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Macrophages, as specialized, long-lasting phagocytic cells of the innate immune system, have garnered increasing attention due to their wide distribution and various functions. The skin, being the largest immune organ in the human body, presents an intriguing landscape for macrophage research, particularly regarding their roles in inflammatory skin diseases and skin tumors. In this review, we compile the latest research on macrophages in conditions such as atopic dermatitis, psoriasis, systemic sclerosis, systemic lupus erythematosus, rosacea, bullous pemphigoid, melanoma and cutaneous T-cell lymphoma. We aim to contribute to illustrating the pathogenesis and potential new therapies for inflammatory skin diseases and skin tumors from the perspective of macrophages.

ObjectiveAnti-EGFR Targeted agents were found to be capable of modulating the antitumor immunity in head and neck cancer and become more and more frequently used in the treatment of nasopharyngeal carcinoma(NPC). We aimed to explore whether adding concurrent chemotherapy influences the survival outcome of patients with stage II-IVb NPC treated with concurrent anti-EGFR agents and intensity-modulated radiation therapy (IMRT) and explore other prognostic factors for the patients.Materials and MethodsA total of 656 stage II-IVb NPC patients treated with concurrent anti-EGFR agents plus IMRT between January 2011 and November 2015 were enrolled. Firstly, from these patients, a well-balanced cohort of 302 patients who received concurrent chemotherapy was created by matching potential prognostic factors. Furthermore, for all 656 stage II-IVb NPC patients, univariate and multivariate analyses of overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) were conducted to identify prognostic factors and to confirm the findings from the matching cohort.ResultsCompared with concurrent anti-EGFR agents alone, combining concurrent cisplatin and anti-EGFR agents significantly improved the OS (5-year 94.7% versus 84.3%, P=0.012) and PFS (5-year 82.0% versus 71.7%, P=0.039) of NPC patients with more severe hematologic toxicity and mucositis. The independent prognostic factors identified by multivariate analysis of OS and PFS included concurrent chemotherapy, epstein-barr virus(EBV) status and clinical stage. Patients treated without induction chemotherapy (IC) may achieve more benefits from the addition of concurrent chemotherapy to concurrent anti-EGFR agents.ConclusionsFor stage II-IVb NPC patients treated with concurrent anti-EGFR agents, the addition of concurrent chemotherapy can significantly improve the survival outcome.

The design life can be longer than 50 years for critical structures or infrastructures and shorter than 50 years for non-residential structures or construction periods. Some building codes provide methods to derive factors for adjusting the design wind speeds for construction periods. Eurocode 1 provides a probability factor for calculating the design wind speeds for a specific return period regulated for a construction period of less than 1 year. The Australian ABCB Temporary Structures standard provides design wind speed for construction using a different assumption. The ASCE 37 in the USA provides design wind speed reduction factors for a design life less than 5 years by maintaining the probability of exceedance of the factored wind load for 50-year design life the same for a shorter design life. These approaches can result in different results and deserve some comparisons. The present study included another method that maintains the structural reliability of the non-standard design life the same as the structural reliability for the design life of 50 years. The derived factors for a design life shorter than 50 years using these methods were compared considering the Canadian wind climates. The calculated design wind speed adjustment factors for design life longer than 50 years were evaluated using various techniques and compared with the commonly used importance factors. The present study also characterized the directionality and seasonality of the Canadian wind climates.

Huntington’s disease (HD) is an inherited autosomal dominant neurodegenerative disorder that leads to progressive motor and cognitive impairment. There are currently no available disease modifying treatments for HD patients. We have previously shown that pharmacological blockade of metabotropic glutamate receptor 5 (mGluR5) signaling rescues motor deficits, improves cognitive impairments and mitigates HD neuropathology in male zQ175 HD mice. Mounting evidence indicates that sex may influence HD progression and we have recently reported a sex-specific pathological mGluR5 signaling in Alzheimer’s disease (AD) mice. Here, we compared the outcomes of treatment with the mGluR5 negative allosteric modulator CTEP (2-chloro-4-[2-[2,5-dimethyl-1-[4-(trifluoromethoxy)phenyl]imidazol-4-yl]ethynyl]pyridine) in both male and female symptomatic zQ175 mice. We found that female zQ175 mice required a longer treatment duration with CTEP than male mice to show improvement in their rotarod performance. Unlike males, chronic CTEP treatment did not improve the grip strength nor reverse the cognitive decline of female zQ175 mice. However, CTEP reduced the number of huntingtin aggregates, improved neuronal survival and decreased microglia activation in the striatum of both male and female zQ175 mice. Together, our results indicate that mGluR5 antagonism can reduce HD neuropathology in both male and female zQ175 HD mice, but sex has a clear impact on the efficacy of the treatment and must be taken into consideration for future HD drug development.

The duration of wind storms over a threshold wind speed value is known to be an important parameter in determining damage and losses, with losses tending to increase with the duration. This is because peak pressures tend to increase with longer duration, many building components and cladding systems are vulnerable to different types of fatigue mechanisms, and the yielding of linear elastic materials in the plastic range depends on the number of load cycles. A hurricane model was used to examine the duration of high winds in the United States at Miami, Galveston, and Charleston with the goal of establishing duration statistics for hurricanes as a function of peak wind speed. It was found that the duration of high winds, defined as the time that the 10 min wind speeds are within 30% of the peak 10 min wind speed, had a significant variation with a range from tens of minutes to more than 20 h, depending on location. The median duration ranged from 1.5 to 4 h at the three locations, depending on location and the design wind speed level (i.e., the risk Category of the building). These results were used to establish a simple normalized model for wind speed as a function of time, which could be used together with the design wind speed to establish load cycles for design.