Faster \dot{V}{\text{O}}_{ 2} kinetics after eccentric contractions is explained by better matching of O2 delivery to O2 utilization

Purpose

This study examined the impact of eccentric exercise-induced muscle damage on the rate of adjustment in muscle deoxygenation and pulmonary O₂ uptake ( \(\dot{V}{\text{O}}_{{2{\text{p}}}}\) ) kinetics during moderate exercise.

Methods

Fourteen males (25 ± 3 year; mean ± SD) completed three step transitions to 90 % θ_L before (Pre), 24 h (Post24) and 48 h after (Post48) eccentric exercise (100 eccentric leg-press repetitions with a load corresponding to 110 % of the participant’s concentric 1RM). Participants were separated into two groups: phase II \(\dot{V}{\text{O}}_{{2{\text{p}}}}\) time constant (τ \(\dot{V}{\text{O}}_{{2{\text{p}}}}\) ) ≤ 25 s (fast group; n = 7) or τ \(\dot{V}{\text{O}}_{{2{\text{p}}}}\)  > 25 s (slow group; n = 7). \(\dot{V}{\text{O}}_{{2{\text{p}}}}\) and [HHb] responses were modeled as a mono-exponential.

Results

In both groups, isometric peak torque (0°/s) at Post24 was decreased compared to Pre (p < 0.05) and remained depressed at Post48 (p < 0.05). τ \(\dot{V}{\text{O}}_{{2{\text{p}}}}\) was designed to be different (p < 0.05) at Pre between the Fast (τ \(\dot{V}{\text{O}}_{{2{\text{p}}}}\) ; 19 ± 4 s) and Slow (32 ± 6 s) groups. There were no differences among time points (τ \(\dot{V}{\text{O}}_{{2{\text{p}}}}\) : Pre, 19 ± 4 s; Post24, 22 ± 3 s; Post48, 20 ± 4 s) in the Fast group. In Slow, there was a speeding (p < 0.05) from the Pre (32 ± 6 s) to the Post24 (25 ± 6) but not Post48 (31 ± 6), resulting in no difference (p > 0.05) between groups at Post24. This reduction of τ \(\dot{V}{\text{O}}_{{2{\text{p}}}} \,\) was concomitant with the abolishment (p < 0.05) of an overshoot in the [HHb]/ \(\dot{V}{\text{O}}_{{2{\text{p}}}}\) ratio.

Conclusion

We propose that the sped \(\dot{V}{\text{O}}_{{2{\text{p}}}}\) kinetics observed in the Slow group coupled with an improved [HHb]/ \(\dot{V}{\text{O}}_{{2{\text{p}}}}\) ratio suggest a better matching of local muscle O₂ delivery to O₂ utilization following eccentric contractions.     

Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model

Nitric oxide (NO) has many biological roles (e.g. antimicrobial agent, promoter of angiogenesis, prevention of platelet activation) that make NO releasing materials desirable for a variety of biomedical applications. Localized NO release can be achieved from biomedical grade polymers doped with diazeniumdiolated dibutylhexanediamine (DBHD/N₂O₂) and poly(lactic-co-glycolic acid) (PLGA). In this study, the optimization of this chemistry to create film/patches that can be used to decrease microbial infection at wound sites is examined. Two polyurethanes with different water uptakes (Tecoflex SG-80A (6.2 ± 0.7 wt.%) and Tecophilic SP-60D-20 (22.5 ± 1.1 wt.%)) were doped with 25 wt.% DBHD/N₂O₂ and 10 wt.% of PLGA with various hydrolysis rates. Films prepared with the polymer that has the higher water uptake (SP-60D-20) were found to have higher NO release and for a longer duration than the polyurethane with the lower water uptake (SG-80A). The more hydrophilic polymer enhances the hydrolysis rate of the PLGA additive, thereby providing a more acidic environment that increases the rate of NO release from the NO donor. The optimal NO releasing and control SG-80A patches were then applied to scald burn wounds that were infected with Acinetobacter baumannii. The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24 h (∼4 log reduction). The NO release patches are also able to reduce the level of transforming growth factor-β in comparison to controls, which can enhance re-epithelialization, decrease scarring and reduce migration of bacteria. The combined DBHD/N₂O₂ and PLGA-doped polymer patches, which could be replaced periodically throughout the wound healing process, demonstrate the potential to reduce risk of bacterial infection and promote the overall wound healing process.     

Interdisciplinary Methods for Zoonotic Tissue Acellularization for Natural Heart Valve Substitute of Biomimetic Materials

The goal of this work was to create a bioactive tissue-based scaffold using multi-disciplinary engineering materials and tissue engineering techniques. Materials & methods: Physical techniques such as direct laser interference lithography and proton radiation were selected as alternative methods of enzymatic and chemical decellularization to remove cells from a tissue without degradation of the extracellular matrix nor its protein structure. This study was an attempt to prepare a functional scaffold for cell culture from tissue of animal origin using new physical methods that have not been considered before. The work was carried out under full control of the histological and molecular analysis. Results & conclusions: The most important finding was that the physical methods used to obtain the decellularized tissue scaffold differed in the efficiency of cell removal from the tissue in favour of the laser method. Both the laser method and the proton method exhibited a destructive effect on tissue structure and the genetic material in cell nuclei. This effect was visible on histology images as blurred areas within the cell nucleus. The finite element 3D simulation of decellularization process of the three-layer tissue of animal origin sample reflected well the mechanical response of tissue described by hyperelastic material models and provided results comparable to the experimental ones.     

Radiotherapy Confined to the Tumor Bed Following Breast Conserving Surgery

BACKGROUND: The standard technique of radiotherapy (RT) after breast conserving surgery (BCS) is to treat the entire breast up to a total dose of 45-50 Gy with or without tumor bed boost. The majority of local recurrences occur in close proximity to the tumor bed. Thus, the necessity of whole breast radiotherapy has been questioned, and several centers have evaluated the feasibility and efficacy of sole tumor bed irradiation. The aim of this study was to review the current status, controversies, and future prospects of tumor bed irradiation alone after breast conserving surgery. MATERIAL AND METHODS: Published prospective trials evaluating the feasibility and efficacy of radiotherapy confined to the tumor bed following breast conserving surgery were reviewed in order to analyze treatment results. RESULTS: In three earlier studies, using tumor bed radiotherapy for unselected patients, the incidence of intra-breast relapse was reported in the range of 15.6-37%. However, in nine prospective phase I-II trials, sole brachytherapy (BT) with different dose rates, strict patient selection, and meticulous quality assurance, resulted in 95.6-100% local control rates. To date, only one phase III protocol has been initiated comparing the efficacy of tumor bed brachytherapy alone with conventional whole breast radiotherapy. The ideal extend of the planning target volume (PTV) for tumor bed radiotherapy alone has not been established yet. In most series, PTV was defined as the excision cavity with generous (1-3 cm) safety margins. Minimal requirement for PTV localization is the use of titanium clips to mark the walls of the excision cavity intraoperatively, but the combination of clip demarcation and three-dimensional (3-D) visual information obtained from cross-sectional images seems to be the best method to determine the target volume. 3-D virtual brachytherapy is also a promising method to minimize the chance of geographic miss. Recently developed techniques, such as intraoperative radiotherapy (IORT), as well as accelerated 3-D conformal external beam radiation therapy (3-D-CRT) were also found to be feasible for tumor bed radiotherapy alone. CONCLUSIONS: In spite of the existing arguments against limiting radiotherapy to the tumor bed after breast conserving surgery, results of phase I-II studies suggest that tumor bed radiotherapy alone might be an appropriate treatment option for selected breast cancer patients. Whole breast radiotherapy remains the standard radiation modality used in the treatment of breast cancer, and brachytherapy as the sole modality should be considered as investigational. Further phase-III trials are suggested to determine the equivalence of sole tumor bed radiotherapy, compared with whole breast radiotherapy. Preliminary results with recently developed techniques (CT-image based conformal brachytherapy, 3-D virtual brachytherapy, IORT, 3-D-CRT) are promising. However, more experience is required to define whether these methods might improve outcome for patients treated with tumor bed radiotherapy alone.     

Predictors and outcomes of jejunostomy tube placement at the time of pancreatoduodenectomy

BackgroundClinically relevant postoperative pancreatic fistula and delayed gastric emptying cause substantial morbidity after pancreatoduodenectomy. Per international guidelines, the placement of jejunostomy tubes may be considered for patients at risk for malnutrition, such as those with a high risk for clinically relevant postoperative pancreatic fistula and related complications. This study determined predictors and postoperative outcomes of jejunostomy tube placement.MethodsPatients undergoing pancreatoduodenectomy in 2014 to 2015 were identified using the American College of Surgeons National Surgical Quality Improvement Program and Procedure-Targeted Pancreatectomy Participant Use Files. Multivariable logistic regressions were used to identify factors associated with concurrent jejunostomy tube placement and postoperative outcomes.ResultsOf 3,600 patients, 8.9% underwent jejunostomy tube placement. Patients given a jejunostomy tube were more likely white (odds ratio 1.46, P = .016), to have low preoperative serum albumin levels (odds ratio 2.13, P < .001), to have received neoadjuvant radiotherapy (odds ratio 2.14, P < .001), and to have received an intraoperative transfusion (odds ratio 1.50, P = .004). We observed no association between jejunostomy tube placement and an increasing number of risk factors for clinically relevant postoperative pancreatic fistula (P = .96) or delayed gastric emptying (P = .54). Overall, jejunostomy tube placement was associated with increased morbidity (odds ratio 1.34, P = .020) and duration of stay (P < .001), but not mortality (P = .12). Among patients with low serum albumin or those who developed clinically relevant postoperative pancreatic fistula or delayed gastric emptying, jejunostomy tube utilization was not associated with morbidity or mortality.ConclusionJejunostomy tube placement during pancreatoduodenectomy was not driven by risk factors for clinically relevant postoperative pancreatic fistula or delayed gastric emptying, suggesting that practice patterns play a role. Among patients with at-risk preoperative albumin or who developed these complications, jejunostomy tube placement was not associated with worse outcomes, supporting selective utilization per guideline recommendations.