The molar extinction coefficients of 20 amino acids and the peptide bond were measured at 214 nm in the presence of acetonitrile and formic acid to enable quantitative comparison of peptides eluting ...from reversed-phase high-performance liquid chromatography, once identified with mass spectrometry (RP-HPLC-MS). The peptide bond has a molar extinction coefficient of 923 M-1 cm-1. Tryptophan has a molar extinction coefficient that is ∼30 times higher than that of the peptide bond, whereas the molar extinction coefficients of phenylalanine, tyrosine, and histidine are ∼six times higher than that of the peptide bond. Proline, as an individual amino acid, has a negligible molar extinction coefficient. However, when present in the peptide chain (except at the N terminus), it absorbs ∼three times more than a peptide bond. Methionine has a similar molar extinction coefficient as the peptide bond, while all other amino acids have much lower molar extinction coefficients. The predictability of the molar extinction coefficients of proteins and peptides, calculated by the amino acid composition and the number of peptide bonds present, was validated using several proteins and peptides. Most of the measured and calculated molar extinction coefficients were in good agreement, which shows that it is possible to compare peptides analyzed by RP-HPLC-MS in a quantitative way. This method enables a quantitative analysis of all peptides present in hydrolysates once identified with RP-HPLC-MS. Keywords: Molar extinction coefficient; molar absorption coefficient; UV absorbance; proteins; peptides; amino acids
1. Climate change has been inducing range shifts for many species as they follow their suitable climate space and further shifts are projected. Whether species will be able to colonize regions where ...climate conditions become suitable, so-called 'new climate space', depends on species traits and habitat fragmentation. 2. By combining bioclimate envelope models with dispersal models, we identified areas where the spatial cohesion of the ecosystem pattern is expected to be insufficient to allow colonization of new climate space. 3. For each of three ecosystem types, three species were selected that showed a shift in suitable climate space and differed in habitat fragmentation sensitivity. 4. For the 2020 and 2050 time slices, the amount of climatically suitable habitat in northwest Europe diminished for all studied species. Additionally, significant portions of new suitable habitat could not be colonized because of isolation. Together, this will result in a decline in the amount of suitable habitat protected in Natura 2000 sites. 5. We develop several adaptation strategies to combat this problem: (i) link isolated habitat that is within a new suitable climate zone to the nearest climate-proof network; (ii) increase colonizing capacity in the overlap zone, the part of a network that remains suitable in successive time frames; (iii) optimize sustainable networks in climate refugia, the part of a species' range where the climate remains stable. 6. Synthesis and applications. Following the method described in this study, we can identify those sites across Europe where ecosystem patterns are not cohesive enough to accommodate species' responses to climate change. The best locations for climate corridors where improving connectivity is most urgent and potential gain is highest can then be pinpointed.
Background: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac and major non‐cardiac surgery with general anaesthesia in the elderly. We hypothesized that the ...incidence of POCD would be less with regional anaesthesia rather than general.
Methods: We included patients aged over 60 years undergoing major non‐cardiac surgery. After giving written informed consent, patients were randomly allocated to general or regional anaesthesia. Cognitive function was assessed using four neuropsychological tests undertaken preoperatively and at 7 days and 3 months postoperatively. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in two or more test parameters.
Results: At 7 days, POCD was found in 37/188 patients (19.7%, 14.3–26.1%) after general anaesthesia and in 22/176 (12.5%, 8.0–18.3%) after regional anaesthesia, P = 0.06. After 3 months, POCD was present in 25/175 patients (14.3%, 9.5–20.4%) after general anaesthesia vs. 23/165 (13.9%, 9.0–20.2%) after regional anaesthesia, P = 0.93.
The incidence of POCD after 1 week was significantly greater after general anaesthesia when we excluded patients who did not receive the allocated anaesthetic: 33/156 (21.2%15.0–28.4%) vs. 20/158 (12.7%7.9–18.9%) (P = 0.04). Mortality was significantly greater after general anaesthesia (4/217 vs. 0/211 (P < 0.05)).
Conclusion: No significant difference was found in the incidence of cognitive dysfunction 3 months after either general or regional anaesthesia in elderly patients. Thus, there seems to be no causative relationship between general anaesthesia and long‐term POCD. Regional anaesthesia may decrease mortality and the incidence of POCD early after surgery.
Background
Extended resections (i.e., major hepatectomy and/or pancreatoduodenectomy) are rarely performed for gallbladder cancer (GBC) because outcomes remain inconclusive. Data regarding extended ...resections from Western centers are sparse. This Dutch, multicenter cohort study analyzed the outcomes of patients who underwent extended resections for locally advanced GBC.
Methods
Patients with GBC who underwent extended resection with curative intent between January 2000 and September 2018 were identified from the Netherlands Cancer Registry. Extended resection was defined as a major hepatectomy (resection of ≥ 3 liver segments), a pancreatoduodenectomy, or both. Treatment and survival data were obtained. Postoperative morbidity, mortality, survival, and characteristics of short- and long-term survivors were assessed.
Results
The study included 33 patients. For 16 of the patients, R0 resection margins were achieved. Major postoperative complications (Clavien Dindo ≥ 3A) occurred for 19 patients, and 4 patients experienced postoperative mortality within 90 days. Recurrence occurred for 24 patients. The median overall survival (OS) was 12.8 months (95% confidence interval, 6.5–19.0 months). A 2-year survival period was achieved for 10 patients (30%) and a 5-year survival period for 5 patients (15%). Common bile duct, liver, perineural and perivascular invasion and jaundice were associated with reduced survival. All three recurrence-free patients had R0 resection margins and no liver invasion.
Conclusion
The median OS after extended resections for advanced GBC was 12.8 months in this cohort. Although postoperative morbidity and mortality were significant, long-term survival (≥ 2 years) was achieved in a subset of patients. Therefore, GBC requiring major surgery does not preclude long-term survival, and a subgroup of patients benefit from surgery.
This systematic review summarizes the research of previous studies that used resistance training in the post-treatment phase of cancer patients with a focus on methodological quality, training ...methods and physical outcome measures. We found twenty-four studies (10 RCTs, 4 controlled clinical trials and 10 uncontrolled trials) that met all inclusion criteria. The studies were of moderate methodological quality. The majority of studies involved breast cancer patients (54%), followed by prostate cancer patients (13%). Most studies used a combination of resistance and aerobic training, which was mostly supervised. Resistance training involved large muscle groups, with 1-3 sets of 8-12 repetitions. The duration of the resistance training programs varied from 3-24 weeks, with a training frequency of 1-5 sessions per week. The training intensity ranged from 25% to 85% of the one-repetition maximum. Overall, positive training effects were observed for cardiopulmonary and muscle function, with significant increases in peak oxygen uptake (range: 6-39%), and in the one-repetition maximum (range: 11-110%). In general, there were no effects of training on body composition, endocrine and immune function, and haematological variables. No adverse effects of the resistance training were reported. Based upon these results, we recommend to incorporate resistance training in cancer rehabilitation programmes.
Currently, the potential benefits of additional resection after positive proximal intraoperative frozen sections (IFS) in perihilar cholangiocarcinoma (pCCA) on residual disease and oncological ...outcome remain uncertain. Therefore, the aim of this study is to investigate the number of R0 resections after additional resection of a positive proximal IFS and the influence of additional resections on overall survival (OS) in patients with pCCA.
A retrospective, multicenter, matched case-control study was performed, including patients undergoing resection for pCCA between 2000 and 2019 at three tertiary centers. Primary outcome was the number of achieved ‘additional’ R0 resections. Secondary outcomes were OS, recurrence, severe morbidity and mortality.
Forty-four out of 328 patients undergoing resection for pCCA had a positive proximal IFS. An additional resection was performed in 35 out of 44 (79.5%) patients, which was negative in 24 (68.6%) patients. Nevertheless, seven out of these 24 patients were eventually classified as R1 resection due to other positive resection margins. Therefore, 17 (48.6%) patients could be classified as “true” R0 resection after additional resection. Ninety-day mortality after R1 resections was high (25%) and strongly influenced OS. After correction for 90-day mortality, median OS after negative additional resection was 33 months (95%CI:29.5–36.5) compared to 30 months (95%CI:24.4–35.6) after initial R1 (P = 0.875) and 46 months (95%CI:32.7–59.3) after initial R0 (P = 0.348).
There were only 17 patients (out of a total of 328 patients) that potentially benefitted from routine IFS. Additional resection for a positive IFS leading to R0 resection was not associated with improved long-term survival.
Summary
Recently, there has been considerable interest in using 4‐methylumbelliferone (4‐MU) to inhibit hyaluronan (HA) synthesis in mouse models of cancer, autoimmunity and a variety of other ...inflammatory disorders where HA has been implicated in disease pathogenesis. In order to facilitate future studies in this area, we have examined the dosing, treatment route, treatment duration and metabolism of 4‐MU in both C57BL/6 and BALB/c mice. Mice fed chow containing 5% 4‐MU, a dose calculated to deliver 250 mg/mouse/day, initially lose substantial weight but typically resume normal weight gain after 1 week. It also takes up to a week to see a reduction in serum HA in these animals, indicating that at least a 1‐week loading period on the drug is required for most protocols. At steady state, more than 90% of the drug is present in plasma as the glucuronidated metabolite 4‐methylumbelliferyl glucuronide (4‐MUG), with the sulphated metabolite, 4‐methylumbelliferyl sulphate (4‐MUS) comprising most of the remainder. Chow containing 5% but not 0·65% 4‐MU was effective at preventing disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis, as well as in the DORmO mouse model of autoimmune diabetes. While oral 4‐MU was effective at preventing EAE, daily intraperitoneal injections of 4‐MU were not. Factors potentially affecting 4‐MU uptake and plasma concentrations in mice include its taste, short half‐life and low bioavailability. These studies provide a practical resource for implementing oral 4‐MU treatment protocols in mice.
Background: Major surgery is frequently associated with postoperative cognitive dysfunction (POCD) in elderly patients. Type of surgery and hospitalization may be important prognostic factors. The ...aims of the study were to find the incidence and risk factors for POCD in elderly patients undergoing minor surgery.
Methods: We enrolled 372 patients aged greater than 60 years scheduled for minor surgery under general anesthesia. According to local practice, patients were allocated to either in‐ (199) or out‐patient (173) care. Cognitive function was assessed using neuropsychological testing preoperatively and 7 days and 3 months postoperatively. Postoperative cognitive dysfunction was defined using Z‐score analysis.
Results: At 7 days, the incidence (confidence interval) of POCD in patients undergoing minor surgery was 6.8% (4.3–10.1). At 3 months the incidence of POCD was 6.6% (4.1–10.0). Logistic regression analysis identified the following significant risk factors: age greater than 70 years (odds ratio OR: 3.8 1.7–8.7, P = 0.01) and in‐ vs. out‐patient surgery (OR: 2.8 1.2–6.3, P = 0.04).
Conclusions: Our finding of less cognitive dysfunction in the first postoperative week in elderly patients undergoing minor surgery on an out‐patient basis supports a strategy of avoiding hospitalization of older patients when possible.
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