Atherosclerotic cardiovascular disease is a major cause of death in renal transplant (TX) recipients. Atherosclerotic lesions are characterized by monocytic infiltration. Circulating monocytes can be ...divided into functionally distinct subpopulations, among which CD14++CD16+ and CD14+CD16+ monocytes (summarized as CD16+ monocytes) are proinflammatory cells. We hypothesized that the frequency of circulating CD16+ monocytes is associated with subclinical atherosclerosis in TX patients. Monocyte subpopulations were quantified in 95 TX and 31 hemodialysis patients (HD). In TX patients, subclinical atherosclerosis was determined by carotid intima media thickness (IMT) measurement. TX patients had lower frequencies of CD16+ monocytes than HD patients. When stratifying by immunosuppressive treatment, patients on methylprednisolone (MP) therapy had fewer CD14+CD16+ monocytes than patients not receiving MP. CD14+CD16+ monocytes decrease very shortly after transplantation. CD14+CD16+ monocyte frequency correlated with IMT in TX recipients (r = 0.34, p < 0.001). This correlation was most pronounced among patients without MP treatment (r = 0.55, p = 0.02). In a multivariate regression analysis, the association of CD14+CD16+ monocytes with IMT was independent from traditional cardiovascular risk factors. The frequency of proinflammatory CD14+CD16+ monocytes is independently associated with subclinical atherosclerosis in transplant recipients. Further studies on the association between circulating leukocytes and atherosclerosis should take monocyte heterogeneity into account.
The frequency of circulating CD14+CD16+ monocytes in blood correlates with carotid intima media thickness in renal transplant recipients independently from traditional cardiovascular risk factors.
Enantioselective synthesis of chiral alcohols through asymmetric addition of water across an unactivated alkene is a highly sought‐after transformation and a big challenge in catalysis. Herein we ...report the identification and directed evolution of a fatty acid hydratase from Marinitoga hydrogenitolerans for the highly enantioselective hydration of styrenes to yield chiral 1‐arylethanols. While directed evolution for styrene hydration was performed in the presence of heptanoic acid to mimic fatty acid binding, the engineered enzyme displayed remarkable asymmetric styrene hydration activity in the absence of the small molecule activator. The evolved styrene hydratase provided access to chiral alcohols from simple alkenes and water with high enantioselectivity (>99 : 1 e.r.) and could be applied on a preparative scale.
The enantioselective addition of water across unactivated alkenes is a much sought‐after chemical transformation and a major challenge in catalysis. Now a promiscuous engineered fatty acid hydratase produces chiral alcohols with high enantioselectivity, also on a preparative scale, using simple alkenes and water as reactants.
Thalidomide is a potent teratogen that causes dysmelia in humans. Recently, in vitro data suggested that it inhibits angiogenesis. Prostate cancer is dependent on the recruitment of new blood vessels ...to grow and metastasize. Based on those data, we initiated a Phase II trial of thalidomide in patients with metastatic androgen-independent prostate cancer.
This was an open-label, randomized Phase II study. Thalidomide was administered either at a dose of 200 mg/day (low-dose arm) or at an initial dose of 200 mg/day that escalated to 1200 mg/day (high-dose arm).
A total of 63 patients were enrolled onto the study (50 patients on the low-dose arm and 13 patients on the high-dose arm). Serum prostate-specific antigen (PSA) decline of > or = 50% was noted in 18% of patients on the low-dose arm and in none of the patients on the high-dose arm. Four patients were maintained for > 150 days. The most prevalent complications were constipation, fatigue, neurocortical, and neurosensory.
Thalidomide, an antiangiogenesis agent, has some activity in patients with metastatic prostate cancer who have failed multiple therapies. A total of 27% of all patients had a decline in PSA of > or = 40%, often associated with an improvement of clinical symptoms. Because our preclinical studies had shown that thalidomide increases PSA secretion, we believe that the magnitude of PSA decline seen in our trial justifies further study.
The welfare of dairy cows is becoming increasingly important. While diseases like mastitis and lameness are common ailments, injuries to the tail tip go largely unnoticed. This study aimed to ...investigate whether tail tip lesions, which are mostly described in beef cattle, also occurred on n=5 dairy farms, along with determining what type and at what frequency. The study consisted of two phases. During the first part of the study, tail tips of 78 dairy cows were examined over a period of 6 months; based on these results, we developed a training card on tail tip lesions in dairy cows, which was used in part two of the study to train further examiners to inspect four more flocks. In total, we collected n=3587 tail records from n=513 Holstein and n= 128 Simmental dairy cows. The overall frequency regarding all types of lesions ranged between 84.0 % (±2.0) and 94.1 % (±1.8) in Holstein herds and between 97.0 % (±2.2) and 99.0 % (±2.2) in Simmental herds. To our knowledge, this is the first investigation of tail tip lesions in German dairy cows. We concluded that tail tip lesions might be a frequent yet unnoticed condition in German dairy cows.
Small fiber neuropathy (SFN) has been suggested as a trigger of restless legs syndrome (RLS). An increased prevalence of peripheral neuropathy has been demonstrated in Parkinson's disease (PD). We ...aimed to investigate, in a cross-sectional manner, whether SFN is overrepresented in PD patients with concurrent RLS relative to PD patients without RLS, using in vivo corneal confocal microscopy (IVCCM) and quantitative sensory testing (QST) as part of small fiber assessment. Study participants comprised of age- and sex-matched PD patients with (n = 21) and without RLS (n = 21), and controls (n = 13). Diagnosis of RLS was consolidated with the sensory suggested immobilization test. Assessments included nerve conduction studies (NCS), Utah Early Neuropathy Scale (UENS), QST, and IVCCM, with automated determination of corneal nerve fiber length (CNFL) and branch density (CNBD) from wide-area mosaics of the subbasal nerve plexus. Plasma neurofilament light (p-NfL) was determined as a measure of axonal degeneration. No significant differences were found between groups when comparing CNFL (p = 0.81), CNBD (p = 0.92), NCS (p = 0.82), and QST (minimum p = 0.54). UENS scores, however, differed significantly (p = 0.001), with post-hoc pairwise testing revealing higher scores in both PD groups relative to controls (p = 0.018 and p = 0.001). Analysis of all PD patients (n = 42) revealed a correlation between the duration of L-dopa therapy and CNBD (ρ = -0.36, p = 0.022), and p-NfL correlated with UENS (ρ = 0.35, p = 0.026) and NCS (ρ = -0.51, p = 0.001). Small and large fiber neuropathy do not appear to be associated with RLS in PD. Whether peripheral small and/or large fiber pathology associates with central neurodegeneration in PD merits further longitudinal studies.
Abstract Orbital exanteration is usually performed for advanced neoplasms of the eyelids and is associated with significant distress for patients. Its reconstruction should aim for functional and ...aesthetic results and safety for further oncological treatment. The ideal reconstruction should provide adequate cutaneous covering, short healing time, obliteration and closure of communication with facial sinuses and nasal cavity, resistance to radiotherapy, low morbidity and favorable rehabilitation. In 10 patients, a flap based on the frontal branch of the temporal artery was used for immediate reconstruction after orbital exenteration. Flap demarcation began through the frontal midline from the glabella to 0.5 cm above the hairline. Its elevation was performed in a plane above the periosteum and galea, including skin, subcutaneous tissue and frontal muscle. It was rotated tension-free over the defect. In all patients, adequate closure of the defect and obliteration of the orbital cavity was achieved. There was no flap loss or major complications. The lateral frontal flap is easy and fast to execute, with a reliable blood supply and reproducible technique. Its main applicability is for patients with orbital defects and high surgical risks with contraindications for microsurgical reconstruction.
A reference material designed for the determination of natural radionuclides in solid samples (glass pellets) is described and the results of certification are presented. The material has been ...certified for 7 natural radionuclides (
40
K,
226
Ra,
228
Ra,
228
Th,
232
Th,
235
U and
238
U). An information value is given for
210
Pb. Radon (
222
Rn) emanation experiments showed results comparable within participating laboratories, however, the number of data and precision was too low to carry out a certification process. The reference material may be used for quality management of analytical laboratories engaged in the high-sensitive analysis of radionuclides in the construction materials of detectors placed in ultra low background underground laboratories.
Cisplatin preferentially accumulates in cells of the S3 segment of the renal proximal tubule and is toxified intracellularly by hydration. The earliest manifestation of toxicity is inhibition of ...protein synthesis. GSH depletion is another important mechanism causing CP toxicity. Intracellular binding to SH groups leads to GSH depletion, resulting in lipid peroxidation and eventually mitochondrial damage. New measures to prevent GSH depletion and scavenge intracellular free oxygen radicals have been tried in clinical studies. Promising results indicate that cisplatin nephrotoxicity can be further reduced in the future.
We aimed to develop and validate a risk-scoring system for distant metastases (DMs) in oral cavity carcinoma (OCC).
Patients with OCC who were treated at 4 tertiary cancer institutions with curative ...surgery with or without postoperative radiation/chemoradiation therapy were randomly assigned to discovery or validation cohorts (3:2 ratio). Cases were staged on the basis of tumor, node, and metastasis staging according to the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control guidelines. Predictors of DMs on multivariable analysis in the discovery cohort were used to develop a risk-score model and classify patients into risk groups. The utility of the risk classification was evaluated in the validation cohort.
Overall, 2749 patients were analyzed. Predictors (risk score coefficient) of DMs in the discovery cohort were the following: pathological stage (p)T3-4 (0.4), pN+ (N1: 0.8; N2: 1.0; N3: 1.5), histologic grade (G) 3 (G3, 0.7), and lymphovascular invasion (0.4). The DM risk groups were defined by the sum of the following risk score coefficients: high (>1.7), intermediate (0.7-1.7), and standard risk (<0.7). The 5-year DM rates (high/intermediate/standard risk groups) were 30%/15%/4% in the discovery cohort (C-index = 0.79) and 35%/16%/5% in the validation cohort, respectively (C-index = 0.77; both P < .001). In the whole cohort, this predictive model showed excellent discriminative ability in predicting DMs without locoregional failure (29%/11%/1%), later (>2 year) DMs (11%/4%/2%), and DMs in patients treated with surgery (20%/12%/5%), postoperative radiation therapy (34%/17%/4%), and postoperative chemoradiation therapy (39%/18%/7%) (all P < .001). The 5-year overall survival rates in the overall cohort were 25%/51%/67% (P < .001).
Patients at higher risk for DMs were identified by use of a predictive-score model for DMs that included pT3-4, pN1/2/3, G3, and lymphovascular invasion. Identified patients may be evaluated for individualized risk-adaptive treatment escalation and/or surveillance strategies.
Objectives The aortic augmentation index (AIx), a marker of arterial stiffness, and peripheral arterial disease (PAD) are associated with an increased cardiovascular risk. In claudicants, the effect ...of balloon angioplasty (percutaneous transluminal angioplasty, PTA) on AIx has not been determined so far. Methods Measurements of the ankle–brachial pressure index (ABI) and AIx were performed before and 3 months after PTA and compared to age- and sex-matched PAD patients under best medical treatment. Results The data of 61 patients (44% female, mean age 68 years) who underwent lower-limb PTA was compared to 48 conservatively treated patients (38% female, mean age 68 years). ABI significantly improved after PTA from 0.73 ± 0.02 to 0.85 ± 0.03 ( p = 0.001), but remained unchanged in the control group (0.85 ± 0.23 and 0.80 ± 0.21; p = 0.16). Revascularisation was associated with a significant reduction of AIx from 31.5 ± 1.1% to 28.8 ± 1.1% after 3 months ( p = 0.01). In the conservatively treated group, AIx did not change during follow-up (29.9 ± 1.1% to 29.9 ± 1.1%; p = 0.83). Conclusion Lower-limb revascularisation in PAD Rutherford stage II–III is associated with an improvement of markers for arterial stiffness.
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