Iron-related dietary pattern increases the risk of poor cognition

© 2019 The Author(s). Introduction: High iron intake has been shown to be associated with poor cognition. We aimed to examine the association between iron-related dietary pattern (IDP) and cognitive function in Chinese adults. Method: Longitudinal study data from the China Health and Nutrition Survey (CHNS) during 1991-2006 were used (N = 4852, ≥55 years old). Dietary intake was obtained from a 3-day food record during home visits. Reduced rank regression was used to construct IDP with iron intake as a response variable. Cognitive function was assessed in 1997, 2000, 2004 and 2006. Multivariable mixed linear regression and logistic regression were used in the analyses. Results: IDP was characterised by high intake of fresh vegetable, wheat, legume, beverage, offal, rice and whole grain. High IDP intake was associated with poor cognition. In fully adjusted models, across the quartiles of IDP, the odds ratio (95% CI) for poor cognitive function were: 1.00, 1.06 (0.86-1.30), 1.24 (0.99-1.54), and 1.50 (1.17-1.93), respectively. There was a borderline significant interaction between IDP and meat intake (p interaction 0.085). The association between high IDP and poor cognition was only observed among those with no or low intake of meat. With the adjustment of carbohydrate or iron intake, the IDP and cognition association became non-significant. IDP was positively associated with lead intake. The association between IDP and poor cognition was partly mediated by lead intake. Conclusions: Iron-related dietary pattern is associated with poor cognition in Chinese adults, partly due to high intake of carbohydrate, iron and lead

Injectable Resin Technique as a Restorative Alternative in a Cleft Lip and Palate Patient: A Case Report

Objective: The objective of this study is to present a case report in which the injectable composite resin technique was used as a restorative alternative for dental re-anatomization in a patient with cleft lip and palate and aesthetic complaints. Materials and Methods: The treatment plan included the re-anatomization of the maxillary premolars and canines using a flowable composite resin. This resin was injected and cured through a transparent matrix, which was a copy of the diagnostic wax-up model. Some parameters such as application time and marginal adaptation were also observed when performing the restorations. Additionally, old composite resin restorations on the upper lateral incisors were replaced using the incremental technique with conventional resins, which helped to assess color stability and fracture/wear deterioration for both restorative techniques. Results: The clinical case report shows that the injectable technique was a simple and quick method for restoring the anatomy of teeth (shape and contour) in one session, since the injectable resin can be easily applied in interproximal areas without the need to manually sculpt the resin. In this case, no clinical, visual, or photographic differences were found in marginal discoloration, color stability, and fracture/wear deterioration for the two restorative techniques after one year of follow-up. Conclusions: The professional may have another clinical option for restorative treatment in the case of small re-anatomizations. In addition, the injectable technique seems to require less operator skill and chair time and better marginal adaptation in cases of small anatomical changes

Change in acetabular version after lumbar pedicle subtraction osteotomy to correct post-operative flat back: EOS® measurements of 38 acetabula

AbstractBackgroundAbnormalities in acetabular orientation can promote the development of hip osteoarthritis, femoro-acetabular impingement, or even acetabular cup malposition. The objective of the present study was to determine whether pedicle substraction osteotomy (PSO) to correct sagittal spinal imbalance affected acetabular orientation.HypothesisPSO performed to correct sagittal spinal imbalance affects acetabular orientation by changing the pelvic parameters.Materials and methodsThis was a descriptive study in which two observers measured the acetabular parameters on both sides in 19 patients (38 acetabula) before and after PSO for post-operative flat-back syndrome. Mean time from PSO to post-operative measurements was 19months. Measurements were taken twice at a 2-week interval, on standing images obtained using the EOS® imaging system and sterEOS® software to obtain 3D reconstructions of synchronised 2D images. Acetabular anteversion and inclination were measured relative to the vertical plane. Mean pre-PSO and post-PSO values were compared using the paired t-test, and P values lower than 0.05 were considered significant. To assess inter-observer and intra-observer reproducibility, we computed the intra-class correlation coefficients (ICCs).ResultsThe measurements showed significant acetabular retroversion after PSO, of 7.6° on the right and 6.5° on the left (P<0.001). Acetabular inclination diminished significantly, by 4.5° on the right and 2.5° on the left (P<0.01). Inclination of the anterior pelvic plane decreased by 8.4° (P<0.01). Pelvic incidence was unchanged, whereas sacral slope increased by 10.5° (P<0.001) and pelvic tilt decreased by 10.9° (P<0.001). The ICC was 0.98 for both inter-observer and intra-observer reproducibility.ConclusionChanging the sagittal spinal alignment modifies both the pelvic and the acetabular parameters. PSO significantly increases sacral slope, thus inducing anterior pelvic tilt with significant acetabular retroversion. The measurements obtained using sterEOS® showed good inter-observer and intra-observer reproducibility. To our knowledge, this is the first study of changes in acetabular version after PSO

Reactivity of Phenylacetylene toward Unsymmetrical Disilenes: Regiodivergent [2+2] Cycloaddition vs. CH Addition

We report the regiodivergent reaction of phenylacetylene with a selection of disilenes Tip2Si=SiTipR as well as bridged tetrasiladienes Tip2Si=SiTip−LU−SiTip=SiTip2 (Tip=2,4,6-iPr3C6H2, R=aryl groups; LU=arylene linkers). The regioselectivity of the [2+2] cycloaddition as determined by NMR spectroscopy and X-ray crystallography is shown to strongly depend on the nature of the substituent R. The small size of the substituents compared to the Tip groups in both cases suggests a change in mechanism between the substrates with only hydrogen in the ortho-positions of R and LU and those with either ortho-methyl groups or condensed aromatic rings. In contrast, the presence of catalytic quantities of base completely suppresses cycloaddtion in favor of the formal CH addition of phenylacetylene. Quenching reactions with either MeI or MeOH after the stoichiometric application of deprotonated phenylacetylene as well as NMR studies at low temperature prove the intermediacy of an alkynyl-substituted disilanyl lithium and thus suggest a carbolithiation pathway for the net CH addition

Personalized Cytokine-Directed Therapy With Tocilizumab for Refractory Immune Checkpoint Inhibitor-Related Cholangiohepatitis.

For patients with corticosteroid (CS)-refractory immune checkpoint inhibitor-related cholangiohepatitis (irCH), no consensus exists regarding treatment, and outcomes remain poor. We evaluated the possibility of personalized treatment according to the patient's cytokine profile and the immunohistopathologic assessment of the predominant immune infiltrate type of liver tissue. NSCLCs with CS-refractory irCH were analyzed by immunohistochemistry of liver biopsy specimen, serum cytokine panel, and assessment of peripheral blood mononuclear cell immune cell monitoring by mass cytometry. A total of three consecutive patients with irCH were identified. We found a predominant T-cell infiltrate and an interferon-gamma or T helper 1 proinflammatory cytokine profile. Here, we report for the first time that a T-cell-targeted therapy with the interleukin (IL)-6 receptor-neutralizing antibody tocilizumab, which inhibits signaling downstream of interferon-gamma and several other Janus kinase-dependent cytokines, is an effective single cytokine-directed therapy for CS-refractory irCH. Three patients with severe, CS-refractory irCH who were treated with tocilizumab were found to have persistent clinical and biological remission. Dysregulation of the IL-6/T-cell axis may contribute to the pathogenesis of CS-refractory irCH. Our observations suggest that IL-6 blockade seems to have promise in the treatment of CS-refractory irCH. The results from our three patients need to be confirmed in a larger patient population

Effectiveness of Allopurinol and Quercetin inclusion in a complex treatment of stable angina pectoris – peculiarities of biomarkers and homeostatic indices changes

Objective – to study the effectiveness of Allopurinol and Quercetin inclusion in a complex treatment of stable angina pectoris and peculiarities of biomarkers and homeostatic indices changes. Materials and Methods. 120 patients with the diagnosis of stable angina pectoris (SAP) and hyperuricemia (HU) were examined and three groups were formed: patients receiving a complex standard therapy (70 persons – 58,33%), patients receiving the standard therapy with addition of Allopurinol (23 persons – 19,17%), and patients receiving Quercetin in addition to the standard therapy (27 individuals – 22,50%). At the beginning of in-patient treatment and 6 months later during out-patient period all patients were clinically and laboratory examined (uric acid, total cholesterol (TC), triglycerides (TG), creatinine, NT-proBNP, С-reactive protein (СRP) and total testosterone (TT) in the blood serum). Results. Reduced content of TC and TG in the 1st, 2nd and 3rd groups of a complex treatment was found (р<0,05; р<0,001 and р<0,001 respectively) with prevailing effect of Allopurinol compared with the standard treatment. In case of standard treatment elevated initial plasma levels of uric acid and creatinine were found (р<0,001 in both cases) that can probable be explained by the loop diuretics administration to achieve euvolemic condition. The indicated effect of diuretics is compensated by Allopurinol and Quercetin inclusion in the therapy (р<0,001 by all indices) with prevailing effect of Allopurinol compared with the standard (р<0,05). In comparison with the standard therapy addition of both Allopurinol and Quercetin promotes reduction of NT-proBNP initial content (in both cases р<0,05). A positive dynamics concerning inflammatory activity with reduction of the initial concentration of CRP (р<0,001) is achieved only with addition of Allopurinol to the therapy. Conclusions. Addition of Allopurinol into the standard therapy of patients with SAP and asymptomatic HU promotes the dynamics of inflammatory activity with reduction of CRP initial concentration. Addition of Allopurinol or Quercetin to the standard therapy normalizes dyslipidemia by means of TC and TG content decreasing, improves renal function and reduces creatinine level with prevailing effect of Allopurinol, promotes reduction of NT-proBNP initial content. Inflammatory activity and dyslipidemia with elevated levels of TC and TG are the criteria for additional Allopurinol administration for the patients with SAP and asymptomatic HU

A severe case of neuro-Sjögren's syndrome induced by pembrolizumab.

The prevalence of connective tissue disease (CTD) induced by immune checkpoint inhibitors (CPIs) in the absence of pre-existing autoimmunity is unknown. We report the case of a melanoma patient treated for 8 months with pembrolizumab who developed a subacute ataxic sensory neuronopathy (SNN), including a right trigeminal neuropathy. Salivary gland biopsy showed inflammatory changes suggestive of Sjögren's syndrome, while brain MRI revealed enhancement of the right trigeminal ganglia. A high level of protein and pleocytosis was found in the cerebrospinal fluid, with negative cultures. Nerve conduction studies revealed the absence of sensory nerve action potentials in the upper and lower limbs and reduced motor responses in the upper limbs, fulfilling criteria for SNN. Blood tests revealed an important inflammatory syndrome, hemolytic anemia, elevation of total IgG levels and the presence of ANA autoantibodies specific to anti-SSA (52 and 60 kd). All these elements were absent before the initiation of the treatment with pembrolizumab. Initially, there was a clinical response following intravenous frontline methylprednisone, but the subacute relapse required the introduction of second-line treatment with intravenous immunoglobulins and then rituximab, which led to a quick clinical improvement. Herein, we describe the first case of a patient who developed a typical SNN as a complication of severe neuro-Sjögren's syndrome induced by pembrolizumab treatment

Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during chemotherapy of acute myeloid leukemia

<p>Abstract</p> <p>Background</p> <p>The molecular changes <it>in vivo </it>in acute myeloid leukemia cells early after start of conventional genotoxic chemotherapy are incompletely understood, and it is not known if early molecular modulations reflect clinical response.</p> <p>Methods</p> <p>The gene expression was examined by whole genome 44 k oligo microarrays and 12 k cDNA microarrays in peripheral blood leukocytes collected from seven leukemia patients before treatment, 2–4 h and 18–24 h after start of chemotherapy and validated by real-time quantitative PCR. Statistically significantly upregulated genes were classified using gene ontology (GO) terms. Parallel samples were examined by flow cytometry for apoptosis by annexin V-binding and the expression of selected proteins were confirmed by immunoblotting.</p> <p>Results</p> <p>Significant differential modulation of 151 genes were found at 4 h after start of induction therapy with cytarabine and anthracycline, including significant overexpression of 31 genes associated with p53 regulation. Within 4 h of chemotherapy the BCL2/BAX and BCL2/PUMA ratio were attenuated in proapoptotic direction. FLT3 mutations indicated that non-responders (5/7 patients, 8 versus 49 months survival) are characterized by a unique gene response profile before and at 4 h. At 18–24 h after chemotherapy, the gene expression of p53 target genes was attenuated, while genes involved in chemoresistance, cytarabine detoxification, chemokine networks and T cell receptor were prominent. No signs of apoptosis were observed in the collected cells, suggesting the treated patients as a physiological source of pre-apoptotic cells.</p> <p>Conclusion</p> <p>Pre-apoptotic gene expression can be monitored within hours after start of chemotherapy in patients with acute myeloid leukemia, and may be useful in future determination of therapy responders. The low number of patients and the heterogeneity of acute myeloid leukemia limited the identification of gene expression predictive of therapy response. Therapy-induced gene expression reflects the complex biological processes involved in clinical cancer cell eradication and should be explored for future enhancement of therapy.</p

Effect of axillary brachial plexus blockade on baroreflex-induced skin vasomotor responses: Assessing the effectiveness of sympathetic blockade

Background: The combination of laser Doppler flowmetry and non-invasive blood pressure monitoring allows the continuous observation of cutaneous vascular resistance (CVR). Continuous recording of unmodulated skin blood flow (SBF) is very sensitive to artefacts, rendering the method unreliable. In contrast, intermittent short lasting challenges of the CVR by cardiovascular autonomic reflexes may provide information about the responsiveness of the sympathetic nervous system in the skin. Methods: Eleven patients with below-wrist hand surgery (six males and five females; aged 35.2 ± 7.1 years) performed Valsalva maneuver following axillary blockade. Skin blood flow was continuously monitored on the forearm of the side axillary blockade, as well as on the contra-lateral forearm, which was used as the control. The responses were expressed as changes compared with the baseline level derived from a resting period of 30s. The maxima

Identification of the Rheumatoid Arthritis Shared Epitope Binding Site on Calreticulin

Background: The rheumatoid arthritis (RA) shared epitope (SE), a major risk factor for severe disease, is a five amino acid motif in the third allelic hypervariable region of the HLA-DRb chain. The molecular mechanisms by which the SE affects susceptibility to – and severity of- RA are unknown. We have recently demonstrated that the SE acts as a ligand that interacts with cell surface calreticulin (CRT) and activates innate immune signaling. In order to better understand the molecular basis of SE-RA association, here we have undertaken to map the SE binding site on CRT. Principal Findings: Surface plasmon resonance (SPR) experiments with domain deletion mutants suggested that the SE binding site is located in the P-domain of CRT. The role of this domain as a SE-binding region was further confirmed by a sulfosuccinimidyl-2-[6-(biotinamido)-2-(p-azido-benzamido) hexanoamido] ethyl-1,3-dithiopropionate (sulfo-SBED) photoactive cross-linking method. In silico analysis of docking interactions between a conformationally intact SE ligand and the CRT P-domain predicted the region within amino acid residues 217–224 as a potential SE binding site. Site-directed mutagenesis demonstrated involvement of residues Glu 217 and Glu 223- and to a lesser extent residue Asp 220- in cell-free SPR-based binding and signal transduction assays. Significance: We have characterized here the molecular basis of a novel ligand-receptor interaction between the SE and CRT. The interaction represents a structurally and functionally well-defined example of cross talk between the adaptive an