Paradoxical Decline Research Articles

Pre-movement muscle co-contraction associated with motor performance deterioration under high reward conditions

Reward usually enhances task performance, but exceptionally large rewards can impede performance due to psychological pressure. In this study, we investigated motor activity changes in high-reward situations and identified indicators for performance decline. Fourteen healthy adults practiced a velocity-dependent right-hand motor task for three days, followed by a test day with varying monetary reward for each trial. Participants were divided into low performers (LPs) and high performers (HPs) according to whether success rate decreased or increased, respectively, on the highest reward trials compared to lower reward trials. Both LPs and HPs demonstrated increased hand velocity during higher reward trials, but only LPs exhibited a significant increase in velocity variance. There was also a negative correlation between the pre-movement co-contraction index (CCI) of the biceps and triceps muscles and success rate on the highest reward trials. This correlation was confirmed in a second experiment with 12 newly recruited participants, suggesting that pre-movement CCI is a marker for performance decline caused by high reward. These findings suggest that interventions to reduce pre-movement CCI such as biofeedback training could be useful for preventing the paradoxical decline in motor performance associated with high rewards.

The Paradoxical Decline in Cardiovascular Hospitalizations in the US

The Paradoxical Decline in Cardiovascular Hospitalizations in the US

The Paradoxical Decline of Geriatric Medicine as a Profession

In this Viewpoint, author Jerry Gurwitz discusses the attrition of geriatric medicine as a profession, attributing it in part to societal attitudes about aging and compounded by the negative effects of lower compensation and lack of career prestige.

Developing informatics infrastructure to curate datasets using electronic health record data from five hospitals for translational cardiovascular research

Abstract Introduction It has been challenging for researchers to access granular electronic health record (EHR) data at scale. One emerging prospect is to use big data to traverse the translational spectrum from an early discovery phase to a later implementation phase. Purpose To create a research-ready dataset to support translational research in cardiovascular medicine, using routinely-collected EHR data from multiple hospitals. As an early discovery phase study, we estimated the effect of invasive versus non-invasive management on the survival of patients with non-ST elevation myocardial infarction (NSTEMI) aged 80 years or older (SENIOR-NSTEMI Study). As a later implementation phase study, we determined the relationship between the full spectrum of troponin level and mortality in patients in whom troponin testing was performed for clinical purposes (TROP-RISK Study). Methods Using Microsoft SQL we developed a dataset of 257948 consecutive patients who had a troponin measured between 2010 and 2017 at five hospitals. We extracted phenotypically detailed data, including demographics, blood tests, procedural data, and survival status. For the SENIOR-NSTEMI Study, eligible patients were 80 years or older who were diagnosed with NSTEMI. We estimated mortality hazard ratios comparing invasive with non-invasive management. For the TROP-RISK Study, we modelled the relation between peak troponin level and all-cause mortality using multivariable adjusted restricted cubic spline Cox regression analyses. Results For the SENIOR-NSTEMI Study, 1500 patients with NSTEMI were included who had a median age of 86 (interquartile range (IQR) 82–89) years of whom (845 [56%]) received non-invasive management. During a median follow-up of 3 (IQR 1.2–4.8) years, the adjusted cumulative five-year mortality was 36% in the invasive and 55% in the non-invasive group (hazard ratio 0.68, 95% confidence interval 0.55–0.84). For the TROP-RISK Study, during a median follow-up of 1198 days (IQR 514–1866 days), 55850 (21.7%) deaths occurred. There was an unexpected inverted U-shaped relation between troponin level and mortality in acute coronary syndrome (ACS) patients (n=120049) (Figure 1A). The paradoxical decline in mortality at very high troponin levels may be driven in part by the changing case mix as troponin levels increase; a higher proportion of patients with very high troponin levels received invasive management (Figure 1B). Conclusion Routine EHR data can be aggregated across multiple sites to create highly granular datasets for research. The SENIOR-NSTEMI Study showed a survival advantage of invasive compared with non-invasive management of elderly patients with NSTEMI, who were underrepresented in previous trials. The inverted U-shaped relationship between troponin and mortality in ACS patients in the TROP-RISK Study demonstrates that assembling sufficiently large datasets can cast light on patterns of disease that are impossible to adequately define in single centre studies. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1) NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative, and 2) British Heart Foundation

Developing informatics infrastructure to curate datasets using electronic health record data from five hospitals for translational cardiovascular research

Abstract Introduction It has been challenging for researchers to access granular electronic health record (EHR) data at scale. One emerging prospect is to use big data to traverse the translational spectrum from an early discovery phase to a later implementation phase. Purpose To create a research-ready dataset to support translational research in cardiovascular medicine, using routinely-collected EHR data from multiple hospitals. As an early discovery phase study, we estimated the effect of invasive versus non-invasive management on the survival of patients with non-ST elevation myocardial infarction (NSTEMI) aged 80 years or older (SENIOR-NSTEMI Study). As a later implementation phase study, we determined the relationship between the full spectrum of troponin level and mortality in patients in whom troponin testing was performed for clinical purposes (TROP-RISK Study). Methods Using Microsoft SQL we developed a dataset of 257948 consecutive patients who had a troponin measured between 2010 and 2017 at five hospitals. We extracted phenotypically detailed data, including demographics, blood tests, procedural data, and survival status. For the SENIOR-NSTEMI Study, eligible patients were 80 years or older who were diagnosed with NSTEMI. We estimated mortality hazard ratios comparing invasive with non-invasive management. For the TROP-RISK Study, we modelled the relation between peak troponin level and all-cause mortality using multivariable adjusted restricted cubic spline Cox regression analyses. Results For the SENIOR-NSTEMI Study, 1500 patients with NSTEMI were included who had a median age of 86 (interquartile range (IQR) 82–89) years of whom (845 [56%]) received non-invasive management. During a median follow-up of 3 (IQR 1.2–4.8) years, the adjusted cumulative five-year mortality was 36% in the invasive and 55% in the non-invasive group (hazard ratio 0.68, 95% confidence interval 0.55–0.84). For the TROP-RISK Study, during a median follow-up of 1198 days (IQR 514–1866 days), 55850 (21.7%) deaths occurred. There was an unexpected inverted U-shaped relation between troponin level and mortality in acute coronary syndrome (ACS) patients (n=120049) (Figure 1A). The paradoxical decline in mortality at very high troponin levels may be driven in part by the changing case mix as troponin levels increase; a higher proportion of patients with very high troponin levels received invasive management (Figure 1B). Conclusion Routine EHR data can be aggregated across multiple sites to create highly granular datasets for research. The SENIOR-NSTEMI Study showed a survival advantage of invasive compared with non-invasive management of elderly patients with NSTEMI, who were underrepresented in previous trials. The inverted U-shaped relationship between troponin and mortality in ACS patients in the TROP-RISK Study demonstrates that assembling sufficiently large datasets can cast light on patterns of disease that are impossible to adequately define in single centre studies. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1) NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative, and 2) British Heart Foundation

A paradoxical decline in semen parameters in men treated with clomiphene citrate: A systematic review.

Clomiphene, a selective oestrogen receptor modulator, has been utilised in managing male sub-fertility since 1967. Numerous controlled and uncontrolled studies have been published regarding the efficacy of clomiphene citrate in male sub-fertility cohorts. Although the primary intention of treating men with clomiphene citrate is to improve sperm parameters and testosterone levels, some studies have reported paradoxical decline in semen parameters. The information available on decline in sperm parameters following treatment with clomiphene is sparse. We conducted a systemic review using PubMed, Embase, Cochrane Library and Scopus databases for original studies reporting adverse effects of clomiphene citrate therapy on sperm parameters. This systematic review includes 384 men from 11 different studies that reported adverse effects of clomiphene citrate therapy. Of the men included in these studies, 19%, 21%, 17% and 24% of clomiphene-treated men demonstrated a decrease in sperm count, concentration, motility and total motile sperm count respectively. In up to 17% of patients, deterioration of semen parameters did not recover following discontinuation of therapy. In the future, more studies should report on this aspect so the magnitude of this effect can be more clearly understood.

Heart Rate Variability in a Patient with Coronavirus Disease 2019

This case study investigates the heart rate (HR) and heart rate variability (HRV) in a patient with coronavirus disease 2019 (COVID-19). We report the case of a 58-year old male who contracted COVID-19. During his disease, 24-hour Holter electrocardiography (ECG) was performed continuously. For comparison, his 24-hour Holter ECGs from the previous 10 years were available. In this patient, COVID-19 was associated with a decrease in HR and a paradoxical decline in HRV. An abrupt decline in HRV and a decrease in HR may signal the onset of COVID-19 before common symptoms such as dry cough or fever appear. In addition, HRV and HR measurements may help to evaluate the course of the disease.

The paradoxical decline and growth of trust as a function of borderline personality disorder trait count: Using discontinuous growth modelling to examine trust dynamics in response to violation and repair.

Borderline personality disorder (BPD) is associated with paradoxical trust cognitions and behaviours. While BPD is associated with difficulty forming trust and maintaining cooperation in trust-based exchanges, design and analytical methodology best suited to reveal the temporal ebb and flow of trust have been underutilized. We used an economic game to examine the trajectories of trust as it forms, dissolves, and restores in response to trust violation and repair, and to explain how these vary as a function of borderline pathology. Young adults (N = 234) played a 15-round trust game in which partner trustworthiness was varied to create three phases: trust formation, trust violation, and trust restoration. Discontinuous growth modelling was employed to capture the trends in trust over time and their relationship with BPD trait count. BPD trait count was associated with an incongruous pattern of trust behaviour in the form of declining trust when interacting with a new and cooperative partner, and paradoxically, increasing trust following multiple instances of trust violation by that partner. BPD trait count was also associated with trust restoring at a faster rate than it was originally formed. By adopting a methodology that recognizes the dynamic nature of trust, this study illustrated at a micro level how relational disturbances may be produced and maintained in those with a moderate to high BPD trait count. Further investigation of the factors and processes that underlie these incongruous trust dynamics is recommended.

Evaluación del papel de la PET/TC con [68Ga]Ga-PSMA I&T en la evaluación de la respuesta a la terapia con docetaxel en pacientes con cáncer de próstata resistente a la castración

ObjectiveThere have been only few studies investigating the role of PSMA ligands in the therapy response assessment of metastasized castration resistant prostate cancer (mCRPC) cases. In this study we aimed at evaluating the capability of 68Ga- prostate-specific membrane antigen (PSMA) I&T positron emission tomography/computerized tomography (PET/CT) in the assessment of therapeutic response in patients under docetaxel therapy for prostate cancer (PCa). Material and methodsThe clinical records of all mCRPC patients treated with docetaxel and referred to our department for 68Ga-PSMA I&T PET/CT imaging were retrospectively analysed. Sixteen patients (mean age 69 years, range 52–82 years) with castration-resistant prostate cancer patients receiving palliative docetaxel therapy and had undergone 68Ga-PSMA I&T PET/CT scan were included in the study. 68Ga-PSMA I&T PET/CT imaging was done and prostate specific antigen (PSA) levels were measured at baseline before administration of docetaxel (PET1) and after at least 3 cycles (range 4–12) of chemotherapy (PET2). Patient-based as well as lesion-based comparison of PET2 findings with PET1 findings were done. ResultsThe change (decrease) observed in lymph node and prostate gland/prostatic bed SUVmax values after treatment compared to pretreatment was found to be statistically significant (P=.033).3/16 patients (19%) were classified as progressive disease (PD), 4/16 (25%) as stable disease (SD), 9/16 (56%) as partial remission (PR) radiologically. An increasing PSA trend (IT) was observed in 4 patients (25%) and a decreasing PSA trend (DT) in 3 patients (18%). Nine patients showed a PSA response of ≥ 50% (56%). Of the 4 patients showing SD, 3 had IT, 3 had BR. Of the 9 patients who showed PR on PET studies, 8 patients showed BR and 1 patient showed DT. ConclusionImaging with 68Ga-PSMA PET/CT showed great concordance with biochemical response evaluation in terms of PSA levels, especially in patients showing good response to therapy. 68Ga-PSMA PET/CT was also successful in identifying progressive disease in patients showing paradoxical decline in PSA levels.

Assessment of the role of Ga-68 PSMA I&T PET/CT in response evaluation to docetaxel therapy in castration resistant prostate cancer patients

ObjectiveThere have been only few studies investigating the role of PSMA ligands in the therapy response assessment of metastasized castration resistant prostate cancer (mCRPC) cases. In this study we aimed at evaluating the capability of 68Ga- prostate-specific membrane antigen (PSMA) -I&T positron emission tomography/computerized tomography (PET/CT) in the assessment of therapeutic response in patients under docetaxel therapy for prostate cancer (PCa). Material and methodsThe clinical records of all mCRPC patients treated with docetaxel and referred to our department for 68Ga-PSMA I&T PET/CT imaging were retrospectively analysed. Sixteen patients (mean age 69 years, range 52–82 years) with castration-resistant prostate cancer patients receiving palliative docetaxel therapy and had undergone 68Ga-PSMA I&T PET/CT scan were included in the study. 68Ga-PSMA I&T PET/CT imaging was done and prostate specific antigen (PSA) levels were measured at baseline before administration of docetaxel (PET1) and after at least 3 cycles (range 4–12) of chemotherapy (PET2). Patient-based as well as lesion-based comparison of PET2 findings with PET1 findings were done. ResultsThe change (decrease) observed in lymph node and prostate gland/prostatic bed SUVmax values after treatment compared to pretreatment was found to be statistically significant (p=0.033).3/16 patients (19%) were classified as progressive disease (PD), 4/16 (25%) as stable disease (SD), 9/16 (56%) as partial remission (PR) radiologically. An increasing PSA trend (IT) was observed in 4 patients (25%) and a decreasing PSA trend (DT) in 3 patients (18%). Nine patients showed a PSA response of ≥50% (56%). Of the 4 patients showing SD, 3 had IT, 3 had BR. Of the 9 patients who showed PR on PET studies, 8 patients showed BR and 1 patient showed DT. ConclusionImaging with 68Ga-PSMA PET/CT showed great concordance with biochemical response evaluation in terms of PSA levels, especially in patients showing good response to therapy. 68Ga-PSMA PET/CT was also successful in identifying progressive disease in patients showing paradoxical decline in PSA levels.

Revision of ‘golden hour’ for hemodynamically unstable trauma patients: an analysis of nationwide hospital-based registry in Japan

BackgroundThe ‘golden hour’ is a well-known concept, suggesting that shortening time from injury to definitive care is critically important for better outcome of trauma patients. However, there was no established...

Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres

ObjectiveTo determine the relation between age and troponin level and its prognostic implication.DesignRetrospective cohort study.SettingFive cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC).Participants257...

Identification of rare HIV-1-infected patients with extreme CD4+ T cell decline despite ART-mediated viral suppression.

The goal of antiretroviral therapy (ART) is to suppress HIV-1 replication and reconstitute CD4+ T cells. Here, we report on HIV-infected individuals who had a paradoxical decline in CD4+ T cells despite ART-mediated suppression of plasma HIV-1 load (pVL). We defined such an immunological outcome as extreme immune decline (EXID). EXID's clinical and immunological characteristics were compared to immunological responders (IRs), immunological nonresponders (INRs), healthy controls (HCs), and idiopathic CD4+ lymphopenia (ICL) patients. T cell immunophenotyping and assembly/activation of inflammasomes were evaluated by flow cytometry. PBMC transcriptome analysis and genetic screening for pathogenic variants were performed. Levels of cytokines/chemokines were measured by electrochemiluminescence. Luciferase immunoprecipitation system and NK-mediated antibody-dependent cellular cytotoxicity (ADCC) assays were used to identify anti-lymphocyte autoantibodies. EXIDs were infected with non-B HIV-1 subtypes and after 192 weeks of consistent ART-mediated pVL suppression had a median CD4+ decrease of 157 cells/μl, compared with CD4+ increases of 193 cells/μl and 427 cells/μl in INR and IR, respectively. EXID had reduced naive CD4+ T cells, but similar proportions of cycling CD4+ T cells and HLA-DR+CD38+CD8+ T cells compared with IR and INR. Levels of inflammatory cytokines were also similar in EXID and INR, but the IL-7 axis was profoundly perturbed compared with HC, IR, INR, and ICL. Genes involved in T cell and monocyte/macrophage function, autophagy, and cell migration were differentially expressed in EXID. Two of the 5 EXIDs had autoantibodies causing ADCC, while 2 different EXIDs had an increased inflammasome/caspase-1 activation despite consistently ART-suppressed pVL. EXID is a distinct immunological outcome compared with previously described INR. Anti-CD4+ T cell autoantibodies and aberrant inflammasome/caspase-1 activation despite suppressed HIV-1 viremia are among the mechanisms responsible for EXID.

Introduction

American federalism is a highly institutionalized compound of dual, cooperative, and coercive federalism that are coexisting states as well as historical phases. Contemporary coercive federalism has several systemic consequences including a shift in federal policy-making from places to persons, long-term fiscal stress, deceased intergovernmental institutions, rising polarization, a relegitimizing of states’ rights, and a paradoxical decline of public trust in the federal government coupled with public dedication to federal policy-making. Trump’s presidency, therefore, will likely be more of an interlude than a transformative moment in American federalism. Long-term trends highlighted in this issue will likely outlast Trump, although the trends point toward more centralization and polarization even while states and localities remain independently innovative on many fronts.

Arctic greening from warming promotes declines in caribou populations.

The migratory tundra caribou herds in North America follow decadal population cycles, and browsing from abundant caribou could be expected to counteract the current climate-driven expansion of shrubs in the circumpolar tundra biome. We demonstrate that the sea ice cover in the Arctic Ocean has provided a strong signal for climate-induced changes on the adjacent caribou summer ranges, outperforming other climate indices in explaining the caribou-plant dynamics. We found no evidence of a negative effect of caribou abundance on vegetation biomass. On the contrary, we found a strong bottom-up effect in which a warmer climate related to diminishing sea ice has increased the plant biomass on the summer pastures, along with a paradoxical decline in caribou populations. This result suggests that this climate-induced greening has been accompanied by a deterioration of pasture quality. The shrub expansion in Arctic North America involves plant species with strong antibrowsing defenses. Our results might therefore be an early signal of a climate-driven shift in the caribou-plant interaction from a system with low plant biomass modulated by cyclic caribou populations to a system dominated by nonedible shrubs and diminishing herds of migratory caribou.

Blood pressure and age-related GFR decline in the general population

BackgroundHypertension is one of the most important causes of end-stage renal disease, but it is unclear whether elevated blood pressure (BP) also accelerates the gradual decline in the glomerular filtration rate (GFR) seen in the general population with increasing age. The reason may be that most studies have considered only baseline BP and not the effects of changes in BP, antihypertensive treatment and other determinants of GFR during follow-up. Additionally, the use of GFR estimated from creatinine or cystatin C instead of measurements of GFR may have biased the results because of influence from non-GFR related confounders. We studied the relationship between BP and GFR decline using time-varying variables in a cohort representative of the general population using measurements of GFR as iohexol clearance.MethodsWe included 1594 subjects aged 50 to 62 years without baseline diabetes, kidney-, or cardiovascular disease in the Renal Iohexol-clearance Survey in Tromsø 6 (RENIS-T6). GFR, BP, antihypertensive medication and all adjustment variables were ascertained at baseline, and at follow-up after a median observation time of 5.6 years in 1299 persons (81%). The relationship between GFR decline and BP was analyzed in linear mixed models.ResultsThe mean (standard deviation) GFR decline rate was 0.95 (2.23) mL/min/year. The percentage of persons with hypertension (systolic BP ≥ 140 mmHg, diastolic BP ≥ 90 mmHg or antihypertensive medication) increased from 42 to 52% between baseline and follow-up. In multivariable adjusted linear mixed models using time-varying independent variables measured at baseline and follow-up, higher systolic and diastolic BP were associated with slower GFR decline rates by 0.10 and 0.20 mL/min/year/10 mmHg, respectively (p < 0.05). The association was stronger in persons on antihypertensive medication than in others (p < 0.05 for the interaction between BP and antihypertensive medication).ConclusionsIn the medium-term, elevated BP is not associated with accelerated GFR decline in the general middle-aged population. In persons using antihypertensive medication, elevated BP is associated with a paradoxical slower GFR decline. Studies with even longer observation periods are needed to evaluate the ultimate effect of BP on kidney function.

Selective Enhancement of Insulin Sensitivity in the Endothelium In Vivo Reveals a Novel Proatherosclerotic Signaling Loop.

In the endothelium, insulin stimulates endothelial NO synthase (eNOS) to generate the antiatherosclerotic signaling radical NO. Insulin-resistant type 2 diabetes mellitus is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. To answer this question, we generated a mouse with endothelial cell (EC)-specific overexpression of the human insulin receptor (hIRECO) using the Tie2 promoter-enhancer. hIRECO demonstrated significant endothelial dysfunction measured by blunted endothelium-dependent vasorelaxation to acetylcholine, which was normalized by a specific Nox2 NADPH oxidase inhibitor. Insulin-stimulated phosphorylation of protein kinase B was increased in hIRECO EC as was Nox2 NADPH oxidase-dependent generation of superoxide, whereas insulin-stimulated and shear stress-stimulated eNOS activations were blunted. Phosphorylation at the inhibitory residue Y657 of eNOS and expression of proline-rich tyrosine kinase 2 that phosphorylates this residue were significantly higher in hIRECO EC. Inhibition of proline-rich tyrosine kinase 2 improved insulin-induced and shear stress-induced eNOS activation in hIRECO EC. Enhancing insulin sensitivity specifically in EC leads to a paradoxical decline in endothelial function, mediated by increased tyrosine phosphorylation of eNOS and excess Nox2-derived superoxide. Increased EC insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide. Inhibition of proline-rich tyrosine kinase 2 restores insulin-induced and shear stress-induced NO production. This study demonstrates for the first time that increased endothelial insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide.

Autonomic Nervous System Responses to Concussion: Arterial Pulse Contour Analysis.

The arterial pulse wave (APW) has a distinct morphology whose contours reflect dynamics in cardiac function and peripheral vascular tone as a result of sympathetic nervous system (SNS) control. With a transition from rest to increased metabolic demand, the expected augmentation of SNS outflow will not only affect arterial blood pressure and heart rate but it will also induce changes to the contours of the APW. Following a sports concussion, a transient state cardiovascular autonomic dysfunction is present. How this state affects the APW has yet to be described. A prospective, parallel-group study on cardiovascular autonomic control (i.e., digital electrocardiogram and continuous beat-to-beat blood pressure) was performed in the seated upright position in 10 athletes with concussion and 7 non-injured control athletes. Changes in APW were compared at rest and during the first 60 s (F60) of an isometric handgrip test (IHGT) in concussed athletes and non-injured controls within 48 h and 1 week of injury. The concussion group was further separated by the length of time until they were permitted to return to play (RTP > 1week; RTP ≤ 1week). SysSlope, an indirect measurement of stroke volume, was significantly lower in the concussion group at rest and during F60 at 48 h and 1week; a paradoxical decline in SysSlope occurred at each visit during the transition from rest to IHGT F60. The RTP > 1week group had lower SysSlope (405 ± 200; 420 ± 88; 454 ± 236 mmHg/s, respectively) at rest 48 h compared to the RTP ≤ 1week and controls. Similarly at 48 h rest, several measurements of arterial stiffness were abnormal in RTP > 1week compared to RTP ≤ 1week and controls: peak-to-notch latency (0.12 ± 0.04; 0.16 ± 0.02; 0.17 ± 0.05, respectively), notch relative amplitude (0.70 ± 0.03; 0.71 ± 0.04; 0.66 ± 0.14, respectively), and stiffness index (6.4 ± 0.2; 5.7 ± 0.4; 5.8 ± 0.5, respectively). Use of APW revealed that concussed athletes have a transient increase in peripheral artery stiffness, which may be a compensatory adaptation to a paradoxical decline of stroke volume during the transition from rest to a state of increased metabolic demand within 48 h of concussion. This dysfunction of the SNS appeared to be more pronounced among concussed athletes who were removed from participation for >1 week compared to those who resumed play within 7 days.

Phase-dependent changes in local dynamic stability during walking in elderly with and without knee osteoarthritis

Previously, we reported reduced time-averaged knee local stability, in the unaffected, but not the affected leg of elderly with knee osteoarthritis OA compared to controls. Since stability may show phase-related changes, we reanalyzed the dataset reported previously using time-dependent local stability, λ(t), and also calculated time-averaged local stability, λs, for comparison.We studied treadmill walking at increasing speeds, focusing on sagittal plane knee movements. 16 patients, 12 healthy peers and 15 young subjects were measured. We found a clear maximum in λ(t) (i.e. minimum in stability) at around 60% of the stride cycle (StanceMax λ(t)), a second clear maximum (SwingMax λ(t)) at around 95% followed by a minimum between 70% and 100% (SwingMin λ(t)).StanceMax λ(t) of both legs was significantly higher in the OA than the young control group. Values for healthy elderly fell between those of the other groups, were significantly higher than in young adults, but there was only a trend towards a significant difference with the StanceMax λ(t) of the OA group׳s affected side. Time-averaged and time-dependent stability measures within one leg were uncorrelated, while time-dependent stability measures at the affected side were inversely correlated with λs at the unaffected side.The results indicate that time-dependent local dynamic stability might provide a more detailed insight into the problems of gait stability in OA than conventional averaged local dynamic stability measures and support the notion that the paradoxical decline in unaffected side time-averaged local stability may be caused by a trade-off between affected and unaffected side stability.

Effect of sleep deprivation on the electrophysiological signature of habituation to noxious laser stimuli.

Sleep deprivation induces hyperalgesia. However, this pro-nociceptive effect is not reflected at the electrophysiological level, since sleep restricted subjects show amplitude reduction of Laser-evoked Potentials (LEP). We aimed to explore the contribution of habituation to this paradoxical LEP amplitude decline. We compared LEP's of 12 healthy students (23.2 ± 1.1 years) after habitual sleep (HS) and a night of total sleep deprivation (TSD). Twelve repetitive laser stimulus blocks (each comprising twenty stimuli) were applied under three attention conditions ('focusing' - 'neutral' - 'distraction' condition). Stimulus blocks were split in part 1 (stimulus 1-10) and part 2 (stimulus 11-20). The contribution of habituation to the TSD-induced LEP amplitude decline was studied by calculating the percentage amplitude reduction of part 2 as compared to part 1. Individual sleepiness levels were correlated with (1) averaged LEP's and (2) the degree of habituation. TSD induced hyperalgesia to laser stimuli (p < 0.001). In contrast, depending on the attention condition, the P2 amplitude of the N2P2-complex was significantly reduced ('focusing': p = 0.004; 'neutral': p = 0.017; distraction: p = 0.71). Habituation of the P2 amplitude to radiant heat was increased after TSD ('focusing': p = 0.04; 'neutral': p < 0.001; distraction: p = 0.88). TSD had no significant effect on N1 amplitudes (p > 0.05). Individual sleepiness correlated negatively with averaged P2 amplitudes (p = 0.02), but not with the degree of habituation (p = 0.14). TSD induces hyperalgesia and results in attention-dependent enhanced habituation of the P2 component. Increased habituation may--to a substantial degree--explain the TSD-induced LEP-amplitude decline. For this article, a commentary is available at the Wiley Online Library.