Neuromuscular recovery from severe- and extreme-intensity exercise in men and women

Maximal voluntary contraction force (MVC), potentiated twitch force (Qpot), and voluntary activation (%VA) recover to baseline within 90s following extreme-intensity exercise. However, methodological limitations masked important recovery kinetics. We hypothesized reductions in MVC, Qpot, and %VA at task failure following extreme-intensity exercise would be less than following severe-intensity exercise, and Qpot and MVC following extreme-intensity exercise would show significant recovery within 120s but remain depressed following severe-intensity exercise. Twelve subjects (6 men) completed two severe-intensity (40, 50%MVC) and two extreme-intensity (70, 80%MVC) isometric knee-extension exercise bouts to task failure (Tlim). Neuromuscular function was measured at baseline, Tlim, and through 150s of recovery. Each intensity significantly reduced MVC and Qpot compared to baseline. MVC was greater at T¬lim (p<0.01) and at 150s of recovery (p=0.004) following exercise at 80%MVC compared to severe-intensity exercise. Partial recovery of MVC and Qpot were detected within 150s following Tlim for each exercise intensity; Qpot recovered to baseline values within 150s of recovery following exercise at 80%MVC. No differences in %VA were detected pre- to post-exercise or across recovery for any intensity. Although further analysis showed sex-specific differences in MVC and Qpot, future studies should closely examine sex-dependent responses to extreme-intensity exercise. It is clear, however, that these data reinforce that mechanisms limiting exercise tolerance during extreme-intensity exercise recover quickly. NOVELTY: •Severe- and extreme-intensity exercise cause independent responses in fatigue accumulation and the subsequent recovery time courses. •Recovery of MVC and Qpot occurs much faster following extreme-intensity exercise in both men and women.

Clofarabine with topotecan, vinorelbine, and thiotepa reinduction regimen for children and young adults with relapsed AML

Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML) as outcomes remain poor. Therapeutic options are limited in this heavily pre-treated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a clofarabine-based regimen with topotecan, vinorelbine, and thiotepa (TVTC) in patients with relapsed acute leukemias. Here we report on an expanded bicenter cohort of 33 patients, &lt;25 years of age, with relapsed/refractory (R/R) AML treated with up to 2 cycles of the TVTC reinduction regimen from 2007 to 2018. The overall response rate (ORR), defined as complete remission (CR) or CR with partial recovery of platelet count (CRp), was 71.4% (95%CI: 41.9 to 91.6%) for those patients in first relapse (n=14) and 47.4% ( 95%CI: 24.4 to 71.1%) for patients in 2nd or greater relapse or refractory disease. Responses were seen across multiple high risk cytogenetic and molecular subtypes, with 84% of responders successfully bridged to allogeneic stem cell transplantation. The 5-year OS for patients in first relapse was 46.2% (95%CI: 19.1 to 73.3%) and 50.0% (95%CI: 26.9 to 73.1%) for patients who responded to TVTC. For pediatric and young adult patients with R/R AML, TVTC reinduction compares favorably with currently used salvage regimens and warrants further exploration.

Impact of Gut Microbiota on Radiation-Associated Cognitive Dysfunction and Neuroinflammation in Mice

Radiation-induced brain injury is a common complication of brain irradiation that eventually leads to irreversible cognitive impairment. Evidence has shown that the gut microbiome may play an important role in radiation-induced cognitive function. However, the effects of gut microbiota on radiation-induced brain injury (RIBI) remain poorly understood. Here we studied the link between intestinal microbes and radiation-induced brain injury to further investigate the effects of intestinal bacteria on neuroinflammation and cognitive function. We first verified the differences in gut microbes between male and female mice and administered antibiotics to C57BL/6 male mice to deplete the gut flora and then expose mice to radiation. We found that depletion of intestinal flora after irradiation may act as a protective modulator against radiation-induced brain injury. Moreover, we found that pretreatment with depleted gut microbes in RIBI mice suppressed brain pro-inflammatory factor production, and high-throughput sequencing analysis of mouse feces at 1-month postirradiation revealed microbial differences. Interestingly, a proportion of Verrucomicrobia Akkermansia showed partial recovery. Additionally, short-chain fatty acid treatments increased neuroinflammation in the radiation-induced brain injury model. Although a further increase in cognitive function was not observed, brain injury was aggravated in whole-brain irradiated mice to some extent. The protective effects of depleted intestinal flora and the utilization of the brain-gut axis open new avenues for development of innovative therapeutic strategies for radiation-induced brain injury.

Low CO2 Levels Are Detrimental for In Vitro Plantlets through Disturbance of Photosynthetic Functionality and Accumulation of Reactive Oxygen Species

Photosynthesis of plantlets in tissue culture containers is not considered important, compared to photosynthesis of ex vitro plants, due to the exogenous source of carbohydrates present in tissue culture media. However, CO2 starvation can generate a burst of reactive oxygen species (ROS). We examined this phenomenon in tissue culture, since CO2 levels may become very low during the light period. The research was carried out with lily scales, regenerating adventitious bulblets, and with Arabidopsis seedlings. CO2 starvation was achieved by placing a small vial of concentrated KOH solution in the culture container. CO2 removal reduced the growth of regenerated lily bulblets by 33% or 23%, with or without sucrose in the medium, respectively. In Arabidopsis seedlings, CO2 removal decreased growth by 50% or 78% in the presence or absence of sucrose in the medium, respectively. Therefore, the addition of sucrose as a replacement for photosynthesis resulted in only partial recovery of growth. Staining with nitroblue tetrazolium (NBT) showed little to no ROS in ex vitro growing seedlings, while abundant ROS were detected in seedlings grown under in vitro CO2 starvation. Seedlings grown under normal tissue culture conditions (no CO2 withdrawal) showed low levels of ROS. In lily tissue culture, CO2 starvation decreased the maximum quantum efficiency of photosystem II (Fv/Fm) from 0.69 to 0.60, and in Arabidopsis from 0.76 to 0.62. Fv/Fm of ex vitro lily and Arabidopsis seedlings was 0.77 and 0.79, respectively. This is indicative of a disturbance in photosynthesis functionality and the occurrence of in vitro stress under reduced CO2 concentrations. We conclude that poor growth, in the absence of CO2, was partly due to strongly reduced photosynthesis, while the detrimental effects were most likely due to a burst of ROS.

Efficacy of Serial Ultrasonographic Examinations in Predicting Return to Play in Agility Dogs with Shoulder Lameness

The aim of this study is to investigate the use of shoulder ultrasound as a method of predicting the likelihood of returning to competition in agility dogs with shoulder teno-muscular injuries after a standardised rehabilitation protocol. Thirty-two agility dogs with a clinical and ultrasonographic diagnosis of shoulder teno-muscular injury were included in a prospective study with physical and ultrasound examinations at the time of diagnosis (T0) and at two (T2), four (T4) and six (T6) months; during this period, the dogs received rehabilitation treatments. The endpoint of the study was to obtain information regarding participation in agility competitions 12 months after diagnosis, based on telephone interviews with the owners. The clinical lameness score (CLS) and the ultrasound lesion score (ULS) were used as outcome measurements. The CLS indicated partial recovery from a shoulder injury at T2 (78%), while the ULS indicated no satisfactory recovery at T2 in any patient. At 4 months, the CLS alone was not a valuable predictor of full recovery from a shoulder injury in agility dogs. Relative Risk indicated that, at T2, ultrasound was 23.8 times more valuable in identifying a shoulder lesion as compared to clinical lameness score (CLS), and it was 2.53 times more valuable at T4.

IPET-CT in inflammatory diseases of kidneys and bladder: diagnostic efficacy

Introduction. The incorporation of combined positron emission tomography-computed tomography (PET-CT) into clinical practice has significantly expanded the understanding of the pathogenesis of many diseases. Evidence-based data on the diagnostic efficacy in infectious and inflammatory diseases is increasing, making this imaging method very promising. Purpose of the study. To study the diagnostic efficacy of 18F-FDG PET-CT in various chronic inflammatory diseases of kidneys and bladder.Materials and methods. A retrospective study of the results of whole-body 18F-FDG PET-CT in 45 patients was carried out. Patients underwent an investigation at various times after surgical treatment of localized oncology of the anogenital zone at the T1N0M0 stage without the involvement of the genitourinary system. It was found that 24 patients had a history of chronic pyelonephritis and 21 patients had manifestations of radiation cystitis. Repeated PET/CT scans were performed after a course of therapy for inflammatory urological diseases to assess the treatment results of the underlying pathology.Results. The latent course of chronic renal failure was accompanied by a diffuse decrease in 18F-FDG metabolism in the renal parenchyma with its partial recovery after etiotropic therapy and urine sanitation. Hypermetabolism of 18F-FDG was detected in the bladder wall during manifestations of radiation cystitis, which was leveled during therapy and relief of urinary syndrome manifestations. Bacterial and radiation inflammation differed in molecular-cell responses to the pathogen, while the results of urinalysis, indicating the effectiveness of the treatment, coincided with the visual and digital indicators of the restoration of adequate energy metabolism in the studied tissues.Conclusions. Metabolism of 18F-FDG in the kidneys and bladder can objectively reflect the nature of inflammation and complement the data on the effectiveness of the treatment.

Physiological and biochemical mechanisms of the hen’s body recovery from dermanyssosis associated with deacarization

The purpose of the research is to study the efficacy of the insectoacaricide "5% D-cyphenotrine emulsion" against infestation of birds with Dermanyssus gallinae (dermanyssosis) after the deacarization of the poultry building and to characterize physiological and biochemical mechanisms of the recovery of Hy-Line hens after removed parasites.Materials and methods. A parasitological examination of the poultry farm found D. gallinae in one of the poultry buildings. Given positive results of the drug efficacy against the poultry red mite, we analyzed the morpho-physiological and physiological and biochemical parameters of the hen’s blood before and 10 and 20 days after the treatments. Changes in the ethological status of birds were recorded. We used 0.005% aqueous emulsion of "5% D-cyphenothrin emulsion" for treatment. To obtain it, the drug was diluted with water at a ratio of 1:1000 immediately before use.Results and discussion. After double treatment with "5% D-cyphenotrine emulsion" of the shop with hens from the test group, no live poultry red mite was found. Within 20 days after the disease reduction, representatives of this group showed high concentrations of cortisol which were 2.3–2.4 times (p < 0.001) higher than those of healthy hens. This indicates that the stress state of hens still remains after the parasitizing of D. gallinae. In addition, the recovery process takes a long time and with great stress for all systems of their body. This is also confirmed by a high level of lipid peroxidation. At the same time, high intensity of gluconeogenesis and, as a result, deterioration of lipid and protein metabolism were recorded in the hens in question. The positive results indicate an increasing need for additional energy expenditures which are paramount for the effective and well-timed implementation of adaptation mechanisms. It should be noted here that the values of all the above-mentioned indicators tend to normalize by the end of the study period. The changes noted in the blood of birds indicate the restoration of a number of body systems. The poultry red mite as an emergency factor affects the morphophysiology of the blood, in particular, the level of white blood cells, which is restored by the 10th day after deacarization, which triggers regenerative and reparative processes. There were also changes in the number of cells of the immune system, an increase in hemoglobin concentration to control values and optimization of behavior in representatives of the test group which are largely related to the normalized physiological activity of the thyroid gland after the poultry building deacarization. We found a partial recovery of the hen’s body systems after the poultry building deacarization with the drug "5% D-cyphenotrine emulsion", which is due to the long-term parasitizing of D. gallinae, a stressor of extreme strength.

Dynamic regimes of the Greenland Ice Sheet emerging from interacting melt-elevation and glacial isostatic adjustment feedbacks

The stability of the Greenland Ice Sheet under global warming is governed by a number of dynamic processes and interacting feedback mechanisms in the ice sheet, atmosphere and solid Earth. Here we study the long-term effects due to the interplay of the competing melt-elevation and glacial isostatic adjustment (GIA) feedbacks for different temperature step forcing experiments with a coupled ice-sheet and solid-Earth model. Our model results show that for warming levels above 2 °C, Greenland could become essentially ice-free on the long-term, mainly as a result of surface melting and acceleration of ice flow. These ice losses can be mitigated, however, in some cases with strong GIA feedback even promoting the partial recovery of the Greenland ice volume. We further explore the full-factorial parameter space determining the relative strengths of the two feedbacks: Our findings suggest distinct dynamic regimes of the Greenland Ice Sheets on the route to destabilization under global warming – from recovery, via quasi-periodic oscillations in ice volume to ice-sheet collapse. In the recovery regime, the initial ice loss due to warming is essentially reversed within 50,000 years and the ice volume stabilizes at 61–93 % of the present-day volume. For certain combinations of temperature increase, atmospheric lapse rate and mantle viscosity, the interaction of the GIA feedback and the melt-elevation feedback leads to self-sustained, long-term oscillations in ice-sheet volume with oscillation periods of tens to hundreds of thousands of years and oscillation amplitudes between 15–70 % of present-day ice volume. This oscillatory regime reveals a possible mode of internal climatic variability in the Earth system on time scales on the order of 100,000 years that may be excited by or synchronized with orbital forcing or interact with glacial cycles and other slow modes of variability. Our findings are not meant as scenario-based near-term projections of ice losses but rather providing insight into of the feedback loops governing the "deep future" and, thus, long-term resilience of the Greenland Ice Sheet.

Partial recovery of amblyopia following fellow eye ischemic optic neuropathy

Background: Recovery from amblyopia in adulthood following fellow eye (FE) vision loss is a well-known phenomenon. Incidence of recovery varies widely following different FE pathologies and rate of recovery following FE ischemic optic neuropathy (ION) has not been examined. We aimed to determine frequency and degree of improvement in amblyopic eye (AE) visual function following ION in the FE. Methods: We performed a retrospective chart review of patients between 2007-2021 confirmed to have amblyopia and ischemic optic neuropathy in different eyes. Patients with unstable ocular pathology potentially limiting vision were excluded. We compared best-corrected visual acuity (VA) in each eye before and after FE ION over time. For patients with available data, we examined change in perimetric performance over time. Results: Among the 12 patients who met inclusion criteria (mean age 67+/-8 years), 9 (75%) improved ≥1 line and 2 (17%) improved ≥3 lines. Median time from ION symptom onset to maximal improvement was 6 months (range: 2-101 months). Reliable perimetric data were available for 6 patients. Mean sensitivity improved in the amblyopic eye for all patients, with a mean improvement of 1.9+/-1.1 dB. There was no correspondence between foci of ION-related field loss and gains in field sensitivity in the AE. Conclusion: A high proportion of patients with amblyopia and contralateral ION experience improvement in their amblyopic eye. Modest gains in perimetric sensitivity in the AE may accompany FE ION. These findings support the view that residual plasticity in the adult visual cortex can be tapped to support functional improvement in amblyopia.

Mechanisms of somatic transformation in inherited bone marrow failure syndromes

Inherited bone marrow failure syndromes (IBMFS) cause hematopoietic stem progenitor cell (HSPC) failure due to germline mutations. Germline mutations influence the number and fitness of HSPC by various mechanisms, for example, abnormal ribosome biogenesis in Shwachman-Diamond syndrome and Diamond-Blackfan anemia, unresolved DNA cross-links in Fanconi anemia, neutrophil maturation arrest in severe congenital neutropenia, and telomere shortening in short telomere syndrome. To compensate for HSPC attrition, HSPCs are under increased replication stress to meet the need for mature blood cells. Somatic alterations that provide full or partial recovery of functional deficit implicated in IBMFS can confer a growth advantage. This review discusses results of recent genomic studies and illustrates our new understanding of mechanisms of clonal evolution in IBMFS.