Structural and magnetic studies of the frustratedS = 1 kagome magnet NH4Ni2Mo2O10H3.

The strong geometric frustration of the kagome antiferromagnets (KAFMs) can destabilise conventional magnetic order and lead to exotic electronic states, such as the quantum spin-liquid state observed in someS=12KAFM materials. However, the ground state ofS = 1 KAFM systems are less well understood. Spin nematic phases and valence bond solid ground states have been predicted to form but a paucity of experimental realisations restricts understanding. Here, theS = 1 KAFM NH4Ni2Mo2O10H3is presented, which has the 3-fold symmetry of the kagome lattice but significant site depletion, with∼64%site occupancy. Frustration and a competition between exchange interactions are evidenced through the suppression of order below the Weiss temperature|θW|and observation of ferromagnetic and antiferromagnetic characteristics in the magnetisation data. A semi spin glass ground state is predicted based on the ac-field frequency dependence of the magnetic transition and ferromagnetic signal.

Meta-analysis of the effects of furosemide combined with hydration therapy on contrast-induced acute kidney injury after coronary intervention.

OBJECTIVE: A meta-analysis was performed to evaluate the effect of furosemide combined with hydration therapy on the incidence and prognosis of contrast-induced acute kidney injury (CI-AKI) in patients after coronary intervention. MATERIALS AND METHODS: Through the PubMed, EMBASE, Cochrane Library and Web of Science databases, all relevant literature from database establishment until October 1, 2020, was retrieved and screened. Quality evaluation was performed using the risk of bias evaluation tool recommended by the Cochrane Collaboration network, data extraction was performed based on pre-selected effect indicators, and statistics were calculated using Review Manager 5.3 analysis software. RESULTS: A total of 2084 patients in 9 studies were included in the meta-analysis. The results showed that furosemide combined with hydrotherapy had no effect on the incidence of CI-AKI (OR = 0.85, 95% CI [0.46, 1.60], p = 0.62) and can significantly decrease the incidence of major adverse cardiovascular events (MACEs) (OR = 0.43, 95% CI [0.27, 0.67], p = 0.0003) and mortality (OR = 0.24, 95% CI [0.08, 0.79], p = 0.02) in patients. However, it had no significant impact on the need for postoperative dialysis treatment, postoperative creatinine level or length of hospital stay. CONCLUSIONS: Furosemide combined with hydration therapy has no significant effect on the incidence of CI-AKI in patients after coronary intervention but can reduce the incidence of MACEs and mortality, thereby providing clinical benefits.

[Effects of remote ischemic preconditioning on contrast-induced acute kidney injury after percutaneous coronary intervention in patients with chronic total occlusion].

Objective: To investigate the effect of remote ischemic preconditioning (RIPC) on contrast-induced acute kidney injury (CI-AKI) in patients with chronic total occlusion (CTO) after percutaneous coronary intervention (PCI). Methods: A total of 282 patients undergoing PCI at Zhongda Hospital Affiliated to Southeast University between June 2017 and January 2019 were prospectively enrolled. The patients were randomly divided into RIPC group (n=142) and control group (n=140). CI-AKI was defined as an increase in level of cystatin C (CysC)≥10% above baseline at 24 h after contrast administration. Baseline characteristics and the incidence of CI-AKI were compared between the two groups. The multivariate logistic regression analysis was further used to analyze the independent risk factors of CI-AKI. Results: There were no significant differences in age, gender, smoking, hypertension, diabetes, stroke and old myocardial infarction, coronary artery bypass graft surgery, previous PCI history and laboratory test indicators, target vessel and pathological characteristics of CTO lesions, contrast agent dosage, J-CTO (Multicenter CTO Registry in Japan) score, SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score, PCI success rate and stent number between the two groups (P>0.05). The incidence of CI-AKI was significantly lower (18.3% vs 29.3%, P=0.036) in RIPC group than that of control group. Multivariate logistic analysis found that creatinine [odds ratio (OR)=1.018,95%CI: 1.006-1.030, P=0.003], CysC (OR=5.200, 95%CI:2.714-9.963, P<0.001),contrast agent dosage (OR=1.013,95%CI: 1.007-1.019, P<0.001) and J-CTO score (OR=1.834, 95%CI: 1.145-2.939, P=0.012) were independent risk factors of CI-AKI. However, RIPC was an independent protective factor of CI-AKI (OR=0.391, 95%CI: 0.199-0.765, P=0.006). Conclusion: RIPC before contrast agent administration prevents CI-AKI in CTO patients undergoing PCI.

Accelerated diversification correlated with functional traits shapes extant diversity of the early divergent angiosperm family Annonaceae.

A major goal of phylogenetic systematics is to understand both the patterns of diversification and the processes by which these patterns are formed. Few studies have focused on the ancient, species-rich Magnoliales clade and its diversification pattern. Within Magnoliales, the pantropically distributed Annonaceae are by far the most genus-rich and species-rich family-level clade, with c. 110 genera and c. 2,400 species. We investigated the diversification patterns across Annonaceae and identified traits that show varied associations with diversification rates using a time-calibrated phylogeny of 835 species (34.6% sampling) and 11,211 aligned bases from eight regions of the plastid genome (rbcL, matK, ndhF, psbA-trnH, trnL-F, atpB-rbcL, trnS-G, and ycf1). Twelve rate shifts were identified using BAMM: in Annona, Artabotrys, Asimina, Drepananthus, Duguetia, Goniothalamus, Guatteria, Uvaria, Xylopia, the tribes Miliuseae and Malmeeae, and the Desmos-Dasymaschalon-Friesodielsia-Monanthotaxis clade. TurboMEDUSA and method-of-moments estimator analyses showed largely congruent results. A positive relationship between species richness and diversification rate is revealed using PGLS. Our results show that the high species richness in Annonaceae is likely the result of recent increased diversification rather than the steady accumulation of species via the 'museum model'. We further explore the possible role of selected traits (habit, pollinator trapping, floral sex expression, pollen dispersal unit, anther septation, and seed dispersal unit) in shaping diversification patterns, based on inferences of BiSSE, MuSSE, HiSSE, and FiSSE analyses. Our results suggest that the liana habit, the presence of circadian pollinator trapping, androdioecy, and the dispersal of seeds as single-seeded monocarp fragments are closely correlated with higher diversification rates; pollen aggregation and anther septation, in contrast, are associated with lower diversification rates.

In situ study of sigma phase formation in Cr-Co-Ni ternary alloys at 800°C using the long duration experiment facility at Diamond Light Source.

The new long duration experiment facility on beamline I11 at Diamond Light Source has been used to study the kinetics of sigma phase formation in three Cr-Co-Ni alloys. Diffraction data acquired during in situ exposure at 800°C for 50 d showed progressive increases in the sigma fraction. This was accompanied by changes in the proportions of the other phases, which differed markedly between the alloys studied. These results demonstrate the capabilities of the long duration facility for the study of metallurgical phenomena over periods of months to years, a capability not previously available at a synchrotron source.

Symptom experiences in patients with advanced pancreatic cancer as reported during healthcare encounters.

Symptom management is one of the primary goals of care for advanced pancreatic cancer (APC) patients. The purpose of this study was to examine recorded healthcare encounters to better understand the symptom experiences of APC patients as told to healthcare providers (HCP). In this qualitative descriptive study, content analysis was used to analyze 37 transcripts of audio-recorded, naturally occurring encounters among APC patients, caregivers, and HCP. Transcripts were drawn from a larger randomized controlled study, which recruited advanced cancer patients and caregivers across the United States. Findings revealed that APC patients and caregivers experienced multiple troubling symptoms. Thirty-seven APC patients and 34 caregivers discussed 10 types of symptoms: pain, fatigue, abnormal bowel movements, decreased appetite, nausea and vomiting, sleeping problems, neurological problems, skin problems, psychological distress, and taste changes. The patients and caregivers discussed various aspects of the symptoms, including the nature of the symptoms, how the symptoms affected their lives, and the way they managed symptoms. Some symptoms were described as severe, life-changing, and highly distressing. HCP should be attuned to the wide variety of ways in which APC patients experience, manage, and live with symptoms. A systematic approach to address symptoms during encounters may improve care and efficiency.

Processing two-dimensional X-ray diffraction and small-angle scattering data in DAWN 2.

A software package for the calibration and processing of powder X-ray diffraction and small-angle X-ray scattering data is presented. It provides a multitude of data processing and visualization tools as well as a command-line scripting interface for on-the-fly processing and the incorporation of complex data treatment tasks. Customizable processing chains permit the execution of many data processing steps to convert a single image or a batch of raw two-dimensional data into meaningful data and one-dimensional diffractograms. The processed data files contain the full data provenance of each process applied to the data. The calibration routines can run automatically even for high energies and also for large detector tilt angles. Some of the functionalities are highlighted by specific use cases.

"I couldn't even talk to the patient": Barriers to communicating with cancer patients as perceived by nursing students.

Communication is closely related to safe practice and patient outcomes. Given that most clinicians fall into routines when communicating with patients, it is important to address communication issues early. This study explores Taiwanese nursing students' experiences of communication with patients with cancer and their families. Senior nursing students who had cared for cancer patients were recruited to participate in focus group interviews. These semi-structured interviews were recorded and transcribed for content analysis. Among the 45 participants, about 36% of them never received any communication training. Up to 76% of the participants stated that their communication with cancer patients was difficult and caused them emotional stress. Subsequent data analysis revealed four themes: disengagement, reluctance, regression and transition. Students' negative communication experiences were related to the patients' terminally ill situation; the students' lack of training, low self-efficacy and power status, poor emotional regulation, and cultural considerations. The findings of this study provide a deeper understanding of nursing students' communication experiences in oncology settings within the cultural context. Early and appropriate communication training is necessary to help students regulate their emotions and establish effective communication skills. Further studies are needed to examine the relationship among students' emotional labour, communication skills and outcomes.

Phenotypical and functional profiles of natural killer cells exhibiting matrix metalloproteinase-mediated CD16 cleavage after anti-HIV antibody-dependent activation.

Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) has been linked to protection from HIV infection and slower progression towards AIDS. However, antibody-dependent activation of NK cells results in phenotypical alterations similar to those observed on NK cells from individuals with progressive HIV infection. Activation of NK cells induces matrix metalloproteinase (MMP)-mediated cleavage of cell surface CD16. In the present study we assessed the phenotype and functional profile of NK cells exhibiting post-activation MMP-mediated CD16 cleavage. We found that NK cells achieving the highest levels of activation during stimulation exhibit the most profound decreases in CD16 expression. Further, we observed that educated KIR3DL1(+) NK cells from human leucocyte antigen (HLA)-Bw4-carrying donors exhibit larger decreases in CD16 expression post-activation than the KIR3DL1(-) NK cell subset containing cells educated via other inhibitory receptor/ligand combinations and non-educated NK cells. Lastly, we assessed the ex-vivo expression of CD16 on educated KIR3DL1(+) NK cells and the KIR3DL1(-) NK cell subset from HLA-Bw4-carrying HIV-uninfected and HIV-infected donors. Suggestive of in-vivo activation of KIR3DL1(+) NK cells during HIV infection, CD16 expression was higher on KIR3DL1(+) than KIR3DL1(-) NK cells in uninfected donors but similar on both subsets in HIV-infected donors. These results are discussed in the context of how they may assist with understanding HIV disease progression and the design of immunotherapies that utilize antibody-dependent NK cell responses.

Effects of tibolone on osteoarthritis in ovariectomized rats: association with nociceptive pain behaviour.

BACKGROUND: To investigate the role of the synthetic steroid tibolone in the progression of osteoarthritis (OA) and in nociceptive behaviour in an experimental rat model of OA and ovariectomy (OVX)-induced osteoporosis. METHODS: OA was induced in Wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. Osteoporosis was induced by bilateral OVX. Groups of animals were subjected to ACLT, OVX, sham or OVX + ACLT. In addition, two groups were subjected to OVX + ACLT surgeries and were orally administered 0.1 or 0.5 mg tibolone every other day for 14 consecutive weeks, starting 6 weeks after surgery. Nociceptive behaviours (secondary mechanical allodynia and weight-bearing distribution of the hind paws) were analysed prior to and every 3 weeks after surgery up to 24 weeks. At 24 weeks, histopathological studies were performed on the cartilage and synovial membranes of the knee joints, and bone metabolism was assessed by measuring serum concentrations of calcium, phosphorus and alkaline phosphatase. RESULTS: Rats undergoing ACLT or OVX + ACLT surgeries showed obvious OA changes in the joints. Animals subjected to ACLT + OVX and treated with tibolone had significantly less cartilage degeneration and synovitis and showed improved nociceptive tests compared with animals undergoing ACLT + OVX surgeries alone. OVX increased the severity of the ACLT-induced OA changes. There was a significant increase in serum alkaline phosphatase in the tibolone-treated ACLT + OVX groups. CONCLUSIONS: Treatment with tibolone attenuated the development of OA, concomitantly reduced nociception and increased serum alkaline phosphatase in ACLT + OVX rats.

Intra-articular injection of the selective cyclooxygenase-2 inhibitor meloxicam (Mobic) reduces experimental osteoarthritis and nociception in rats.

OBJECTIVE: To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes. METHODS: OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes. RESULTS: OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage. CONCLUSIONS: Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.

Network correlates of disease severity in multiple system atrophy.

OBJECTIVE: Multiple system atrophy (MSA), the most common of the atypical parkinsonian disorders, is characterized by the presence of an abnormal spatial covariance pattern in resting state metabolic brain images from patients with this disease. Nonetheless, the potential utility of this pattern as a MSA biomarker is contingent upon its specificity for this disorder and its relationship to clinical disability in individual patients. METHODS: We used [(18)F]fluorodeoxyglucose PET to study 33 patients with MSA, 20 age- and severity-matched patients with idiopathic Parkinson disease (PD), and 15 healthy volunteers. For each subject, we computed the expression of the previously characterized metabolic covariance patterns for MSA and PD (termed MSARP and PDRP, respectively) on a prospective single-case basis. The resulting network values for the individual patients were correlated with clinical motor ratings and disease duration. RESULTS: In the MSA group, disease-related pattern (MSARP) values were elevated relative to the control and PD groups (p < 0.001 for both comparisons). In this group, MSARP values correlated with clinical ratings of motor disability (r = 0.57, p = 0.0008) and with disease duration (r = -0.376, p = 0.03). By contrast, MSARP expression in the PD group did not differ from control values (p = 1.0). In this group, motor ratings correlated with PDRP (r = 0.60, p = 0.006) but not with MSARP values (p = 0.88). CONCLUSIONS: MSA is associated with elevated expression of a specific disease-related metabolic pattern. Moreover, differences in the expression of this pattern in patients with MSA correlate with clinical disability. The findings suggest that the MSARP may be a useful biomarker in trials of new therapies for this disorder.

Network correlates of the cognitive response to levodopa in Parkinson disease.

OBJECTIVE: Cognitive dysfunction is common in Parkinson disease (PD), even early in its clinical course. This disease manifestation has been associated with impaired verbal learning performance as well as abnormal expression of a specific PD-related cognitive spatial covariance pattern (PDCP). It is not known, however, how this metabolic network relates to the cognitive response to dopaminergic therapy on the individual patient level. METHODS: We assessed treatment-mediated changes in verbal learning and PDCP expression in 17 patients with PD without dementia who underwent cognitive testing and metabolic imaging in the unmedicated and levodopa-treated conditions. We also determined whether analogous changes were present in 12 other patients with PD without dementia who were evaluated before and during the treatment of cognitive symptoms with placebo. RESULTS: Levodopa-mediated changes in verbal learning correlated with concurrent changes in PDCP expression (r = -0.60, p < 0.01). The subset of patients with meaningful cognitive improvement on levodopa (n = 8) exhibited concurrent reductions in PDCP expression (p < 0.01) with treatment; network modulation was not evident in the remaining subjects. Notably, the levodopa cognitive response correlated with baseline PDCP levels (r = 0.70, p = 0.002). By contrast, placebo did not affect PDCP expression, even in the subjects (n = 7) with improved verbal learning during treatment. CONCLUSIONS: These findings suggest that cognitive dysfunction in PD may respond to treatment depending upon the degree of baseline PDCP expression. Quantification of treatment-mediated network changes can provide objective information concerning the efficacy of new agents directed at the cognitive manifestations of this disease.

Abnormal metabolic brain networks in Tourette syndrome.

OBJECTIVES: To identify metabolic brain networks that are associated with Tourette syndrome (TS) and comorbid obsessive-compulsive disorder (OCD). METHODS: We utilized [(18)F]-fluorodeoxyglucose and PET imaging to examine brain metabolism in 12 unmedicated patients with TS and 12 age-matched controls. We utilized a spatial covariance analysis to identify 2 disease-related metabolic brain networks, one associated with TS in general (distinguishing TS subjects from controls), and another correlating with OCD severity (within the TS group alone). RESULTS: Analysis of the combined group of patients with TS and healthy subjects revealed an abnormal spatial covariance pattern that completely separated patients from controls (p < 0.0001). This TS-related pattern (TSRP) was characterized by reduced resting metabolic activity of the striatum and orbitofrontal cortex associated with relative increases in premotor cortex and cerebellum. Analysis of the TS cohort alone revealed the presence of a second metabolic pattern that correlated with OCD in these patients. This OCD-related pattern (OCDRP) was characterized by reduced activity of the anterior cingulate and dorsolateral prefrontal cortical regions associated with relative increases in primary motor cortex and precuneus. Subject expression of OCDRP correlated with the severity of this symptom (r = 0.79, p < 0.005). CONCLUSION: These findings suggest that the different clinical manifestations of TS are associated with the expression of 2 distinct abnormal metabolic brain networks. These, and potentially other disease-related spatial covariance patterns, may prove useful as biomarkers for assessing responses to new therapies for TS and related comorbidities.

The structural parameters for antimicrobial activity, human epithelial cell cytotoxicity and killing mechanism of synthetic monomer and dimer analogues derived from hBD3 C-terminal region.

Understanding the molecular mechanisms of antimicrobial peptide-membrane interactions is crucial in predicting the design of useful synthetic antimicrobial peptide analogues. Defensins are small (3-5 kDa) cysteine-rich cationic proteins which constitute the front line of host innate immunity. In this study, a series of eight 10 AA C-terminal analogues of hBD3 [sequence: RGRKXXRRKK, X = W, F, Y, V, L, I, H, C(Acm); net charge = +7, coded as W2, F2, Y2, V2, L2, I2, H2, and C2] and covalent V2-dimer [(RGRKVVRR)(2)KK] (18 AA, net charge = +11) were synthesized using solid phase peptide synthesis (SPPS) in Fmoc chemistry. Wild-type hBD3 was used as a control in all analyses. W2, V2, and especially Y2 showed high activity selectively against Gram-negative bacteria Pseudomonas aeruginosa in the concentration range of 4.3-9.7 microM. The covalent dimeric form of V2-monomer, V2-dimer, showed increased antibacterial killing compared to the monomeric form, V2-monomer. Cytotoxicity assays on a human conjunctival epithelial cell line (IOBA-NHC cells) showed that no change in viable cell number 24 h after constant exposure to all the eight peptide analogues even at concentrations up to 200 microg/ml. Fluorescence correlation spectroscopy (FCS) was used to study the interaction of these peptides against POPC vesicles (neutral; mammalian cell membrane mimic) and POPG vesicles (negatively charged; bacterial cell membrane mimic). Using FCS, significant aggregation and some leakage of Rhodamine dye were observed with POPG with Y2, W2 and V2 at the concentration of 5-10 mmicroM and no significant aggregation or disruption of vesicles was observed for all peptide analogues tested against POPC. V2-dimer induced more leakage and aggregation than the monomeric form. Overall, V2-dimer is the most effective antimicrobial peptide, with aggregation of POPG vesicles observed at concentrations as low as 1 microM. The concentration of 5-10 microM for Y2 from FCS correlated with the concentration of 5 microM (6.25 microg/ml), at which Y2 showed a cooperative increase in the activity. This suggests a structural transition of Y2 in the 2.5-5 microM concentration range resulting in the correlated increased antimicrobial activity. These results and the FCS together with previous NMR and molecular dynamics (MD) suggested that the charge density-based binding affinity, stable covalent dimerization, the ability to dimerize or even oligomerize and adopt a well-defined structure are important physicochemical properties distinguishing more effective cationic antimicrobial peptides.

Glucosamine sulfate reduces experimental osteoarthritis and nociception in rats: association with changes of mitogen-activated protein kinase in chondrocytes.

OBJECTIVE: To study the effects of oral glucosamine sulfate on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. METHODS: OA was induced in Wistar rats by anterior cruciate ligament transection (ACLT) of the right knee; the left knee was untreated. The OA+glucosamine group received oral glucosamine sulfate (250 mg/kg/day) in a 2-g wafer once a day for 10 consecutive weeks starting at week 5 after ACLT. The OA group was treated as above with 2-g wafers (placebo). The control group of naïve rats received 2-g wafers only. The glucosamine alone group comprised naïve rats receiving glucosamine sulfate only. Nociceptive behavior (mechanical allodynia and weight-bearing distribution of hind paws) during OA development was analyzed pre- and 3, 6, 9, 12, 15, and 18 weeks post-ACLT. Macroscopic and histologic studies were then performed on the cartilage and synovia. Immunohistochemical analysis was performed to examine the effect of glucosamine on expression of mitogen-activated protein kinases (MAPKs) in the articular cartilage chondrocytes. RESULTS: OA rats receiving glucosamine showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Glucosamine treatment also suppressed synovitis. Mechanical allodynia and weight-bearing distribution studies showed significant improvement in the OA+glucosamine group as compared to the OA group. Moreover, glucosamine attenuated p38 and c-Jun N-terminal kinase (JNK) but increased extracellular signal-regulated kinase 1/2 (ERK) expression in OA-affected cartilage. CONCLUSION: Our results indicate that treatment with oral glucosamine sulfate in a rat OA model (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cell p38 and JNK and increase of ERK expression.

Characterization of wax as a potential diffraction intensity standard for macromolecular crystallography beamlines.

A number of commercially available waxes in the form of thin disc samples have been investigated as possible diffraction intensity standards for macromolecular crystallography synchrotron beamlines. Synchrotron X-ray powder diffraction measurements show that beeswax offers the best performance of these waxes owing to its polycrystallinity. Crystallographic lattice parameters and diffraction intensities were examined between 281 and 309 K, and show stable and predictable thermal behaviour. Using an X-ray beam of known incident flux at lambda = 1 A, the diffraction power of two strong Bragg reflections for beeswax were quantified as a function of sample thickness and normalized to 10(10) photons s(-1). To demonstrate its feasibility as a diffraction intensity standard, test measurements were then performed on a new third-generation macromolecular crystallography synchrotron beamline.

Beamline I11 at Diamond: a new instrument for high resolution powder diffraction.

The performance characteristics of a new synchrotron x-ray powder diffraction beamline (I11) at the Diamond Light Source are presented. Using an in-vacuum undulator for photon production and deploying simple x-ray optics centered around a double-crystal monochromator and a pair of harmonic rejection mirrors, a high brightness and low bandpass x-ray beam is delivered at the sample. To provide fast data collection, 45 Si(111) analyzing crystals and detectors are installed onto a large and high precision diffractometer. High resolution powder diffraction data from standard reference materials of Si, alpha-quartz, and LaB6 are used to characterize instrumental performance.

Intra-articular magnesium sulfate (MgSO4) reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes.

OBJECTIVE: To study the effects of intra-articular injection of magnesium sulfate (MgSO(4)) on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. METHODS: OA was induced in Wistar rats with intra-articular injection of collagenase (500 U) in the right knee; the left knee was left untreated. In the OA+MgSO(4) group (n=7), the treated knee was injected with 500-microg (0.1-ml) MgSO(4) twice a week for 5 consecutive weeks starting at 1 week after collagenase injection; in the OA group (n=7), the same knee was injected with the same amount of physiological normal saline. In the MgSO(4) group (n=6), naïve rats received only MgSO(4) injections; in the control group (n=6), naïve rats received only physiological normal saline injections. Nociceptive behavior (mechanical allodynia and thermal hyperalgesia) on OA development was measured before and at 1, 2, 4, 6, and 8 weeks after collagenase injection, following which the animals were sacrificed. Gross morphology and histopathology were examined in the femoral condyles, tibial plateau, and synovia. Immunohistochemical analysis was performed to examine the effect of MgSO(4) on N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation (p-NR1) and apoptosis in the articular cartilage chondrocytes. RESULTS: OA rats receiving intra-articular MgSO(4) injections showed a significantly lower degree of cartilage degeneration than the rats receiving saline injections. MgSO(4) treatment also suppressed synovitis. Mechanical allodynia and thermal hyperalgesia showed significant improvement in the OA+MgSO(4) group as compared to the OA group. Moreover, MgSO(4) attenuated p-NR1 and chondrocyte apoptosis in OA-affected cartilage. CONCLUSIONS: Our results indicate that local intra-articular administration of MgSO(4) following collagenase injection in an experimental rat OA model (1) modulates chondrocyte metabolism through inhibition of cell NMDA receptor phosphorylation and apoptosis, (2) attenuates the development of OA, and (3) concomitantly reduces nociception.