Exploring the acute cardiovascular effects of Floatation-REST.

The central nervous system (CNS) exerts a strong regulatory influence over the cardiovascular system in response to environmental demands. Floatation-REST (Reduced Environmental Stimulation Therapy) is an intervention that minimizes stimulation from the environment, yet little is known about the autonomic consequences of reducing external sensory input to the CNS. We recently found that Floatation-REST induces a strong anxiolytic effect in anxious patients while paradoxically enhancing their interoceptive awareness for cardiorespiratory sensations. To further investigate the physiologic nature of this anxiolytic effect, the present study measured acute cardiovascular changes during Floatation-REST using wireless and waterproof equipment that allowed for concurrent measurement of heart rate, heart rate variability (HRV), breathing rate, and blood pressure. Using a within-subjects crossover design, 37 clinically anxious participants with high levels of anxiety sensitivity and 20 non-anxious comparison participants were randomly assigned to undergo a 90-min session of either Floatation-REST or an exteroceptive comparison condition that entailed watching a relaxing nature film. Measures of state anxiety and serenity were collected before and after each session, while indices of autonomic activity were measured throughout each session. HRV was calculated using both time-series and frequency domain analyses. Linear mixed-effects modeling revealed a significant main effect of condition such that relative to the film condition, Floatation-REST elicited significant decreases (p < 0.001) in diastolic blood pressure, systolic blood pressure, breathing rate, and certain metrics of HRV including the standard deviation of the interbeat interval (SDNN), low-frequency HRV, and very low-frequency HRV. Heart rate showed a non-significant trend (p = 0.073) toward being lower in the float condition, especially toward the beginning of the session. The only metric that showed a significant increase during Floatation-REST was normalized high-frequency HRV (p < 0.001). The observed physiological changes were consistent across both anxious and non-anxious participants, and there were no significant group by condition interactions. Blood pressure was the only cardiac metric significantly associated with float-related reductions in state anxiety and increases in serenity. These findings suggest that Floatation-REST lowers sympathetic arousal and alters the balance of the autonomic nervous system toward a more parasympathetic state. Clinical trial registration: [https://clinicaltrials.gov/show/NCT03051074], identifier [NCT03051074].

Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a "Two Hit" Stressor Model.

Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M. vaccae), a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, is a potentially useful countermeasure against negative outcomes to stressors. Here we used male C57BL/6NCrl mice to determine if repeated immunization with M. vaccae is an effective countermeasure in a "two hit" stress exposure model of chronic disruption of rhythms (CDR) followed by acute social defeat (SD). On day -28, mice received implants of biotelemetric recording devices to monitor 24-h rhythms of locomotor activity. Mice were subsequently treated with a heat-killed preparation of M. vaccae (0.1 mg, administered subcutaneously on days -21, -14, -7, and 27) or borate-buffered saline vehicle. Mice were then exposed to 8 consecutive weeks of either stable normal 12:12 h light:dark (LD) conditions or CDR, consisting of 12-h reversals of the LD cycle every 7 days (days 0-56). Finally, mice were exposed to either a 10-min SD or a home cage control condition on day 54. All mice were exposed to object location memory testing 24 h following SD. The gut microbiome and metabolome were assessed in fecal samples collected on days -1, 48, and 62 using 16S rRNA gene sequence and LC-MS/MS spectral data, respectively; the plasma metabolome was additionally measured on day 64. Among mice exposed to normal LD conditions, immunization with M. vaccae induced a shift toward a more proactive behavioral coping response to SD as measured by increases in scouting and avoiding an approaching male CD-1 aggressor, and decreases in submissive upright defensive postures. In the object location memory test, exposure to SD increased cognitive function in CDR mice previously immunized with M. vaccae. Immunization with M. vaccae stabilized the gut microbiome, attenuating CDR-induced reductions in alpha diversity and decreasing within-group measures of beta diversity. Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience.

Finding intestinal fortitude: Integrating the microbiome into a holistic view of depression mechanisms, treatment, and resilience.

Depression affects at least 322 million people globally, or approximately 4.4% of the world's population. While the earnestness of researchers and clinicians to understand and treat depression is not waning, the number of individuals suffering from depression continues to increase over and above the rate of global population growth. There is a sincere need for a paradigm shift. Research in the past decade is beginning to take a more holistic approach to understanding depression etiology and treatment, integrating multiple body systems into whole-body conceptualizations of this mental health affliction. Evidence supports the hypothesis that the gut microbiome, or the collective trillions of microbes inhabiting the gastrointestinal tract, is an important factor determining both the risk of development of depression and persistence of depressive symptoms. This review discusses recent advances in both rodent and human research that explore bidirectional communication between the gut microbiome and the immune, endocrine, and central nervous systems implicated in the etiology and pathophysiology of depression. Through interactions with circulating inflammatory markers and hormones, afferent and efferent neural systems, and other, more niche, pathways, the gut microbiome can affect behavior to facilitate the development of depression, exacerbate current symptoms, or contribute to treatment and resilience. While the challenge of depression may be the direst mental health crisis of our age, new discoveries in the gut microbiome, when integrated into a holistic perspective, hold great promise for the future of positive mental health.

Preoperative autologous blood donation. Linkage of the public and private hospital sectors.

OBJECTIVE: To evaluate the safety and efficacy of a preoperative autologous blood donation (PABD) program with liberal patient exclusion criteria. DESIGN: Prospective patient accrual from September 1990 to May 1992. SETTING: A PABD program in a public tertiary care hospital linked with a specialist orthopaedic practice in a private hospital. PATIENTS: One hundred and twenty patients consecutively scheduled for orthopaedic surgery were referred for PABD. There were 77 women (median age, 63 years) and 43 men (median age, 62 years). One-third of patients were 70 or more years old. Coexistent medical disease, mainly cardiovascular, was present in 46% of patients and 3% were excluded because of coexisting morbidity. Total hip or total knee replacement was performed in a private hospital with intraoperative or postoperative blood salvage in 37% of the patients. OUTCOME MEASURES: Adverse effects of PABD, autologous blood collected and used and homologous blood transfused. RESULTS: One hundred and sixteen patients donated 267 units of autologous blood. In 70 patients undergoing total hip replacement, 78% donated three and 20% donated two units, with 95% of autologous blood being used. In 38 patients undergoing total knee replacement, 42% donated two units and 55% donated one unit, with 87% of autologous blood being transfused. Seventy-eight per cent of all patients only received autologous blood. In the remaining patients, homologous blood use was confined to two units or less in 80%. Hypotensive episodes associated with phlebotomy occurred in 3% of patients, and 13% of patients had preoperative haemoglobin levels ranging from 85-100 g/L without adverse clinical effects. CONCLUSION: A hospital-based PABD program with less strict patient exclusion criteria does not prejudice the clinical status of the donors. Its linkage to private hospitals can significantly reduce the use of homologous blood in selected elective surgery.

Physical properties of purified human respiratory mucus glycoproteins: effects of sodium chloride concentration on the aggregation properties and shape.

The biophysical properties of purified native (nonreduced) mucus glycoproteins (mucins) isolated from lung mucus secretions of cystic fibrosis (CF) patients and subjects with normal lungs were studied using the technique of light scattering. The effects of different NaCl concentrations and 6 M guanidine hydrochloride on the molecular size of mucins, their ability to form aggregates, and their shape were investigated. Under the concentration range studied (0.05-3.5 mg/ml), in buffered 0.03 and 0.01 M NaCl, the CF mucins had higher molecular weights (12.2 x 10(6) to 17.1 x 10(6) and 9.5 x 10(6) to 10.4 x 10(6), respectively) than those observed in buffered 0.15 M NaCl (4.3 x 10(6) to 6.6 x 10(6]. These results were interpreted in terms of CF mucins self-aggregating in buffered 0.03 and 0.01 M NaCl. In contrast, in the both buffered 0.3 and 0.15 M NaCl, the normal respiratory mucins had molecular weights of 6.3 x 10(6) to 8.6 x 10(6), thus suggesting the absence of normal mucin aggregation in buffered 0.03 M NaCl. In the presence of 6 M guanidine HCl both CF and normal mucins had molecular weights of about 5 x 10(6) and showed more extended structure (i.e., larger radius of gyration) than in the presence of 0.03 or 0.15 M NaCl. Studies of the relationship of the light scattering intensity with scattering angle showed that, under the above experimental conditions studied, both CF and normal respiratory mucins were polydisperse flexible coil-shaped molecules. The increased aggregation of CF mucins observed at lower salt concentrations may alter the viscoelastic properties of CF lung mucus secretions.

Breast-milk composition in women with cystic fibrosis: report of two cases and a review of the literature.

Breast milk was collected from two women with cystic fibrosis (CF) and data from the literature was reviewed. The sodium concentration was within normal limits, 11-24 mmol/L in colostrum and 7-8 mmol/L in mature milk. Normal physiologic changes in milk composition after parturition (decreases in Na and increases in lactose) and during individual feeding periods (increases in fat and decreases in protein) were observed. Concentrations of milk protein, fat, and sugars were normal when the pulmonary disease of these patients was mild. During exacerbations of pulmonary disease, the concentrations of milk macronutrients were reduced. Milk secreted by women with CF appears to be physiologically normal, safe for the infant, and breast-feeding by mothers with CF should no longer be discouraged. Variations in the macronutrient content of CF milk warrants routine monitoring of the mother with CF and the breast-fed infant, especially during exacerbations in the pulmonary aspects of this disease.

Coincidence of seizure susceptibility to caffeine and to the benzodiazepine inverse agonist, DMCM, in SWR and CBA inbred mice.

Several lines of evidence suggest that the convulsant actions of caffeine are mediated through benzodiazepine receptors. A pharmacogenetic approach has been used to further explore the relationship of these receptors to caffeine-induced seizures. The susceptibility of two inbred strains of mice (CBA and SWR) to the convulsant actions of picrotoxinin, strychnine, Ro 5-4864 and DMCM was examined. Previous studies have demonstrated these two strains differ in their susceptibilities to the convulsant action of caffeine. While no differences were observed between these two strains in susceptibility to tonic seizures induced by picrotoxinin, RO 5-4864 or strychnine, SWR mice were significantly less sensitive to tonic seizures induced by DMCM compared to CBA mice (CD50 values in CBA and SWR mice were 6 and 12 mg/kg IP). Both clonazepam and the benzodiazepine receptor antagonist, Ro 15-1788, significantly blocked caffeine-induced seizures. Further, when subconvulsant doses of caffeine and DMCM were combined, a synergistic action was observed. Taken together, these findings support the hypothesis that the convulsant actions of caffeine result from an action at benzodiazepine receptors, and that the hyporesponsiveness of the SWR strain to both caffeine- and DMCM-induced seizures could result from an inherited abnormality in these sites.

Comparison of physicochemical properties of purified mucus glycoproteins isolated from respiratory secretions of cystic fibrosis and asthmatic patients.

The major nonreduced mucus glycoproteins (mucins) from sputa of cystic fibrosis (CF) and asthmatic patients have been purified to electrophoretic homogeneity and subjected to physical and chemical characterization. The sputum specimens were solubilized in buffer containing 0.22 M KSCN and fractionated on Bio-Gel A-5m, followed by digestion with DNase, rechromatography on the same column, and chromatography on hydroxylapatite. Sodium dodecyl sulfate gel electrophoresis of purified mucins gave a single band. Carbohydrate analyses of the purified mucins showed no significant differences in the sugar components from the two mucins. However, the CF mucin contained substantially higher (11%) sulfate content than that observed for the asthmatic mucin (5.9%). Amino acid analyses indicated that the CF mucin had higher levels of serine plus threonine (35%) as compared to the asthmatic mucin (29%). In contrast, CF mucin contained a lower content of aspartate, glutamate, and glycine than that observed for the asthmatic mucin. Molecular weights of 3.8 X 10(6) and 3.5 X 10(6) were obtained for CF and asthmatic mucins, respectively, from light-scattering studies of mucins in the presence of 6 M guanidine hydrochloride. Reduction of the disulfide bonds of the two mucins did not alter their molecular weights. Liquid chromatographic studies on Sepharose CL2B showed that CF mucin forms aggregates sufficiently large to be excluded from the gel. As compared to the CF mucin, the asthmatic mucin formed fewer of these large aggregates under identical experimental conditions. Reduction and alkylation of the mucins resulted in their inability to form aggregates. The higher state of aggregation of CF mucin may influence the viscoelastic properties of the CF lung's mucus secretions.

Deficient vasoactive intestinal peptide innervation in the sweat glands of cystic fibrosis patients.

The innervation of acini and ducts of eccrine sweat glands by immunoreactive, vasoactive intestinal peptide-containing nerve fibers was sharply reduced in seven patients with cystic fibrosis compared to eight normal subjects. The decrease in innervation by this neuropeptide, which has been shown to promote blood flow and the movement of water and chloride across epithelial surfaces in other systems, may be a basic mechanism for the decreased water content and relative impermeability of the epithelium to chloride and other ions that characterize cystic fibrosis.

Reproductive defects in patients of both sexes with cystic fibrosis: a review.

Current knowledge of reproductive duct function in both male and female cystic fibrosis patients is reviewed. Almost all male patients are sterile because of azoospermia. The mechanistic basis of the obstructive defect leading to pre- and post-natal destruction of selected portions of the sperm-conducting network remains unknown. Female cystic fibrosis patients are fertile. Pulmonary status appears to be the most important factor in determining pregnancy outcome. In contrast to earlier concerns about the normality of breast milk, breast milk composition of cystic fibrosis mothers is normal, and they can successfully breast feed their infants.

Penetration of latamoxef, cefoperazone and piperacillin into the sputum of patients with cystic fibrosis.

Concentrations of latamoxef, cefoperazone and piperacillin, administered intravenously, were measured in serum and sputum of cystic fibrosis patients with recurrent pulmonary infections, chronically colonized with Pseudomonas aeruginosa. Serum pharmacokinetic data were consistent with prior reports. Peak sputum to peak serum concentrations were approximately 3% for each antimicrobial. However, the more prolonged sputum concentrations of piperacillin were reflected in greater areas under the sputum concentration-time curve and a longer duration above the MIC50 of tested P. aeruginosa strains for that drug.

Plasma and submandibular saliva lysosomal enzymes in cystic fibrosis.

This study determined in a blind fashion the activity levels and thermostability properties of two lysosomal hydrolytic enzymes, acid phosphatase and alpha-mannosidase, in plasma samples from 25 cystic fibrosis (CF) patients and 25 age- and sex-matched normal controls. Mean alpha-mannosidase activity (3.2 +/- 1.0 mU/ml) and acid phosphatase activities (6.5 +/- 2.9 mU/ml) in CF patients were not significantly different from those found in normal individuals (2.8 +/- 0.7 and 7.6 +/- 3.4 mU/ml, respectively). Using stringent conditions no differences in thermostability properties of these enzymes were found between plasma from CF patients as compared to that of normal controls. When activity levels of these enzymes and of four additional hydrolytic enzymes, alpha-L-fucosidase, alpha-galactosidase, alpha-glucosidase and beta-galactosidase, were determined in submandibular saliva, no significant differences in enzyme levels between CF and age- and sex-matched controls were noted nor were thermostability differences found. Our data do not support the concept that altered properties of these enzymes are useful as markers for detection of CF homozygotes and heterozygotes, nor the hypothesis that the defect underlying this disease is a deficiency of post-translational modification of glycoproteins leading to their mis-compartmentalization and qualitative alteration.

Respiratory mucous secretions in patients with cystic fibrosis: relationship between levels of highly sulfated mucin component and severity of the disease.

The tracheobronchial secretions from cystic fibrosis patients contained higher levels of protein, DNA and sialic acid than the tracheobronchial secretions from healthy donors. In contrast, the neutral hexose content in CF secretions was strikingly lower than in secretions from normal subjects. The levels of neutral hexose and sialic acid in the CF secretions were found to increase with increasing severity of the disease. The alterations in the levels of these chemical parameters in the secretions of patients with increased disease severity are as a result of increased levels of the mucin content of the secretions, especially of the highly sulfated mucin component. Since mucins are considered, to a large extent, responsible for the viscoelastic properties of the secretions, the enhanced levels of the highly sulfated mucin component in the secretions of the patients with increased disease severity, may contribute to altered rheological properties and hence decreased mucociliary transport of the secretions.

Cystic fibrosis factors: effect of serum on the secretory response of dispersed rat submandibular cells.

The action of serum from cystic fibrosis patients on the intracellular maintenance, efflux, and uptake of potassium ions in dispersed acinar cells from the rat submandibular gland, a seromucous salivary gland, was investigated in an attempt to demonstrate the presence of factors affecting ion-coupled secretion. No effects specific to cystic fibrosis serum were demonstrated upon the following parameters of potassium transport: (1) maximal stimulation of K+ efflux by the cholinergic agonists carbamylcholine; (2) the dose-response curve of K+ efflux in response to carbamylcholine; (3) re-entry of K+ into cells after carbamylcholine stimulation; (4) the maintenance of K+ in the absence of added effectors. No differences were observed between cells pretreated with serum and cells to which serum was added at the time of cholinergic stimulation of secretion. At high concentrations, serum from both normal individuals and those with cystic fibrosis severely damaged the cells in a rapid and irreversible fashion. K+ transport has a direct, closely coupled, specific relationship to secretory activity and is Ca++ dependent in this system. From these observations, we conclude that serum from individuals with cystic fibrosis does not contain chemical compounds which specifically alter the major components of ion-coupling to secretion or the secretory process itself in salivary gland acinar cells.

Serotypes and antibiotic susceptibilities of Pseudomonas aeruginosa isolates from single sputa of cystic fibrosis patients.

A phenotypic characterization of Pseudomonas aeruginosa from single sputum samples of 21 typical cystic fibrosis patients indicated a high frequency of heterogeneity among isolates on the basis of differences in antibiotic resistance, colony morphology, pigmentation, and serotype. Two or more isolates with different but stable susceptibilities to carbenicillin, gentamycin, streptomycin, tetracycline, chloramphenicol, and sulfamethoxazole plus trimethoprim were detected in 38% of the sputa. Differences generally were independent of the mucoid state of the strain. O-antigen group determination with the Difco typing set showed that two or more serologically distinct strains were present in 10/21 sputum specimens. Nonmucoid derivatives of mucoid isolates almost always retained both the antibiotic susceptibilities and serotype of their parent strain. These data suggest that cystic fibrosis patients may be cocolonized/coinfected by different strains of P. aeruginosa more frequently than generally believed. Alternatively, phenotypically distinct strains from a single patient might arise as phenotypic dissociants from a single infecting strain. Because of the frequency and multiplicity of phenotypically distinct P. aeruginosa isolates which we obtained from our cystic fibrosis patients, it is important to select multiple isolates from sputum cultures for antimicrobial susceptibility testing so as to assess adequately the susceptibility of this organism to antibiotic therapy in cystic fibrosis. We recommend that several colonies of each distinguishable colony type of P. aeruginosa be pooled for the antibiogram.

Altitude tolerance of general aviation pilots with normal or partially impaired spirometric function.

The altitude tolerance of 10 spirometrically impaired (SI) general aviation pilots with an average forced midexpiratory flow (FEF25--75%) value of 65.1% was compared to that of 10 spirometrically normal (SN) pilots. Cardiorespiratory parameters assessed at ground level (GL) and at 8,000- and 12,500-ft altitudes were blood pressure, pulmonary ventilation, oxyhemoglobin saturation, temporal artery flow velocity, heart rate, and single-lead electrocardiogram. Although altitude exposure quantitatively displaced the SI group more than the SN group, the differences were not statistically significant at the probability level of 0.05. Unifocal premature ventricular contractions were present at GL in three of the pilots and showed no further changes at altitude. Therefore, the mean FEF25--75%, values of 65% of predicted normal for the SI group becomes a reasonable option as an objective screening norm for acceptable tolerance to general aviation altitudes in the ambient-air-breathing range.

Spirometric assessment of potential respiratory impairment in general aviation airmen.

Chronic obstructive pulmonary disease continues to manifest an increasing prevalence in male Americans. A recent study of commercial airline pilots revealed a 12% prevalence of more-than-minor spirometric impairment. Because commensurate data were not available for general aviation pilots, in whom such impairment could also compromise flight safety, a parallel study was made. The BMRC and smoking questionnaires, chest expansion, and spirometric measurements of FEV1, FVC, FEV1%, MVV, and FFF 25-75% were assessed in 181 male general aviation pilots. All showed a general relationship to increasing age and smoking amount. Based on FEV1% and FEF 25-75% combined, minor or more-than-minor degrees of spirometric impairment were manifested by 25.4% of the pilots and moderate degrees by 12.7%. Very little impairment was reflected in the remaining spirometric parameters. Subsequent testing of such spirometrically impaired pilots for altitude, fatigue, and orthostatic tolerances related to general aviation flight safety is planned.