2,028 research outputs found
Knee arthroplasty: are patients' expectations fulfilled?: A prospective study of pain and function in 102 patients with 5-year follow-up
Background and purpose With an aging population expecting an active life after retirement, patientsâ expectations of improvement after surgery are also increasing. We analyzed the relationship between preoperative expectations and postoperative satisfaction and self-reported outcomes with regard to pain and physical function after knee arthroplasty
Early structural brain development in infants exposed to HIV and antiretroviral therapy in utero in a South African birth cohort
INTRODUCTION:
There is a growing population of children who are HIV-exposed and uninfected (HEU) with the successful expansion of antiretroviral therapy (ART) use in pregnancy. Children who are HEU are at risk of delayed neurodevelopment; however, there is limited research on early brain growth and maturation. We aimed to investigate the effects of in utero exposure to HIV/ART on brain structure of infants who are HEU compared to HIV-unexposed (HU).
METHODS:
Magnetic resonance imaging using a T2-weighted sequence was undertaken in a subgroup of infants aged 2â6 weeks enrolled in the Drakenstein Child Health Study birth cohort, South Africa, between 2012 and 2015. Motherâchild pairs received antenatal and postnatal HIV testing and ART per local guidelines. We compared subcortical and total grey matter volumes between HEU and HU groups using multivariable linear regression adjusting for infant age, sex, intracranial volume and socio-economic variables. We further assessed associations between brain volumes with maternal CD4 cell count and ART exposure.
RESULTS:
One hundred forty-six infants (40 HEU; 106 HU) with high-resolution images were included in this analysis (mean age 3 weeks; 50.7% male). All infants who were HEU were exposed to ART (88% maternal triple ART). Infants who were HEU had smaller caudate volumes bilaterally (5.4% reduction, p 0.2). Total grey matter volume was also reduced in infants who were HEU (2.1% reduction, p < 0.05). Exploratory analyses showed that low maternal CD4 cell count (<350 cells/mm3) was associated with decreased infant grey matter volumes. There was no relationship between timing of ART exposure and grey matter volumes.
CONCLUSIONS:
Lower caudate and total grey matter volumes were found in infants who were HEU compared to HU in the first weeks of life, and maternal immunosuppression was associated with reduced volumes. These findings suggest that antenatal HIV exposure may impact early structural brain development and improved antenatal HIV management may have the potential to optimize neurodevelopmental outcomes of children who are HEU
An Open-System Quantum Simulator with Trapped Ions
The control of quantum systems is of fundamental scientific interest and
promises powerful applications and technologies. Impressive progress has been
achieved in isolating the systems from the environment and coherently
controlling their dynamics, as demonstrated by the creation and manipulation of
entanglement in various physical systems. However, for open quantum systems,
engineering the dynamics of many particles by a controlled coupling to an
environment remains largely unexplored. Here we report the first realization of
a toolbox for simulating an open quantum system with up to five qubits. Using a
quantum computing architecture with trapped ions, we combine multi-qubit gates
with optical pumping to implement coherent operations and dissipative
processes. We illustrate this engineering by the dissipative preparation of
entangled states, the simulation of coherent many-body spin interactions and
the quantum non-demolition measurement of multi-qubit observables. By adding
controlled dissipation to coherent operations, this work offers novel prospects
for open-system quantum simulation and computation.Comment: Pre-review submission to Nature. For an updated and final version see
publication. Manuscript + Supplementary Informatio
Human Monocytes Undergo Excessive Apoptosis following Temozolomide Activating the ATM/ATR Pathway While Dendritic Cells and Macrophages Are Resistant
Immunodeficiency is a severe therapy-limiting side effect of anticancer chemotherapy resulting from sensitivity of immunocompetent cells to DNA damaging agents. A central role in the immune system is played by monocytes that differentiate into macrophages and dendritic cells (DCs). In this study we compared human monocytes isolated from peripheral blood and cytokine matured macrophages and DCs derived from them and assessed the mechanism of toxicity of the DNA methylating anticancer drug temozolomide (TMZ) in these cell populations. We observed that monocytes, but not DCs and macrophages, were highly sensitive to the killing effect of TMZ. Studies on DNA damage and repair revealed that the initial DNA incision was efficient in monocytes while the re-ligation step of base excision repair (BER) can not be accomplished, resulting in an accumulation of DNA single-strand breaks (SSBs). Furthermore, monocytes accumulated DNA double-strand breaks (DSBs) following TMZ treatment, while DCs and macrophages were able to repair DSBs. Monocytes lack the DNA repair proteins XRCC1, ligase IIIα and PARP-1 whose expression is restored during differentiation into macrophages and DCs following treatment with GM-CSF and GM-CSF plus IL-4, respectively. These proteins play a key role both in BER and DSB repair by B-NHEJ, which explains the accumulation of DNA breaks in monocytes following TMZ treatment. Although TMZ provoked an upregulation of XRCC1 and ligase IIIα, BER was not enhanced likely because PARP-1 was not upregulated. Accordingly, inhibition of PARP-1 did not sensitize monocytes, but monocyte-derived DCs in which strong PARP activation was observed. TMZ induced in monocytes the DNA damage response pathways ATM-Chk2 and ATR-Chk1 resulting in p53 activation. Finally, upon activation of the Fas-receptor and the mitochondrial pathway apoptosis was executed in a caspase-dependent manner. The downregulation of DNA repair in monocytes, resulting in their selective killing by TMZ, might impact on the immune response during cancer chemotherapy
How simple can a model of an empty viral capsid be? Charge distributions in viral capsids
We investigate and quantify salient features of the charge distributions on
viral capsids. Our analysis combines the experimentally determined capsid
geometry with simple models for ionization of amino acids, thus yielding the
detailed description of spatial distribution for positive and negative charge
across the capsid wall. The obtained data is processed in order to extract the
mean radii of distributions, surface charge densities and dipole moment
densities. The results are evaluated and examined in light of previously
proposed models of capsid charge distributions, which are shown to have to some
extent limited value when applied to real viruses.Comment: 10 pages, 10 figures; accepted for publication in Journal of
Biological Physic
Tau pathology as determinant of changes in atrophy and cerebral blood flow: a multi-modal longitudinal imaging study
PURPOSE: Tau pathology is associated with concurrent atrophy and decreased cerebral blood flow (CBF) in Alzheimer's disease (AD), but less is known about their temporal relationships. Our aim was therefore to investigate the association of concurrent and longitudinal tau PET with longitudinal changes in atrophy and relative CBF. METHODS: We included 61 individuals from the Amsterdam Dementia Cohort (mean age 65.1â±â7.5 years, 44% female, 57% amyloid-ÎČ positive [AÎČâ+], 26 cognitively impaired [CI]) who underwent dynamic [18F]flortaucipir PET and structural MRI at baseline and 25â±â5 months follow-up. In addition, we included 86 individuals (68 CI) who only underwent baseline dynamic [18F]flortaucipir PET and MRI scans to increase power in our statistical models. We obtained [18F]flortaucipir PET binding potential (BPND) and R1 values reflecting tau load and relative CBF, respectively, and computed cortical thickness from the structural MRI scans using FreeSurfer. We assessed the regional associations between i) baseline and ii) annual change in tau PET BPND in Braak I, III/IV, and V/VI regions and cortical thickness or R1 in cortical gray matter regions (spanning the whole brain) over time using linear mixed models with random intercepts adjusted for age, sex, time between baseline and follow-up assessments, and baseline BPND in case of analyses with annual change as determinant. All analyses were performed in AÎČ-â cognitively normal (CN) individuals and AÎČ+ â(CN and CI) individuals separately. RESULTS: In AÎČ+ individuals, greater baseline Braak III/IV and V/VI tau PET binding was associated with faster cortical thinning in primarily frontotemporal regions. Annual changes in tau PET were not associated with cortical thinning over time in either AÎČ+ or AÎČ-â individuals. Baseline tau PET was not associated with longitudinal changes in relative CBF, but increases in Braak III/IV tau PET over time were associated with increases in parietal relative CBF over time in AÎČâ+âindividuals. CONCLUSION: We showed that higher tau load was related to accelerated cortical thinning, but not to decreases in relative CBF. Moreover, tau PET load at baseline was a stronger predictor of cortical thinning than change of tau PET signal
Tertiary osteochondral defect of the talus treated by a novel contoured metal implant
The primary treatment of most osteochondral defects of the talus is arthroscopic debridement and bone marrow stimulation. There is no optimal treatment for large lesions or for those in which primary treatment has failed. We report a 20-year-old female patient with persistent symptoms after two previous arthroscopic procedures. Computed tomography showed a cystic defect of the medial talar dome, sized 17Â ĂÂ 8Â ĂÂ 8Â mm. The patient was treated with a novel contoured metal implant. At 1 and 2Â years after surgery, the patient reported considerable reduction in pain and had resumed playing korfball at competitive level
Outcome of anal symptoms and anorectal function following two obstetric anal sphincter injuries (OASIS)-a nested case-controlled study.
INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury (OASI) is a significant risk factor for developing anal incontinence. It can therefore be hypothesised that recurrent OASI in a subsequent delivery may predispose women to further anal sphincter dysfunction. METHODS: A nested case-controlled study based on data collected prospectively between 2006 and 2019. Women matched for age and ethnicity, with a history of one OASI and no sphincter damage in a subsequent delivery (control) were compared to women sustaining a second OASI. Assessment was carried out using the St Mark's score (SMIS), anorectal manometry and endoanal ultrasound scan (findings quantified using the modified Starck score). RESULTS: Eighty-four women were included and equally distributed between the two groups, who were followed up 12 weeks postnatally. No difference in SMIS scores was found. Maximum resting pressure (MRP, mmHg) and maximum squeeze pressure (MSP, mmHg) were significantly reduced in the study group. Median (IQR) MRP in the study group was 40.0 (31.3-54.0) versus 46.0 (39.3-61.5) in the control group (p =â0.030). Median (IQR) MSP was 73.0 (58.3-93.5) in the study group versus 92.5 (70.5-110.8) (p =â0.006) in the control group. A significant difference (p =â0.002) was found in the modified Starck score between the study group (median 0.0 [IQR 0.0-6.0]) and control group (median 0.0 [IQR 0.0-0.0]). CONCLUSIONS: We have demonstrated that women with recurrent OASI do not have significant anorectal symptoms compared to those with one OASI 12 weeks after delivery, but worse anal sphincter function and integrity. Therefore, on long-term follow-up, symptoms may possibly develop. This information will be useful when counselling women in a subsequent pregnancy
Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials.
BACKGROUND: Treatment efficacy of physical agents in osteoarthritis of the knee (OAK) pain has been largely unknown, and this systematic review was aimed at assessing their short-term efficacies for pain relief. METHODS: Systematic review with meta-analysis of efficacy within 1-4 weeks and at follow up at 1-12 weeks after the end of treatment. RESULTS: 36 randomised placebo-controlled trials (RCTs) were identified with 2434 patients where 1391 patients received active treatment. 33 trials satisfied three or more out of five methodological criteria (Jadad scale). The patient sample had a mean age of 65.1 years and mean baseline pain of 62.9 mm on a 100 mm visual analogue scale (VAS). Within 4 weeks of the commencement of treatment manual acupuncture, static magnets and ultrasound therapies did not offer statistically significant short-term pain relief over placebo. Pulsed electromagnetic fields offered a small reduction in pain of 6.9 mm [95% CI: 2.2 to 11.6] (n = 487). Transcutaneous electrical nerve stimulation (TENS, including interferential currents), electro-acupuncture (EA) and low level laser therapy (LLLT) offered clinically relevant pain relieving effects of 18.8 mm [95% CI: 9.6 to 28.1] (n = 414), 21.9 mm [95% CI: 17.3 to 26.5] (n = 73) and 17.7 mm [95% CI: 8.1 to 27.3] (n = 343) on VAS respectively versus placebo control. In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to 22.2 mm [95% CI: 18.1 to 26.3] for TENS, and 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS. Follow-up data up to 12 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of LLLT, EA and TENS treatment was stopped. CONCLUSION: TENS, EA and LLLT administered with optimal doses in an intensive 2-4 week treatment regimen, seem to offer clinically relevant short-term pain relief for OAK
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