A new perspective of hypothalamic disease: Shapiro's syndrome

Shapiro's syndrome (SS) is characterized by spontaneous periodic hypothermia. It occurs to patients regardless of age or sex. To date, <60 cases have been reported worldwide. Current knowledge of the disease is limited to clinical feature since the pathogenesis and etiology are still controversial. In this review, the clinical characteristics, pathological mechanism, and possible etiology of the syndrome were reviewed to improve the clinical understanding of the disease

Causality between sarcopenia and diabetic nephropathy: a bidirectional Mendelian randomization study

Background and purposeObservational studies have shown that sarcopenia and diabetic nephropathy (DN), are closely related; however, the causal relationship is unclear. This study aims to address this issue using a bidirectional Mendelian randomization (MR) study.MethodologyWe data from genome-wide association studies including appendicular lean mass (n = 244,730), grip strength (right: n = 461,089, left: n = 461026), walking speed (n = 459,915), and DN (3283 cases and 181,704 controls) to conduct a bidirectional MR study. First, we conducted a Forward MR analysis to evaluate the causality of sarcopenia on the risk of DN from the genetic perspective with appendicular lean mass, grip strength, and walking speed as exposure and DN as the outcome. Then, DN as the exposure, we performed a Reverse MR analysis to determine whether DN impacted the appendicular lean mass, grip strength, and walking speed of the appendices. Finally, a series of sensitivity studies, such as heterogeneity tests, pleiotropy evaluations, and Leave-one-out analyses, were conducted to assess the MR analysis’s accuracy further.ResultsAccording to a forward MR analysis, a genetically predicted decrease in appendicular lean mass is associated with an increased risk of developing DN risk (inverse variance weighting[IVW]: odd ratio [OR] = 0.863, 95% confidence interval [CI] 0.767-0.971; P = 0.014). According to reverse MR results, grip strength decreased as DN progressed (IVW: right β = 0.003, 95% CI: - 0.021 to - 0.009, P = 5.116e-06; left β = 0.003, 95% CI: - 0.024 to - 0.012, P = 7.035e-09). However, the results of the other MR analyses were not statistically different.ConclusionNotably, our findings suggest that the causal relationship between sarcopenia and DN cannot be generalized. According to analysis of the individual characteristic factors of sarcopenia, reducing in appendicular lean mass increases the risk of developing DN and DN is linked to reduced grip strength. But overall, there is no causal relationship between sarcopenia and DN, because the diagnosis of sarcopenia cannot be determined by one of these factors alone

In vivo self-assembled albumin nanoparticle elicit antitumor immunity of PD-1 inhibitor by imaging and clearing tumor-associated macrophages

Eliciting anti-tumor immune responses and improving the tumor microenvironment crucial for boosting the effectiveness of anti-PD-1 immunotherapy. Tumor-associated macrophages (TAMs), the primary types of immune cells infiltrating tumors, play a critical role in the formation of an immunosuppressive microenvironment. In this study, we constructed a novel Evans Blue (EB)-based in vivo self-assembled nanocarrier system, mUNO-EB-ICG-Fc@Alb nanoparticles (designated as MA NPs), for targeted imaging and clearance of M2-TAMs to elicit antitumor immunotherapy of PD-1 inhibitor. In vitro experiments demonstrated the specific fluorescence imaging and killing effect of MA NPs on M2-TAMs. In vivo experiments shown that MA NPs-induced chemodynamic therapy (CDT) successfully reversed the tumor immunosuppressive microenvironment (ITM), promoted intratumoral infiltration of T lymphocytes, and ultimately enhancing the anti-tumor immunotherapy effect of PD-1 inhibitors. This study might provide good inspiration for improving the therapeutic efficacy of cancer immunotherapy

Promoting equitable genetic testing in ovarian cancer:the demonstration of improvement for molecular ovarian cancer testing (DEMO) project

Parallel genetic testing (testing for both tumour and germline gene changes) after the diagnosis of ovarian cancer should be considered the standard of care and is crucial to support treatment decisions. The demonstration of improvement for molecular ovarian cancer testing (DEMO) project aimed to develop patient-focused tools to promote equitable genetic care in diverse communities with high proportions of patients with limited English proficiency and biopsy guidelines to address the variations in specimen quality in different geographical regions in the UK. Our three work packages (WP) aimed to promote awareness by addressing the information gaps in different community groups (WP1), develop infrastructure to evaluate the different tissue collection pathways in different regions (WP2) and support continuing professional development (CPD) to encourage best practices with the involvement of patients (WP3). Our output included a multimedia multilanguage information package with paired National Health Service-branded written materials to support genetic testing after ovarian cancer diagnosis (https://ovarian.org.uk/demo-uk/), a scalable database to enable a multisite audit of parallel genetic testing pathways and a collection of CPD events that had patient involvement as an essential component. In addition, we have collaborated with patient and community groups to contribute to a national consensus guidance on genetic testing in ovarian cancer. Our co-production work has been recognised by local and regional awards as an exemplar for patient and public involvement (PPI). This has supported the start of a legacy co-production group in gynaeoncology (https://www.dhlnetwork.com/gohildas) to address the critical unmet need for sustainable and equity-oriented PPI to advocate for underserved communities. The DEMO project has contributed to raising awareness of the importance of equitable genetic care in ovarian cancer. We will continue to build on this groundwork to support future quality improvement projects and research, with the ultimate goal of improving the outcomes of patients with ovarian cancer.</p

Novel albumin-binding multifunctional probe for synergistic enhancement of FL/MR dual-modal imaging and photothermal therapy

The fluorescence/magnetic resonance (FL/MR) dual-modal imaging could provide accurate tumor visualization to guide photothermal therapy (PTT) of cancer, which has attracted widespread attention from scientists. However, facile and effective strategies to synergistically enhance fluorescence intensity, MR contrast and photothermal efficacy have rarely been reported. This study presents a novel multifunctional probe Gd-EB-ICG (GI) for FL/MR dual-modal imaging-guided PTT of cancer. GIs can self-assemble with endogenous albumin to form drug-albumin complexes (GIAs), which exhibit excellent biocompatibility. Albumin can protect GIAs from the recognition and clearance by the mononuclear phagocytic system (MPS). High plasma concentration and long half-life allow GIAs to accumulate continuously in the tumor area through EPR effect and specific uptake of tumor. Because of the prolonged rotational correlation time (τR) of Gd chelates, GIAs exhibited superior MR contrast performance over GIs with more than 3 times enhancement of longitudinal relaxation efficiency (r1). The fluorescence quantum yield and photothermal conversion efficiency of GIAs was also significantly improved due to the constrained geometry, disrupted aggregation and enhanced photothermal stability. This simple and feasible strategy successfully resulted in a synergistic effect for FL/MR dual-modal imaging and photothermal therapy, which can cast a new light for the clinical translation of multifunctional probes

Structural Relationships between Counselors&rsquo; Sense of Calling, Meaning of Work, Living a Calling, and Psychological Burnout

This study examined the influence of counselors&rsquo; sense of calling on psychological burnout, mediated by meaning of work and living a calling, based on the work as a calling theory (WCT) and preceding studies. Furthermore, the sequential mediating effects of meaning of work and living a calling were investigated. Data were collected from 420 Korean counselors working in counseling centers located nationwide and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). The results revealed that a sense of calling negatively impacted psychological burnout. Second, the sense of calling did not affect psychological burnout through the mediation of meaning of work. Third, the sense of calling negatively impacted psychological burnout through the mediation of living a calling. Fourth, the sense of calling negatively affected psychological burnout through the sequential mediation of meaning of work and living a calling. Based on this study&rsquo;s findings, implications can be provided to enhance counselors&rsquo; professional calling and reduce psychological burnout, thereby aiding them in resolving their psychological issues during counseling practice and providing higher-quality psychological services to clients. Suggestions for improvements and future research are also discussed

Reversible Flash-Bonding Of Zirconia And Nickel Alloys

A electric field-assisted flash-joining technique of ceramic and metal was shown here. It was demonstrated that when the voltage and current density were higher than critical values, the zirconia ceramic and Ni based superalloy were strongly bonded in as fast as 1 s at 800 °C. Another important advantage of the technique is that the resultant joint can be readily de-bonded by reversing the electric field, which provides significant manufacturing flexibility. The underlying bonding mechanism follows an electric field-induced internal reaction, and the novel method could be extended to a wide range of ceramic-metal systems in principle