Effects of Sport Participation on Gait Coordination, Symmetry, and Variability in Older Adults.

The aim of this study was to compare the interlimb coordination, asymmetry, and variability between older adults who participated in sports (n = 25; age = 72.6 ± 6.46 years) and sedentary older adults (n = 20; age = 70.85 ± 3.82 years). The sport participants were selected from tennis and badminton clubs, whereas the sedentary participants were recruited from local community centers. The participants walked at their preferred speed in a 10-m walkway for 2 min. The interlimb coordination was measured by the phase coordination index. Other walking metrics were speed, cadence, swing time, stance time, double-support time, stride time, and swing time asymmetry. The results showed that the sport participants relative to the sedentary group had better interlimb coordination, higher walking speed and cadence, and less swing time variability. Young older adults also had a better interlimb coordination. In conclusion, the findings of this study showed that long-term participation in sports has some antiaging benefits on gait coordination and symmetry in older adults.

Effect of environmental constraints on multi-segment coordination patterns during the tennis service in expert performers.

The aims of this study were to examine the effect of different environmental constraints on kinematic multi-segment coordination patterns during the service and its coordination with service time variability. Ten expert tennis players (Age: 34.1 ± 5.3) volunteered to take part in this study. Participants served 30 times in 3 different conditions: control, target and opposition. The order of conditions was counterbalanced between participants. A wireless 3D motion capture system (STT Co, Spain) was used to measure 7 joint motions, with a 17 degrees of freedom biomechanical model created to capture the entire service action. Results of the principal component analysis showed that 4 synergies were created; however, their roles were changed relative to the perception of the environment. The results of repeated-measures analysis of variance did not show any significant difference on total variance and individual principal components between conditions; however, one synergy pattern significantly predicted the service time variability in both control and opposition conditions. In conclusion, the findings demonstrated that expert performers reduce the joint dimensionality by creating functional synergies in different phases of service and adapt the service action according to the perception of the environment.

Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

OBJECTIVES: Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. DESIGN: Randomized blinded placebo-controlled trial. SETTING: Preclinical research laboratory. SUBJECTS: Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. INTERVENTIONS: Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. MEASUREMENTS AND MAIN RESULTS: Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD µg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. CONCLUSIONS: A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

Orthobunyavirus entry into neurons and other mammalian cells occurs via clathrin-mediated endocytosis and requires trafficking into early endosomes.

La Crosse virus (LACV) is a leading cause of pediatric encephalitis and aseptic meningitis in the midwestern and southern United States, where it is considered an emerging human pathogen. No specific therapies or vaccines are available for LACV or any other orthobunyaviruses. Inhibition of LACV entry into cells is a potential target for therapeutic intervention, but this approach is limited by our current knowledge of the entry process. Here, we determined that clathrin-mediated endocytosis is the primary mechanism of orthobunyavirus entry and identified key cellular factors in this process. First, we demonstrated that LACV colocalized with clathrin shortly after infection in HeLa cells; we then confirmed the functional requirement of dynamin- and clathrin-mediated endocytosis for orthobunyavirus entry using several independent assays and, importantly, extended these findings to primary neuronal cultures. We also determined that macropinocytosis and caveolar endocytosis, both established routes of virus entry, are not critical for cellular entry of LACV. Moreover, we demonstrated that LACV infection is dependent on Rab5, which plays an important regulatory role in early endosomes, but not on Rab7, which is associated with late endosomes. These findings provide the first description of bunyavirus entry into cells of the central nervous system, where infection can cause severe neurological disease, and will aid in the design and development of antivirals and therapeutics that may be useful in the treatment of LACV and, more broadly, arboviral infections of the central nervous system.

Venous blood for the analysis of acid-base status in a model of septic shock.

OBJECTIVE: To determine the relationship between arterial and venous acid-base status in a model of septic shock. METHODS: Paired samples (n = 435) of arterial and femoral venous blood from 57 sheep (47 septic, 10 non-septic) managed with protocol-guided ventilation, sedation, parenteral fluids and inotropic support. RESULTS: The arterial-venous difference in acid-base parameters was similar with and without sepsis. There was a consistent arterio-venous relationship for metabolic (pH, lactate, bicarbonate, base excess), but not respiratory parameters (partial pressures of oxygen, carbon dioxide, and haemoglobin-oxygen saturation), independent of sepsis. CONCLUSIONS: Venous blood provides a reliable measure of metabolic but not respiratory disturbance.

Targeted Mutations in the Fusion Peptide Region of La Crosse Virus Attenuate Neuroinvasion and Confer Protection against Encephalitis.

La Crosse virus (LACV) is a major cause of pediatric encephalitis and aseptic meningitis in the Midwestern, Mid-Atlantic, and Southern United States, where it is an emerging pathogen. The LACV Gc glycoprotein plays a critical role in the neuropathogenesis of LACV encephalitis as the putative virus attachment protein. Previously, we identified and experimentally confirmed the location of the LACV fusion peptide within Gc and generated a panel of recombinant LACVs (rLACVs) containing mutations in the fusion peptide as well as the wild-type sequence. These rLACVs retained their ability to cause neuronal death in a primary embryonic rat neuronal culture system, despite decreased replication and fusion phenotypes. To test the role of the fusion peptide in vivo, we tested rLACVs in an age-dependent murine model of LACV encephalitis. When inoculated directly into the CNS of young adult mice (P28), the rLACV fusion peptide mutants were as neurovirulent as the rLACV engineered with a wild-type sequence, confirming the results obtained in tissue culture. In contrast, the fusion peptide mutant rLACVs were less neuroinvasive when suckling (P3) or weanling (P21) mice were inoculated peripherally, demonstrating that the LACV fusion peptide is a determinant of neuroinvasion, but not of neurovirulence. In a challenge experiment, we found that peripheral challenge of weanling (P21) mice with fusion peptide mutant rLACVs protected from a subsequent WT-LACV challenge, suggesting that mutations in the fusion peptide are an attractive target for generating live-attenuated virus vaccines. Importantly, the high degree of conservation of the fusion peptide amongst the Bunyavirales and, structurally, other arboviruses suggests that these findings are broadly applicable to viruses that use a class II fusion mechanism and cause neurologic disease.

Effects of task and environmental constraints on axial kinematic synergies during the tennis service in expert players.

The aims of this study were to examine the effects of task and environmental constraints on axial synergies and to find an association between synergies and arm acceleration as a performance variable. Participants of this study were 10 expert tennis players (age: 34.4 ± 7.46) who voluntarily took part and executed 60 serves under two different conditions: no-opponent and opponent. An inertial motion unit (IMU) capture system was used to calculate the 3D angular joint motions in the neck, back and lumbar segments. The results of the principal component analysis showed that the redundancy in the axial segments is decomposed into 2 main synergies that are responsible for the loading (backward swing) and firing phase (forward swing). The total variance and loading synergy variance were significantly lower in the topspin service than other service types. The emerged firing synergy was strongly associated with the arm acceleration regardless of service type. In conclusion, the effective strategy to utilise the axial motions in the trunk is through creating functional synergies that have a flexible role based on the type of service and conditions. The topspin service showed less coordination variability relative to other types of service and serving in the opponent condition required participants to change the nature of synergy among the axial segments. These findings support the design of practice that emphasises the importance of more realistic contexts with special attention given to the order of different service types.

Radiological difficulty in identifying unicompartmental knee replacement dislocation.

Unicondylar knee replacement is a relatively common elective orthopedic procedure but is not often seen in the Emergency Department setting. Familiarity with normal clinical and radiological appearances is difficult to gain. Dislocation of the mobile bearing component "spacer" is a known complication of unicondylar knee replacements, and these patients will initially present to the accident and Emergency Department. In this setting, an accurate and prompt diagnosis is necessary to appropriately manage the patient's condition. There is normally a radiological challenge in identifying dislocated mobile bearings on plain radiographs. These patients may need to have further imaging, such as a computer tomographic scan to identify the dislocated mobile bearing.

The effect of exogenous glucose-dependent insulinotropic polypeptide in combination with glucagon-like peptide-1 on glycemia in the critically ill.

OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have additive insulinotropic effects when coadministered in health. We aimed to determine whether GIP confers additional glucose lowering to that of GLP-1 in the critically ill. RESEARCH DESIGN AND METHODS: Twenty mechanically ventilated critically ill patients without known diabetes were studied in a prospective, randomized, double-blind, crossover fashion on 2 consecutive days. Between T0 and T420 minutes, GLP-1 (1.2 pmol/kg·min(-1)) was infused intravenously with either GIP (2 pmol/kg·min(-1)) or 0.9% saline. Between T60 and T420 minutes, nutrient liquid was infused into the small intestine at 1.5 kcal/min. RESULTS: Adding GIP did not alter blood glucose or insulin responses to small intestinal nutrient. GIP increased glucagon concentrations slightly before nutrient delivery (P=0.03), but not thereafter. CONCLUSIONS: The addition of GIP to GLP-1 does not result in additional glucose-lowering or insulinotropic effects in critically ill patients with acute-onset hyperglycemia.