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They also lead to a decline in the patient's quality of life and impact their self-esteem. This review summarises findings on the immune response against dermatophytes.α-Synuclein oligomers are thought to have a pivotal role in sporadic and familial Parkinson's disease (PD) and related α-synucleinopathies, causing dysregulation of protein trafficking, autophagy/lysosomal function, and protein clearance, as well as synaptic function impairment underlying motor and cognitive symptoms of PD. Moreover, trans-synaptic spread of α-synuclein oligomers is hypothesized to mediate disease progression. Therapeutic approaches that effectively block α-synuclein oligomer-induced pathogenesis are urgently needed. Here, we show for the first time that α-synuclein species isolated from human PD patient brain and recombinant α-synuclein oligomers caused similar deficits in lipid vesicle trafficking rates in cultured rat neurons and glia, while α-synuclein species isolated from non-PD human control brain samples did not. Recombinant α-synuclein oligomers also increased neuronal expression of lysosomal-associated membrane protein-2A (LAMP-2A), the lysosomal receptor that has a critical role in chaperone-mediated autophagy. Unbiased screening of several small molecule libraries (including the NIH Clinical Collection) identified sigma-2 receptor antagonists as the most effective at blocking α-synuclein oligomer-induced trafficking deficits and LAMP-2A upregulation in a dose-dependent manner. These results indicate that antagonists of the sigma-2 receptor complex may alleviate α-synuclein oligomer-induced neurotoxicity and are a novel therapeutic approach for disease modification in PD and related α-synucleinopathies.Indigenous therapies, or traditional medicines (TMs), constitute a highly accessible and continuously growing health system in many parts of the world, including Sub-Saharan Africa (SSA). Shea butter, a fat produced from the kernels of the shea tree, has historically been used as an indigenous therapy for dermatologic ailments in SSA. Characterizing traditional therapeutic applications for shea butter is important to inform the continued development of TM in SSA. We conducted a literature review aimed at identifying all available publications on the use of shea butter to treat dermatoses within SSA and evaluating patterns of use. c-RET inhibitor We found 24 dermatologic uses across 30 references. The most common study design was descriptive cross-sectional analysis (46.7%), often relying on the use of in-depth interviews, focus groups, and surveys. Eight SSA countries were represented and there were disparities in availability of information across SSA with the eastern and southern regions less likely to be represented. The most frequently investigated conditions were scabies, wound healing, and umbilical cord care. Shea butter was most commonly used in combination with other ingredients to produce a medical treatment with the most frequent adjuvant being Elaeis guineensis, African oil palm. Broad use of TM to treat varied skin diseases throughout SSA warrants increased investigations into this field in order to further develop the capacity of TM as a source of healthcare.

In practice, the goal of treatment for patients with psoriasis is to achieve almost clear or clear skin and maintain disease control, regardless of baseline disease severity. However, identifying absolute Psoriasis Area and Severity Index (PASI) values for new treatment goals is challenging, as most clinical trials report relative PASI 50, 75, 90 or 100 improvements but rarely absolute PASI values achieved.

Our objective was to illustrate a statistical conversion method that was developed to derive absolute PASI values from available clinical trial data on relative PASI improvements. The results of network meta-analyses (NMAs) based on these derived data were then compared with those of NMAs based on the corresponding relative PASI improvement data for selected biologics for moderate-to-severe psoriasis.

The PASI statistical conversion method was applied to relative PASI improvement data for 11 biologic treatment regimens and placebo at 12weeks using data from 50 published studies. The respective proporls in the absence of primary absolute PASI data for all available treatments for moderate-to-severe plaque psoriasis.Inflammation of brain tissue is a complex response of the immune system to the presence of toxic compounds or to cell injury, leading to a cascade of pathological processes that include glial cell activation. Noninvasive MRI markers of glial reactivity would be very useful for in vivo detection and monitoring of inflammation processes in the brain, as well as for evaluating the efficacy of personalized treatments. Due to their specific location in glial cells, myo-inositol (mIns) and choline compounds (tCho) seem to be the best candidates for probing glial-specific intra-cellular compartments. However, their concentrations quantified using conventional proton MRS are not specific for inflammation. In contrast, it has been recently suggested that mIns intra-cellular diffusion, measured using diffusion-weighted MRS (DW-MRS) in a mouse model of reactive astrocytes, could be a specific marker of astrocytic hypertrophy. In order to evaluate the specificity of both mIns and tCho diffusion to inflammation-driven glial alterations, we performed DW-MRS in a volume of interest containing the corpus callosum and surrounding tissue of cuprizone-fed mice after 6 weeks of intoxication, and evaluated the extent of astrocytic and microglial alterations using immunohistochemistry. Both mIns and tCho apparent diffusion coefficients were significantly elevated in cuprizone-fed mice compared with control mice, and histologic evaluation confirmed the presence of severe inflammation. Additionally, mIns and tCho diffusion showed, respectively, strong and moderate correlations with histological measures of astrocytic and microglial area fractions, confirming DW-MRS as a promising tool for specific detection of glial changes under pathological conditions.Disasters and climate-related risks displace millions of people each year. Planned relocation is one strategy used to address displacement and is increasingly being analyzed for the potential opportunities and challenges it creates for relocated people. However, little attention has been paid to the secondary impacts of planned relocations, and how they influence the risk, vulnerability and well-being of other groups, particularly people who live on the land that is selected for relocation sites, or in neighboring areas. This paper explores how current and potential future planned relocations in Fiji and the Philippines redistribute vulnerabilities to non-target communities who previously lived on, or alongside, relocation site land. The notion of cascading displacement is introduced to illustrate a serious consequence of planned relocations in which insecurity and displacement are re-created and perpetuated due to a failure to consider the needs of non-target groups who are directly disadvantaged by relocation processes. link2 Insights from this paper may be used to inform future relocation policy and practice for more equitable and sustainable outcomes for all involved. This article is protected by copyright. All rights reserved.Structural color colloidal sols of perovskite nanosheets were synthesized and were immobilized in a polymer hydrogel film by in situ photopolymerization, leading to a novel mechanochromic material. Visible absorption spectroscopy, polarized optical microscopy and small-angle X-ray scattering revealed that the nanosheets are aligned parallel to the film surface with the periodic distance of up to ca. 300 nm, giving the structural color tunable over full color range. link3 The present structural color gel showed reversible mechanochromic response that detects weak stress of 1 kPa with the quick response time less than 1 ms as well as high mechanical toughness (compressive breaking stress of up to 3 MPa). These excellent properties are suitable for applications for mechano-sensors and displays.Traditional diagnosis and understanding of the pathophysiology of obesity are based on excessive fat storage due to a chronically positive energy balance characterized by body mass index (BMI). Quantitative and qualitative analysis of lean and adipose tissue compartments by body composition analysis reveals that characterization of obesity as "overfat" does not facilitate a comprehensive understanding of obesity-associated health risk. Instead of being related to fat mass, body composition characteristics underlying BMI-associated prognosis may depend (i) on accelerated growth by a gain in lean mass or fat-free mass (FFM) in children with early BMI rebound or adolescents with early puberty; (ii) on a low muscle mass in aging, associated chronic disease, or severe illness; and (iii) on impaired adipose tissue expandability with respect to cardiometabolic risk. It is therefore time to call the adipocentric paradigm of obesity into question and to avoid the use of BMI and body fat percentage. By contrast, obesity should be seen in face of a limited FFM/muscle mass together with a limited capacity of fat storage.Breast fat necrosis (BFN) is usually a benign inflammatory response to breast trauma. However, an extremely rare cause of fat necrosis is calciphylaxis, a calcification of small- and medium-sized arteries causing thrombosis and ischemia. It is classified into (A) uremic (B) nonuremic-induced calciphylaxis. Calciphylaxis has been reported to be encountered in different parts of the body. However, to the best of our knowledge there is only one case in the English literature of BFN 2ry to warfarin-induced calciphylaxis. We report a 65-year-old female, known case of atrial fibrillation on warfarin, presented with a left breast mass of 4-month duration. The mass was painful and progressively enlarging. Examination of the left breast showed 7 × 4 cm mass, spanning from 10-2 o'clock, free from surrounding structures, with preserved overlying skin. However, the mass was not visualized on mammogram. Ultrasound showed a left breast lobulated hypoechoic mass containing a hyperechoic component. Biopsy showed fat necrosis. After 1 month, she presented with ulceration of the overlying skin. After wide local excision, histopathology demonstrated a calciphylaxis-induced fat necrosis. Considering the patient's background, the diagnosis was BFN secondary to warfarin-induced calciphylaxis. Hence, the warfarin was shifted to Rivaroxaban, 6 months follow-up showed no evidence of recurrence. In conclusion, the rarity of nonuremic calciphylaxis is reflected on the delay of diagnosis in some of the reported cases and the lack of grading system used to guide the management of such difficult wounds. However, keeping a high index of suspicion is important whenever such wounds are encountered with presence of risk factors other than end-stage kidney disease.

Natural orifice transluminal endoscopic surgery (NOTES) is aided by the instrument channel of an endoscope. Limited by the diameter of the endoscope, the construction of the operation triangle is affected. This paper presents a deployable arm that can increase the distance between the arms.

The manipulation arm is composed of a continuum arm and a deployable arm. The deployable arm can be locked by a stay cable and a mechanical structure. The angle between the end-effectors and the common workspace of the two manipulation arms are comprehensively analysed. Through experiments, the design parameters are validated and justified.

The experiment shows that the deployment arm can maintain the deformation within 3.5mm under a 300 g load, and the angle between the two end-effectors can be maintained within the range of [88°, 110°].

The novel deployment arms enlarge the angle between the end effectors, which significantly improves the flexibility of the arms.

The novel deployment arms enlarge the angle between the end effectors, which significantly improves the flexibility of the arms.