Reduction of soluble uranium U(VI) to less-soluble uranium U(IV) isUranium contamination is a persistent legacy of the cold war era. When uranium mining and processing for nuclear weapons and fuel were at their peak, uranium-containing wastes accumulated, resulting in a multitude of contaminated sites worldwide. In the United States specifically, there are more than 120 uranium contaminated sites, containing approximately 6.4 trillion liters of waste (33). The dominant uranium isotope in this waste, 238

House dust mites (HDMs) induce allergic diseases such as asthma. Neutrophil apoptosis is an important process of innate immunity, and its dysregulation is associated with asthma. In this study, we examined the effects of HDM on constitutive apoptosis of normal and asthmatic neutrophils. Extract of Dermatophagoides pteronissinus (DP) inhibited neutrophil apoptosis, but Dermatophagoides farinae extract had no effect. Anti-apoptotic signaling mediated by DP involves in TLR4, Lyn, PI3K, Akt, ERK, and NF-κB in normal neutrophils. DP delayed cleavage of procaspase 9 and procaspase 3 and the decrease in Mcl-1 expression. Supernatant collected from DP-treated normal neutrophils inhibited the constitutive apoptosis of normal neutrophils, and S100A8 and S100A9 were identified as anti-apoptotic proteins in the supernatant. S100A8 and S100A9 transduced the anti-apoptotic signal via TLR4, Lyn, PI3K, Akt, ERK, and NF-κB. DP also suppressed asthmatic neutrophil apoptosis and induced secretion of S100A8 and S100A9, which delayed the constitutive apoptosis. The anti-apoptotic effects of DP, S100A8 and S100A9 in asthmatic neutrophils are associated with TLR4, Lyn, PI3K, Akt, ERK, and NF-κB. The concentrations of S100A8 and S100A9 were significantly elevated in asthmatic bronchoalveolar lavage fluid (BALF) when compared to normal BALF (p<0.01), but not in serum. S100A8 concentration in BALF was positively correlated with the number of BALF neutrophils and negatively correlated with FEV1(%). These findings improve our understanding of the role of HDM in regulation of neutrophil apoptosis in normal individuals and asthmatics and will enable elucidation of asthma pathogenesis.

House dust mite (HDM) is a primary allergen in allergic rhinitis (AR) and asthma. Neutrophil apoptosis is associated with allergic diseases and innate immunity to infection. The present study examined how HDM affects constitutive neutrophil apoptosis in normal and AR subjects. Total IgE increased in AR subjects when compared to normal subjects, and patients with AR were HDM-specific IgE positive (+), which is specific IgE to Dermatophagoides pteronissinus and Dermatophagoides farinae. In normal and AR subjects, neutrophil apoptosis was inhibited by extract of Dermatophagoides pteronissinus (DP), but not by extract of Dermatophagoides farina (DF). Aprotinin (serine protease inhibitor) and E64 (cysteine protease inhibitor) have no effect on neutrophil apoptosis due to DP. The anti-apoptotic effect of DP was blocked by TLR4i, an inhibitor of TLR4, rottlerin, an inhibitor of PKCδ, PD98059, an inhibitor of ERK, and BAY-11-7085, an inhibitor of NF-κB. DP induced PKCδ, ERK, and NF-κB activation in a time-dependent manner. DP inhibited the cleavage of procaspase 3 and procaspase 9. The expression of IL-6, IL-8, TNF-α, G-CSF, GM-CSF, and CCL2 increased in the supernatant collected from the normal and AR neutrophils after DP treatment and the supernatant inhibited the apoptosis of normal and AR neutrophils. In summary, DP has anti-apoptotic effects on neutrophils of normal and AR subjects through the TLR4/PKCδ/ERK/NF-κB pathway, and this finding may contribute to solution of the pathogenic mechanism of allergic diseases triggered by DP.

Despite clinical evidence indicating a close relationship between olfactory dysfunction and Alzheimer’s disease (AD), further investigations are warranted to determine the diagnostic potential of nasal surrogate biomarkers for AD. In this study, we first identified soluble amyloid-β (Aβ), the key biomarker of AD, in patient nasal discharge using proteomic analysis. Then, we profiled the significant differences in Aβ oligomers level between patient groups with mild or moderate cognitive decline (n = 39) and an age-matched normal control group (n = 21) by immunoblot analysis and comparing the levels of Aβ by a self-standard method with interdigitated microelectrode sensor systems. All subjects received the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and the Global Deterioration Scale (GDS) for grouping. We observed higher levels of Aβ oligomers in probable AD subjects with lower MMSE, higher CDR, and higher GDS compared to the normal control group. Moreover, mild and moderate subject groups could be distinguished based on the increased composition of two oligomers, 12-mer Aβ*56 and 15-mer AβO, respectively. The longitudinal cohort study confirmed that the cognitive decline of mild AD patients with high nasal discharge Aβ*56 levels advanced to the moderate stage within three years. Our clinical evidence strongly supports the view that the presence of oligomeric Aβ proteins in nasal discharge is a potential surrogate biomarker of AD and an indicator of cognitive decline progression.

BackgroundThe old age population, including the very old aged (≥ 85 years), is rapidly increasing, and femur neck fracture from accidents is commonly seen in the elderly. Use of bone cement during bipolar hemiarthroplasty can cause bone cement implantation syndrome.MethodsThis study was prospectively conducted on the elderly who were scheduled to undergo elective cemented bipolar hemiarthroplasty under spinal anesthesia. Patients were divided into 2 groups: the old age (65-84 years) and very old age groups (≥ 85 years). Hemodynamic parameters were recorded at the following time points: the start of the operation, femoral reaming, cement insertion, every 2 minutes after cement insertion for 10 minutes, femoral joint reduction, and the end of operation. When hypotension occurred, ephedrine was given.ResultsSixty-five patients in the old age group and 32 patients in the very old age group were enrolled. Mean ages were 78.9 and 89.4 years, respectively, in the old age and very old age groups. The very old age group showed constantly decreased levels of cardiac index and stroke volume from cementing until the end of the operation compared to the old age group. To maintain hemodynamic stability after cement insertion, the requirement of ephedrine was higher in the very old age group than in the old age group (13.52 ± 7.76 vs 8.65 ± 6.38 mg, P = 0.001).ConclusionsBone cement implantation during bipolar hemiarthroplasty may cause more prominent hemodynamic changes in very elderly patients. Careful hemodynamic monitoring and management are warranted in very elderly patients undergoing cemented bipolar hemiarthroplasty.

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Background: Interscalene brachial plexus block (ISBPB) is commonly used with general anesthesia for postoperative pain management in shoulder surgery. This study investigated the incidence of hypothermia and changes in the body temperature in patients undergoing arthroscopic shoulder surgery under ISBPB with propofol sedation.Methods: This retrospective study enrolled 220 patients who underwent arthroscopic shoulder surgery. Patients were divided into general anesthesia (n = 34) and ISBPB with propofol sedation (n = 186) groups, and medical records were retrospectively compared. In addition, patients from the ISBPB group were further divided according to age (elderly, [≥ 65 years]; n = 98 vs. young, [< 65 years]; n = 88), and the incidence of hypothermia and changes in the body temperature were compared. Results: Twenty-seven patients (12.3%) experienced perioperative hypothermia (range; 35.3–35.9℃). The incidence of perioperative hypothermia was 29.4% and 9.1% in the general anesthesia and ISBPB groups, respectively, and there was a significant difference between the two groups (P = 0.002). The incidence of perioperative hypothermia according to age in the ISBPB group was 9.2% and 9.1% in the elderly and young groups, respectively, and there was no significant difference between the two groups (P = 0.983).Conclusions: The incidence of perioperative hypothermia during arthroscopic shoulder surgery under ISBPB with propofol sedation is lower than that under general anesthesia. Furthermore, when using ISBPB with propofol sedation, the incidence of perioperative hypothermia in elderly patients is similar to that in younger patients.

Intervertebral disc (IVD) degeneration is associated with imbalances between catabolic and anabolic responses, regulated by extracellular matrix (ECM)-modifying enzymes such as matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinases (TIMPs). Potential contributing factors, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, derived from infiltrated, activated macrophages within IVD tissues, can trigger abnormal production of ECM-modifying enzymes and progression of IVD degeneration. Novel therapies for regulating ECM-modifying enzymes can prevent or ameliorate IVD degeneration. Photobiomodulation (PBM), known to regulate wound repair, exhibits regenerative potential by modulating biological molecules. This study examined the effects of PBM, administered at various wavelengths (630, 525, and 465 nm) and energy densities (16, 32, and 64 J/cm2), on the production of ECM-modifying enzymes in replicated degenerative IVD. Our results showed that PBM selectively inhibited the production of ECM-modifying enzymes in a dose- and wavelength-dependent manner, suggesting that it could be a novel tool for treating symptomatic IVD degeneration.