Health disparities in mortality among individuals with HIV-associated dementia in South Carolina.

HIV disproportionately affects the South compared to other regions of the US. Some people living with HIV (PLWH) may acquire HIV-associated neurocognitive disorders (HAND), of which HIV-associated dementia (HAD) is the most severe form. This study aimed to examine the disparities in mortality among individuals with HAD. Data were obtained from the South Carolina Alzheimer's Disease and Related Dementias Registry from 2010 to 2016 (HAD: n = 505; N = 164,982). Logistic regression and Cox proportional hazards models were used to determine mortality related to HIV-associated dementia and potential sociodemographic differences. Adjusted models controlled for age, gender, race, rurality, and place of diagnosis. Individuals diagnosed in a nursing facility were three times more likely to die with HAD compared to those diagnosed in the community (OR: 3.25; 95% CI: 2.08-5.08). Black populations were more likely to die with HAD compared to White populations (OR: 1.52; 95% CI: 0.953-2.42). Disparities in mortality among patients with HAD were found in place of diagnosis and by race. Future research should determine if mortality among individuals with HAD were as a result of HAD or non-HIV related decline.

Evidence of Electron Heating by Alpha Particles in JET Deuterium-Tritium Plasmas.

The fusion-born alpha particle heating in magnetically confined fusion machines is a high priority subject for studies. The self-heating of thermonuclear fusion plasma by alpha particles was observed in recent deuterium-tritium (D-T) experiments on the joint European torus. This observation was possible by conducting so-called "afterglow" experiments where transient high fusion yield was achieved with neutral beam injection as the only external heating source, and then termination of the heating at peak performance. This allowed the first direct evidence for electron heating of plasmas by fusion-born alphas to be obtained. Interpretive transport modeling of the relevant D-T and reference deuterium discharges is consistent with the alpha particle heating observation.

Third-trimester ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from the ADoPAD study.

OBJECTIVE: To evaluate the performance of third-trimester ultrasound for the diagnosis of clinically significant placenta accreta spectrum disorder (PAS) in women with low-lying placenta or placenta previa. METHODS: This was a prospective multicenter study of pregnant women aged ≥ 18 years who were diagnosed with low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the internal cervical os) on ultrasound at ≥ 26 + 0 weeks' gestation, between October 2014 and January 2019. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs on grayscale ultrasound: (1) obliteration of the hypoechogenic space between the uterus and the placenta; (2) interruption of the hyperechogenic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. Histopathological examinations were performed according to a predefined protocol, with pathologists blinded to the ultrasound findings. To assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprising the need for active management at delivery and histopathological confirmation of PAS was considered the reference standard. PAS was considered to be clinically significant if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation or uterine artery embolization. The diagnostic performance of each ultrasound sign for clinically significant PAS was evaluated in all women and in the subgroup who had at least one previous Cesarean section and anterior placenta. Post-test probability was assessed using Fagan nomograms. RESULTS: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations during the study period. Of these, 95 delivered in local hospitals, and placental pathology according to the study protocol was therefore not available. Among the 473 women for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%), comprising 36 cases of placenta accreta, 19 of placenta increta and 44 of placenta percreta. The median gestational age at the time of ultrasound assessment was 31.4 (interquartile range, 28.6-34.4) weeks. A normal hypoechogenic space between the uterus and the placenta reduced the post-test probability of clinically significant PAS from 21% to 5% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 9% in the subgroup with previous Cesarean section and anterior placenta. The absence of placental lacunae reduced the post-test probability of clinically significant PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 36% in the subgroup with previous Cesarean section and anterior placenta. When abnormal placental lacunae were seen on ultrasound, the post-test probability of clinically significant PAS increased from 21% to 59% in the whole cohort and from 62% to 78% in the subgroup with previous Cesarean section and anterior placenta. An interrupted hyperechogenic interface between the uterine serosa and bladder wall increased the post-test probability for clinically significant PAS from 21% to 85% in women with low-lying placenta or placenta previa and from 62% to 88% in the subgroup with previous Cesarean section and anterior placenta. When all three sonographic markers were present, the post-test probability for clinically significant PAS increased from 21% to 89% in the whole cohort and from 62% to 92% in the subgroup with previous Cesarean section and anterior placenta. CONCLUSIONS: Grayscale ultrasound has good diagnostic performance to identify pregnancies at low risk of PAS in a high-risk population of women with low-lying placenta or placenta previa. Ultrasound may be safely used to guide management decisions and concentrate resources on patients with higher risk of clinically significant PAS. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Insights into the CuO nanoparticle ecotoxicity with suitable marine model species.

Metal oxide nanoparticles, among them copper oxide nanoparticles (CuO NPs), are widely used in different applications (e.g. batteries, gas sensors, superconductors, plastics and metallic coatings), increasing their potential release in the environment. In aquatic matrix, the behavior of CuO NPs may strongly change, depending on their surface charge and some physical-chemical characteristics of the medium (e.g. ionic strength, salinity, pH and natural organic matter content). Ecotoxicity of CuO NPs to aquatic organisms was mainly studied on freshwater species, few tests being performed on marine biota. The aim of this study was to assess the toxicity of CuO NPs on suitable indicator species, belonging to the ecologically relevant level of consumers. The selected bioassays use reference protocols to identify Effect/Lethal Concentrations (E(L)C), by assessing lethal and sub-lethal endpoints. Mortality tests were performed on rotifer (Brachionus plicatilis), shrimp (Artemia franciscana) and copepod (Tigriopus fulvus). While moult release failure and fertilization rate were studied, as sub-lethal endpoints, on T. fulvus and sea urchin (Paracentrotus lividus), respectively. The size distribution and sedimentation rates of CuO NPs, together with the copper dissolution, were also analyzed in the exposure media. The CuO NP ecotoxicity assessment showed a concentration-dependent response for all species, indicating similar mortality for B. plicatilis (48hLC50 = 16.94 ± 2.68mg/l) and T. fulvus (96hLC50 = 12.35 ± 0.48mg/l), followed by A. franciscana (48hLC50 = 64.55 ± 3.54mg/l). Comparable EC50 values were also obtained for the sub-lethal endpoints in P. lividus (EC50 = 2.28 ± 0.06mg/l) and T. fulvus (EC50 = 2.38 ± 0.20mg/l). Copper salts showed higher toxicity than CuO NPs for all species, with common sensitivity trend as follows: P. lividus ≥ T. fulvus (sublethal endpoint) ≥ B. plicatilis >T. fulvus (lethal endpoint) >A. franciscana. CuO NP micrometric aggregates and high sedimentation rates were observed in the exposure media, with different particle size distributions depending on the medium. The copper dissolution was about 0.16% of the initial concentration, comparable to literature values. The integrated ecotoxicological-physicochemical approach was used to better describe CuO NP toxicity and behavior. In particular, the successful application of ecotoxicological reference protocols allowed to produce reliable L(E)C data useful to identify thresholds and assess potential environmental hazard due to NPs.

The neurokinin-2 receptor antagonist ibodutant improves overall symptoms, abdominal pain and stool pattern in female patients in a phase II study of diarrhoea-predominant IBS.

BACKGROUND: Tachykinins have been implicated in the pathophysiology of IBS with diarrhoea (IBS-D). Our aim was to study the efficacy and safety of ibodutant, a selective neurokinin-2 (NK2) receptor antagonist, in patients with IBS-D. METHODS: This multinational double-blind, placebo-controlled study recruited 559 patients with IBS-D according to Rome III criteria. After a 2-week treatment-free run-in, patients were randomised to ibodutant 1 mg, 3 mg, 10 mg or placebo once daily for eight consecutive weeks. Responders were those with a combined response of satisfactory relief (weekly binary question yes/no) of overall IBS symptoms and abdominal pain/discomfort on ≥75% weeks (primary end point). Secondary end points included abdominal pain and stool pattern. Data were also analysed according to US Food and Drug Administration (FDA)-approved interim end points (improvement of pain and stool consistency). Safety was assessed by monitoring adverse events and laboratory tests. Prespecified statistical analysis involved the whole group as well as gender subgroups. RESULTS: Demographics and baseline characteristics were comparable for all treatment arms. In the overall population, responsiveness tended to increase with escalating ibodutant doses. In the prespecified analysis by gender, ibodutant 10 mg demonstrated significant superiority over placebo in females (p=0.003), while no significant effect occurred in males. This was confirmed for secondary end points and for the responder analysis according to FDA-approved end points. The tolerability and safety of ibodutant was excellent at all doses. CONCLUSIONS: Ibodutant showed dose-dependent efficacy response in IBS-D, reaching statistical significance at the 10 mg dose in female patients. The safety and tolerability profile of ibodutant was similar to placebo. TRIAL REGISTRATION NUMBER: NCT01303224.

Stationary Zonal Flows during the Formation of the Edge Transport Barrier in the JET Tokamak.

High spatial resolution Doppler backscattering measurements in JET have enabled new insights into the development of the edge Er. We observe fine-scale spatial structures in the edge Er well with a wave number krρi≈0.4-0.8, consistent with stationary zonal flows, the characteristics of which vary with density. The zonal flow amplitude and wavelength both decrease with local collisionality, such that the zonal flow E×B shear increases. Above the minimum of the L-H transition power threshold dependence on density, the zonal flows are present during L mode and disappear following the H-mode transition, while below the minimum they are reduced below measurable amplitude during L mode, before the L-H transition.

Guidelines on dermatomyositis--excerpt from the interdisciplinary S2k guidelines on myositis syndromes by the German Society of Neurology.

The present guidelines on dermatomyositis (DM) represent an excerpt from the interdisciplinary S2k guidelines on myositis syndromes of the German Society of Neurology (available at www.awmf.org). The cardinal symptom of myositis in DM is symmetrical proximal muscle weakness. Elevated creatine kinase, CRP or ESR as well as electromyography and muscle biopsy also provide important diagnostic clues. Pharyngeal, respiratory, cardiac, and neck muscles may also be affected. Given that approximately 30% of patients also develop interstitial lung disease, pulmonary function tests should be part of the diagnostic workup. Although the cutaneous manifestations in DM are variable, taken together, they represent a characteristic and crucial diagnostic criterion for DM. Approximately 5-20% of individuals exhibit typical skin lesions without any clinically manifest muscle involvement (amyopathic DM). About 30% of adult DM cases are associated with a malignancy. This fact, however, should not delay the treatment of severe myositis. Corticosteroids are the therapy of choice in myositis (1-2 mg/kg). Additional immunosuppressive therapy is frequently required (azathioprine, for children methotrexate). In case of insufficient therapeutic response, the use of intravenous immunoglobulins is justified. The benefit of rituximab has not been conclusively ascertained yet. Acute therapeutic management is usually followed by low-dose maintenance therapy for one to three years. Skin lesions do not always respond sufficiently to myositis therapy. Effective treatment for such cases consists of topical corticosteroids and sometimes also calcineurin inhibitors. Systemic therapies shown to be effective include antimalarial agents (also in combination), methotrexate, and corticosteroids. Intravenous immunoglobulins or rituximab may also be helpful. UV protection is an important prophylactic measure.

FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk.

BACKGROUND: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention. PATIENTS AND METHODS: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety. RESULTS: A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms. CONCLUSION: In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile. CLINICAL TRIAL REGISTRATION: NCT01724528.

Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain.

BACKGROUND: Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective. METHODS: This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. RESULTS: 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72%) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95% confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. CONCLUSIONS: Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. TRIAL REGISTRATION: EudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).

Activity of temozolomide in patients with advanced chemorefractory colorectal cancer and MGMT promoter methylation.

BACKGROUND: No evidence-based treatment options are available for patients with advanced colorectal cancer (CRC) progressing after standard therapies. MGMT is involved in repair of DNA damage and MGMT promoter methylation may predict benefit from alkylating agents such as temozolomide. The aim of our study was to evaluate the activity of temozolomide in terms of response rate in patients with metastatic CRC and MGMT methylation, after failure of approved treatments. PATIENTS AND METHODS: Patients were enrolled in a monocentre, open-label, phase II study and treated with temozolomide at a dose of 150 mg/m2/day for 5 consecutive days in 4-weekly cycles. The treatment was continued for at least six cycles or until progressive disease. RESULTS: Thirty-two patients were enrolled from August 2012 to July 2013. Treatment was well tolerated with one grade 4 thrombocytopenia and no other grade≥3 toxicities. No complete response occurred. The objective response rate was 12%, reaching the pre-specified level for promising activity. Median progression-free survival and overall survival were 1.8 and 8.4 months, respectively. Patients with KRAS, BRAF and NRAS wild-type CRC showed significantly higher response when compared with those with any RAS or BRAF mutation (44% versus 0%; P=0.004). TP53 status had no influence on the primary end point. CONCLUSIONS: Temozolomide is tolerable and active in heavily pre-treated patients with advanced CRC and MGMT promoter methylation. Further studies in biomolecularly enriched populations or in a randomized setting are necessary to demonstrate the efficacy of temozolomide after failure of standard treatments.

Directed transport of active particles over asymmetric energy barriers.

We theoretically and numerically investigate the transport of active colloids to target regions, delimited by asymmetric energy barriers. We show that it is possible to introduce a generalized effective temperature that is related to the local variance of particle velocities. The stationary probability distributions can be derived from a simple diffusion equation in the presence of an inhomogeneous effective temperature resulting from the action of external force fields. In particular, transition rates over asymmetric energy barriers can be unbalanced by having different effective temperatures over the two slopes of the barrier. By varying the type of active noise, we find that equal values of diffusivity and persistence time may produce strongly varied effective temperatures and thus stationary distributions.

Physical activity initiated from midlife on risk of dementia and cognitive impairment: The Health and Retirement Study.

BACKGROUND: Physical activity is associated with lower risk of dementia and cognitive impairment, but existing randomized controlled trials have shown conflicting results. As cognitive decline occurs decades before the onset of dementia, physical activity interventions initiated in late life may have missed the potential window for prevention. An ideal trial of physical activity initiated from midlife and lasts till incident dementia and cognitive impairment in late life is not feasible. We aimed to estimate the effectiveness of a hypothetical physical activity intervention initiated from midlife on reducing dementia and cognitive impairment by emulating target trials using observational data. METHODS: The Health and Retirement Study was used to emulate target trials among noninstitutionalized participants aged 45 to 65 years with normal cognition who were physically inactive in the previous 2 years. Cognitive status was determined based on Langa-Weir classification of cognitive function (including immediate and delayed word recall tests, serial sevens subtraction, counting backward). Individuals were categorized as initiating physical activity or not, based on the self-reported physical activity. Intention-to-treat and per-protocol analysis were conducted with pooled logistic regression models with inverse-probability of treatment and censoring weights to estimate risk ratios (RRs), and 95% confidence intervals (95% CIs) were calculated with 200 sets of bootstrapping. RESULTS: Among 1505 participants (average age 57.6 ± 4.8 years, 67% women, 76.5% White), 72 cases of dementia and 409 cases of cognitive impairment occurred. After 12 years of follow-up, physical activity reduced dementia (RR = 0.70, 95% CI: 0.43, 0.99) for intention-to-treat analysis, and reduced dementia (RR = 0.51, 95% CI: 0.19, 0.99) and cognitive impairment (RR = 0.77, 95% CI: 0.61, 0.92) for per-protocol analysis. No significant reduction was found among older adults. CONCLUSIONS: Physical activity initiated during midlife may reduce dementia and cognitive impairment in late life, which highlights the importance of preventing cognitive outcomes at an earlier stage of life.

Longevity in the South Carolina Alzheimer's disease registry.

Background: South Carolina has arguably the most robust Alzheimer's Registry in the United States. For enhanced planning in both clinical practice and research and better utilization of the Registry data, it is important to understand survival after Registry entry. To this end, we conducted exploratory analyses to examine the patterns of longevity/survival in the South Carolina Alzheimer's Disease Registry. Methods: The sample included 42,028 individuals in the South Carolina Alzheimer's Disease Registry (SCADR). Participants were grouped into four cohorts based on their year of diagnosis. Longevity in the Registry (LIR), or the length of survival in the registry, was calculated based on the years of reported diagnosis and death. Results: The median LIR varied between 24 to 36 months depending on the cohort, with 75% of individuals in the three recent cohorts surviving for at least 12 months. Across all cohorts, 25% of the participants survived at least 60 months. The median LIR of females was longer than that of males. Individuals whose race was classified as Asian, American Indian, and other than listed had longer LIR compared to White, African American, and Hispanic individuals. Median LIR was shorter for Registry cases diagnosed at an earlier age (less than 65 years). Conclusion: Our data indicate that significant longevity is to be expected in the SCADR but that there is interesting variability which needs to be explored in subsequent studies. The SCADR is a rich data source prime for use in research studies and analyses.

Features of the Physical and Social Neighborhood Environment and Neighborhood-Level Alzheimer's Disease and Related Dementia in South Carolina.

BACKGROUND: Studies are increasingly examining the relationship between the neighborhood environment and cognitive decline; yet, few have investigated associations between multiple neighborhood features and Alzheimer's disease and related dementias (ADRD). OBJECTIVE: We investigated the relationship between neighborhood features and ADRD cumulative incidence from 2010 to 2014 in the South Carolina Alzheimer's Disease Registry (SCADR). METHODS: Diagnosed ADRD cases ≥50 years of age were ascertained from the SCADR by ZIP code and census tract. Neighborhood features from multiple secondary sources included poverty, air pollution [particulate matter with a diameter of 2.5 micrometers or less (PM2.5)], and rurality at the census-tract level and access to healthy food, recreation facilities, and diabetes screening at the county level. In addition to using Poisson generalized linear regression to estimate ADRD incident rate ratios (IRR) with 95% confidence intervals (CIs), we applied integrated nested Laplace approximations and stochastic partial differential equations (INLA-SPDE) to address disparate spatial scales. We estimated associations between neighborhood features and ADRD cumulative incidence. RESULTS: The average annual ADRD cumulative incidence was 690 per 100,000 people per census tract (95% CI: 660, 710). The analysis was limited to 98% of census tracts with a population ≥50 years old (i.e., 1,081 of 1,103). The average percent of families living below the federal poverty line per census tract was 18.8%, and ∼20% of census tracts were considered rural. The average percent of households with limited access to healthy food was 6.4%. In adjusted models, every 5µg/m3) increase of PM2.5 was associated with 65% higher ADRD cumulative incidence (IRR=1.65; 95% CI: 1.30, 2.09), where PM2.5 at or below 12 µg/m3 is considered healthy. Compared to large urban census tracts, rural and small urban tracts had 10% (IRR=1.10; 95% CI: 1.00, 1.23) and 5% (IRR=1.05; 95% CI: 0.96, 1.16) higher ADRD, respectively. For every percent increase of the county population with limited access to healthy food, ADRD was 2% higher (IRR=1.02; 95% CI: 1.01, 1.04). CONCLUSIONS: Neighborhood environment features, such as higher air pollution levels, were associated with higher neighborhood ADRD incidence. The INLA-SPDE method could have broad applicability to data collected across disparate spatial scales. https://doi.org/10.1289/EHP13183.

Blockade of nociceptive sensory afferent activity of the rat knee joint by the bradykinin B2 receptor antagonist fasitibant.

OBJECTIVE: The aim of this study was to determine in intact and inflamed knee joints of the rat, the effect of the bradykinin (BK) B2 receptor antagonist fasitibant (MEN16132) on nociceptor mechanosensitivity and hyperalgesia. METHODS: Joint afferent sensory fibers of the medial articular nerve of anesthetized animals were electrophysiologically recorded, measuring nerve impulse activity evoked by passive innocuous and noxious movements of the joint, in intact and kaolin and carrageenan-injected joints. Knee joints of rats were also acutely inflamed by intra-articular injection of carrageenan alone. Long term duration of fasitibant antinociceptive effects were behaviorally evaluated using the incapacitance test. RESULTS: BK (100 µM) injected into the saphenous artery, induced excitation and sensitization of multi- and single unit recordings. Fasitibant (300 µM) injected prior to BK, reduced its excitatory effects as well as the overall increase of movement-evoked activity resulting from repeated injections of BK. Fasitibant did not affect movement-evoked activity of sensory fibers of intact, non-inflamed knee joints. Intra-articular fasitibant (100 µg/knee) significantly reduced the carrageenan-induced inflammatory hyperalgesia measured with the incapacitance test up to four days after treatment. This antinociceptive effect was not obtained with systemic endovenous injection of the drug. CONCLUSIONS: Fasitibant prevents B2 receptor-mediated activation and sensitization of peripheral joint afferents and the ensuing inflammatory hyperalgesia, and may be a useful, novel drug for arthritis pain treatment.

Synovial fluid levels of bradykinin correlate with biochemical markers for cartilage degradation and inflammation in knee osteoarthritis.

OBJECTIVE: To determine the content of bradykinin (BK) and markers of cartilage degradation and inflammation in the synovial fluid (SF) of patients with knee osteoarthritis (OA), and to evaluate correlations with biomarkers or clinical parameters. METHODS: SFs were obtained from 30 patients with knee OA. Levels of basal and generated BK, cartilage oligomeric matrix protein (COMP), interleukin (IL) 1, IL-6, IL-8 and matrix metalloprotease (MMP) 1, MMP-3, MMP-13 and sulfated glycosaminoglycans (GAGs) were measured by enzyme-linked immunosorbent assay (ELISA) or colorimetric assays. RESULTS: The mean concentration of basal BK (in the presence of peptidase and protease inhibitors to avoid degradation and de novo formation of BK) was 422 pg/ml (95% confidence interval, CI, 281-563) whereas that of in vitro generated BK (in the presence of peptidase inhibitors SFs were incubated 60 min at 37°C to measure the potential capability to generate BK) was 3427 pg/ml (2591-4264). The content of MMP-13, IL-1α, and IL-1ß was under assay sensitivity. Basal BK levels positively correlated (Spearman's rank correlation) with GAGs (40 µg/ml, 26-54, r = 0.4834, P = 0.0308) and IL-6 (553 pg/ml, 171-935, r = 0.3946, P = 0.0377) similarly to the generated BK (GAGs, r = 0.4563, P = 0.0431; IL-6, r = 0.5605, P = 0.0019). Statistical analysis of basal BK and biomarkers was significant (P = 0.0483). When applying a stepwise logistic regression analysis considering biomarkers together with clinical parameters, results indicated that K/L radiographic OA grade and COMP improved the model (P = 0.0032). CONCLUSION: The presence of BK in the knee OA SF and its correlations with cartilage degradation and inflammation markers of OA support its participation in OA pathology.

Safety of intra-articular hip injection of hyaluronic acid products by ultrasound guidance: an open study from ANTIAGE register.

OBJECTIVE: We developed a standardized technique for ultrasound guided intra-articular injection of the hip joint with the purpose of extending routine intra-articular injection of hyaluronans and steroids to the hip, as commonly used in the knee. In this article we report the safety of this technique in an extended series of patients. PATIENTS AND METHODS: Patients were injected supine with an anterosuperior approach under ultrasound guidance. The Us probe is applied with a target device for biopsy. RESULTS: The standardised technique was used to inject 1906 patients with 4002 injections of hyaluronan products over a four-year period. The treatment was well tolerated with few, and exclusively local, side effects. CONCLUSIONS: The administration of hyaluronans under ultrasound-guided intra-articular injection is a safe technique for treatment of rheumatic diseases of the hip.

Lost alpha Faraday cup foil noise characterization during Joint European Torus plasma post-processing analysis.

Capacitive plasma pickup is a well-known and difficult problem for plasma-facing edge diagnostics. This problem must be addressed to ensure an accurate and robust interpretation of the real signal measurements vs noise. The Faraday cup fast ion loss detector array of the Joint European Torus (JET) is particularly prone to this issue and can be used as a testbed to prototype solutions. The issue of separation and distinction between warranted fast ion signal and electromagnetic plasma noise has traditionally been solved with hardware modifications, but a more versatile post-processing approach is of great interest. This work presents post-processing techniques to characterize the signal noise. While hardware changes and advancements may be limited, the combination with post-processing procedures allows for more rapid and robust analysis of measurements. The characterization of plasma pickup noise is examined for alpha losses in a discharge from JET's tritium campaign. In addition to highlighting the post-processing methodology, the spatial sensitivity of the detector array is also examined, which presents significant advantages for the physical interpretation of fast ion losses.

Neighborhood characteristics and dementia symptomology among community-dwelling older adults with Alzheimer's disease.

Background: Neuropsychiatric symptoms (NPSs) lead to myriad poor health outcomes among individuals with Alzheimer's disease (AD). Prior studies have observed associations between the various aspects of the home environment and NPSs, but macro-level environmental stressors (e.g., neighborhood income) may also disrupt the neuronal microenvironment and exacerbate NPSs. Yet, to our knowledge, no studies have investigated the relationship between the neighborhood environment and NPSs. Methods: Using 2010 data among older adults with AD collected from a sample of the South Carolina Alzheimer's Disease Registry, we estimated cross-sectional associations between neighborhood characteristics and NPSs in the overall population and by race/ethnicity. Neighborhood measures (within a 1/2-mile radius of residence) came from the American Community Survey and Rural Urban Commuting Area Code. We categorized median household income into tertiles: < $30,500, $30,500-40,000, and > $40,000, and rurality as: rural, small urban, and large urban. Residential instability was defined as the percent of residents who moved within the past year. NPSs were defined using the Neuropsychiatric Inventory Questionnaire that included the composite measure of all 12 domains. Adjusting for age, sex/gender, race/ethnicity, and caregiver educational attainment, we used negative binomial regression to estimate prevalence ratios (PR) and 95% confidence intervals (CI) for NPSs by neighborhood characteristics. Results: Among 212 eligible participants, mean age was 82 ± 8.7 years, 72% were women, and 55% non-Hispanic (NH)-Black. Individuals with AD living in < $30,500 vs. > $40,000 income neighborhoods had a 53% (PR = 1.53; 95% CI = 1.06-2.23) higher prevalence of NPSs while individuals living in rural vs. large urban neighborhoods had a 36% lower prevalence of NPSs (PR = 0.64; 95% CI = 0.45-0.90), after adjustment. We did not observe an association between residential instability and NPSs (PR = 0.92; 95% CI = 0.86-1.00); however, our estimates suggested differences by race/ethnicity where NH-White older adults living in residential instable areas had lower NPSs (PR = 0.89; 95% CI = 0.82-0.96) compared to NH-Black older adults (PR = 0.96; 95% CI = 0.86-1.07). Discussion: Across racial/ethnic groups, individuals with AD had more symptomology when living in lower income areas. Pending replication, intervention efforts should consider resource allocation to high-need neighborhoods (e.g., lower income), and studies should investigate underlying mechanisms for this relationship.

Fusion product measurements by nuclear diagnostics in the Joint European Torus deuterium-tritium 2 campaign (invited).

A new deuterium-tritium experimental, DTE2, campaign has been conducted at the Joint European Torus (JET) between August 2021 and late December 2021. Motivated by significant enhancements in the past decade at JET, such as the ITER-like wall and enhanced auxiliary heating power, the campaign achieved a new fusion energy world record and performed a broad range of fundamental experiments to inform ITER physics scenarios and operations. New capabilities in the area of fusion product measurements by nuclear diagnostics were available as a result of a decade long enhancement program. These have been tested for the first time in DTE2 and a concise overview is provided here. Confined alpha particle measurements by gamma-ray spectroscopy were successfully demonstrated, albeit with limitations at neutron rates higher than some 1017 n/s. High resolution neutron spectroscopy measurements with the magnetic proton recoil instrument were complemented by novel data from a set of synthetic diamond detectors, which enabled studies of the supra-thermal contributions to the neutron emission. In the area of escaping fast ion diagnostics, a lost fast ion detector and a set of Faraday cups made it possible to determine information on the velocity space and poloidal distribution of the lost alpha particles for the first time. This extensive set of data provides unique information for fundamental physics studies and validation of the numerical models, which are key to inform the physics and scenarios of ITER.