Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury,hyperammonemia and brain edema

Cerebral edema is a feared complication to acute liver failure (ALF), but the pathogenesis is still poorly understood. The water channels Aquaporin-1 (Aqp1) and -4 (Aqp4) has been associated with brain edema formation in several neuropathological conditions, indicating a possible role of Aqp1 and/or Aqp4 in ALF mediated brain edema. We induced acute liver injury and hyperammonemia in mice, to evaluate brain edema formation and the parallel expression of Aqp1 and Aqp4 in ALF. Liver injury and hyperammonemia were induced by +D-galactosamine (GLN) plus lipopolysaccharide (LPS) intraperitoneally and intravenous ammonia-acetate (NH₄ ⁺), the GLN+LPS+NH₄ ⁺ group. The vehicle control group (CONTROL) was treated with NaCl and phosphate-buffered saline. The GLN+LPS+NH₄ ⁺ group showed significantly elevated p-alanine aminotransferase, p-INR and p-ammonium vs. CONTROL (p < 0.001). Cortical brain water content was significantly elevated in the GLN+LPS+NH₄ ⁺ group vs. CONTROL, mean (SEM) 80.8(0.3) vs 80.0(0.1) % (p < 0.05). Western blot of membrane enriched cortical brain tissue showed significantly upregulation of Aqp4 in the GLN+LPS+NH₄ ⁺ group vs. CONTROL, mean AU (SEM) 100775(14820) vs. 58857(6266) (p < 0.05), and stationary levels for Aqp1. Aqp1 and Aqp4 mRNA were stationary. This study indicates that Aqp4, but not Aqp1, may be of importance in the pathogenesis of cortical brain edema in mice with ALF.     

新冠疫情前后成都市臭氧和呼吸系统疾病死亡之间的关联分析

目的 分析不同时间段成都市臭氧浓度和呼吸系统疾病死亡人数之间的关联。方法 成都市2018—2021年呼吸系统疾病的每日死亡数来自于四川省疾病预防控制中心,以新冠为断点描述两个时期呼吸系统疾病死亡数和臭氧浓度的变化,采用分布滞后非线性模型进行断点前后对比分析臭氧和呼吸道死亡风险之间的暴露-滞后-反应关联。结果 新冠发生前,成都市呼吸系统疾病死亡总数为41 465人,新冠疫情期间死亡总数为39 300人,除了臭氧,其余空气污染物浓度在新冠疫情期间有所下降。新冠发生前,臭氧与呼吸系统疾病死亡的关系曲线总体呈上升趋势,低浓度的RR值为0.477 6 (95%CI:0.282 1～0.808 5),各浓度下均存在滞后效应,中位浓度下滞后1天的RR值为0.974 5(95%CI:0.957 3～0.992 1)。在新冠疫情管控期间,臭氧与呼吸系统疾病死亡的暴露关联曲线总体呈下降趋势,低浓度对应的RR值为1.946 4 (95%CI:1.217 7～3.111 1),仅高浓度臭氧存在滞后效应,滞后1天的RR为0.999 4(95%CI:0.999 0～0.999 8)。结论 成都市的臭氧与呼吸系统疾...     

A review of sleep research in patients with spinal cord injury

Study design: Systematic review.Objectives: Sleep disturbances are a common complaint among individuals with spinal cord injury (SCI) and were not usually present before the SCI. Their sleep disturbances, including disrupted sleep, spasms, and problems with initiating and sustaining sleep through the night, affect SCI individuals’ overall quality of life due to excessive tiredness and low energy levels during the day. Despite the high prevalence of sleep complaints in this population, current knowledge about sleep in the SCI population has not been systematically assessed.Setting: Capital Region of Denmark.Methods: We systematically reviewed literature identified from the PubMed and EMBASE databases following PRISMA guidelines.Thirty-seven articles met our inclusion criteria, as only controlled studies were included. This could be a comparison of (1) SCI individuals and able-bodied controls, (2) cervical with thoracolumbar SCI individuals, or (3) cervical, thoracolumbar SCI individuals and able-bodied controls.Results: Individuals with SCI have a higher prevalence of sleep-disordered breathing and periodic leg movements during sleep (PLMS), lower heart rate, but no nocturnal lowering of blood pressure. 24-hour energy expenditure and sleeping metabolic rate were significantly lower, and bowel movements were altered. Endocrine alterations were found in investigations of melatonin, cortisol and antidiuretic hormone. Questionnaires revealed a high prevalence of subjectively poorer sleep quality in individuals with SCI compared with able-bodied controls.Conclusions: There are significant differences between groups with SCI and able-bodied controls. SCI objectively and subjectively markedly affects an individual’s sleep.     

Alzheimer’s and other dementias in Canada, 2011 to 2031: a microsimulation Population Health Modeling (POHEM) study of projected prevalence,health burden,health services,and caregiving use

Background

Worldwide, there is concern that increases in the prevalence of dementia will result in large demands for caregivers and supportive services that will be challenging to address. Previous dementia projections have either been simple extrapolations of prevalence or macrosimulations based on dementia incidence.

Methods

A population-based microsimulation model of Alzheimer’s and related dementias (POHEM:Neurological) was created using Canadian demographic data, estimates of dementia incidence, health status (health-related quality of life and mortality risk), health care costs and informal caregiving use. Dementia prevalence and 12 other measures were projected to 2031.

Results

Between 2011 and 2031, there was a projected two-fold increase in the number of people living with dementia in Canada (1.6-fold increase in prevalence rate). By 2031, the projected informal (unpaid) caregiving for dementia in Canada was two billion hours per year, or 100 h per year per Canadian of working age.

Conclusions

The projected increase in dementia prevalence was largely related to the expected increase in older Canadians, with projections sensitive to changes in the age of dementia onset.

     

Amplitude-modulated electromagnetic fields for the treatment of cancer: Discovery of tumor-specific frequencies and assessment of a novel therapeutic approach

Purpose

Because in vitro studies suggest that low levels of electromagnetic fields may modify cancer cell growth, we hypothesized that systemic delivery of a combination of tumor-specific frequencies may have a therapeutic effect. We undertook this study to identify tumor-specific frequencies and test the feasibility of administering such frequencies to patients with advanced cancer.

Patients and methods

We examined patients with various types of cancer using a noninvasive biofeedback method to identify tumor-specific frequencies. We offered compassionate treatment to some patients with advanced cancer and limited therapeutic options.

Results

We examined a total of 163 patients with a diagnosis of cancer and identified a total of 1524 frequencies ranging from 0.1 Hz to 114 kHz. Most frequencies (57–92%) were specific for a single tumor type. Compassionate treatment with tumor-specific frequencies was offered to 28 patients. Three patients experienced grade 1 fatigue during or immediately after treatment. There were no NCI grade 2, 3 or 4 toxicities. Thirteen patients were evaluable for response. One patient with hormone-refractory breast cancer metastatic to the adrenal gland and bones had a complete response lasting 11 months. One patient with hormone-refractory breast cancer metastatic to liver and bones had a partial response lasting 13.5 months. Four patients had stable disease lasting for +34.1 months (thyroid cancer metastatic to lung), 5.1 months (non-small cell lung cancer), 4.1 months (pancreatic cancer metastatic to liver) and 4.0 months (leiomyosarcoma metastatic to liver).

Conclusion

Cancer-related frequencies appear to be tumor-specific and treatment with tumor-specific frequencies is feasible, well tolerated and may have biological efficacy in patients with advanced cancer.

Trial registration

clinicaltrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00805337","term_id":"NCT00805337"}}NCT00805337     

包皮环扎术并发症的分析处理

目的：探讨包皮环扎术并发症的处置办法,以便进一步提高手术成功率,减少并发症。方法：采用CBV包皮除去环行包皮环扎术520例,总结早期开展包皮环扎术的经验及对并发症进行分析处理。结果：520例均治愈,各种并发症的发生按其产生后果的严重性由高到低依次为出血、感染、环扎器滑脱、环扎器过早脱落致内外板分离、创缘水肿以及环扎器延迟脱落等。结论：（1）包皮环扎术手术简单、快速、切口整齐美观,适宜在基层医院推广;（2）通过积极处置可以减少并发症,获得满意疗效。     

Fusion of the Fc part of human IgG1 to CD14 enhances its binding to gram-negative bacteria and mediates phagocytosis by Fc receptors of neutrophils

Microbial resistance to antimicrobial drugs is promoting a search for new antimicrobial agents that target highly conservative structures of pathogens. Human CD14 - a known pattern recognition receptor (PRR) which recognizes multiple ligands from different microbes might be a worthy candidate. The aim of our work was to create a CD14/Fc dimer protein and evaluate its whole bacteria binding and opsonizing capabilities. Fusion of CD14 with the fragment crystallisable (Fc) part of human IgG1 could not only lead to an artificial opsonin but the dimerization through the Fc part might also increase its affinity to different ligands. Human CD14 and the Fc part of human IgG1 was fused and expressed in HEK293 cells. A histidine tagged CD14 (CD14/His) was also expressed as control. Using flow cytometry we could prove that CD14/Fc bound to whole Gram-negative bacteria, especially to short lipopolysaccharide (Ra and Re) mutants, and weak interaction was observed between the fusion protein and Listeria monocytogenes. Other Gram-positive bacteria and fungi did not show any association with CD14/Fc. CD14/His showed about 50-times less potent binding to Gram-negative bacteria. CD14/Fc acted as an opsonin and enhanced phagocytosis of these bacteria by neutrophil granulocytes, monocyte-derived macrophages and dendritic cells. Internalization of bacteria was confirmed by trypan blue quenching and confocal microscopy. On neutrophils the Fc part of the fusion protein was recognized by Fc receptors (CD16, CD32), as determined by blocking experiments. CD14/Fc enhanced the killing of bacteria in an ex vivo whole blood assay. Our experiments confirm that PRR/Fc fusion proteins can give a boost to FcR dependent phagocytosis and killing provided the antimicrobial part binds efficiently to microbes.     

Complement inhibition by gram-positive pathogens: molecular mechanisms and therapeutic implications

The plasma proteins of the complement system are essential in the innate immune response against bacteria. Complement labels bacteria with opsonins to support phagocytosis and generates chemoattractants to attract phagocytes to the site of infection. In turn, bacterial human pathogens have evolved different strategies to specifically impair the complement response. Here, we review the large arsenal of complement inhibitors produced by the gram-positive pathogens Staphylococcus aureus and Group A Streptococcus. We discuss how these bacterial molecules provide us with new tools to treat both infectious and inflammatory disease conditions in humans.