Using training impulse and monotony methods to monitor aerobic training load in rats.

This study is the first to apply training impulse (TRIMP) and Training Monotony (TM) methodologies, within the realm of sport science, in animal model studies. Rats were divided into Sedentary (SED, n=10) and Training (TR, n=13). TR performed a four-week moderate-intensity interval training with load progression. Lactate kinetics, lactate training impulse (TRIMPLac), maximal speed training impulse (TRIMPSmax) and TM were utilized to develop and monitor training protocol. TR showed an 11.9% increase in time to exhaustion at the second maximum incremental test and a 17.5% increase at the third test. External work was increased by 17.8% at the second test and 30.3% at the third. There was a 10.6% increase in external work at the third test compared to the second for TR. No difference in TRIMPLac between the 1st week (94±9 A.U) and 3rdweek (83±10 A.U) were seen. TRIMPSmax was 2400 A.U. in the 1st week, 2760 A.U. in the 2nd and 3rd weeks, and 3120 A.U. in the 4th week. The TM remained at 1.24 A.U throughout the protocol and there was no dropouts. TRIMPLac and TRIMPSmax contributed to the development and monitoring loads, demonstrating their potential to improve the accuracy of training protocols in animal model research.

The Skeletal Muscle, the Heart, and the Liver Are the Major Organs of the Accumulation of Nitric Oxide Metabolites after Oral Nitrite Treatment.

Nitrite is a nitric oxide (NO) metabolite, which may be bioactivated to generate NO in vivo and supplement endogenous NO formation, especially in cardiovascular and metabolic diseases. However, it is not known whether treatment with oral nitrite results in the accumulation of NO metabolites in different organs. Moreover, treatment with omeprazole, an inhibitor of gastric acid secretion, severely affects the gastric formation of S-nitrosothiols induced with oral nitrite treatment. However, no previous study has examined whether omeprazole affects the nitrite-induced accumulation of NO metabolites in different organs. This study examined in rats the effects of oral sodium nitrite treatment (15 mg/kg via gavage for 1 or 7 days) associated with omeprazole (10 mg/kg or vehicle) on nitrite and nitrate and nitrosylated species (RXNO) concentrations (measured using ozone-based chemiluminescence methods) assessed in the plasma, aorta, heart, liver, brain, and muscle. While our results showed that NO metabolite accumulation in different organs is not uniform, we found that the skeletal muscle, the heart, and the liver accumulate NO metabolites, particularly RXNO. This response was significantly attenuated by omeprazole in the heart and in the skeletal muscle. Together, these findings may indicate that the skeletal muscle, the heart, and the liver are major reservoir sites for NO metabolites after oral nitrite treatment, with major increases in nitrosylated species.

Combined physical exercise reverses the reduced expression of Bmal1 in the liver of aged mice.

Aging can modify the morphology and function of the liver, such as generating a decrease in the mitochondria content, autophagy, and cell senescence. Although exercise training has several beneficial effects on hepatic metabolism, its actions on autophagy processes, mitochondrial function, and cellular senescence need to be more widely explored. The present study verified the effects of aging and exercise on hepatic circadian markers, autophagy, and mitochondria activity in 24-month-old mice with a combined exercise training protocol. In addition, we used public datasets from human livers in several conditions and BMAL1 knockout mice. C57BL/6 mice were distributed into Control (CT, young, 6-month-old mice), sedentary old (Old Sed, sedentary, 24-month-old mice), and exercised old (Old Ex, 24-month-old mice submitted to a combined exercise training protocol). The exercise training protocol consisted of three days of endurance exercise - treadmill running, and two days of resistance exercise - climbing a ladder, for three weeks. At the end of the protocol, the liver was removed and prepared for histological analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunoblotting technique, and oxygen consumption. Heatmaps were built using a human dataset and Bmal1 knockout samples. In summary, the Old Sed had reduced strength, coordination, and balance, as well as a decrease in Bmal1 expression and the presence of degenerated liver cells. Still, this group upregulated the transcription factors related to mitochondrial biogenesis. The Old Ex group had increased strength, coordination, and balance, improved glucose sensitivity, as well as restored Bmal1 expression and the mitochondrial transcription factors. The human datasets indicated that mitochondrial markers and autophagy strongly correlate with specific liver diseases but not aging. We can speculate that mitochondrial and autophagy molecular markers alterations may depend on long-term training.

Strength training with and without arteriovenous blood flow restriction improves performance, regardless of changes in muscle hypertrophy, in Wistar rats.

Strength training (ST) with blood flow restriction (BFR) is known to promote increases in hypertrophy and strength sometimes similar to traditional ST despite the effects of the arterial BFR on muscle adaptations and safety are not well established. The aim of this study was to assess whether ST with arterial BFR is able to improve muscular adaptations, performance and its safety in Wistar rats. Animals aging 8 weeks were divided in four groups: sedentary sham (S/S), sedentary with arterial BFR (S/BFR), trained sham (T/S), and trained with arterial BFR (T/BFR). Training protocol consisted of four weeks of ST composed by six sets of 10 ladder climbing with 50% of 1 maximal voluntary contraction. Body weight, epididymal fat, maximum loaded weight, manual grip strength, muscular hypertrophy index, systolic blood pressure, enzyme activity of superoxide dismutase, nitrite/nitrate concentration and tumor necrosis factor alpha were analyzed. The BFR rate was between 36% and 38%. T/BRF was effective to promote strength and hypertrophy. T/S is an alternative to improve strength, but it did not promote hypertrophy. Furthermore, we found no significant cardiac and metabolic changes. Thus, T/BFR is able to improve muscle adaptations and performance in rats, without causing cardiovascular and metabolic damage.

Genetic deletion of IL-6 increases CK-MB, a classic cardiac damage marker, and decreases UPRmt genes after exhaustive exercise.

The intensity, duration, type of contraction, and muscle damage influence interleukin-6 (IL-6) response to acute exercise. However, in response to an exhaustive exercise session, the upregulation of IL-6 in the serum and heart is associated with an inflammatory condition and can inhibit autophagy. This study aimed to investigate the role of IL-6 in autophagy pathway responses and mitochondrial function in the heart of mice submitted to acute exhaustive physical exercise. The mice were allocated into three groups, five animals per group, for the wild type (WT) and the IL-6 knockout (IL-6 KO): Basal (sedentary; Basal), 1 h (after 1 h of the acute exercise; 1 h), and 3 h (after 3 h of the acute exercise; 3 h). After the specific time for each group, the blood was collected, each mouse heart was removed, and the left ventricle (LV) was isolated. In summary, under basal conditions, without the influence of the acute exercise, the IL-6 KO group showed lower number of nuclei in the cardiac tissue, but higher collagen deposition; lower messenger RNA (mRNA) levels of Prkaa1 and Mtco1, but higher mRNA levels of Ulk1; and higher protein levels of the ratio p-AMPK/AMPK in the heart when compared to WT at the same time point. After the acute exercise (1 and 3 h), the IL-6 KO group had lower mRNA levels of Tfam, Mtnd1, Mtco1, and Nampt in the heart when compared to WT after exercise; higher serum levels of creatine kinase (CK), CK-MB, and lactate dehydrogenase for the IL-6 group when compared to the WT group after the exercise. Specifically, the heat-shock protein 60 protein levels in the heart increased 3 h after exhaustive exercise in the WT group, but not in the IL-6 KO group. The study emphasizes that IL-6 may offer cardioprotective effects, including mitochondrial adaptations in response to acute exhaustive exercise.

Nanostructured Catalysts for Dry-Reforming of Methane.

The manuscript deals on the main progress achieved by global scientific research on the development of nanostructured catalysts for dry-reforming reaction. The importance to have a global vision on this topic is strictly related to the most currently and important challenges in the sustainable energy production. In fact, dry-reforming is one of the few known processes in which greenhouse gases are utilized as reactants (methane and carbon dioxide) to produce syngas. Syngas represents the basis for liquid fuel production by Fischer-Tropsch process. In this broad and current context, the catalyst development plays a pivotal role due to its great influence on efficiency, and therefore on the costs, of the whole process. Several are the aspects to consider during the catalyst design: role of metal, interaction between metal and support, role of promoters and resistance to the coke deactivation. These issues, as well as the thermodynamics of the process, are the main aspects of which this review speaks about.

CO2 Adsorption Investigation on an Innovative Nanocomposite Material with Hierarchical Porosity.

A NaX nanozeolite-geopolymer monolith, with hierarchical porosity, has been produced by a one-pot hydrothermal synthesis using metakaolin as alluminosilicate source and a sodium silicate solution as activator. Its final composition, reported in terms of oxides, is 1.3-Na2O-3.0SiO2-1Al2O3-12H2O. Its microstructural and chemical features and CO2 adsorption performance have been investigated. The microstructure of the composite is characterized by NaX zeolite nanocrystals glued by the geopolymeric binder to form a complex three-dimensional network of pores. Overall porosity resulted ~23.5%, whereas compressive strength is 16±0.7 MPa. Monolith showed BET surface area of 350 m²/g, a micropore surface area of 280 m²/g and a mesopore volume, due to the geopolymeric binder, of 0.09 cm³/g. Its CO2 adsorption capacity has been measured at the temperatures of 7, 25 and 42 °C up to 15 bar using an optimized Sievert-type (volumetric) apparatus. All the adsorption data were evaluated by Toth/Langmuir isotherm model and commercial pure NaX zeolite was used as reference. CO2 adsorption isotherms show a maximum uptake value around 21 wt% at (~7 °C) that decrease to 18 wt% at high temperature (~42 °C) passing through 19 wt% at room temperature (~25 °C). The homogeneity grade of the surface, as obtained using Toth analysis performed on the adsorption isotherm, is close to t ≅ 0.40, lower than the 0.61 obtained for pure commercial NaX zeolite, as a consequence of the binder formation. Monolith exhibits a notably higher K values and quicker saturation with respect to reference that can be ascribed to the presence of mesoporosity that provides an easier and faster transport of CO2 in the NaX nanozeolite framework. The produced composite is a potential solid adsorbent candidate in industrial process.

Avances en la gestión del bloque quirúrgico. El papel del coordinador de quirófano / Advances in operating room management. The role of operating room director

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Chaperone patterns in vernal keratoconjunctivitis are distinctive of cell and Hsp type and are modified by inflammatory stimuli.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a severe ocular allergy with pathogenic mechanism poorly understood and no efficacious treatment. The aims of the study were to determine quantities and distribution of Hsp chaperones in the conjunctiva of VKC patients and assess their levels in conjunctival epithelial and fibroblast cultures exposed to inflammatory stimuli. METHODS: Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, Hsp105, and Hsp110 were determined in conjunctiva biopsies from nine patients and nine healthy age-matched normal subjects, using immunomorphology and qPCR. Conjunctival epithelial cells and fibroblasts were cultured and stimulated with IL-1ß, histamine, IL-4, TNF-α, or UV-B irradiation, and changes in Hsp levels were determined by Western blotting. RESULTS: Hsp27, Hsp40, Hsp70, and Hsp90 levels increased in the patients' conjunctiva, whereas Hsp10, Hsp60, Hsp100, and Hsp105 did not. Double immunofluorescence demonstrated colocalization of Hsp27, Hsp40, Hsp70, and Hsp90 with CD68 and tryptase. Testing of cultured conjunctival cells revealed an increase in the levels of Hsp27 in fibroblasts stimulated with IL-4; Hsp40 in epithelial cells stimulated with IL-4 and TNF-α and in fibroblasts stimulated with IL-4, TNF-α, and IL-1ß; Hsp70 in epithelial cells stimulated with histamine and IL-4; and Hsp90 in fibroblasts stimulated with IL-1ß, TNF-α, and IL-4. UV-B did not induce changes. CONCLUSIONS: VKC conjunctiva displays distinctive quantitative patterns of Hsps as compared with healthy controls. Cultured conjunctival cells respond to cytokines and inflammatory stimuli with changes in the Hsps quantitative patterns. The data suggest that interaction between the chaperoning and the immune systems drives disease progression.

Hsp10, Hsp70, and Hsp90 immunohistochemical levels change in ulcerative colitis after therapy.

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) characterized by damage of large bowel mucosa and frequent extra-intestinal autoimmune comorbidities. The role played in IBD pathogenesis by molecular chaperones known to interact with components of the immune system involved in inflammation is unclear. We previously demonstrated that mucosal Hsp60 decreases in UC patients treated with conventional therapies (mesalazine, probiotics), suggesting that this chaperonin could be a reliable biomarker useful for monitoring response to treatment, and that it might play a role in pathogenesis. In the present work we investigated three other heat shock protein/molecular chaperones: Hsp10, Hsp70, and Hsp90. We found that the levels of these proteins are increased in UC patients at the time of diagnosis and decrease after therapy, supporting the notion that these proteins deserve attention in the study of the mechanisms that promote the development and maintenance of IBD, and as biomarkers of this disease (e.g., to monitor response to treatment at the histological level).

Patient and physician perceptions of treatment of moderate-to-severe chronic pain with oral opioids.

OBJECTIVE: To study physician and patient perceptions of moderate-to-severe chronic pain and its management with oral opioids. METHODS: Two separate surveys were developed and administered to one of two respective study groups: patients and physicians. All study participants recruited from a pool of individuals who had previously agreed to participate in market research. Survey questions addressed the impact of various factors (e.g., quality of life indicators, potential for opioid addiction, side-effects) on pain management decision making, patient satisfaction and compliance. Responses for the first 500 patients and 275 physicians to respond were assessed using descriptive statistics. RESULTS: On average, patients were 53 years of age, white (89%), and female (71%). The majority of patients (80%) had been taking oral opioids longer than 6 months. Physicians reported that 45% of their patients received schedule II opioids, with 27% having severe chronic pain. Patients indicated the most common activities interfered with by chronic pain were exercising (76% of patients), working outside the home (67%), and job responsibilities (60%). When developing a treatment approach physicians considered patients' sleeping (91%), walking (86%), maintaining an independent lifestyle (84%), and job responsibilities (83%). Patients and physicians both rated the ability to relieve pain and the duration of relief as the most important factors when considering opioid therapy. The majority (63%) of patients reported experiencing opioid side effects. When physicians discontinued opioids due to side effects, the most frequent reason was nausea (78%) for immediate-release opioids, and constipation (64%) for extended-release formulations. CONCLUSION: The ability to relieve pain and the duration of that pain relief are the most important factors for both patients and physicians when selecting an opioid. A high percentage of patients surveyed experienced side effects related to their treatment, which may impact adherence and overall treatment effectiveness. Study results should be assessed within study limitations including responder and selection biases, physicians responded about their patients, who were not the same patients surveyed, and the fact that the survey instruments were not formally validated. Further research is warranted to address these limitations.

Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells.

Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Exposure to increasing concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present before and after OS induction. Immunoprecipitation experiments showed an Hsp60/p-C3 complex before OS that persisted after it, while an Hsp60/p53 complex was not detected in either condition. The presence of wild type (wt) p53 was confirmed by RT-PCR, and p21 detection suggested p53 activation after OS. We postulate that, although OS may induce early apoptosis in NCI-H292 cells, Hsp60 exerts an anti-apoptotic effect in these cells and, by extension, it may do so in other cancer cells.

Vaginal twin delivery: a survey and review of location, anesthesia coverage and interventions.

BACKGROUND: Twin pregnancies are associated with increased perinatal morbidity and mortality. No consensus exists whether vaginal twin delivery should take place in the labor room or operating room, or whether anesthesiologists should be present. We surveyed members of the California Society of Anesthesiologists (CSA) to review management of vaginal twin delivery, and examined anesthetic intervention retrospectively at our institution. METHODS: 230 CSA members were asked to complete an online survey on location of vaginal twin delivery in their institution and whether they were required to be present throughout. We then retrospectively reviewed charts of vaginal twin deliveries at our institution over a 36-month period to analyze frequency and type of anesthetic intervention. RESULTS: The online survey response rate was 58%; 64% of responders reported that vaginal twin deliveries were performed in the operating room and 55% that an anesthesiologist was present. There was a strong association between anesthesiologist's presence and delivery in the operating room (OR 7; 95% CI 3-20). We reviewed 81 charts of women who underwent vaginal twin delivery. The median (range) time that the anesthesiologist was present for each delivery was 60 (20-380) min. Of women undergoing vaginal twin delivery, 27% required anesthetic intervention during the second stage of labor with 6% having emergency cesarean delivery. CONCLUSION: There is a lack of consensus regarding the appropriate location for vaginal twin delivery and the role of anesthesiologists. A significant percentage of women undergoing vaginal twin delivery in our institution received anesthetic intervention in the immediate delivery period.

Ketorolaco en la era de los AINEs selectivos de la COX-2.Una revisión sistemática de su eficacia, sus efectos secundarios y sus aspectos reglamentarios / Ketorolac in the era of COX-2 selective NSAIDs. A systematic review of its effectiveness, side effects and regulatory issues

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Variation in practice patterns of anesthesiologists in California for prophylaxis of postoperative nausea and vomiting.

STUDY OBJECTIVE: To assess the responses to a survey asking anesthesiologists to report their clinical practice patterns for postoperative nausea and vomiting (PONV) prophylaxis. These practice patterns data may be useful for understanding how to optimize the decision to provide PONV prophylaxis. DESIGN: A written questionnaire with three detailed clinical scenarios with differing levels of a priori risk of PONV (a low-risk patient, a medium-risk patient, and a high-risk patient) was mailed to 454 anesthesiologists. SETTING: Survey was completed by anesthesiologists (n = 240) in 3 university and 3 community practices in California. MEASUREMENTS: Type and number of pharmacological and nonpharmacological interventions for PONV prophylaxis were recorded. To assess the variability in the responses (by the a priori risk of patient), we counted the number of different regimens that would be necessary to account for 80% of the responses. MAIN RESULTS: For the 240 respondents, we found that 1, 9, and 11 different pharmacological prophylaxis regimens were required to account for 80% of the variability in practice patterns for the low-, medium-, and high-risk patients, respectively. For the low-risk patient, 19% of practitioners would use pharmacological prophylaxis, and 37% would use nonpharmacological prophylaxis. For the medium-risk patient, 61% would use nonpharmacological prophylaxis and 67% of practitioners would use multidrug prophylaxis: 45% of patients would receive a 5HT(3) antagonist, 35% would receive metoclopramide, and 16% would receive droperidol. For the high-risk patient, 94% of practitioners would administer a 5HT(3) antagonist, whereas 84% would use multi-drug prophylaxis. CONCLUSIONS: We found a wide range of PONV prophylaxis management patterns. This variation in clinical practice may reflect uncertainty about the efficacy of available interventions, or differences in practitioners' clinical judgment and beliefs about how to treat PONV. Some therapies with proven benefit for PONV may be underused. Our results may be useful for designing studies aimed at determining the impact on PONV rates when physicians develop and implement guidelines for PONV prophylaxis.

Hospital profitability per hour of operating room time can vary among surgeons.

The operating margins (i.e., profits) of hospitals are decreasing. An important aspect of a hospital's finances is the profitability of individual surgical cases, which is measured by contribution margin. We sought to determine the extent to which contribution margin per hour of operating room (OR) time can vary among surgeons. We retrospectively analyzed 2848 elective cases performed by 94 surgeons at the Stanford University School of Medicine. For each case, we subtracted variable costs from the total payment to the hospital to compute contribution margin. We found moderate variability in contribution margin per hour of OR time among surgeons, relative to the variability in contribution margins per OR hour among each surgeon's cases (Cohen's f equaled 0.29, 95% lower confidence interval bound 0.27). Contribution margin per OR hour was negative for 26% of the cases. These results have implications for hospitals for which OR utilization is extensive, and for which elective cases are only scheduled if they can be completed during regularly scheduled hours. To increase or achieve profitability, managers need to increase the hours of lucrative cases, rather than encourage surgeons to do more and more cases. Whether the variability in contribution margin among surgeons should be used to more optimally (profitably) allocate OR time depends on the scheduling objectives of the surgical suite.

Cost-effectiveness of a trial of labor after previous cesarean.

OBJECTIVE: To determine the cost-effective method of delivery, from society's perspective, in patients who have had a previous cesarean. METHODS: We completed an incremental cost-effectiveness analysis of a trial of labor relative to cesarean using a computerized model for a hypothetical 30-year old parturient. The model incorporated data from peer-reviewed studies, actual hospital costs, and utilities to quantify health-related quality of life. A threshold of $50,000 per quality-adjusted life-years was used to define cost-effective. RESULTS: The model was most sensitive to the probability of successful vaginal delivery. If the probability of successful vaginal birth after cesarean (VBAC) was less than 0.65, elective repeat cesarean was both less costly and more effective than a trial of labor. Between 0.65 and 0.74, elective repeat cesarean was cost-effective (the cost-effectiveness ratio was less than $50,000 per quality-adjusted life-years), because, although it cost more than VBAC, it was offset by improved outcomes. Between 0.74 and 0.76, trial of labor was cost-effective. If the probability of successful vaginal delivery exceeded 0.76, trial of labor became less costly and more effective. Costs associated with a moderately morbid neonatal outcome, as well as the probabilities of infant morbidity occurring, heavily impacted our results. CONCLUSION: The cost-effectiveness of VBAC depends on the likelihood of successful trial of labor. Our modeling suggests that a trial of labor is cost-effective if the probability of successful vaginal delivery is greater than 0.74. Improved algorithms are needed to more precisely estimate the likelihood that a patient with a previous cesarean will have a successful vaginal delivery.