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BackgroundCoformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) was shown to prolong survival and slow functional decline in amyotrophic lateral sclerosis (ALS).ObjectiveDetermine whether PB/TURSO prolonged tracheostomy/ventilation-free survival and/or reduced first hospitalisation in participants with ALS in the CENTAUR trial.MethodsAdults with El Escorial Definite ALS ≤18 months from symptom onset were randomised to PB/ TURSO or placebo for 6 months. Those completing randomised treatment could enrol in an open-label extension (OLE) phase and receive PB/TURSO for ≤30 months. Times to the following individual or combined key events were compared in the originally randomised treatment groups over a period spanning trial start through July 2020 (longest postrandomisation follow-up, 35 months): death, tracheostomy, permanent assisted ventilation (PAV) and first hospitalisation.ResultsRisk of any key event was 47% lower in those originally randomised to PB/TURSO (n=87) versus placebo (n=48, 71% of whom received delayed-start PB/TURSO in the OLE phase) (HR=0.53; 95% CI 0.35 to 0.81; p=0.003). Risks of death or tracheostomy/PAV (HR=0.51; 95% CI 0.32 to 0.84; p=0.007) and first hospitalisation (HR=0.56; 95% CI 0.34 to 0.95; p=0.03) were also decreased in those originally randomised to PB/TURSO.ConclusionsEarly PB/TURSO prolonged tracheostomy/PAV-free survival and delayed first hospitalisation in ALS.Trial registration numberNCT03127514; NCT03488524.

An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS.

BackgroundSodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known.MethodsIn this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months. Participants were randomly assigned in a 2:1 ratio to receive sodium phenylbutyrate-taurursodiol (3 g of sodium phenylbutyrate and 1 g of taurursodiol, administered once a day for 3 weeks and then twice a day) or placebo. The primary outcome was the rate of decline in the total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) through 24 weeks. Secondary outcomes were the rates of decline in isometric muscle strength, plasma phosphorylated axonal neurofilament H subunit levels, and the slow vital capacity; the time to death, tracheostomy, or permanent ventilation; and the time to death, tracheostomy, permanent ventilation, or hospitalization.ResultsA total of 177 persons with ALS were screened for eligibility, and 137 were randomly assigned to receive sodium phenylbutyrate-taurursodiol (89 participants) or placebo (48 participants). In a modified intention-to-treat analysis, the mean rate of change in the ALSFRS-R score was -1.24 points per month with the active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% confidence interval, 0.03 to 0.81; P = 0.03). Secondary outcomes did not differ significantly between the two groups. Adverse events with the active drug were mainly gastrointestinal.ConclusionsSodium phenylbutyrate-taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Secondary outcomes were not significantly different between the two groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol in persons with ALS. (Funded by Amylyx Pharmaceuticals and others; CENTAUR ClinicalTrials.gov number, NCT03127514.).

Birth parents are the most stigmatized and least researched part of the adoption triad and they experience microaggressions from a number of sources. With the recent U.S. Supreme Court decision Dobbs v. Jackson Women's Health Organization, birth parents' needs and stories deserve to be elevated. Using the adoption microaggressions framework, this qualitative study examined birth parents' lived experiences and the microaggressions they have heard and internalized. Microaggressions specific to birth parents and the adoption process were identified. The most frequently occurring microaggressions against birth parents included: Shameful Inadequate, Institutional Microaggressions, and Phantom Birth Parents. Implications for counseling and training are provided for working with members of the adoption triad. [ABSTRACT FROM AUTHOR]

Values integration is the process by which counselors strengthen their commitment to the values of the counseling profession in the service of their clients. While literature over the last decade has brought attention to values integration in counselor training, there has been little attention to this process concerning new professionals. Clinical supervisors are positioned to support new professionals in the values integration process but may need strategies. This manuscript offers suggested approaches for supervisors to implement with new counselors to engage in values integration. A case vignette illustrating values integration is included. [ABSTRACT FROM AUTHOR]

Three related series of peri-substituted bis(tellurides) bearing naphthalene, acenaphthene and acenaphthylene backbones (Nap/Acenap/Aceyl(TeY)2 (Nap=naphthalene-1,8-diyl N; Acenap=acenaphthene-5,6-diyl A; Aceyl=acenaphthylene-5,6-diyl Ay; Y=Ph 1; Fp 2; Tol 3; An- p­ 4; An- o­ 5; Tp 6; Mes 7; Tip 8) have been synthesised and their solid-state structures determined by X-ray crystallography. Molecular conformations were classified as a function of the two C9-C-Te-C(Y) dihedral angles ( θ); in the solid all members adopt AB or CC t configurations, with larger Te(aryl) moieties exclusively imposing the CC t variant. Exceptionally large J(125Te,125Te) spin-spin coupling constants between 3289-3848 Hz were obtained for compounds substituted by bulky Te(aryl) groups, implying these species are locked in a CC t-type conformation. In contrast, compounds incorporating smaller Te(aryl) moieties are predicted to be rather dynamic in solution and afford much smaller J values (2050-2676 Hz), characteristic of greater populations of AB conformers with lower couplings. This conformational dependence of through-space coupling is supported by DFT calculations. [ABSTRACT FROM AUTHOR]

Spin – spin coupling constants (SSCCs) provide valuable information about the environment surrounding coupled atomic nuclei within a molecule and are becoming an increasingly important tool for analysing structures. In their Full Paper on page 3613 ff., J. D. Woollins et al. use X ‐ ray crystallography, NMR spectroscopy and DFT calculations to investigate the conformational dependence of through ‐ space J(125Te,125Te) spin – spin coupling in three related series of peri ‐ substituted bis(tellurides). [ABSTRACT FROM AUTHOR]

Three related series of peri-substituted bis(tellurides) bearing naphthalene, acenaphthene and acenaphthylene backbones (Nap/Acenap/Aceyl(TeY)2 (Nap = naphthalene-1,8-diyl N; Acenap = acenaphthene-5,6-diyl A; Aceyl = acenaphthylene-5,6-diyl Ay; Y = Ph 1; Fp 2; Tol 3; An-p- 4; An-o- 5; Tp 6; Mes 7; Tip 8) have been synthesised and their solid-state structures determined by X-ray crystallography. Molecular conformations were classified as a function of the two C9-C-Te-C(Y) dihedral angles (θ); in the solid all members adopt AB or CCt configurations, with larger Te(aryl) moieties exclusively imposing the CCt variant. Exceptionally large J((125)Te,(125)Te) spin-spin coupling constants between 3289-3848 Hz were obtained for compounds substituted by bulky Te(aryl) groups, implying these species are locked in a CCt-type conformation. In contrast, compounds incorporating smaller Te(aryl) moieties are predicted to be rather dynamic in solution and afford much smaller J values (2050-2676 Hz), characteristic of greater populations of AB conformers with lower couplings. This conformational dependence of through-space coupling is supported by DFT calculations., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)