The Therapeutic Effects of Noninvasive Brain Stimulation Combined with Cognitive Training in Elders with Alzheimer's Disease or Amnesic Mild Cognitive Impairment.

BACKGROUND: Recent studies have indicated that noninvasive brain stimulation combined with cognitive interval (NIBS-CI) improved cognitive function in people with Alzheimer's disease (AD) or Amnesic mild cognitive impairment (a-MCI). While previous interventions have demonstrated that a single targeted cognitive intervention can improve cognitive function, the outcomes of using both interventions simultaneously are less well-established. Therefore, this study aims to perform a meta-analysis to determine the effectiveness of NIBS-CI in treating cognitive impairment associated with AD and a-MCI, with the goal of obtaining novel insights into this combined intervention. METHODS: PubMed, Web of Science, ProQuest and Central Cochrane library databases were searched up to December 2022. The primary cognitive outcomes were extracted from the included article. A mean difference (MD) and standardized mean difference (SMD) with a 95% confidence interval were calculated by using random-effect models. RESULTS: Twelve studies with a total of 587 AD patients were included. The findings demonstrated that NIBS-CI significantly improved cognitive function of AD patients in cognitive outcomes (SMD = -0.52, 95%CI (-0. 93, -0.11)) and ADAS-COG (MD = -1.16, 95%CI (-1.69, -0.63)). The pooled results showed that NIBS-CI did not improve cognitive function of AD patients in short-time memory (SMD = 0.057, 95%CI (-0.13, 0.25), P = 0.56) and long-time memory (SMD = 0.001, 95%CI (-0.20, 0.20), P = 0.99). CONCLUSIONS: There is evidence for a positive effect of NIBS-CI on overall cognitive function of AD and a-MCI. Considering the limited sample size, it is important to interpret the findings related to memory with caution. To obtain more robust results, future studies should be conducted with larger sample sizes and incorporate objective neurophysiological and neuroimaging tools. These methodological enhancements will allow for a better understanding of the therapeutic targets and provide a more comprehensive assessment of the effects of NIBS-CI treatment.

A randomised controlled trial of dexmedetomidine for delirium in adults undergoing heart valve surgery.

Dexmedetomidine might reduce delirium after cardiac surgery. We allocated 326 participants to an infusion of dexmedetomidine at a rate of 0.6 µg kg-1 for 10 min and then at 0.4 µg.kg-1 .h-1 until the end of surgery; 326 control participants received comparable volumes of saline. We detected delirium in 98/652 (15%) participants during the first seven postoperative days: 47/326 after dexmedetomidine vs. 51/326 after placebo, p = 0.62, adjusted relative risk (95%CI) 0.86 (0.56-1.33), p = 0.51. Postoperative renal impairment (Kidney Disease Improving Global Outcomes stages 1, 2 and 3) was detected in 46, 9 and 2 participants after dexmedetomidine and 25, 7 and 4 control participants, p = 0.040. Intra-operative dexmedetomidine infusion did not reduce the incidence of delirium after cardiac valve surgery but might impair renal function.

Strength-fracture toughness synergy strategy in ostrich tibia's compact bone: Hierarchical and gradient.

Ostriches are the fastest bipeds in the world, but their tibias are very thin. How the thin tibia can withstand the huge momentum impacts of the heavy body during running? The present work revealed that the combination of hierarchical and gradient design strategies was the main reason for their high strength and fracture toughness. The microstructure of ostrich's tibias compact bone was self-assembled into the 6-level hierarchical structure from the hydroxyapatite (HAP) crystals, collagen fiber (sub-nano), mineralized collagen fiber (nano-), mineralized collagen fiber bundle (sub-micro), lamellae (micro-) and osteon (macro-scales). The most distinctive design in the ostrich compact bone was that the HAP crystals were embedded in collagen fibers as well as wrapped in the outer layer of mineral collagen fibers (MCFs) in the form of HAP nanocrystals, thus achieving a high degree of soft and hard combination from the nanoscale. The bending strength was gradient-structure dependent and up to 787.2 ± 40.5 MPa, 4 times that of a human's compact bone. The fracture toughness (KJc) is 5.8 ± 0.1 MPa m1/2. Several toughening mechanisms, such as crack deflection/twist, bridging, HAP fibers pulling-out, and fracture of the MCF bundles were found in the compact bone.

[Effects of tranexamic acid on the blood conservation and the long-term prognosis in pediatric patients undergoing repair for tetralogy of fallot].

Objective: To evaluate the perioperative tranexamic acid (TXA) on blood conservation in pediatric patients undergoing complete repair for tetralogy of fallot (TOF) and its impact on short-term or long-term adverse event and mortality. Methods: The study was a retrospective cohort study. From January 2009 to December 2010, 386 consecutive patients aged from 31 days to 8 years old, ASA physical status Ⅱ or Ⅲ, receiving primary complete repair for TOF in Fuwai Hospital were enrolled in the study. They were divided into two groups: the control group (n=161) and the TXA group (n=225), according to whether TXA was used during the operation. Patients and their families were followed up by telephone in the 8th-year after surgery. The amount of perioperative blood loss, allogeneic transfusion, short-term or long-term adverse event and mortality were recorded and analyzed. Results: The patients in the TXA group were associated with significant decreased 12 h and total postoperative blood loss compared with the control group [(7.8±0.3) ml/kg vs (8.8±0.3) ml/kg, t=2.412, P<0.05; and (14.0±0.6) ml/kg vs (17.0±0.7) ml/kg, t=3.141, P<0.05]. There were no significant differences in both the volume and incidence of red blood cell, plasma, and platelet transfusion, postoperatively (P>0.05). There were no significant differences in the incidence of reoperation for bleeding and prolonged mechanical ventilation, ICU stay, postoperative hospital length of stay, the short-term and long-term incidence of seizure, stroke, renal failure, deep venous thrombosis, pulmonary embolism and death between the two groups(P>0.05). Conclusion: TXA can decrease postoperative blood loss, but has little impact on the allogeneic blood transfusion, as well as the short-term or long-term adverse event and mortality in pediatric patients undergoing complete repair for TOF.

[Efficacy of coarctation resection and aortoplasty with autologous pulmonary artery patch strategy for treating coarctation of the aorta combined with hypoplastic aortic arch in infants].

Objective: To investigate the outcomes of coarctation resection and aortoplasty with autologous pulmonary artery patch for treating coarctation of the aorta combined with hypoplastic aortic arch in infants. Methods: Clinical data of 21 infants with coarctation of the aorta and hypoplastic aortic arch, who underwent coarctation resection and aortoplasty with autologous pulmonary artery patch in Fuwai hospital from January 2009 to June 2016 were retrospectively analyzed. The age of the patients was 4 (2, 5) months,and the body weight of the patients was (5.3±1.6) kg. The patients were followed up to observe the surgery effect. Results: No perioperative death and serious complications occurred. When the patients were discharged,the systolic blood pressure of the right upper limb was lower than the preoperative systolic blood pressure ((85.7±5.9) mmHg(1 mmHg=0.133 kPa) vs. (100.7±16.6) mmHg, P<0.001),and the systolic blood pressure of the right lower limb was higher than the preoperative systolic blood pressure ((98.7±13.3) mmHg vs. (85.6±20.8) mmHg, P<0.001). The pressure gradient of aortic coarctation detected by echocardiography was lower than the preoperative pressure gradient ((13.1±3.8) mmHg vs. (46.2±17.1) mmHg, P<0.001). No restenosis was detected by echocardiography at discharge. Follow-up data were obtained in 19 patients, and the follow-up time was 18 (8, 45) months.The patients grew well, and no death occurred. Restenosis occurred in 3 cases, 1 patient underwent aortic balloon dilatation and the remaining 2 patients were under follow up observation. Computed tomography angiography showed that the morphology of aortic arch was normal without signs of aortic aneurysm. Conclusion: Coarctation resection with autologous pulmonary artery patch aortoplastystrategy is considered as a safe and effective surgical method for management of infant coarctation with hypoplastic aortic arch, and this surgery method is related with satisfactory early and mid-term outcomes in this patient cohort.

Loss of labelling efficiency caused by carotid stent in pseudocontinuous arterial spin labelling perfusion study.

AIM: To elucidate the cause of cerebral hypoperfusion on the stent placement side after carotid artery stent placement (CAS) measured by pseudocontinuous arterial spin labelling (PCASL) perfusion imaging. MATERIALS AND METHODS: Consecutive patients with symptomatic internal carotid artery stenosis receiving CAS were included in the study. Cerebral blood flow (CBF) was measured by PCASL perfusion imaging at 3 T magnetic resonance imaging (MRI) the day before and 3 days after the procedure. Changes in cerebral haemodynamics after CAS were assessed. RESULTS: Twenty-two patients were included; 17 patients had increased or stationary CBF after CAS and five patients had significantly reduced CBF on the stenting side after CAS whereas CBF increased on the contralateral side. High stent position was noticed in the five patients. After labelling plane adjustment to avoid labelling on the stent, no more cerebral hypoperfusion was noticed. CONCLUSION: When using PCASL perfusion imaging to monitor post-stenting CBF, the stent may cause an artefact that leads to a low CBF in the territory of the stented vessel. Routinely adding a fast T2 star gradient-echo echo-planar-imaging covering the upper neck region before PCASL perfusion imaging to identify the stent position and avoid the stent-related artefact is recommended.

Risk factors for treatment default in close contacts with latent tuberculous infection.

OBJECTIVE: 1) To characterize risk factors for non-completion of latent tuberculous infection treatment (LTBIT), and 2) to assess the impact of LTBIT regimens on subsequent risk of tuberculosis (TB). METHODS: Close contacts of adults aged ⩾15 years with pulmonary TB were prospectively enrolled in a multi-center study in the United States and Canada from January 2002 to December 2006. Close contacts of TB patients were screened and cross-matched with TB registries to identify those who developed active TB. RESULTS: Of 3238 contacts screened, 1714 (53%) were diagnosed with LTBI. Preventive treatment was recommended in 1371 (80%); 1147 (84%) initiated treatment, of whom 723 (63%) completed it. In multivariate analysis, study site, initial interview sites other than a home or health care setting and isoniazid preventive treatment (IPT) were significantly associated with non-completion of LTBIT. Fourteen TB cases were identified in contacts, all of whom initiated IPT: two TB cases among persons who received ⩾6 months of IPT (66 cases/100 000 person-years [py]), and nine among those who received 0-5 months (median 2 months) of IPT (792 cases/100 000 py, P < 0.001); data on duration of IPT were not available for three cases. CONCLUSION: Only 53% (723/1371) of close contacts for whom IPT was recommended actually completed treatment. Close contacts were significantly less likely to complete LTBIT if they took IPT. Less than 6 months of IPT was associated with increased risk of active TB.

Effects of the histone methyltransferase inhibitor UNC0638 on histone H3K9 dimethylation of cultured ovine somatic cells and development of resulting early cloned embryos.

Aberrant hypermethylation of histone H3 lysine 9 (H3K9) may be involved in the developmental failure of cloned embryos. UNC0638 is a type of small molecule that can specifically inhibit the enzyme activity of histone methyltransferase EHMT2 and reduce the H3K9 dimethylation (H3K9me2) levels in cells. The objective of this study was to investigate the effect of UNC0638 in regulating H3K9me2 and development of cloned embryos. Results showed that UNC0638 could efficiently reduce H3K9me2 levels of cultured sheep foetal fibroblast cells in a concentration-dependent manner. Cloned embryos were subsequently produced from UNC0638-treated donor cells with down-regulated H3K9me2, but their in vitro development was not improved when compared with the control. Our study suggested that revision of the single histone H3K9me2 modification may be not sufficient for rescuing the development of cloned embryos. However, because of its low cellular toxicity, UNC0638 may still be a potential chemical that could be used in regulating epigenetic modification of cloned embryos.

Abnormal histone H3K9 dimethylation but normal dimethyltransferase EHMT2 expression in cloned sheep embryos.

The objective was to investigate the relationship between histone H3 lysine 9 (H3K9) dimethylation (me2) and the histone methyltransferase EHMT2 (also known as G9A) in ovine embryos cloned by somatic cell nuclear transfer (SCNT). Levels of H3K9me2 or EHMT2 were detected (with immunostaining) and compared between SCNT and IVF-derived preimplantation embryos. In one-cell embryos, SCNT zygotes had significantly higher levels of H3K9me2 and EHMT2 than IVF zygotes. In cloned embryos, H3K9me2 remained hypermethylated relative to IVF embryos at two-cell and late developmental stages (morula and blastocyst), with no difference (P > 0.05) between IVF and SCNT embryos in EHMT2 levels from two-cell to blastocyst stages. The EHMT2-specific inhibitor, BIX01294, reduced global H3K9me2 levels in cultured ovine cells or SCNT embryos, but it was not appropriate for somatic cell nuclear transfer because of its high cellular toxicity. We inferred that abnormal H3K9me2 hypermethylation in SCNT embryos may not completely arise from EHMT2 expression error.

Extension of a pilot study: impact from the cytochrome P450 2D6 polymorphism on outcome and costs associated with severe mental illness.

The influence of cytochrome P450 2D6 (CYP2D6) genetic variability was examined in psychiatric inpatients by evaluating adverse drug events (ADEs), hospital stays, and total costs over a 1-year period in an extension of a previously published brief report. One hundred consecutive psychiatric patients from Eastern State Hospital in Lexington, Kentucky, were genotyped for CYP2D6 expression. ADEs were evaluated by a neurologic rating scale, modified Udvalg for Kliniske Undersogelser Side Effect Rating Scale, or chart review. Information on total hospitalization days and total costs were gathered for a 1-year period. Forty-five percent of the patients received medications that were primarily dependent on the CYP2D6 enzyme for their elimination. When the analysis was restricted to just those patients in each group receiving medication heavily dependent on the CYP2D6 enzyme, the following were observed: (1) a trend toward greater numbers of ADEs from medications as one moved from the group with ultrarapid CYP2D6 activity (UM) to the group with absent CYP2D6 activity (PM); (2) the cost of treating patients with extremes in CYP2D6 activity (UM and PM) was on average $4,000 to $6,000 per year greater than the cost of treating patients in the efficient metabolizer (EM) and intermediate metabolizer (IM) groups; and (3) total duration of hospital stay was more pronounced for those in CYP2D6 PM group. Variance of hospital stays and costs calculated from these preliminary data suggests that 1,500 to 2,000 patients must be evaluated over at least a 1-year period to determine whether the CYP2D6 genetic variation significantly alters the duration of hospital stay and costs.

Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele.

The incidence of the S-mephenytoin polymorphism was compared in two Chinese ethnic groups, Han (n = 101) and Bai (n = 202) by phenotype and genotype analysis. The frequency of poor metabolizers (PMs) in Han vs. Bai subjects was 19.8% vs. 13.4%. Han subjects had a higher frequency of the mutant CYP2C19m1 allele (0.366 vs. 0.257, P < .01) and a lower frequency of the wild-type allele (0.559 vs. 0.688, P < .01) than Bai subjects, which is consistent with the difference in the frequencies of PMs between the two ethnic groups. This results in a lower percentage of homozygous wild-type extensive metabolizers of mephenytoin (EMs) in Han subjects than in Bai subjects (40% vs. 59%, P = .005). Therefore, Han subjects may be more susceptible than Bai subjects to the drugs metabolized by the CYP2C19 enzyme. Ratios of urinary S/R-mephenytoin in homozygous EMs were lower than those of heterozygous EMs for both Han and Bai subjects, which shows a gene-dosage effect. Genotype analysis identified all but one PM as homozygous or heterozygous for the two known mutant CYP2C19m1 and/or CYP2C19m2 alleles. A single Bai PM outlier was shown to be heterozygous for CYP2C19m1 and a new mutant CYP2C19 allele containing a single amino acid change of Arg433 --> Trp433. A genotyping test demonstrated that only this one individual carried this rare allele (frequency of 0.0025 in Bai subjects).