Effects of total knee arthroplasty on skeletal muscle structure and function at the cellular, organellar, and molecular levels.

Total knee arthroplasty (TKA) is an important treatment option for knee osteoarthritis (OA) that improves self-reported pain and physical function, but objectively measured physical function typically remains reduced for years after surgery due, in part, to precipitous reductions in lower extremity neuromuscular function early after surgery. The present study examined intrinsic skeletal muscle adaptations during the first 5 weeks post-TKA to identify skeletal muscle attributes that may contribute to functional disability. Patients with advanced stage knee OA were evaluated prior to TKA and 5 weeks after surgery. Biopsies of the vastus lateralis were performed to assess muscle fiber size, contractility, and mitochondrial content, along with assessments of whole muscle size and function. TKA was accompanied by marked reductions in whole muscle size and strength. At the fiber (i.e., cellular) level, TKA caused profound muscle atrophy that was approximately twofold higher than that observed at the whole muscle level. TKA markedly reduced muscle fiber force production, contractile velocity, and power production, with force deficits persisting in myosin heavy chain (MHC) II fibers after expression relative to fiber size. Molecular level assessments suggest reduced strongly bound myosin-actin cross bridges and myofilament lattice stiffness as a mechanism underlying reduced force per unit fiber size. Finally, marked reductions in mitochondrial content were apparent and more prominent in the subsarcolemmal compartment. Our study represents the most comprehensive evaluation of skeletal muscle cellular adaptations to TKA and uncovers novel effects of TKA on muscle fiber size and intrinsic contractility early after surgery that may contribute to functional disability.NEW & NOTEWORTHY We report the first evaluation of the effects of total knee arthroplasty (TKA) on skeletal muscle at the cellular and subcellular levels. We found marked effects of TKA to cause skeletal muscle fiber atrophy and contractile dysfunction in older adults, as well as molecular mechanisms underlying impaired contractility. Our results reveal profound effects of TKA on muscle fiber size and intrinsic contractility early after surgery that may contribute to functional disability.

Effect of neuromuscular electrical stimulation on skeletal muscle size and function in patients with breast cancer receiving chemotherapy.

Exercise has numerous benefits for patients with cancer, but implementation is challenging because of practical and logistical hurdles. This study examined whether neuromuscular electrical stimulation (NMES) can serve as a surrogate for classic exercise by eliciting an exercise training response in skeletal muscle of women diagnosed with breast cancer undergoing chemotherapy. Patients (n = 22) with histologically confirmed stage I, II, or III breast cancer scheduled to receive neoadjuvant or adjuvant chemotherapy were randomized to 8 wk of bilateral neuromuscular electrical stimulation (NMES; 5 days/wk) to their quadriceps muscles or control. Biopsy of the vastus lateralis was performed at baseline and after 8 wk of intervention to assess muscle fiber size, contractility, and mitochondrial content. Seventeen patients (8 control/9 NMES) completed the trial and were included in analyses. NMES promoted muscle fiber hypertrophy (P < 0.001), particularly in fast-twitch, myosin heavy chain (MHC) IIA fibers (P < 0.05) and tended to induce fiber type shifts in MHC II fibers. The effects of NMES on single-muscle fiber contractility were modest, and it was unable to prevent declines in the function in MHC IIA fibers. NMES did not alter intermyofibrillar mitochondrial content/structure but was associated with reductions in subsarcolemmal mitochondria. Our results demonstrate that NMES induces muscle fiber hypertrophy and fiber type shifts in MHC II fibers but had minimal effects on fiber contractility and promoted reductions in subsarcolemmal mitochondria. Further studies are warranted to evaluate the utility of NMES as an exercise surrogate in cancer patients and other conditions.NEW & NOTEWORTHY This is the first study to evaluate whether neuromuscular electrical stimulation (NMES) can be used as an exercise surrogate to improve skeletal muscle fiber size or function in cancer patients receiving treatment. We show that NMES promoted muscle fiber hypertrophy and fiber type shifts but had minimal effects on single-fiber contractility and reduced subsarcolemmal mitochondria.

Three-dimensional radar imaging of structures and craters in the Martian polar caps.

Over the last decade, observations acquired by the Shallow Radar (SHARAD) sounder on individual passes of the Mars Reconnaissance Orbiter have revealed the internal structure of the Martian polar caps and provided new insights into the formation of the icy layers within and their relationship to climate. However, a complete picture of the cap interiors has been hampered by interfering reflections from off-nadir surface features and signal losses associated with sloping structures and scattering. Foss et al. (2017) addressed these limitations by assembling three-dimensional data volumes of SHARAD observations from thousands of orbital passes over each polar region and applying geometric corrections simultaneously. The radar volumes provide unprecedented views of subsurface features, readily imaging structures previously inferred from time-intensive manual analysis of single-orbit data (e.g., trough-bounding surfaces, a buried chasma, and a basal unit in the north, massive carbon-dioxide ice deposits and discontinuous layered sequences in the south). Our new mapping of the carbon-dioxide deposits yields a volume of 16,500 km3, 11% larger than the prior estimate. In addition, the radar volumes newly reveal other structures, including what appear to be buried impact craters with no surface expression. Our first assessment of 21 apparent craters at the base of the north polar layered deposits suggests a Hesperian age for the substrate, consistent with that of the surrounding plains as determined from statistics of surface cratering rates. Planned mapping of similar features throughout both polar volumes may provide new constraints on the age of the icy layered deposits. The radar volumes also provide new topographic data between the highest latitudes observed by the Mars Orbiter Laser Altimeter and those observed by SHARAD. In general, mapping of features in these radar volumes is placing new constraints on the nature and evolution of the polar deposits and associated climate changes.

An ice age recorded in the polar deposits of Mars.

Layered ice deposits at the poles of Mars record a detailed history of accumulation and erosion related to climate processes. Radar investigations measure these layers and provide evidence for climate changes such as ice advance and retreat. We present a detailed analysis of observational data showing that ~87,000 cubic kilometers of ice have accumulated at the poles since the end of the last ice age ~370,000 years ago; this volume is equivalent to a global layer of ~60 centimeters. The majority of the material accumulated at the north pole. These results provide both a means to understand the accumulation history of the polar deposits as related to orbital Milankovitch cycles and constraints for better determination of Mars' past and future climates.

Massive CO2 ice deposits sequestered in the south polar layered deposits of Mars.

Shallow Radar soundings from the Mars Reconnaissance Orbiter reveal a buried deposit of carbon dioxide (CO(2)) ice within the south polar layered deposits of Mars with a volume of 9500 to 12,500 cubic kilometers, about 30 times that previously estimated for the south pole residual cap. The deposit occurs within a stratigraphic unit that is uniquely marked by collapse features and other evidence of interior CO(2) volatile release. If released into the atmosphere at times of high obliquity, the CO(2) reservoir would increase the atmospheric mass by up to 80%, leading to more frequent and intense dust storms and to more regions where liquid water could persist without boiling.

Onset and migration of spiral troughs on Mars revealed by orbital radar.

The landscape of the north polar layered deposits of Mars (NPLD) is dominated by a pinwheel array of enigmatic spiral troughs. The troughs have intrigued planetary scientists since the Mariner 9 spacecraft returned the first close-up image in 1972, but conclusive evidence of their origin has remained elusive. Debate continues regarding all aspects of the troughs, including the possibility that they have migrated, their age in relation to the current NPLD surface, and whether they are fundamentally erosional or constructional features. The troughs are probably related to climatic processes, yet the nature of this relationship has remained a mystery. Previous data characterizing only the exposed NLPD surface were insufficient to test these hypotheses. Here we show that the central spiral troughs initiated after deposition of three-quarters of the NPLD, quickly reached a stable morphology and migrated approximately 65 kilometres poleward and 600 metres in altitude over the past two million years or so. Our radar stratigraphy rules out hypotheses of erosional incision post-dating deposition, and instead largely validates an early hypothesis for constructional trough migration with wind transport and atmospheric deposition as dominant processes. These results provide hard constraints for palaeo-climate models and a new context for evaluating imagery, spectral data, and now radar sounding data, the better to understand the link between orbital parameters and climate, the role of climate in shaping the polar ice of Mars, and eventually, the age of the polar deposits themselves.