Inflammatory stimuli can induce neutrophils to release nuclear DNA combined with histones into the extracellular space, forming neutrophil extracellular traps. Because inflammation contributes to ...diabetic retinopathy, it is plausible that neutrophil extracellular trap formation actively occurs in diabetic retinopathy. This case-control study investigated the clinical relevance of circulating levels of neutrophil extracellular trap components as risk factors of diabetic retinopathy, and further evaluated whether glucose induced neutrophil extracellular trap formation in vitro using whole blood from healthy volunteers.
Circulating levels of DNA-histone complexes, cell free double-stranded DNA, and polymorphonuclear neutrophil elastase, considered to be markers of neutrophil extracellular trap formation, were measured in patients with diabetic retinopathy (n=28) and without (n=62) and in 28 healthy controls.
Circulating DNA-histone complex and polymorphonuclear neutrophil elastase levels were significantly increased in patients with diabetic retinopathy compared with those without retinopathy. Multivariable logistic regression analysis, adjusted for glycated hemoglobin levels and fasting blood glucose, revealed that DNA-histone complex and polymorphonuclear neutrophil elastase levels were significant independent risk factors of retinopathy. In vitro experiments also showed that glucose significantly increased markers of neutrophil extracellular trap formation in a dose-dependent manner.
Markers of neutrophil extracellular trap formation were independent risk factors of diabetic retinopathy. This finding provides a new insight into the potential therapeutic and preventive approaches to dampen neutrophil extracellular trap formation.
Objective: The aim was to investigate the white matter abnormalities of drug‐naïve patients with obsessive–compulsive disorder (OCD) using diffusion tensor‐imaging and the white matter changes in ...the patients after pharmacotherapy.
Method: Thirteen drug‐naïve OCD patients and 13 age‐ and sex‐matched healthy comparison subjects were examined using diffusion tensor‐imaging and structural magnetic resonance imaging. Measurements were made in OCD patients before and after 12 weeks of citalopram treatment.
Results: Compared with controls, the drug‐naïve OCD patients showed significant increases in fractional anisotropy (FA) in the corpus callosum, the internal capsule and white matter in the area superolateral to the right caudate. The increases in FA were mostly no longer observed in patients after 12 weeks of treatment compared with controls.
Conclusion: Our findings suggest that white matter alterations are associated with the pathophysiology of OCD, and the abnormalities may be partly reversible with pharmacotherapy.
Levels of obesity-linked non-insulin-dependent diabetes mellitus (NIDDM) and hypertension are highest among indigenous communities in North America. This is linked to changes in dietary pattern ...towards high calorie foods such as sugar, refined grain flour, and sweetened beverages. Therefore, a return to traditional dietary patterns may help to reduce these disease problems because of better balance of calories and beneficial nutrients. Further protective non-nutrient phenolic phytochemicals against NIDDM and hypertension are potentially high in these foods but less understood. In this study antidiabetic- and antihypertension-relevant potentials of phenolic phytochemicals were confirmed in select important traditional plant foods of indigenous communities such as pumpkin, beans, and maize using in vitro enzyme assays for -glucosidase, alpha-amylase, and angiotensin I-converting enzyme (ACE) inhibitory activities. In vitro inhibitory activities of these enzymes provide a strong biochemical rationale for further in vivo studies and dietary management strategy for NIDDM through the control of glucose absorption and reduction of associated hypertension. These enzyme inhibitory activities were further compared to total soluble phenolic content and antioxidant activity of the above-targeted plant foods. Pumpkin showed the best overall potential. Among the varieties of pumpkin extracts P5 (round orange) and P6 (spotted orange green) had high content of total phenolics and moderate antioxidant activity coupled to moderate to high alpha-glucosidase and ACE inhibitory activities. Therefore this phenolic antioxidant-enriched dietary strategy using specific traditional plant food combinations can generate a whole food profile that has the potential to reduce hyperglycemia-induced pathogenesis and also associated complications linked to cellular oxidation stress and hypertension.
The Taiwanese-American Occultation Survey (TAOS) aims to detect serendipitous occultations of stars by small (~1 km diameter) objects in the Kuiper Belt and beyond. Such events are very rare (<10 ...super(-3) events per star per year) and short in duration (~200 ms), so many stars must be monitored at a high readout cadence. TAOS monitors typically ~500 stars simultaneously at a 5 Hz readout cadence with four telescopes located at Lulin Observatory in central Taiwan. In this paper, we report the results of the search for small Kuiper Belt objects (KBOs) in seven years of data. No occultation events were found, resulting in a 95% c.l. upper limit on the slope of the faint end of the KBO size distribution of q - 3.34-3.82, depending on the surface density at the break in the size distribution at a diameter of about 90 km.
The tumor suppressor p53 is an important regulator of intracellular reactive oxygen species (ROS) levels, although downstream mediators of p53 remain to be elucidated. Here, we show that p53 and its ...downstream targets, p53-inducible ribonucleotide reductase (p53R2) and p53-inducible gene 3 (PIG3), physically and functionally interact with catalase for efficient regulation of intracellular ROS, depending on stress intensity. Under physiological conditions, the antioxidant functions of p53 are mediated by p53R2, which maintains increased catalase activity and thereby protects against endogenous ROS. After genotoxic stress, high levels of p53 and PIG3 cooperate to inhibit catalase activity, leading to a shift in the oxidant/antioxidant balance toward an oxidative status, which could augment apoptotic cell death. These results highlight the essential role of catalase in p53-mediated ROS regulation and suggest that the p53/p53R2-catalase and p53/PIG3-catalase pathways are critically involved in intracellular ROS regulation under physiological conditions and during the response to DNA damage, respectively.
Five referral hospitals, South Korea.
To assess epidemiological changes in TB before and during the COVID-19 pandemic.
This was a multicentre cohort study of 3,969 patients diagnosed with TB.
We ...analysed 3,453 patients diagnosed with TB prior to the COVID-19 pandemic (January 2016-February 2020) and 516 during the pandemic (March-November 2020). During the pandemic, the number of patients visits declined by 15% from the previous 4-year average, and the number of patients diagnosed with TB decreased by 17%. Patients diagnosed during the pandemic were older than those diagnosed before the pandemic (mean age, 60.2 vs. 56.6 years,
< 0.001). The proportion of patients to have primary TB at a younger age (births after 1980) among those diagnosed with TB was significantly lower during the pandemic than before (17.8% in 2020 vs. 23.5% in 2016, 24.0% in 2017, 22.5% in 2018, 23.5% in 2019;
= 0.005).
The COVID-19 pandemic resulted in a reduction in the number of visits to respiratory departments, leading to fewer patients being diagnosed with TB. However, our results suggest that universal personal preventive measures help to suppress TB transmission in regions with intermediate TB burden.
Magnetic resonance imaging and optical microscopy are key technologies in the life sciences. For microbiological studies, especially of the inner workings of single cells, optical microscopy is ...normally used because it easily achieves resolution close to the optical wavelength. But in conventional microscopy, diffraction limits the resolution to about half the wavelength. Recently, it was shown that this limit can be partly overcome by nonlinear imaging techniques, but there is still a barrier to reaching the molecular scale. In contrast, in magnetic resonance imaging the spatial resolution is not determined by diffraction; rather, it is limited by magnetic field sensitivity, and so can in principle go well below the optical wavelength. The sensitivity of magnetic resonance imaging has recently been improved enough to image single cells, and magnetic resonance force microscopy has succeeded in detecting single electrons and small nuclear spin ensembles. However, this technique currently requires cryogenic temperatures, which limit most potential biological applications. Alternatively, single-electron spin states can be detected optically, even at room temperature in some systems. Here we show how magneto-optical spin detection can be used to determine the location of a spin associated with a single nitrogen-vacancy centre in diamond with nanometre resolution under ambient conditions. By placing these nitrogen-vacancy spins in functionalized diamond nanocrystals, biologically specific magnetofluorescent spin markers can be produced. Significantly, we show that this nanometre-scale resolution can be achieved without any probes located closer than typical cell dimensions. Furthermore, we demonstrate the use of a single diamond spin as a scanning probe magnetometer to map nanoscale magnetic field variations. The potential impact of single-spin imaging at room temperature is far-reaching. It could lead to the capability to probe biologically relevant spins in living cells.
The purpose of the study was to investigate whether closed intramedullary (IM) nailing with percutaneous cement augmentation is better than conventional closed nailing at relieving pain and ...suppressing tumours in patients with metastases of the femur and humerus.
A total of 43 patients (27 men, 16 women, mean age 63.7 years, standard deviation (sd) 12.2; 21 to 84) underwent closed IM nailing with cement augmentation for long bone metastases. A further 27 patients, who underwent conventional closed IM nailing, served as controls. Pain was assessed using a visual analogue scale (VAS) score pre-operatively (pre-operative VAS), one week post-operatively (immediate post-operative VAS), and at six weeks post-operatively (follow-up post-operative VAS). Progression of the tumour was evaluated in subgroups of patients using F-18-fludeoxyglucose (F-18-FDG) positron emission tomography (PET)/computed tomography (CT) and/or bone scintigraphy (BS), at a mean of 8.8 and 7.2 months post-operatively, respectively.
The mean pain scores of patients who underwent closed nailing with cement augmentation were significantly lower than those of the control patients post-operatively (immediate post-operative VAS: 3.8, sd 0.9 versus 6.0, sd 0.9; follow-up post-operative VAS: 3.3, sd 2.5 versus 6.6, sd 2.2; all p < 0.001). The progression of the metastasis was suppressed in 50% (10/20) of patients who underwent closed nailing with augmentation, but in only 8% (1/13) of those in the control group.
Percutaneous cement augmentation of closed IM nailing improves the relief of pain and limits the progression of the tumour in patients with metastases to the long bones.
Percutaneous cement augmentation while performing closed IM nailing has some advantages for long bone metastases. Cite this article: Bone Joint J 2016;98-B:703-9.
Liver transplantation (LT) is an established therapeutic modality for patients with end-stage liver disease. The use of marginal donors has become more common worldwide due to the sharp increase in ...recipients, with a consequent shortage of suitable organs. We analyzed our single-center experience over the last 8 years in LT to evaluate the outcomes of using so-called “marginal donors.”
We retrospectively analyzed the database of all LTs performed at our institution from 2009 to 2017. Only patients undergoing deceased-donor LTs were analyzed. Marginal grafts were defined as livers from donors >60 years of age, livers from donors with serum sodium levels >155 mEq, graft steatosis >30%, livers with cold ischemia time ≥12 hours, livers from donors who were hepatitis B or C virus positive, livers recovered from donation after cardiac death, and livers split between 2 recipients. Patients receiving marginal grafts (marginal group) were compared with patients receiving standard grafts (standard group).
A total of 106 patients underwent deceased-donor LT. There were 55 patients in the standard group and 51 patients in the marginal group. There were no significant differences in terms of age, sex, Model for End-Stage Liver Disease score, underlying liver disease, presence of hepatocellular carcinoma, and hospital stay between the 2 groups. Although the incidence of acute cellular rejection, cytomegalovirus infection, and postoperative complications was similar between the 2 groups, the incidence of early allograft dysfunction was higher in the marginal group. With a median follow-up of 26 months, the 1-, 3-, and 5-year overall and graft (death-censored) survivals in the marginal group were 85.5%, 75%, and 69.2% and 85.9%, 83.6%, and 77.2%, respectively. Patient overall survival and graft survival (death-censored) were significantly lower in the marginal group (P = .023 and P = .048, respectively). On multivariate analysis, receiving a marginal graft (hazard ratio HR, 4.862 95% confidence interval (CI), 1.233–19.171; P = .024) and occurrence of postoperative complications (HR, 4.547 95% CI, 1.279–16.168; P = .019) were significantly associated with worse patient overall survival. Also, when factors associated with marginal graft were analyzed separately, graft steatosis >30% was independently associated with survival (HR, 5.947 95% CI, 1.481–23.886; P = .012).
Patients receiving marginal grafts showed lower but acceptable overall survival and graft survival. However, because graft steatosis >30% was independently associated with worse survival, caution must be exercised when using this type of marginal graft by weighing the risk and benefits.
•Patients receiving marginal grafts showed lower but acceptable overall and graft survival.•Graft steatosis >30% was independently associated with worse survival.•Caution must be exercised when using this type of marginal graft by weighing the risk and benefits.
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