Effects of life-long exercise on circulating free fatty acids and muscle triglyceride content in ageing rats.

Regular physical exercise has emerged, together with dietary restriction, as an effective intervention in delaying degenerative diseases and augmenting life span in rodents. The mechanisms involved remain largely unknown, although a beneficial influence on the age-related alteration of insulin sensitivity has been hypothesized. As muscle triglyceride (TG) accumulation is considered a reliable index of muscle insulin resistance, in this study we explored muscle TG content in 23-month-old male Sprague-Dawley rats subjected to life-long training. Plasma glucose. insulin. free fatty acid (FFA) and leptin levels were also measured. Both voluntary running in wheels (RW) and forced training in treadmill (TM) were studied. As RW rats weighed less than controls, a cohort of untrained animals, fed to pair weight (PW) with RW, was added to discriminate the effect of exercise from that of food restriction. Sedentary ad libitum fed rats served as controls. In 23-month-old RW rats. muscle TG content was reduced by 50% with respect to age-matched sedentary controls, while in TM group this reduction was smaller but still highly significant, and occurred independently on the changes in body fat mass. In both the trained rat groups, there was a significant decrease in circulating FFA levels and a trend to reduced insulin levels. In PW rats, muscle TG levels decreased similarly to RW rats, while plasma parameters were less modified. In particular, RW training was more effective than PW in preventing the age-related increase in circulating leptin levels. Our results suggest that voluntary exercise effectively counteracts the development of insulin resistance in the muscles of ageing rats as well as other related changes such as hyperlipacidaemia and compensatory hyperleptinaemia. Forced training or moderate food restriction appear slightly less effective than voluntary exercise in preventing age-dependent alterations in nutrient distribution and/or utilization. (C) 2004 Elsevier Inc. All rights reserved

Yield response, nutritional quality and water productivity of tomato (Solanum lycopersicum L.) are influenced by drip irrigation and straw mulch in the coastal saline ecosystem of Ganges Delta, India

In the coastal zone of the Ganges Delta, water shortages due to soil salinity limit the yield of dry season crops. To alleviate water shortage as a consequence of salinity stress in the coastal saline ecosystem, the effect of different water-saving (WS) and water-conserving options was assessed on growth, yield and water use of tomato; two field experiments were carried out at Gosaba, West Bengal, India in consecutive seasons during the winter of 2016–17 and 2017–18. The experiment was laid out in a randomized block design with five treatments viz., surface irrigation, surface irrigation + straw mulching, drip irrigation at 100% reference evapotranspiration (ET0), drip irrigation at 80% ET0, drip irrigation at 80% ET0 + straw mulching. Application of drip irrigation at 80% ET0 + straw mulching brought about significantly the highest fruit as well as the marketable yield of tomato (Solanum lycopersicum L.). The soil reaction (pH), post-harvest organic carbon, nitrogen, phosphorus and potassium (N, P and K) status and soil microbial population along with the biochemical quality parameters of tomato (juice pH, ascorbic acid, total soluble solids and sugar content of fruits) were significantly influenced by combined application of drip irrigation and straw mulching. Surface irrigation significantly increased the salinity level in surface and sub-surface soil layers while the least salinity development was observed in surface mulched plots receiving irrigation water through drip irrigation. The highest water productivity was also improved from drip irrigation at 80% ET0 + straw mulched plots irrespective of the year of experimentation. Such intervention also helped in reducing salinity stress for the tomato crop. Thus, straw mulching along with drip irrigation at 80% ET0 can be recommended as the most suitable irrigation option for tomato crop in the study area as well as coastal saline regions of South Asia. Finally, it can be concluded that the judicious application of irrigation water not only increased growth, yield and quality tomatoes but also minimized the negative impact of soil salinity on tomatoes grown in the coastal saline ecosystem of Ganges Delta

Cold-Induced Changes in the Protein Ubiquitin

Conformational changes are essential for protein-protein and protein-ligand recognition. Here we probed changes in the structure of the protein ubiquitin at low temperatures in supercooled water using NMR spectroscopy. We demonstrate that ubiquitin is well folded down to 263 K, although slight rearrangements in the hydrophobic core occur. However, amide proton chemical shifts show non-linear temperature dependence in supercooled solution and backbone hydrogen bonds become weaker in the region that is most prone to cold-denaturation. Our data suggest that the weakening of the hydrogen bonds in the β-sheet of ubiquitin might be one of the first events that occur during cold-denaturation of ubiquitin. Interestingly, the same region is strongly involved in ubiquitin-protein complexes suggesting that this part of ubiquitin more easily adjusts to conformational changes required for complex formation

Psychometric validation of the generalized pustular psoriasis physician global assessment (GPPGA) and generalized pustular psoriasis area and severity index (GPPASI)

Background: Generalized pustular psoriasis (GPP) is a rare and life-threatening skin disease often accompanied by systemic inflammation. There are currently no standardized or validated GPP-specific measures for assessing severity. Objective: To evaluate the reliability, validity, and responder definitions of the generalized pustular psoriasis physician global assessment (GPPGA) and generalized pustular psoriasis area and severity index (GPPASI). Methods: The GPPGA and GPPASI were validated using outcome data from Week 1 of the Effisayil™ 1 study. The psychometric analyses performed included confirmatory factor analysis, item-to-item/item-to-total correlations, internal consistency reliability, test-retest reliability, convergent validity, known-groups validity, responsiveness analysis, and responder definition analysis. Results: Using data from this patient cohort (N=53), confirmatory factor analysis demonstrated unidimensionality of the GPPGA total score (root mean square error of approximation <0.08), and GPPGA item-to-item and item-to-total correlations ranged from 0.58–0.90. The GPPGA total score, pustulation subscore, and GPPASI total score all demonstrated good test-retest reliability (intraclass correlation coefficient: 0.70, 0.91, and 0.95, respectively), and good evidence of convergent validity. In anchor-based analyses, all three scores were able to detect changes in symptom and disease severity over time; reductions of -1.4, -2.2, and -12.0 were suggested as clinically meaningful improvement thresholds for the GPPGA total score, GPPGA pustulation subscore, and GPPASI total score, respectively. Anchor-based analyses also supported the GPPASI 50 as a clinically meaningful threshold for improvement. Conclusions: Overall, our findings indicate that the GPPGA and GPPASI are valid, reliable, and responsive measures for the assessment of GPP disease severity, and support their use in informing clinical endpoints in trials in GPP

Ets-1 p51 and p42 isoforms differentially modulate Stromelysin-1 promoter according to induced DNA bend orientation

The Stromelysin-1 gene promoter contains a palindrome of two Ets-binding sites (EBS) that bind the p51 and p42 isoforms of the human Ets-1-transcription factor. A previous study established that full gene transactivation is associated with a ternary complex consisting of two p51 bound to the two EBS on the promoter. p42, only able to bind one of the two EBS, induces only very weak activity. Here, we investigate the mechanism by which the Stromelysin-1 promoter discriminates between p51 and p42. The differential stoichiometry of the two Ets-1 isoforms arises from the Stromelysin-1 EBS palindrome. The ternary complex requires the presence of two inhibitory domains flanking the DNA-binding domain and the ability to form an intramolecular autoinhibition module. Most importantly, the p51-ternary and the p42-binary complexes induce DNA curvatures with opposite orientations. These results establish that differential DNA bending, via p51 and p42 differential binding, is correlated with the Stromelysin-1 promoter activation process

Psychometric validation of the Psoriasis Symptom Scale, Functional Assessment of Chronic Illness Therapy–Fatigue and pain‐Visual Analogue Scale in patients with generalized pustular psoriasis

Background: Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease associated with considerable patient burden. The Psoriasis Symptom Scale (PSS), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) and pain-Visual Analogue Scale (pain-VAS) are patient-reported outcomes (PROs) that have not yet been validated in patients with GPP. Objectives: To evaluate the psychometric properties of the PSS, FACIT-Fatigue and pain-VAS using data from Effisayil 1, a randomised trial of spesolimab in patients with moderate-to-severe GPP. Methods: Inter-item correlations and confirmatory factor analysis (CFA) were performed using Week 1 data. Internal consistency was assessed with Cronbach's α coefficient using baseline and Week 1 data. Test–retest reliability was assessed using intraclass correlation coefficients (ICCs); change data for the GPP Physician Global Assessment total score and pustulation subscore were used to define a stable population. Convergent validity was assessed at baseline and Week 1 using Spearman's rank-order correlations. Known-groups validity was measured by analysis of variance using Week 1 data. Ability to detect change from baseline to Week 1 was evaluated by analysis of covariance. Results: Inter-item and item-to-total correlations were moderate or strong for most PSS and FACIT-Fatigue items. CFA demonstrated the unidimensionality of the PSS and FACIT-Fatigue, with high factor loadings for most items (PSS range, 0.75–0.94; FACIT-Fatigue range, 0.11–0.93) and acceptable fit statistics. Both scores demonstrated internal consistency (Cronbach's α, 0.71 and 0.95, respectively). The PSS, FACIT-Fatigue and pain-VAS demonstrated test–retest reliability (ICCs ≥0.70) and good evidence of convergent validity. Furthermore, the PROs could differentiate between known groups of varying symptom severity (range, p < 0.0001–0.0225) and detect changes in symptom severity from baseline to Week 1 (range, p < 0.0001–0.0002). Conclusions: Overall, these results support the reliability, validity and ability to detect change of the PSS, FACIT-Fatigue and pain-VAS as PROs in patients with GPP

Current practice of trabeculectomy in a cohort of experienced glaucoma surgeons in Australia and New Zealand

Background/Objectives: To evaluate current routine trabeculectomy technique preferences among Australian and New Zealand Glaucoma Society surgeons regularly performing trabeculectomy surgery. Subjects/Methods: Survey of experienced surgeons who perform trabeculectomy. Results: Forty-nine surgeons (33 male:16 female) participated in the survey. Trabeculectomy was performed as day surgery (39/47, 83.0%) under local anesthesia (44/47, 93.6%). The surgical techniques most commonly used were a corneal traction suture (44/47, 93.6%), fornix-based conjunctival flap (43/47, 91.5%) and half-thickness scleral flap (38/47, 81.0%). Mitomycin C antifibrotic agent was used in routine cases by 45/46 (97.8%) surgeons. Surgeons applied the antifibrotic agent under the Tenon layer with a pledget (36/46, 78.2%) with a concentration of 0.02% (37/46, 80.4%) for 2 (11/46, 23.9%) or 3 min (30/46, 65.2%). The Kelly (26/46, 56.5%) and the Khaw Descemet (19/46, 41.3%) punches were used to perform the sclerostomy. Most surgeons performed a peripheral iridectomy in all phakic patients (46/47, 97.9%), but less commonly in pseudophakic patients (34/47, 72.3%). Techniques for closure of the limbal conjunctival edge were quite varied with a combination of suturing including purse string (21/47, 57.4%), wing (20/47, 42.6%) and horizontal mattress sutures (33/47, 70.2%). Surgeons reviewed their routine patients four times in the first month (29/47, 61.7%) and continued the postoperative topical steroids for 3–4 months (28/47, 59.6%). Conclusions: Although a wide range of techniques for trabeculectomy exists among surgeons, there are consistent procedures currently in use to optimize patient outcomes. This report will assist surgeons in choosing which surgical techniques fit their best practice