Triaceto-nitrile-(1,4,7-trimethyl-1,4,7-tri-aza-cyclonona-ne)cobalt(II) bis-(tetra-phenyl-borate).

The title cobalt(II) complex, [Co(C2H3N)3(C9H21N3)](C24H20B)2 or [(tacn)Co(NCMe)3][BPh4]2, has been characterized by single-crystal X-ray diffraction. It incorporates the well-known macrocyclic tacn (1,4,7-trimethyl-1,4,7-tri-aza-cyclo-nona-ne) ligand, which is coordinated facially to the metal center. The complex crystallizes in space group P21/c with Z = 4. The divalent cobalt ion exhibits a six-coordinate octa-hedral geometry by one tacn and three aceto-nitrile ligands. Two non-coordinating tetra-phenyl-borate (BPh4 -) anions are also present.

Safety and efficacy of acupuncture for mild cognitive impairment: a study protocol for clinical study.

Background: Mild cognitive impairment (MCI) is an intermediary condition between typical cognitive decline that occurs owing to aging and dementia. It is necessary to implement an intervention to slow the progression from MCI to Alzheimer's disease. This manuscript reports the protocol for a clinical trial on the effect of acupuncture in patients with MCI. Methods: The trial will be a randomized, prospective, parallel-arm, active-controlled trial. Sixty-four patients with MCI will be randomized to the Rehacom or acupuncture group (n = 32 each). The participants in the acupuncture group will receive electroacupuncture at GV24 (Shenting) and GV20 (Baihui) and acupuncture at EX-HN1 (Sishencong) once (30 min) a day, twice per week for 12 weeks. The patients in the Rehacom group will receive computerized cognitive rehabilitation using RehaCom software once (30 min) daily, twice weekly for 12 weeks. The primary outcome measure is the change in the Montreal Cognitive Assessment Scale score. The secondary outcome measures are the Geriatric Depression Scale, Alzheimer's Disease Assessment Scale-Korean version-cognitive subscale-3 scores, and European Quality of Life Five Dimensions Five Level Scale. The safety outcomes will include the incidence of adverse events, blood pressure, blood chemistry parameters, and pulse rate. The efficacy outcome will be assessed at baseline and at six weeks, 13 weeks, and 24 weeks after baseline. Discussion: The findings of this protocol will provide information regarding the effects of acupuncture on MCI. Clinical trial registration: https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&focus=reset_12&search_page=M&pageSize=10&page=undefined&seq=25579&status=5&seq_group=25579, KCT0008861.

Conformational and functional changes of the native neuropeptide somatostatin occur in the presence of copper and amyloid-ß.

The progression of neurodegenerative disorders can lead to impaired neurotransmission; however, the role of pathogenic factors associated with these diseases and their impact on the structures and functions of neurotransmitters have not been clearly established. Here we report the discovery that conformational and functional changes of a native neuropeptide, somatostatin (SST), occur in the presence of copper ions, metal-free amyloid-ß (Aß) and metal-bound Aß (metal-Aß) found as pathological factors in the brains of patients with Alzheimer's disease. These pathological elements induce the self-assembly of SST and, consequently, prevent it from binding to the receptor. In the reverse direction, SST notably modifies the aggregation profiles of Aß species in the presence of metal ions, attenuating their cytotoxicity and interactions with cell membranes. Our work demonstrates a loss of normal function of SST as a neurotransmitter and a gain of its modulative function against metal-Aß under pathological conditions.

Efficient Nicotinamide Adenine Dinucleotide Regeneration with a Rhodium-Carbene Catalyst and Isolation of a Hydride Intermediate.

Regeneration of nicotinamide adenine dinucleotide (NADH) has been the primary interest in the field of enzymatic transformation, especially associating oxidoreductases given the stoichiometric consumption. The synthesized carbene-ligated rhodium complex [(η5-Cp*)Rh(MDI)Cl]+ [Cp* = pentamethylcyclopentadienyl; MDI = 1,1'-methylenebis(3,3'-dimethylimidazolium)] acts as an exceptional catalyst in the reduction of NAD+ to NADH with a turnover frequency of 1730 h-1, which is over twice that of the higher catalytic activity of the commercially available catalyst [Cp*Rh(bpy)Cl]+ (bpy = 2,2'-bipyridine). Offsetting the contentious atmosphere currently taking place over the specific intermediate of the NADH regeneration, this study presents pivotal evidence of a metal hydride intermediate with a bis(carbene) ligand: a stable form of the rhodium hydride intermediate, [(η5-Cp*)Rh(MDI)H]+, was isolated and fully characterized. This enables thorough insight into the possible mechanism and exact intermediate structure in the NAD+ reduction process.

Light-promoted C-Cl bond-forming reductive elimination of a metal-metal bonded PdIII-PdIII complex.

The excited-state reductive elimination (RE) activities of a metal-metal bonded PdIII2 complex, [(2-phenylpyridyl)Pd(µ-acetate)Cl]2, are described. The C-Cl bond-forming RE reaction is accelerated by up to five orders of magnitude upon visible photoexcitation, which induces the Pd-Pd bond dissociation. This ligand field variation reduces the energy cost for intramolecular charge transfer (ICT) from coupling substrate to the metal center involved in the RE reaction. The correlation found between the ligand field and the RE activity indicates the ICT energy as a fundamental descriptor for RE reactions.

Factors contributing to cognitive improvement effects of acupuncture in patients with mild cognitive impairment: a pilot randomized controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) is generally regarded as the borderline between cognitive changes of aging and very early Alzheimer's disease (AD). It is important to develop easily available interventions to delay the progression of MCI to AD. We investigated factors contributing to the cognitive improvement effects of acupuncture to obtain data for developing optimized acupuncture treatments for MCI. METHODS: This outcome assessor-blinded, randomized controlled trial included a full analysis for comparing the efficacy of different acupuncture methods. Thirty-two participants with MCI (i.e., fulfilling the Peterson diagnostic criteria for MCI, K-MMSE scores of 20-23, and MoCA-K scale scores of 0-22) were randomly assigned to basic acupuncture (BA; GV20, EX-HN1, GB20, and GV24 for 30 min), acupoint specificity (AS; adding KI3 to BA), needle duration (ND; BA for 20 min), or electroacupuncture (EA; electrical stimulation to BA) groups (n=8/group) via 1:1:1:1 allocation and administered acupuncture once daily, three times a week for 8 weeks. The measured outcomes included scores on the Korean version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-K-cog), Korean version of the Montreal Cognitive Assessment scale (MoCA-K), Center for Epidemiological Studies-Depression Scale, Korean Activities of Daily Living scale, Korean Instrumental Activities of Daily Living scale, and European Quality of Life Five Dimension Five Level Scale. Outcome measurements were recorded at baseline (week 0), intervention endpoint (week 8), and 12 weeks after intervention completion (week 20). RESULTS: Twenty-five patients with MCI completed the trial (BA group, 8; AS group, 6; ND group, 5; EA group, 6). MoCA-K scores were significantly increased in the BA group compared with the ND (p=0.008, week 8-week 0) and EA groups (p=0.003, week 8-week 0; p=0.043, week 20-week 0). ADAS-K-cog scores were significantly decreased in the BA group compared with the ND group (p=0.019, week 20-week 0). CONCLUSIONS: The BA group showed significant improvement in cognitive function compared to the ND and EA groups. Electrical stimulation and needle duration may contribute to the cognitive improvement effects of acupuncture in patients with MCI. TRIAL REGISTRATION: Clinical Research Information Service; URL:cris.nih.go.kr .; unique identifier: KCT0003430 (registration date: January 16, 2019).

Ligand-field transition-induced C-S bond formation from nickelacycles.

Photoexcitation is one of the acknowledged methods to activate Ni-based cross-coupling reactions, but factors that govern the photoactivity of organonickel complexes have not yet been established. Here we report the excited-state cross-coupling activities of Ni(ii) metallacycle compounds, which display ∼104 times enhancement for the C-S bond-forming reductive elimination reaction upon Ni-centered ligand-field transitions. The effects of excitation energy and ancillary ligands on photoactivity have been investigated with 17 different nickelacycle species in combination with four corresponding acyclic complexes. Spectroscopic and computational electronic structural characterizations reveal that, regardless of coordinated species, d-d transitions can induce Ni-C bond homolysis, and that the reactivity of the resulting Ni(i) species determines the products of the overall reaction. The photoactivity mechanism established in this study provides general insights into the excited-state chemistry of organonickel(ii) complexes.

Correlation between the C-C Cross-Coupling Activity and C-to-Ni Charge Transfer Transition of High-Valent Ni Complexes.

High-valent Ni complexes have proven to be good platforms for diverse cross-coupling reactions that are otherwise difficult to be achieved with conventional low-valent catalysts. However, their reductive elimination (RE) activities are still significantly variable by up to 5 orders of magnitude, depending on the supporting ligand and oxidation state of the Ni center. To elucidate frontier molecular orbitals (FMOs) that determine the RE activity of the Ni center, the electronic structures of cycloneophyl (CH2C(CH3)2-o-C6H4) NiIII and NiIV complexes have been characterized by utilizing various transition metal-based spectroscopic techniques such as electronic absorption, magnetic circular dichroism, electron paramagnetic resonance, resonance Raman, and X-ray absorption spectroscopies. In combination with density functional theory computations, the spectroscopic analyses have shown that the energies of the C-to-Ni charge-transfer (CT) electronic transitions are strongly correlated to the rates of C-C bond-forming RE reaction. This correlation suggests that the kinetic barrier of the RE reaction is determined by energy cost for internal CT (ICT) from the coordinated carbon moiety to the Ni center, and that FMOs involved in the RE reaction and the C-to-Ni CT electronic transitions are essentially identical. This FMO determination has led us to discover that photoexcitation to the C-to-Ni CT excited states accelerates the C-C cross-coupling reaction by up to 105 times, as the CT electronic transition can substitute for the rate-determining ICT step of the RE reaction at the ground electronic state.

Add-on effect of kinesiotape in patients with acute lateral ankle sprain: a randomized controlled trial.

BACKGROUND: Evidence for the add-on effect of kinesiotape (KT) with acupuncture for treating ankle sprains remains insufficient. We assessed the add-on effect of KT on ankle sprains by comparing acupuncture combined with KT (AcuKT) with acupuncture alone in patients with acute lateral ankle sprain (ALAS). METHODS: This study was a multicenter, randomized controlled clinical trial that included a per-protocol analysis of the add-on effect of KT on ALAS. The randomization was software based and only the assessors were blinded. Sixty participants (20 each from three centers) with grade I or II ALAS were randomly assigned to acupuncture (n = 30) or AcuKT (n = 30) groups. Both groups received acupuncture treatment once daily, 5 days per week for 1 week. The AcuKT group received additional KT treatment. Visual analog scale (VAS) scores for pain and the Foot and Ankle Outcome Score (FAOS) were obtained, and edema measurements were performed at baseline (week 0), at the end of the intervention (week 1), and at 4 weeks after intervention (week 5). The European Quality of Life Five Dimension-Five Level Scale (EQ-5D-5 L) measurements were conducted at week 0, week 1, week 5, and week 26 after the intervention. The number of recurrent ankle sprains was determined at 4, 8, 12 and 26 weeks after the intervention. RESULTS: Fifty-six patients with ALAS completed the trial (AcuKT group, n = 27; acupuncture group, n = 29). There were significant changes in visual analog scale score (AcuKT, P < 0.001; acupuncture, P < 0.001), the FAOS (AcuKT, P < 0.001; acupuncture, P < 0.001), and EQ-5D-5 L measurements (AcuKT, P < 0.001; acupuncture, P < 0.001) within both groups. There were no significant differences between groups in terms of any outcome or in a subanalysis based on symptom severity. CONCLUSIONS: These results indicate that AcuKT did not show a positive add-on effect of KT with acupuncture in terms of pain reduction, edema, recovery of function, activities of daily living, quality of life or relapse of ALAS. TRIAL REGISTRATION: Clinical Research Information Service (cris.nih.go.kr), KCT0002257. Registered on 27 February 2017.

The effects of Kinesiotape on acute lateral ankle sprain: study protocol for a randomized controlled trial.

BACKGROUND: Ankle sprains are some of the most frequent injuries of the musculoskeletal system. However, there is no substantive evidence supporting which treatment strategy is superior. Taping with Kinesiotape (KT) is a new method that is used as an alternative to the more established taping and bracing techniques used for the prophylaxis and treatment of ankle sprains. The aim of this study is to examine the efficacy of KT on ankle sprain by comparing acupuncture combined with KT (AcuKT) with acupuncture alone in patients with acute lateral ankle sprains. METHODS/DESIGN: This study is a prospective, multi-center (DongShin University Gwangju Oriental Hospital, DongShin University Mokpo Oriental Hospital, and KyungHee Korean Medicine Hospital), outcome assessor-blinded, randomized controlled clinical trial with a 1:1 allocation ratio. Participants (n = 60) with a lateral ankle sprain occurring within 1 week of the study will be randomly assigned to either an acupuncture group (n = 10 at each center (total n = 30)) or an AcuKT group (n = 10 at each center (total n = 30)). The acupuncture group will receive acupuncture treatment at ST36, ST41, BL60, BL62, KI3, KI6, GB39, and GB40 once per day, 5 days per week (excluding Saturday and Sunday) for 1 week. The AcuKT group will receive acupuncture treatment at ST36, ST41, BL60, BL62, KI3, KI6, GB39, and GB40 and the ankle meridian tendino-musculature and a figure-of-eight shape form of KT treatment once per day, 5 days per week (excluding Saturday and Sunday) for 1 week. The primary outcome will be pain evaluation assessed according to a Visual Analogue Scale (VAS), while Foot and Ankle Outcome Score (FAOS), edema, European Quality of Life Five Dimension-Five Level Scale (EQ-5D-5 L) score, and number of recurrent ankle sprains will be considered as secondary outcome measures. VAS, FAOS, and edema measurements will be performed at baseline (before intervention), 5 days after the first intervention (i.e., at the end of the intervention), and 4 weeks after the completion of intervention. EQ-5D-5 L measurements will be conducted at baseline, 5 days after the first intervention, 4 weeks after the completion of intervention, and 26 weeks after the completion of intervention. The number of recurrent ankle sprains will be determined at 4, 8, 12, and 26 weeks after the completion of the intervention. DISCUSSION: This study will provide data regarding the efficacy of KT for the treatment of acute lateral ankle sprain. The results may lead to insights into the usefulness of KT in the treatment of acute lateral ankle sprain. TRIAL REGISTRATION: cris.nih.go.kr, ID: KCT0002257. Registered on 27 February 2017, and approved by the Ministry of Food and Drug Safety (Medical Device Clinical Trial Plan Approval #737).

Quantification of IDP-73152, a novel antibiotic, in plasma from mice, rats and humans using an ultra-high performance liquid chromatography/tandem mass spectrometry method for use in pharmacokinetic studies.

IDP-73152, a novel inhibitor of a bacterial peptide deformylase, was recently approved as a new, investigational drug in Korea for the clinical management of infections caused by Gram positive bacteria. The objective of this study was to develop/validate a simple and robust analytical method for the determination of IDP-73152 in plasma samples from rodents and humans, and to assess the feasibility of the assay for use in pharmacokinetic studies using animal models. Plasma samples were processed using a standard method for protein precipitation and an aliquot of the extract then injected onto an UHPLC-MS/MS system. The drug and IDP-117293, an internal standard, were analyzed in the positive ion-mode by electrospray ionization and quantified by monitoring the transition at m/z 555.2→245.2 for IDP-73152 and 563.3→253.1 for the internal standard, respectively. The lower and upper limit of the assay was determined to be 5 and 10000ng/ml, respectively, with an acceptable linearity (R>0.999) in the response-concentration relationship. Validation parameters, including accuracy, precision, dilution, recovery, matrix effect and stability were found to be within the acceptable ranges recommended by the assay validation guidelines of the United States FDA. The method was successfully applied to the quantification of IDP-73152 in plasma from mice/rats that had received a single oral administration of 80mg/kg IDP-73152, in the form of the mesylate salt. These findings suggest that the validated assay can be used in preclinical and clinical pharmacokinetic studies of IDP-73152.

Assessing the quality of reports about randomized controlled trials of scalp acupuncture treatment for vascular dementia.

BACKGROUND: This study aimed to evaluate the quality of reports about randomized controlled trials (RCTs) of scalp acupuncture (SA) for the treatment of vascular dementia (VD). METHOD: A systematic search of reports published through to December 2015 was performed in eight databases. The quality of RCTs that used SA as an intervention for VD was evaluated based on the 2010 Consolidated Standards for Reporting of Trials (CONSORT) and 2010 Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines. Thirteen items from the CONSORT guideline were scored to give an overall quality score (OQS, range 0-13), and a combined key methodological index score (MIS) (range 0-5) of five key methodological items was measured. The OQS of 17 items from the STRICTA guideline (range 0-17) was also measured. RESULTS: In total, 26 reports were evaluated. The median OQS based on the CONSORT guideline was 8 (minimum 5, maximum 11), and "trial design," "sample size," "ancillary analyses," and "harms" had a positive rate of less than 10%. The median MIS was 2 (minimum 0, maximum 5), with "allocation concealment and implementation," "blinding," and "intent-to-treat analysis" having a positive rate of less than 15%. The median OQS based on the STRICTA guideline was 12 (minimum 8, maximum 14), with "extent to which treatment was varied (1c)," "number of needle insertions per subject per session (2a)," and "setting and context of treatment (4b)" having a positive rate of less than 10%. CONCLUSIONS: The overall quality of reports on RCTs of SA treatment for VD was moderate to low. The quality of methodological items was markedly lower than that of other items. The CONSORT and STRICTA guidelines should be used more frequently to standardize the quality of RCT reports of SA treatment for VD.

Scalp acupuncture and electromagnetic convergence stimulation for patients with cerebral infarction: study protocol for a randomized controlled trial.

BACKGROUND: Scalp acupuncture (SA) and repetitive transcranial magnetic stimulation (rTMS) are effective for treating cerebral infarction. This study aims to examine the efficacy and safety of SA and electromagnetic convergence stimulation (SAEM-CS), which was developed through collaboration between conventional medical physicians and doctors who practice traditional Korean medicine. SAEM-CS was designed to improve function in patients with cerebral infarction, compared to the improvement after conventional stroke rehabilitation, SA, and rTMS therapeutic approaches. METHODS/DESIGN: This study is a prospective, outcome assessor-blinded, randomized controlled clinical trial with a 1:1:1:1 allocation ratio. Participants with motion or sensory disabilities caused by a first-time cerebral infarction (n = 60) that had occurred within 1 month of the study onset will be randomly assigned to control, SA, rTMS, or SAEM-CS groups. All groups will receive two sessions of conventional rehabilitation treatment per day. The SA group will receive SA on the upper limb area of MS6 and MS7 (at the lesional hemisphere) for 20 min, the rTMS group will receive low-frequency rTMS (LF-rTMS) treatment on the hot spot of the M1 region (motor cortex at the contralesional hemisphere) for 20 min, and the SAEM-CS group will receive LF-rTMS over the contralesional M1 region hot spot while receiving simultaneous SA stimulation on the lesional upper limb area of MS6 and MS7 for 20 min. SA, rTMS, and SAEM-CS treatments will be conducted once/day, 5 days/week (excluding Saturdays and Sundays) for 3 weeks, for a total of 15 sessions. The primary outcome will be evaluated using the Fugl-Meyer Assessment, while other scales assessing cognitive function, activities of daily living, walking, quality of life, and stroke severity are considered secondary outcome measures. Outcome measurements will be conducted at baseline (before intervention), 3 weeks after the first intervention (end of intervention), and 4 weeks after intervention completion. DISCUSSION: This study aims to explore the efficacy and safety of SAEM-CS on cerebral infarction. Collaborative research combined traditional Korean and conventional medicines, which can be useful in developing new treatment technologies. TRIAL REGISTRATION: KCT0001768 . Registered on 14 January 2016.