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However, no effects on TOPO IIα were detected in the cellular test system. As a subsequent cellular response to TOPO I poisoning, a highly significant increase of DNA damage after 2 h and a decrease of cell viability after 48 h at the same concentration range were found. Furthermore, after 24 h of incubation a G2/M arrest was observed at concentrations ≥ 100 µM by flow cytometry. The analysis of cell death revealed that nevadensin induces the intrinsic apoptotic pathway via activation of caspase-9 and caspase-3. The results suggest that cell cycle disruption and apoptotic events play key roles in the cellular response to TOPO I poisoning caused by nevadensin in HT29 cells.Thifluzamide is widely used fungicide and frequently detected in aquatic system. In this study, the toxicity of fungicide thifluzamide to non-targeted aquatic organisms was investigated for neuroendocrine disruption potentials. Here, zebrafish embryos were exposed to a series of concentrations of thifluzamide for 6 days. The results showed that both the development of embryos/larvae and the behavior of hatched larvae were significantly affected by thifluzamide. Importantly, the decreased activity of acetylcholinesterase (AchE) and the increased contents of neurotransmitters such as serotonin (5-HT) and norepinephrine (NE), along with transcriptional changes of nervous system related genes were observed following 4 days exposure to thifluzamide. Besides, the decreased contents of triiodothyronine (T3) and thyroxine (T4) in whole body, as well as significant expression alteration in hypothalamic-pituitary-thyroid (HPT) axis associated genes were discovered in zebrafish embryos after 4 days of exposure to thifluzamide. Our results clearly demonstrated that zebrafish embryos exposed to thifluzamide could disrupt neuroendocrine, compromise behavior and induce developmental abnormality, suggesting impact of this fungicide on developmental programming in zebrafish.Co-occurrence of mental disorders including severe PTSD, somatic symptoms, and dissociation in the aftermath of trauma is common and sometimes associated with poor treatment outcomes. However, the interrelationships between these conditions at symptom level are not well understood. In the present study, we aimed to explore direct connections between PTSD, somatic symptoms, and dissociation to gain a deeper insight into the pathological processes underlying their comorbidity that can inform future treatment plans. In a sample of 655 adult inpatients with a diagnosis of severe PTSD following childhood abuse (85.6% female; mean age = 47.57), we assessed symptoms of PTSD, somatization, and dissociation. We analyzed the comorbidity structure using a partial correlation network with regularization. Mostly positive associations between symptoms characterized the network structure. Muscle or joint pain was among the most central symptoms. Physiological reactivation was central in the full network and together with concentrations problems acted as bridge between symptoms of PTSD and somatic symptoms. Headaches connected somatic symptoms with others and derealization connected dissociative symptoms with others in the network. Exposure to traumatic events has a severe and detrimental effect on mental and physical health and these consequences worsen each other trans-diagnostically on a symptom level. Strong connections between physiological reactivation and pain with other symptoms could inform treatment target prioritization. We recommend a dynamic, modular approach to treatment that should combine evidence-based interventions for PTSD and comorbid conditions which is informed by symptom prominence, readiness to address these symptoms and preference.Granulomatosis with polyangiitis (GPA) previously known as Wegener's granulomatosis (WG) is a rare rheumatic disease affecting subjects of all ages. Prevalence and incidence of this systemic disease greatly varies across different ethnic groups. GPA is the commonest form of ANCA-associated vasculitis (AAV) with PR3 positivity among 85-95% of the cases. Scientific investigations of GPA is warranted because its severity, clinical heterogeneity, fast disease manifestation and end-organ damage. The etiology of GPA is still unknown. Major role of HLA and non-HLA genes with immune functions were identified, however, very limited replication was observed in different ethnic populations. In the present review, we have discussed the updates on the global epidemiology and contribution of HLA and major non-HLA genes/loci in GPA. We have also highlighted the cross disease association of GPA associated genes that may help in better disease management and predictive medicine. We proposed that high-resolution HLA typing and development of genetic risk model would help in early disease diagnosis and understanding the prognosis.

There is limited literature available regards the frequency and characteristics of COVID-19 + ve status among advanced cancer patients referred to an inpatient supportive care consultation(PC) at a tertiary cancer center. Our study aimed to determine the frequency and characteristics of COVID-19 + ve cancer patients seen by PC.

Advanced cancer patients seen as a consult by PC between June 15 and September 25, 2020, at MD Anderson Cancer Center were eligible for the study. We evaluated the patient demographics, clinical characteristics including symptoms(ESAS), delirium(MDAS), COVID + status prior to, and after PC referral(converters), and type of PC delivery(in person or virtual care).

Sixty-six out of 1380 (4.8%) PC consults were COVID-19 + ve 42 prior to PC (79%), and 14 (21%) were COVID-19 + ve after the PC (converters). COVID-19 + PC patients had lower depression (P = .035), spiritual distress (P = .003), and were more seen frequently virtually (P < 0.001). There was no significant difference betwer delirium. During a new pandemic, universal virtual care might be emphasized especially at initial encounters after admission and further research is needed on the potential efficacy of this intervention.Lung adenocarcinoma (LUAD), the most common type of cancer, is hard to diagnose and has an unfavorable prognosis. Tumor mutation burden (TMB) is a useful predictor and can also determine the efficacy of immunotherapy in various cancers. The present study focused on unraveling the association between immune infiltration and TMB and developing an immune- and TMB-related prognostic model to predict LUAD patients' prognosis. The results revealed that the immune-related prognostic model (IPM) based on TMB was capable of classifying LUAD patients in all cohorts into different risk groups. The IPM was useful and had a significant correlation with LUAD patients' overall survival (OS). Based on the multivariate Cox analysis results, the IPM was proved to be an independent predictive biomarker. Furthermore, the five hub genes and the immune-related model were related to different immune infiltrating cells. The IPM was related to immune checkpoints. At last, an effective nomogram was established to predict LUAD patients' prognosis. To conclude, our IPM is effective in predicting LUAD patients' prognosis and provides novel insights into immunotherapy for LUAD.Accidental foot injuries including metatarsal fractures commonly result from compressive loading. The ability of personal protective equipment to prevent these traumatic injuries depends on the understanding of metatarsal fracture tolerance. However, the in-situ fracture tolerance of the metatarsals under direct compressive loading to the foot's dorsal surface remains unexplored, even though the metatarsals are the most commonly fractured bones in the foot. The goal of this study was to quantify the in-situ fracture tolerance of the metatarsals under simulated quasi-static compressive loading. Fresh-frozen cadaveric feet (n=10) were mounted into a testing apparatus to replicate a natural stance and loaded at the mid-metatarsals with a cylindrical bar to simulate a crushing-type injury. A 900N compressive force was initially applied, followed by 225N successive load increments. Specimens were examined using X-ray imaging between load increments to assess for the presence of metatarsal fractures. Descriptive statistics were conducted for metatarsal fracture force and deformation. Pearson correlation tests were used to quantify the correlation between fracture force with age and BMI. The force and deformation at fracture were 1861 ± 642 N (mean ± SD) and 22.6 ± 3.4 mm, respectively. Fracture force was correlated with donor BMI (r=0.90). Every fractured specimen experienced a transverse fracture in the second metatarsal. New biomechanical data from this study further quantifies the metatarsal fracture risk under compressive loading and will help to improve the development and testing of improved personal protective equipment for the foot.Mutations in mitochondrial DNA encoded subunit of ATP synthase, MT-ATP6, are frequent causes of neurological mitochondrial diseases with a range of phenotypes from Leigh syndrome and NARP to ataxias and neuropathies. Here we investigated the functional consequences of an unusual heteroplasmic truncating mutation m.9154C>T in MT-ATP6, which caused peripheral neuropathy, ataxia and IgA nephropathy. ATP synthase not only generates cellular ATP, but its dimerization is required for mitochondrial cristae formation. Accordingly, the MT-ATP6 truncating mutation impaired the assembly of ATP synthase and disrupted cristae morphology, supporting our molecular dynamics simulations that predicted destabilized a/c subunit subcomplex. Next, we modeled the effects of the truncating mutation using patient-specific induced pluripotent stem cells. Unexpectedly, depending on mutation heteroplasmy level, the truncation showed multiple threshold effects in cellular reprogramming, neurogenesis and in metabolism of mature motor neurons (MN). Interestingly, MN differentiation beyond progenitor stage was impaired by Notch hyperactivation in the MT-ATP6 mutant, but not by rotenone-induced inhibition of mitochondrial respiration, suggesting that altered mitochondrial morphology contributed to Notch hyperactivation. Finally, we also identified a lower mutation threshold for a metabolic shift in mature MN, affecting lactate utilization, which may be relevant for understanding the mechanisms of mitochondrial involvement in peripheral motor neuropathies. These results establish a critical and disease-relevant role for ATP synthase in human cell fate decisions and neuronal metabolism.Perilla seed bugs (Nysius sp.) are considered to be the emerging pests causing nutritional and yield losses in perilla and cereal crops. A survey of perilla seed bugs on weeds and perilla crops was conducted over the course of 2 yr in Korea to determine the species composition, abundance, and seasonal dynamics of perilla seed bugs. Three species of Heteroptera (Nysius plebeius, Nysius hidakai, and Nysius inconspicuus), nymphs of Nysius species, and several parasitoid species were collected from weeds and perilla crops. Nysius hidakai was the most abundant perilla seed bugs. In 2019, adult perilla seed bugs, nymphs of perilla seed bugs, and parasitoid species were more abundant in weed species than in perilla crops. An early peak with a greater number of adult perilla seed bug (N. Oleic activator hidakai) was observed in weeds in 2020. However, an identical peak with a similar number of perilla seed bug (N. hidakai) was found in perilla crops in both years. Peak perilla seed bugs densities were observed in the 4th week of June, 2020 in weeds.