Caveolin1 interacts with the glucocorticoid receptor in the lung but is dispensable for its anti-inflammatory actions in lung inflammation and Trichuris Muris infection.

Glucocorticoids (Gcs) are widely prescribed anti-inflammatory compounds, which act through the glucocorticoid receptor (GR). Using an unbiased proteomics screen in lung tissue, we identified the membrane protein caveolin -1 (Cav1) as a direct interaction partner of the GR. In Cav1 knockout mice GR transactivates anti-inflammatory genes, including Dusp1, more than in controls. We therefore determined the role of Cav1 in modulating Gc action in two models of pulmonary inflammation. We first tested innate responses in lung. Loss of Cav1 impaired the inflammatory response to nebulized LPS, increasing cytokine/chemokine secretion from lung, but impairing neutrophil infiltration. Despite these changes to the inflammatory response, there was no Cav1 effect on anti-inflammatory capacity of Gcs. We also tested GR/Cav1 crosstalk in a model of allergic airway inflammation. Cav1 had a very mild effect on the inflammatory response, but no effect on the Gc response - with comparable immune cell infiltrate (macrophage, eosinophils, neutrophils), pathological score and PAS positive cells observed between both genotypes. Pursuing the Th2 adaptive immune response further we demonstrate that Cav1 knockout mice retained their ability to expel the intestinal nematode parasite T.muris, which requires adaptive Th2 immune response for elimination. Therefore, Cav1 regulates innate immune responses in the lung, but does not have an effect on Th2-mediated adaptive immunity in lung or gut. Although we demonstrate that Cav1 regulates GR transactivation of anti-inflammatory genes, this does not translate to an effect on suppression of inflammation in vivo.

Mitochondrial SIRT3 and its target glutamate dehydrogenase are altered in follicular cells of women with reduced ovarian reserve or advanced maternal age.

STUDY QUESTION: Is the activity of sirtuin 3 (SIRT3) altered in granulosa and cumulus cells from young women with reduced ovarian reserve or women of advanced maternal age? SUMMARY ANSWER: SIRT3 mRNA and active protein in granulosa and cumulus cells were decreased in women with reduced ovarian reserve and advanced maternal age. WHAT IS KNOWN ALREADY: Young women with reduced ovarian reserve or women of advanced maternal age have reduced oocyte viability, possibly due to altered granulosa and cumulus cell metabolism. The mitochondrial SIRT3 protein may be implicated in these processes as it is able to sense the metabolic state of the cell and alter mitochondrial protein function post-translationally. STUDY DESIGN, SIZE, DURATION: This is a prospective cohort study, in which women (n = 72) undergoing routine IVF/ICSI were recruited and allocated to one of three cohorts based on age and ovarian reserve (as assessed by serum anti-Mullerian hormone level). Women were classified as young (≤35 years) or of advanced maternal age (≥40 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Granulosa and cumulus cells were collected. SIRT3 mRNA and protein levels and protein activity was analysed in granulosa and cumulus cells via quantitative PCR, immunohistochemistry and western blotting, and deacetylation activity, respectively. Activity of the glutamate dehydrogenase (GDH) enzyme, a known target of SIRT3, was assessed, and acetylated proteins in mitochondria isolated from granulosa and cumulus cells were separated by immunoprecipitation and acetylation of GDH assessed by western blotting. Data for women with good prognosis (young women with normal ovarian reserve) were compared with those from young women with reduced ovarian reserve and those of advanced maternal age. MAIN RESULTS AND THE ROLE OF CHANCE: SIRT3 mRNA and active protein were present in granulosa and cumulus cells and co-localized to the mitochondria. SIRT3 mRNA in granulosa cells was decreased in young women with reduced ovarian reserve and advanced maternal age versus young women with normal ovarian reserve (P < 0.05). SIRT3 mRNA in cumulus cells was decreased in women of advanced maternal age versus young women with normal ovarian reserve only (P < 0.05). Granulosa cell GDH activity was decreased in young women with reduced ovarian reserve and in women of advanced maternal age (P < 0.05), whereas cumulus cell GDH activity was reduced in the advanced maternal age group only (P < 0.05). The acetylation profile of GDH in mitochondria revealed increased acetylation of GDH in granulosa and cumulus cells from women of advanced maternal age (P < 0.05) while young women with reduced ovarian reserve had increased GDH acetylation in granulosa cells only (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Although patients were allocated to groups based on maternal age and ovarian reserve and matched for BMI, other maternal factors may also alter the 'molecular health' of ovarian cells. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that SIRT3 post-translational modification of mitochondrial enzymes in human granulosa and cumulus cells may regulate GDH activity, thus altering the metabolic milieu surrounding the developing oocyte. Owing to the association between the decline in oocyte quality and pregnancy rates in women of advanced maternal age and the possible association with reduced ovarian reserve, knowledge of perturbed SIRT3 function in granulosa and cumulus cells may lead to novel therapies to improve mitochondrial metabolism in the oocyte and follicular cells in women undergoing IVF treatment. STUDY FUNDING/COMPETING INTEREST(S): No conflicts of interest to declare. Research was funded by an NHMRC project grant.

Fluid balance charts: do they measure up?

Many current nursing activities are performed without regular reviews of their usefulness. The recording of fluid gains and losses on a fluid balance chart is one such activity. This article explores the practice of fluid monitoring on the wards of a university teaching hospital.

A matching-to-sample feedback technique for training self-control of tinnitus.

Thirty individuals with subjective tinnitus aurium of a variety of types and severity were treated with a matching-to-sample feedback procedure. Following initial evaluation measures, the participants' experienced tinnitus sounds were reproduced audiometrically on all characteristics and were presented to them in the noninvolved ear or in both ears when the tinnitus was binaural. This experimental sound was then reduced in 5 decibel (dB) steps within sessions, and participants had the task of concentrating on reducing the loudness of their tinnitus until a match was achieved between it and the experimental sound at each new dB level. Results showed an overall highly significant difference in dB levels from baseline to final training session. Nearly all participants demonstrated a marked reduction in tinnitus loudness, with 84% reducing it by 10 dB to 62 dB and several eliminating it completely. Individual and pathological variables played no role in training or outcome. Our approach appears to have major advantages over other tinnitus treatment strategies in that it provides direct, significant relief and gives the patient the psychological benefit of gaining control over the problem.

EMG biofeedback for handwriting disabilities: a critical examination of the literature.

A critical examination of the literature on the use of electromyographic (EMG) biofeedback for problems of handwriting is presented. Examined are the procedures, results and conclusions of clinical treatments of writer's cramp and the habilitation of writing. The major flaws in each study are discussed and conclusions drawn from the review are presented, the primary one being that EMG biofeedback of the muscles of the upper extremity has yet to be demonstrated as a treatment of choice for handwriting disabilities. The lack of a sound foundation of data is seen as the main reason for the paucity of investigations in this particular area. Suggestions for further work are offered.

A cross-modality approach for treatment of chronic pain: a preliminary report.

Three subjects, presenting a variety of chronic pain problems, were treated with a cross-modality feedback technique. Their presenting pain intensity was matched to a pure tone auditory stimulus decibel level and in each session this stimulus was progressively reduced in loudness, with the subjects having the task of reducing their pain to match each new, lower decibel levels. Audiometric measures, responses to pain assessment scales, self-reports, reports from hospital staff, and reductions in pain medications all demonstrated marked pain reduction in all cases. Follow-up assessments revealed that the improvements were maintained long after treatment had been discontinued.

Biofeedback treatment of upper extremity dysfunction in Guillain-Barré syndrome.

Two cases are presented of the application of electromyographic biofeedback for increasing activity of wrist and finger musculature in patients with Guillain-Barré syndrome. Patient 1, a 59-year-old woman, quadriplegic, and on a portable respirator for more than five years prior to biofeedback was given visual and auditory feedback for increased output of wrist flexor, finger flexor, and thumb opposition muscles, bilaterally. All muscles improved in activity, 9/12 significantly, although no marked improvements in activities of daily living functions were noted. Patient 2, a 51-year-old man who had experienced good motoric return following onset of the disease, was given feedback for increased activity of finger extensor, finger adductor, thumb and fifth finger opposition, wrist extensor, and finger flexor muscles, bilaterally. Of 18 muscles or muscle groups treated, 17 showed significant increases in output. This patient became ADL functional. It is believed that biofeedback can be an important modality of treatment in this disease even following termination of more traditional therapies, as was true in the present cases, and that greater attention should be paid to patients with Guillain-Barré syndrome than has been to date. It is suggested that biofeedback be initiated, along with other therapies, once the acute stage of the disease is past.

EMG biofeedback with upper extremity musculature for relaxation training: a critical review of the literature.

A critical review is presented of studies utilizing EMG biofeedback for relaxation of upper extremity musculature. Examined are experimental investigations with normal subjects and those with psychological problems, and clinical applications of the methodology for treatment of involuntary movements and anxiety. Articles are reviewed in terms of procedures, controls and results. It is determined that few valid conclusions can be drawn regarding the efficacy of upper extremity EMG biofeedback for relaxation and that further research is required prior to utilizing the technique clinically. Suggestions are offered for areas of investigation.

Biofeedback as a treatment for postural hypotension.

Two patients with cervical spinal cord lesions were treated for postural hypotension using auditory and visual feedback for voluntary increases in blood pressure. Following initial measures of blood pressure, feedback was delivered for systolic increases above baseline. Within several weeks, both patients learned to increase their pressure markedly from the start of training sessions to their conclusion. The patients' legs were progressively lowered during and at the end of training sessions without significant blood pressure decreases. Long-term follow-up indicated that they were able to maintain the learned increases in blood pressure despite adverse medical conditions. It is suggested that central nervous system damage disrupts homeostatic regulation, permitting greater voluntary control through biofeedback as a new feedback loop. Motivation is also considered an important variable for success.

Learned self-control of tinnitus through a matching-to-sample feedback technique: a clinical investigation.

Two cases are reported in which subjective tinnitus aurium was treated with a matching-to-sample procedure. Following baseline evaluations, the subjects' experienced tinnitus was reproduced audiometrically in terms of loudness, frequency, and quality. This was presented to them in the noninvolved ear and was gradually reduced within sessions. The subjects were required to concentrate on reducing their tinnitus until an equal match had been achieved between it and the stimulus sound at each new decibel level. Both subjects gained control over their tinnitus and were able to reduce it markedly from baseline levels. This procedure is viewed as an advance over other techniques not only in that it significantly reduces the tinnitus but in the fact that it is done through the subject's own control, providing psychological benefit as well.

Experimental foundations of EMG biofeedback with the upper extremity: a review of the literature.

This article reviews the experimental foundations of EMG biofeedback with the upper extremity. Considered are investigations on recruitment and training of single and multiple motor units in both normal and nonnormal subjects, on transfer of training effects from trained to untrained muscles, and on the relationship of reduced muscle output to relaxation. Examined are procedures, results, and conclusions of these basic studies. Problems noted in the research are discussed and suggestions are made for further work in the area.

The utilization of EMG biofeedback for the treatment of periorbital facial muscle tension.

A case is presented of EMG feedback for reduction of tension in the orbicularis oculi muscle of both eyes. Feedback was provided for reduced firing of the upper and lower segments of the muscle. Within 25 sessions for the left eye and 20 sessions for the right, muscle output was markedly reduced from baseline and the patient reported no longer experiencing discomforting sensations of tightness. Follow-up of the patient 3 months posttreatment revealed that the initial problem of muscle tension no longer existed.

Reflex conditioning in a spinal man.

A man with a completely transected spinal cord and a spastic neurogenic bladder was conditioned to void upon the presentation of an external stimulus. A classical conditioning paradigm was employed in which strong abdominal shock (unconditioned stimulus) was paired with an initially neutral mild electrical stimulation of the thigh (conditioned stimulus; CS). After the pairing trials, a reliable conditioned response of urination was elicited by the CS alone. The conditioned response did not extinguish over time, and the procedure left the bladder with clinically safe residual amounts of urine. Practical implications of the conditioning technique for the treatment of spastic neurogenic bladder conditions in spinally injured patients are discussed, as is the theoretical significance of conditioning at the reflex level in the absence of cortical involvement.

Conditioned responding of the neurogenic bladder.

Classical conditioning techniques were employed to condition responding of the spastic neurogenic bladder in a man with quadriparesis and urinary incontinence secondary to spinal cord injury at the cervical level. A neutral stimulus of mild electrical stimulation to the thigh was paired temporally with an unconditioned stimulus (UCS) of stronger electrical stimulation of the lower abdomen, and then was presented alone as a conditioned stimulus (CS) to elicit the conditioned response (CR) of voiding. The previously neutral CS reliably elicited large amounts of urine and left little residual urine in the subject's bladder. Following the experimental sessions, the subject self-applied the CS on a predetermined schedule during his daily routine outside of the laboratory. The CS initially was successful, but after several days the CR exhibited extinction. Additional CS-UCS pairing sessions did not reinstate the responses satisfactorily. Aspects of the experimental procedure and the results are discussed as well as the feasibility of conditioning the human spinal cord in the absence of an intact central nervous system

Biofeedback as an experimental treatment for postural hypotension in a patient with a spinal cord lesion.

A man having severe postural hypotension resulting from a spinal cord lesion at level T3, was trained to raise and lower his blood pressure with the use of biofeedback. The procedure consisted of 11 learning sessions during which the subject's task was to effect specific changes of his blood pressure without skeletal muscle or respiratory involvement. Blood pressure was continuously monitored and reported to the subject, and positive verbal reinforcement for correct changes was also supplied. Analysis of the results revealed that the subject had learned to produce large voluntary changes in pressure. This learned ability was then applied in a standing position resulting in counteracting the postural hypotension. Suggestions for further research and implications for clinical applications are discussed.

Conditioning bladder responses in patients with spinal cord lesions.

Two patients with spinal cord lesions and spastic neurogenic bladders were treated with classical conditioning techniques to reinstate independent bladder function utilizing electrical stimulation of the abdomen as the unconditioned stimulus and mild electrical stimulation of the thigh as the conditioned stimulus. Successful conditioning was achieved in both cases. Urination was brought under the control of a previously neutral stimulus with a high rate of responding.