Protocol update for a randomised controlled feasibility trial of exercise rehabilitation for people with postural tachycardia syndrome: the PULSE study.

BACKGROUND: The PULSE (PostUraL tachycardia Syndrome Exercise) study is a randomised controlled trial assessing the feasibility of conducting a multicentre RCT testing supervised exercise rehabilitation with behavioural and motivational support, compared to best-practice usual care, for people with Postural Tachycardia Syndrome (PoTS). The original trial protocol was published in BMC Pilot & Feasibility Studies (accessible at https://doi.org/10.1186/s40814-020-00702-1 ). The PULSE intervention consists of (1) individual assessment; (2) 12-week, twice-weekly, supervised exercise training; (3) behavioural and motivational support; and (4) guided lifestyle physical activity. The control intervention is best-practice usual care with a single 30-min, one-to-one practitioner appointment, and general advice on safe and effective physical activity. Sixty-two people (aged 18-60 years) with a confirmed diagnosis of PoTS will be invited to enrol on a feasibility RCT with an embedded qualitative study. The primary outcome will be feasibility; process-related measures will include eligibility, recruitment, randomisation and withdrawal rates, along with indicators of exercise programme adherence and acceptability. Secondary physiological, clinical and health-related outcomes will be assessed. In response to the COVID-19 pandemic, here we describe amendments to the trial protocol. METHODS: Restrictions imposed by the COVID-19 pandemic meant it was necessary to change the delivery of the PULSE and control interventions. These changes reflected the need to limit the risk of COVID-19 transmission in a clinical population, some of whom were at increased risk of contracting the virus and suffering serious illness. The major change was that the originally intended centre-based PULSE and control interventions would now be delivered remotely on-line. Subsequently, there were minor changes to the participant eligibility criteria. These decisions followed an on-line co-creation session with people affected by PoTS, and relevant public and professional stakeholders. CONCLUSIONS: We present an update of the original trial protocol in response to the COVID-19 pandemic. No participants were recruited to the original protocol; thus, results will reflect the on-line delivery of the intervention. PULSE will be the first randomised trial to assess the feasibility of conducting a definitive multi-centre RCT testing supervised on-line exercise rehabilitation with behavioural and motivational support, compared to best-practice usual care, for people with PoTS. TRIAL REGISTRATION: ISRCTN45323485 registered on 7 April 2020.

Synthesis and bioactivity of oxovanadium(IV)tetra(4-methoxyphenyl)porphyrinsalicylates.

Herein, we report the synthesis of metal complexes of vanadium with heterocyclic tetradentate ligand. Four N atoms of the heterocyclic porphyrin ring occupy the equatorial position and O atom of salicylic acid occupies the axial position in the complex. The thermal and chemical stability of the complexes were assessed by thermogravimetric analysis (TGA). The electrochemical behavior of the designed complexes is also studied using cyclic voltammetry. These complexes were then further evaluated for in vitro anticancer effects, anti-oxidant and behavior during acute toxicity of the synthesized porphyrin ligands and their oxovanadium(IV) complexes. The interaction of these metal complexes with radical scavenger 2,2-diphenyl-1-picrylhydrazyl (DPPH), encouraged us to study the anti-oxidant behavior of such complexes. The complex (SSA)VO(TMP) i.e. oxovanadium(IV)tetra(4-methoxyphenyl)porphyrinsulphosalicylate showed in vitro cytotoxic activity against glioblastoma (T986). It would be pertinent to mention here that the complex also did not exhibit any adverse toxicological symptoms and mortality in the target animal at the limit test dose level of 2000 mg/kg body weight.

Axially Ligated Zirconium(IV) Tetraphenylporphyrin: Synthesis, Characterization, and Biological Activity.

A series of 5,10,15,20-tetraphenylporphinatozirconium(IV) acetylacetonatophenolates containing different phenols as axial ligands [Zr(TPP)(Y)(X)] (TPP = 5,10.15,20-tetraphenyl-21H, 23H-porphine; Y = acac; X = different phenolates) have been synthesized and characterized by various spectrochemical studies. The complexes were also screened for antimicrobial activities. Antifungal activity of some adducts has been carried out against the fungal strain Sclerotium rolfsii. Most of the complexes have shown good antibacterial activity.

Synthesis and Spectroscopic Characterization of Some New Axially Ligated Indium(III) Macrocyclic Complexes and Their Biological Activities.

The synthesis and spectroscopic characterization of new axially ligated indium(III) porphyrin complexes were reported. Chloroindium(III) porphyrin (TPPIn-Cl) was obtained in good yield by treating the corresponding free base with indium trichloride. The action of the different phenols on chloroderivatives (TPPIn-Cl) led to the corresponding phenolato complexes (TPPIn-X). These derivatives were characterized on the basis of mass spectrometry, (1)H-NMR, IR, and UV-visible data. The separation and isolation of these derivatives have been achieved through chromatography. The spectral properties of free base porphyrin and its corresponding metallated and axially ligated indium(III) porphyrin compounds were compared with each other. A detailed analysis of UV-Vis, (1)H-NMR, and IR suggested the transformation from free base porphyrin to indium(III) porphyrin. Besides, (13)C-NMR and fluorescence spectra were also reported and interpreted. The stability of these derivatives has also been studied through thermogravimetry. The complexes were also screened for anticancerous activities. Among all the complexes, 4-MePhO-InTPP shows highest anticancerous activity. The title complexe, TPPIn-X (where X = different phenolates), represents a five-coordinate indium(III) porphyrin complex in a square-pyramidal geometry with the phenolate anion as the axial ligand.

Synthesis, Spectroscopic, and Biological Studies on New Zirconium(IV) Porphyrins with Axial Ligand.

A series of parasubstituted tetraphenylporphyrin zirconium(IV) salicylate complexes (SA/5-SSAZr(IV)RTPP, R = p-H, p-CH3, p-NO2, p-Cl, SA = salicylate, and 5-SSA = 5-sulfosalicylate) have been synthesized, and the spectral properties of free base porphyrins, their corresponding metallated, and axially ligated zirconium(IV) porphyrin compounds were compared with each other. A detailed analysis of ultraviolet-visible (UV-vis), proton nulcear magnetic resonance ((1)H NMR) spectroscopy, infrared (IR) spectroscopy, and elemental analysis suggested the transformation from free base porphyrins to zirconium(IV) porphyrins. The ability of the metal in this complex for extra coordination of solvent molecules was confirmed by ESI-MS spectra. Besides the fluorescence, cyclic voltammetry, and thermogravimetric studies, the complexes were also screened for antimicrobial and anticancer activities. Among all the complexes, 5-SSAZr(p-NO2TPP) shows high antibacterial activity.