Prevention and early treatment of the long-term physical effects of COVID-19 in adults: design of a randomised controlled trial of resistance exercise-CISCO-21.

BACKGROUND: Coronavirus disease-19 (COVID-19) infection causes persistent health problems such as breathlessness, chest pain and fatigue, and therapies for the prevention and early treatment of post-COVID-19 syndromes are needed. Accordingly, we are investigating the effect of a resistance exercise intervention on exercise capacity and health status following COVID-19 infection. METHODS: A two-arm randomised, controlled clinical trial including 220 adults with a diagnosis of COVID-19 in the preceding 6 months. Participants will be classified according to clinical presentation: Group A, not hospitalised due to COVID but persisting symptoms for at least 4 weeks leading to medical review; Group B, discharged after an admission for COVID and with persistent symptoms for at least 4 weeks; or Group C, convalescing in hospital after an admission for COVID. Participants will be randomised to usual care or usual care plus a personalised and pragmatic resistance exercise intervention for 12 weeks. The primary outcome is the incremental shuttle walks test (ISWT) 3 months after randomisation with secondary outcomes including spirometry, grip strength, short performance physical battery (SPPB), frailty status, contacts with healthcare professionals, hospitalisation and questionnaires assessing health-related quality of life, physical activity, fatigue and dyspnoea. DISCUSSION: Ethical approval has been granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (REC) (reference: GN20CA537) and recruitment is ongoing. Trial findings will be disseminated through patient and public forums, scientific conferences and journals. TRIAL REGISTRATION: ClinicialTrials.gov NCT04900961 . Prospectively registered on 25 May 2021.

Assessing ototoxicity and patients' satisfaction of topical local anaesthesia in myringotomy and ventilation tube insertion.

OBJECTIVES: Animal studies have suggested that exposure of the middle ear to topical local anaesthesia may be ototoxic. This study aimed to report sensorineural hearing outcomes and patients' satisfaction in those who underwent myringotomy and ventilation tube insertion using topical local anaesthesia. METHODS: Twenty-nine patients (32 ears) were operated on. Pre- and post-operative audiology findings were compared. A Likert-type questionnaire on treatment satisfaction was completed at the end of the procedure. RESULTS: Median patient age was 55 years (range, 27-88 years). Pre- and post-operative bone conduction pure tone averages were 26.76 dB and 25.26 dB respectively (mean reduction of -1.22 dB, 95 per cent confidence interval of -5.91 to 8.13 dB; p = 0.7538). One ear (3 per cent) had a reduction in pure tone average of 10 dB. CONCLUSION: The results suggest that sensorineural hearing loss is not a complication of ear exposure to topical local anaesthesia during myringotomy and ventilation tube insertion. The procedure was well perceived.

Kinetic analysis of nitroxide radical formation under oxygenated photolysis: toward quantitative singlet oxygen topology.

Reaction kinetics for two sterically hindered secondary amines with singlet oxygen have been studied in detail. A water soluble porphyrin sensitizer, 5,10,15,20-tetrakis-(4-sulfunatophenyl)-21,23H-porphyrin (TPPS), was irradiated in oxygenated aqueous solutions containing either 2,2,6,6-tetramethylpiperidin-4-one (TMPD) or 4-[N,N,N-trimethyl-ammonium]-2,2,6,6-tetramethylpiperidinyl chloride (N-TMPCl). The resulting sensitization reaction produced singlet oxygen in high yield, ultimately leading to the formation of the corresponding nitroxide free radicals (R2NO) which were detected using steady-state electron paramagnetic resonance (EPR) spectroscopy. Careful actinometry and EPR calibration curves, coupled with a detailed kinetic analysis, led to a simple and compact expression relating the nitroxide quantum yield ΦR2NO (from the doubly-integrated EPR signal intensity) to the initial amine concentration [R2NH]i. With all other parameters held constant, a plot of ΦR2NOvs. [R2NH]i gave a straight line with a slope proportional to the rate constant for nitroxide formation, kR2NO. This establishment of a rigorous quantitative relationship between the EPR signal and the rate constant provides a mechanism for quantifying singlet oxygen production as a function of its topology in heterogeneous media. Implications for in vivo assessment of singlet oxygen topology are briefly discussed.

Objective assessment of learning curves for the Voxel-Man TempoSurg temporal bone surgery computer simulator.

INTRODUCTION: Simulators are becoming an increasingly important part of surgical training. Temporal bone surgery is one area in which simulators, such as the Voxel-Man TempoSurg simulator, are likely to play a significant role in training. We present learning curve data from novice trainees using this simulator to learn cortical mastoidectomy, exposure of the sigmoid sinus, and exposure of the short process of the incus. METHODS: We measured the time taken to perform the procedures, the volume of reference bone removed, and the structures damaged during dissection. RESULTS: We found improvement in a number of parameters over the course of the study. The overall scores, structural damage scores and time taken improved, to differing degrees, for each task. The volume of reference bone removed remained constant. CONCLUSION: These results indicate that the trainees' efficiency improved as they became more proficient at removing a given volume of reference bone.

Impacts of seedling herbivory on plant competition and implications for species coexistence.

BACKGROUND AND AIMS: Although the causes and consequences of seedling herbivory for plant community composition are well understood, the mechanisms by which herbivores influence plant species recruitment to the established phase remain less clear. The aim was to examine how variation in the intensity of seedling herbivory interacts with growth-defence trade-offs and herbivore feeding preferences to affect plant community development. METHODS: Using 14-d-old seedlings of Trifolium pratense and T. repens, relative growth and susceptibility to herbivory by the snail Helix aspersa was quantified to elucidate putative growth-defence trade-offs for these species. Then mixed assemblages of 14-d-old Trifolium seedlings were exposed to herbivory by zero, two, five or ten snails and determined how variation in the intensity of herbivory affected competitive interactions into the mature phase (as measured by total plant biomass at 120 d old). KEY RESULTS: In the absence of herbivory, communities were dominated by T. pratense; a result expected on the basis that it yielded larger and presumably more competitive seedlings. However, when seedlings were exposed to herbivory, the balance of competition shifted. At low levels of herbivory (two snails), both Trifolium species contributed equally to total plant biomass. More intense herbivory (five snails) resulted in almost total mortality of T. pratense and dominance of the mature community by T. repens. The most intense herbivory (ten snails) effectively removed all seedlings from the experimental community. CONCLUSIONS: The study illustrates a mechanism whereby spatio-temporal fluctuations in seedling herbivory, when coupled with species-specific variation in competitive ability and sensitivity to herbivore attack, can differentially influence plant recruitment into the mature phase. This mechanism may be a key element in our attempts to understand plant species coexistence, since fluctuations in plant recruitment are fundamental to the many theories that view coexistence as a consequence of a spatio-temporal lottery for dominance over regeneration micro-sites.

Applicability of NINDS-sponsored studies to community-based physician involvement.

BACKGROUND: The National Institute of Neurological Disorders and Stroke (NINDS) Clinical Trials Group established the Clinical Research Collaboration (CRC) Project in 2005 to increase community-based physician involvement in NINDS-sponsored research. METHODS: We assessed a random sample of 112 of the more than 1,000 current NINDS-sponsored clinical research studies to determine which could involve community physicians in enrollment or follow-up. Scoring factors were based on the premise that participation is feasible for noninvasive studies with simple screening, and follow-up criteria and visit frequency consistent with usual care. Scored studies included 26 Phase III, 31 Phase I/II, and 55 nonclinical trials. RESULTS: Overall, 41% of the sampled research studies were considered conducive to community physician participation that exceeds referral only; 21% with participation in all study activities and 20% with ability to provide some follow-up. Specialized neuropsychological or neurologic scale testing was judged to exclude community physician participation in 16% of studies. CONCLUSION: Many National Institute of Neurological Disorders and Stroke studies are available in which community-based physicians could participate. Involving community physicians may increase efficiency of completing clinical research and encourage application of research findings in community practices.

Overview of suspected adverse reactions to veterinary medicinal products reported in South Africa (March 2004 - February 2006).

The Veterinary Pharmacovigilance and Medicines Information Centre is responsible for the monitoring of veterinary adverse drug reactions in South Africa. An overview of reports of suspected adverse drug reactions received by the centre during the period March 2004 to February 2006 is presented. A total of 21 reports was received in the 2-year period, continuing the decline in the number of reports to a lower figure than in any previous year. This is surprising considering the legal obligation of the veterinary professionals to report all adverse drug reactions. Once again the majority of reports involved suspected adverse reactions that occurred in dogs and cats. Most of the products implicated were stock remedies. Veterinarians predominantly administered these products.

Overview of suspected adverse reactions to veterinary medicinal products reported in South Africa (March 2003 - February 2004).

The Veterinary Pharmacovigilance and Medicines Information Centre is responsible for the monitoring of veterinary adverse drug reactions in South Africa. An overview of reports of suspected adverse drug reactions received by the centre during the period March 2003 to February 2004 is given. A total of 20 reports was received. This had declined from the previous year. The general apathy with regards to the reporting of adverse drug reaction has prompted the Medicines Control Council to make reporting a legal obligation on all members of the veterinary and medical profession as from August 2004. The majority of reports involved suspected adverse reactions that occurred in dogs and cats. Most of the products implicated were Stock Remedies. Veterinarians predominantly administered these products. Only two reports were received from a veterinary pharmaceutical company.

Refining the primary open-angle glaucoma GLC1C region on chromosome 3 by haplotype analysis.

The GLC1C locus for primary open-angle glaucoma (POAG) is inherited as an autosomal dominant trait. This region on chromosome 3 is 11 cM long. DNA samples from members of a Greek and an American GLC1C family were obtained to determine whether additional typing of microsatellite markers in family members might narrow the region. GLC1C family members were evaluated clinically for POAG on the basis of open angles, intraocular pressures, cupping of discs, and visual fields. DNA samples from the Greek and Oregon GLC1C families were used to further refine the GLC1C region using microsatellite markers. A total of 22 affected members were identified in the two families. Common alleles for D3S3637 and D3S3612 were present in the disease haplotype from both families, suggesting that they may have a common founder. A newly diagnosed patient in the American family had a recombination in the distal portion of the GLC1C haplotype. This recombination narrows the GLC1C region from 11 to 4 cM.

Epilepsy in children in Benin City, Nigeria.

The pattern of epilepsy in children in Nigeria showed little difference from that seen in children in western countries, except that birth asphyxia was relatively common as a cause and there was a longer time between onset of seizures and parents seeking medical care. It was estimated that good control of seizures was achieved in 52.9% of children, but more than a quarter attended the clinic only once or twice and the reasons for this are not known. The response to medication was less satisfactory for children under 1 year, a result consistent with most other studies. Some uncommon forms and associations of epilepsy were recognised. An EEG was not essential for management but was useful for the diagnosis of syndromes. Treatment was equally effective when commenced 5 years or more after the onset of seizures. The anti-convulsant used for most children was phenobarbitone which had to be discontinued in only two cases because of side-effects. Phenobarbitone has been successfully used to treat epilepsy by primary health workers in rural Africa and this is expected to continue in the future.

Supply of veterinary medicinal products to an emerging farming community in the North West Province of South Africa.

A study was conducted in the Madikwe District of the North West Province to investigate the supply of veterinary medicinal products to small-scale, subsistence and emerging farmers. A combination of individual interviews, focus groups and direct observation was used to collect data. Stock remedies were made available to farmers within the district at Field Service Units that were managed by administrative staff of the Directorate of Field Services. The state veterinarian and animal health technicians were not directly involved with the sale of products. Most farmers still travelled to farmers' cooperatives in the larger centres outside the district to purchase the veterinary medicinal products they needed. Factors such as the quality of service provided, affordability and availability of required products as well as inaccessibility of outlets to all farmers contributed to the poor support of these outlets by the farmers of the district.

Expression of functional melanocortin-4 receptor in the hypothalamic GT1-1 cell line.

Mutations in the melanocortin-4 receptor (MC4-R) cause obesity in both mice and humans, and the receptor is presumed to have an important role in the regulation of energy homeostasis. The MC4-R is expressed in discrete sets of neurons in the central nervous system, and thus it has been technically difficult to study the regulation of expression and the signaling mechanisms of this receptor. We report here a neuronal cell line that exhibits endogenous functional expression for the MC4-R. Initially, RT-PCR analysis showed the presence of MC4-R RNA in the hypothalamic GT1-1 and GT1-7 cells. In addition, GT1-7 cells expressed melanocortin-3 receptor while the GT1-1 subclone specifically expressed predominantly the MC4-R RNA. High-affinity binding sites were demonstrated in the GT1-1 and GT1-7 cells for NDP-alpha melanocyte-stimulating hormone (MSH; K(i) = 1.1 x 10(-10) and 1.8 x 10(-10) M) and agouti-related protein (AGRP; K(i) = 1.548 x 10(-9) and 1.663(-9) M). alpha-MSH-stimulated cAMP production in GT1-1 cells with an EC(50) of 2.2 x 10(-8) M, and cAMP production was inhibited in the presence of AGRP, an endogenous antagonist of the MC4-R. Stimulation of gonadotropin-releasing hormone (GnRH) secretion was achieved with 1 nM to 1 microM concentrations of NDP-alpha-MSH while no GnRH secretion was observed when the GT1-1 cells were treated with AGRP. The data presented here show that GT1-1 cells specifically express a functional MC4-R that couples to GnRH release.

A functional study of uncrossed and crossed pulmonary afferent fibres in the cervical vagus nerves of the cat.

The functional distribution of uncrossed and crossed pulmonary afferent fibres in the cervical vagus nerves has been studied in the anaesthetized cat using acute and chronic unilateral pneumonectomized preparations. The heart and lungs were sympathectomized routinely. The vagal afferent pathways of three pulmonary reflexes were investigated: the Hering-Breuer respiratory reflex, the lung inflation cardio-accelerator reflex, and the pulmonary chemoreflex. Inflation of the remaining lung caused temporary inhibition of inspiration. It also resulted in acceleration of the heart, but only when the background cardiac vagal tone was augmented. These respiratory and cardiac responses were abolished in most animals by ipsilateral cervical vagotomy; however, in some, a small response persisted and this was abolished by contralateral vagotomy. Stimulation of pulmonary C-fibre endings with right atrial injections of phenylbiguanide caused a reduction in respiration, bradycardia and systemic hypotension, responses which occurred with a latency of 2.9 +/- 0.15 s. They were mostly abolished by ipsilateral cervical vagotomy, but reduced responses persisted in a few animals. The residual responses were abolished by contralateral cervical vagotomy and by selective denervation of the lung. These results indicate that most afferent fibres subserving the three pulmonary reflexes studied run in the ipsilateral cervical vagus, representing the uncrossed pathway. Some afferent fibres, however, cross to the contralateral cervical vagus. Degenerative changes in cells of the contralateral nodose ganglion in chronic unilateral pneumonectomized animals support these findings.

Acute intermittent porphyria, seizures, and antiepileptic drugs: a report on a 3-year-old Nigerian boy.

A 3-year-old Nigerian boy was treated with phenobarbitone after having a nonfebrile seizure. Two weeks later his urine was found to contain porphobilinogen, indicating that latent acute intermittent porphyria had been unmasked by phenobarbitone. The drug was discontinued and carbamazepine was substituted. The urine became free of porphobilinogen and the patient remained well. In developing countries phenobarbitone is the most widely used anticonvulsant; it must be avoided in acute intermittent porphyria, and carbamazepine may be tolerated.

Luteal phase sertraline treatment for premenstrual dysphoric disorder. Results of a double-blind, placebo-controlled, crossover study.

OBJECTIVE: To test the efficacy of late-luteal phase dosing of sertraline hydrochloride in women with moderate-to-severe premenstrual dysphoric disorder. This highly prevalent disorder often causes significant psychosocial impairment. DESIGN: Double-blind, crossover trial of each 2-menstrual cycle of baseline, sertraline treatment, and placebo. Randomization to sertraline treatment vs placebo occurred after a 2-cycle, drug-free period. SETTING: A large outpatient multispecialty clinic in central Texas. PATIENTS: Fifty-seven women aged 19 to 49 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of premenstrual dysphoric disorder. INTERVENTIONS: Late-luteal phase treatment with sertraline hydrochloride in daily doses of 50 mg (cycle 1) followed by 100 mg (cycle 2) vs placebo. MAIN OUTCOME MEASURES: The 22-item calendar of premenstrual experiences was completed daily and constituted the primary outcome measure, consisting of a total score and behavioral and physical factor scores. RESULTS: A repeated-measures analysis of variance for crossover designs found a significant beneficial effect from sertraline treatment in improving the calendar of premenstrual experiences total (P < .01), behavioral factor (P < .01), and physical factor (P < .04) scores. Most women improved when taking sertraline, 50 mg, although a dose increase to 100 mg yielded further improvement in approximately 25% of women. Use of sertraline was extremely well tolerated; the only adverse event reported by 10% or more of women was insomnia in 8 (14%) of them. CONCLUSIONS: Luteal phase treatment with sertraline was a safe and effective treatment for moderate-to-severe premenstrual dysphoric disorder. Further controlled studies are needed to confirm the results of this preliminary study.