutional neural network (3DCNN) and learning automata (LA) to classify and detect the rate of facial emotional recognition. The reason for choosing 3DCNN in our model is that no dimension is removed from the images, and considering the temporal information in dynamic images leads to more efficient and better classification. In addition, the training of the 3DCNN network in calculating the backpropagation error is adjusted by LA so that both the efficiency of the proposed model is increased, and the working memory part of the SOAR model can be implemented.Results and discussionDue to the importance of the topic, this article presents an efficient method for recognizing emotional states from facial images based on a mixed deep learning and cognitive model called SOAR. Among the objectives of the proposed model, it is possible to mention providing a model for learning the time order of frames in the movie and providing a model for better display of visual features, increasing the recognition rate. The accuracy of recognition rate of facial emotional states in the proposed model is 85.3%. To compare the effectiveness of the proposed model with other models, this model has been compared with competing models. By examining the results, we found that the proposed model has a better performance than other models.

Summary: Background: Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common cutaneous T‐cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. Aim: To identify factors associated with poorer health‐related quality of life (HRQoL) in patients newly diagnosed with MF/SS. Methods: Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex‐29 questionnaire. Skindex‐29 scores were analysed in relation to patient‐ and disease‐specific characteristics. Results: The study population consisted of 237 patients [60·3% male; median age 60 years, (interquartile range 49–70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex‐29, was worse in women, SS, late‐stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (β = 8·61; P = 0·003) and alopecia (β = 9·71, P = 0·02) as independent predictors of worse global HRQoL. Item‐level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2·14, 95% confidence interval (CI) 1·19–3·89] and emotions (OR 1·88, 95% CI 1·09–3·27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. Conclusions: HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex‐29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T‐cell lymphoma‐specific questionnaire is urgently needed to more accurately assess disease‐specific HRQoL in these patients. What's already known about this topic? Cross‐sectional studies of mixed populations of known and newly diagnosed patients with mycosis fungoides (MF)/Sézary syndrome (SS) have shown significant impairment in health‐related quality of life (HRQoL).Previous studies on assessing gender‐specific differences in HRQoL in MF/SS are conflicting.More advanced‐stage disease and pruritus is associated with poorer HRQoL in patients with MF/SS. What does this study add? This is the first prospective study to investigate HRQoL in a homogenous group of newly diagnosed patients with MF/SS.In patients newly diagnosed with MF/SS, HRQoL is worse in women and in those with alopecia and confluent erythema.MF/SS diagnosis has a multidimensional impact on patient HRQoL, including a large burden of cutaneous symptoms, as well as a negative impact on emotional well‐being. Linked Comment:Talpur. Br J Dermatol 2020; 182:541–542. Plain language summary available online [ABSTRACT FROM AUTHOR]

The median time to cutaneous irAE onset was 0.9 months in patients treated with anti-CTLA4/anti-PD-1 combination therapy, compared with 1.7 months and 3.7 months for patients treated with anti-CTLA4 and anti-PD-1 monotherapy, respectively. Overall, 114 patients (58% male, 42% female; mean age 64 years) had experienced cutaneous irAEs following treatment with ICB therapy. [Extracted from the article]

Although 38% of respondents (26 of 69) reported patients using smartphone apps (including MySkinSelfie and Miiskin) to monitor their lesions, only 19% (13 of 69) recommended apps to monitor skin lesions to their patients. Total body photography (TBP) is increasingly used to monitor skin lesions in individuals at high risk of melanoma. [Extracted from the article]

Alzheimer’s disease (AD) is the most common form of dementia. AD is a progressive neurodegenerative disorder characterized by cognitive dysfunction, including learning and memory deficits, and behavioral changes. Neuropathology hallmarks of AD such as amyloid beta (Aβ) plaques and neurofibrillary tangles containing the neuron-specific protein tau is associated with changes in fluid biomarkers including Aβ, phosphorylated tau (p-tau)-181, p-tau 231, p-tau 217, glial fibrillary acidic protein (GFAP), and neurofilament light (NFL). Another pathological feature of AD is neural damage and hyperactivation of astrocytes, that can cause increased pro-inflammatory mediators and oxidative stress. In addition, reduced brain glucose metabolism and mitochondrial dysfunction appears up to 15 years before the onset of clinical AD symptoms. As glucose utilization is compromised in the brain of patients with AD, ketone bodies (KBs) may serve as an alternative source of energy. KBs are generated from the β-oxidation of fatty acids, which are enhanced following consumption of ketogenic diets with high fat, moderate protein, and low carbohydrate. KBs have been shown to cross the blood brain barrier to improve brain energy metabolism. This review comprehensively summarizes the current literature on how increasing KBs support brain energy metabolism. In addition, for the first time, this review discusses the effects of ketogenic diet on the putative AD biomarkers such as Aβ, tau (mainly p-tau 181), GFAP, and NFL, and discusses the role of KBs on neuroinflammation, oxidative stress, and mitochondrial metabolism.