Is there a neuroscience-based, mechanistic rationale for transcranial direct current stimulation as an adjunct treatment for posttraumatic stress disorder?

It is well-known that there is considerable variation in the effectiveness of evidence-based treatments for psychiatric disorders, and a continued need to improve the real-world effectiveness of these treatments. In the last 20+ years the examination of noninvasive brain stimulation techniques for psychiatric treatment has increased dramatically. However, in order to test these techniques for effective therapeutic use, it is critical to understand (a) (what are) the key neural circuits to engage for specific disorders or clusters of symptoms, and (b) (how) can these circuits be reached effectively using neurostimulation? Here we focus on the research toward the application of transcranial direct current stimulation (tDCS) for posttraumatic stress disorder (PTSD). tDCS is a portable and inexpensive technique that lends itself well to be combined with, and thus potentially augment, exposure-based treatment for PTSD. In this review, we discuss the behavioral model of threat and safety learning and memory as it relates to PTSD, the underlying neurobiology of PTSD, as well as the current understandings of tDCS action, including its limitations and opportunities. Through this lens, we summarize the research on the application of tDCS to modulated threat and safety learning and memory to date, and propose new directions for its future research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Early warnings of regime shifts: a whole-ecosystem experiment.

Catastrophic ecological regime shifts may be announced in advance by statistical early warning signals such as slowing return rates from perturbation and rising variance. The theoretical background for these indicators is rich, but real-world tests are rare, especially for whole ecosystems. We tested the hypothesis that these statistics would be early warning signals for an experimentally induced regime shift in an aquatic food web. We gradually added top predators to a lake over 3 years to destabilize its food web. An adjacent lake was monitored simultaneously as a reference ecosystem. Warning signals of a regime shift were evident in the manipulated lake during reorganization of the food web more than a year before the food web transition was complete, corroborating theory for leading indicators of ecological regime shifts.

Leading indicators of trophic cascades.

Regime shifts are large, long-lasting changes in ecosystems. They are often hard to predict but may have leading indicators which are detectable in advance. Potential leading indicators include wider swings in dynamics of key ecosystem variables, slower return rates after perturbation and shift of variance towards lower frequencies. We evaluated these indicators using a food web model calibrated to long-term whole-lake experiments. We investigated whether impending regime shifts driven by gradual increase in exploitation of the top predator can create signals that cascade through food webs and be discerned in phytoplankton. Substantial changes in standard deviations, return rates and spectra occurred near the switch point, even two trophic levels removed from the regime shift in fishes. Signals of regime shift can be detected well in advance, if the driver of the regime shift changes much more slowly than the dynamics of key ecosystem variables which can be sampled frequently enough to measure the indicators. However, the regime shift may occur long after the driver has passed the critical point, because of very slow transient dynamics near the critical point. Thus, the ecosystem can be poised for regime shift by the time the signal is discernible. Field tests are needed to evaluate these indicators.

Emissions of nitrous oxide (N2O) from a tidal, freshwater river, the Hudson River, New York.

Rivers receive a significant fraction of the anthropogenic nitrogen applied to the world's watersheds. Environmental conditions in rivers should be conducive to the formation of N2O, and recent models suggest that rivers could constitute up to 25% of the anthropogenic contribution of N2O to the atmosphere. Few direct measurements exist, however, of N2O flux between rivers, especially large rivers, and the overlying atmosphere. We measured the concentration of N2O over a 2-year period in a large, tidal, freshwater river. We coupled these measurements with a physical model of gas exchange based on inert gas tracer additions to this river and computed the flux of N2O to the atmosphere. The tidal, freshwater Hudson River is persistently supersaturated in N2O with respect to the atmosphere, with average partial pressure of N2O (pN2O) of 0.58 muatm or about 185% of atmospheric equilibrium. At all times during a 2-year cycle and at all locations sampled along a 200 km stretch of the river, the river was a net source of N2O to the atmosphere. We estimate that the tidal, freshwater Hudson River contributes 0.056 g of N2O-N m(-2) to the atmosphere annually. Despite relatively high concentrations of NO3 in the Hudson River, the tidal, freshwater river is a minor source of N2O in comparison to other rivers for which estimates exist and to components of its own watershed. The river itself accounts for only 1.3% of the total N2O contribution to the atmosphere that occurs in the Hudson watershed.

Dialysate made from dry chemicals using citric acid increases dialysis dose.

A new dry dialysate concentrate acidified with citric acid (citrate dialysate) has been used in two separate clinical studies of hemodialysis patients. The first compared a single treatment using this dialysate, with one dialysis using regular standard dialysate acidified with acetic acid (regular dialysate) in a prospective, randomized, crossover study of 74 dialyses. Changes in blood levels of electrolytes and other blood constituents during dialysis were calculated by subtracting postdialysis from predialysis blood concentrations. Compared with acetic acid dialysate, citrate dialysate was associated with significantly greater decreases in total and ionized calcium, magnesium, and chloride levels. Citrate dialysate was also associated with greater increases in serum sodium and citrate concentrations, although their postdialysis concentrations remained within or just outside normal ranges. Changes in other blood constituents were similar with both dialysates. The second study used citrate dialysate exclusively for all dialyses over a 12-week period in 25 patients. Predialysis blood samples were drawn at the start of the study and at 4-week intervals thereafter, and postdialysis blood samples were obtained after the first and last dialysis. Repeated-measure analysis showed that although predialysis blood concentrations of magnesium, potassium, and citrate remained within the normal range, there was a significant declining trend over the course of the study. At the same time, predialysis serum bicarbonate levels increased, and significantly more patients had a predialysis bicarbonate concentration within the normal range at the end of the study than at the start (15 versus 8 patients; P = 0.001, chi-square). In 19 patients (excluding 3 patients for whom the type of dialyzer was changed during the study), the dose of dialysis for the first and last dialysis was calculated by urea reduction ratio and Kt/V. There was a significant increase in both measurements without changes in dialysis time, blood and dialysate flows, or dialyzer used. The urea reduction ratio increased from 68% +/- 5.9% to 73% +/- 5.3% (P < 0. 03), and the Kt/V from 1.23 +/- 0.19 to 1.34 +/- 0.20 (P = 0.01) from the first to last dialysis, respectively. In conclusion, this citric acid dialysate was well tolerated, and intradialytic changes in blood chemistries were similar to those seen with regular dialysate. Using dialysate containing citric instead of acetic acid increases the delivered dialysis dose.

Total energy expenditure in small for gestational age infants.

OBJECTIVE: To measure total energy expenditure and body composition in small for gestational age (SGA) infants, to investigate hypermetabolism. METHODS: A cross-sectional study was performed in 52 small for gestational age (SGA) measured at 5 weeks of age, using existing data from appropriate for gestational age (AGA) infants as controls. The doubly-labelled water technique was used to assess both total energy expenditure and body composition in both cohorts of infants. RESULTS: Multiple regression analysis revealed that expressing energy expenditure per kg fat free mass adjusts for body composition in infants of this age. Regression analysis also showed that the relation between total energy expenditure and fat free mass differed between the two groups. CONCLUSION: These data indicate that for a given fat free mass, the total energy expenditure of SGA infants is greater than that of AGA infants. Such data should be taken into account when energy requirements for SGA infants are being considered.

Total energy expenditure in small for gestational age infants.

AIM: To measure total energy expenditure and body composition in small for gestational age (SGA) infants in order to investigate proposed hypermetabolism in such babies. METHODS: A cross sectional study of 52 SGA infants measured at 5 weeks of age was made, using existing data from appropriate for gestational age (AGA) infants as controls. The double labelled water technique was used to assess both total energy expenditure and body composition. RESULTS: Multiple regression analysis showed that expressing energy expenditure per kg fat free mass adjusts for body composition in infants of this age. The relation between total energy expenditure and fat free mass differed between the two groups. CONCLUSION: These data indicate that for a given fat free mass the total energy expenditure of SGA infants is greater than that of AGA infants. Such data should be taken into account when energy requirements for SGA infants are being considered.

Regulation of planktonic bacterial growth rates: The effects of temperature and resources.

We examined the potential limitation of bacterial growth by temperature and nutrients in a eutrophic lake. Dilution cultures from winter and summer were incubated at both high (>20°C) and low (4°C) temperatures and enriched with various combinations of organic carbon (C), inorganic nitrogen (N), and inorganic phosphorus (P). Bacterial abundance, (3)H-thymidine incorporation, and (3)H-leucine incorporation were measured over the growth cycle. For both winter and summer assemblages, low temperature limited growth even when resources (C, N, and P) were added. When temperature was adequate, bacterial growth in dilution cultures was co-limited by C, N, and P Additions of either C, P, or N and P alone provide little or only modest stimulation of growth, suggesting that under in situ conditions both nutrients and organic carbon limit bacterial growth. Our results provide little evidence of seasonal adaptation to low temperatures for bacterial communities in temperate lakes. Instead, bacterial growth appears to be temperature limited during winter and resource limited during summer. We propose that, in general, bacterial growth rates are temperature dependent up to a threshold, but that the patterns of change across temperature gradients are resource dependent, such that temperature has little effect on growth in resource-rich environments but a strong effect in resource-poor environments.

Carbon dioxide supersaturation in the surface waters of lakes.

Data on the partial pressure of carbon dioxide (CO(2)) in the surface waters from a large number of lakes (1835) with a worldwide distribution show that only a small proportion of the 4665 samples analyzed (less than 10 percent) were within +/-20 percent of equilibrium with the atmosphere and that most samples (87 percent) were supersaturated. The mean partial pressure of CO(2) averaged 1036 microatmospheres, about three times the value in the overlying atmosphere, indicating that lakes are sources rather than sinks of atmospheric CO(2). On a global scale, the potential efflux of CO(2) from lakes (about 0.14 x 10(15) grams of carbon per year) is about half as large as riverine transport of organic plus inorganic carbon to the ocean. Lakes are a small but potentially important conduit for carbon from terrestrial sources to the atmospheric sink.

Comparative and experimental approaches to top-down and bottom-up regulation of bacteria.

The regulation of bacterial community biomass and productivity by resources and predators is a central concern in the study of microbial food webs. Resource or bottom-up regulation refers to the limitation of bacteria by carbon and nutrients derived from allocthonous inputs, primary production, and heterotrophic production. Predatory or top-down regulation refers to the limitation of bacteria below levels supportable by resources alone. Large scale comparative studies demonstrate strong correlations between bacterial productivity and biomass, suggesting significant resource regulation. Comparisons of the abundances of heterotrophic flagellates and bacteria, however, imply that in some cases there may be top-down regulation of bacteria in eutrophic environments. Experimental studies in lakes support the importance of resource regulation and reveal little top-down control from protozoans. Increases in bacterial abundance and production with nutrient enrichment were limited in enclosure experiments with high abundances of the cladoceran, Daphnia. Regulation of bacteria by Daphnia may occur in many lakes seasonally and prevail in some lakes throughout the year where these animals sustain dense populations. In most situations, however, bacteria appear to be limited primarily by resources.

Dysphagia in cerebral palsy: a comparative study of the Exeter Dysphagia Assessment Technique and a multidisciplinary assessment.

Eighteen children with cerebral palsy in a special school, most of whom had feeding difficulties, were studied to compare the diagnostic value of the Exeter Dysphagia Assessment Technique (EDAT) with an exhaustive clinical assessment undertaken by a multidisciplinary team experienced in the diagnosis and treatment of dysphagia of neurological origin. Four feeding skills were assessed by each method independently, viz. anticipation, intraoral sensory perception, oral-motor efficiency, and pharyngeal triggering. Comparison of the two sets of results showed agreement in at least 78% of the assessed skills. The possible reasons for the few discrepancies are discussed. The noninvasive EDAT equipment was easy to use with the children, who had a range of type and severity of cerebral palsy. The test was undertaken in their familiar surroundings and took 15 to 20 min per child. Interpretation of the results showed that EDAT provided a rapid, reliable diagnostic aid which assisted in the assessment of the degree of feeding impairment within each of the four feeding skills tested.

Moral dilemma: to kill or allow to die?

The thesis of this paper is that while allowing a person to die with care can be morally justified in particular cases, the option of mercy killing can never be morally defended. There is a significant moral difference between these two concepts. Furthermore, the wedge argument, the medical fallibility argument, and the medical care and trust argument provide cogent and convincing reasons for maintaining a legal distinction between mercy killing and letting a person die.

Comparison of four methods of cleaning hollow-fiber dialyzers for reuse.

Four methods of cleaning hollow-fiber artificial kidneys (HFAKs) for reuse were compared in a prospective study. Each cleaning method was randomly assigned and HFAKs were reused until volume loss was greater than or equal to 15 ml, unless discarded for other reasons. HFAKs cleaned with 0.3 M sodium hydroxide averaged 14.5 uses, significantly better (p less than 0.01) than reverse ultrafiltration (6.4 uses), 3% hydrogen peroxide (5.7 uses), or water flush (4.7 uses). Only 1 of 10 HFAKs cleaned with NaOH was discarded owing to volume loss, whereas 25 of 30 HFAKs cleaned by the other methods were rejected for this reason. To relate changes in solute clearance to volume loss, urea and creatinine clearances were determined on HFAKs cleaned by water flush. By the fifth use the average volume had declined to 86.3% of original, but creatinine and urea clearances were reduced, respectively, to 97 and 95% of the original values.

An animal model for fungal peritonitis: evaluation of therapeutic options.

An animal model for fungal peritonitis was developed and is described. This model was used to compare various therapeutic options for Candida albicans peritonitis. Twenty-four rabbits were treated on three different protocols. Results from these protocols confirm the clinical observation that removal of the catheter is necessary for successful treatment of fungal peritonitis. Further, the combination of catheter replacement and imidazole anti-fungal therapy appears to be curative in this animal model, and suggests that by using this protocol, discontinuation of peritoneal dialysis may not be necessary.

Molybdenum availability, nitrogen limitation, and phytoplankton growth in natural waters.

Sulfate inhibits molybdate assimilation by phytoplankton, making molybdate less available in seawater than it is in freshwater. As a result, nitrogen fixation and nitrate assimilation, both processes that require molybdenum, may require a greater expenditure of energy in seawater than in freshwater. This may explain in part why coastal marine ecosystems are usually nitrogen limited whereas lakes usually are not. Experimentally increasing the ratio of sulfate to molybdate (i) inhibits molybdate uptake, (ii) slows nitrogen fixation rates, and (iii) slows the growth of organisms that use nitrate as their nitrogen source.

Long-term blood access by catheters implanted into arteriovenous fistulas of sheep.

Reliable long-term blood access in sheep was provided by implanting one or two catheters into the high velocity blood flow in the vein draining an arteriovenous fistula created in the neck. Thrombosis of the catheterized vein occurred in only one of 31 cases in which a catheter with rounded intravascular tip was used, as compared with seven in 10 cases using a sharp-tipped catheter. The mean duration of placement for all rounded-tip catheters was 228.6 days. Extrusion from the vessel occurred with 3 of 8 short catheters (2 cm intravascular length), but only after a period of more than seven months of implantation. Using a program of trice-weekly disinfection of the skin exit site, exterior portion of the catheter, and catheter lumen resulted in failure of only two catheters due to infection. Rounded-tip catheters with 5 cm intravascular length had 75% life table functional rate at 15 months. Implantation of two catheters permitted extracorporeal circulation at flows of up to 300 ml/min using a blood pump to withdraw blood from one catheter while simultaneously returning it through the second.

Barium-induced electro-mechanical uncoupling in myocardial cells.

The heart of the adult moth Hyalophora cecropia requires extracellular calcium to maintain electrogenesis as well as tension development. In this study we ask whether the processes of autorhythmicity, driven electrogenesis and tension development require calcium specifically or whether the divalent cation Ba2+ can be substituted for calcium to support these activities. Ba2+ substituted for Ca2+ in equimolar amounts caused a marked (25 mV) hyperpolarization, suppression both of pacemaker activity and of tension development in spontaneously beating semi-isolated heart cells. Heart cells bathed in Ba2+ saline and paced by action potentials (produced by external stimuli) of greatly increased amplitude, prolonged phase 2 (plateau) and increased latency, and after 30 min, no mechanical activity was observed. These changes were completely reversible when calcium was reintroduced. We conclude that Ba2+ substitution for Ca2+ is an effective electromechanical uncoupler in moth heart cells. Although Ba2+ can support electrogenesis, it cannot replace 'trigger'-Ca2+ needed to release calcium from sarcoplasmic stores to effect tension development.

Action potentials in macrophages derived from human monocytes.

The electrical activity of macrophages derived from human blood monocytes was recorded in vitro with intracellular microelectrodes and was analyzed with computer-assisted data acquisition and analysis techniques. In cells impaled 6 to 8 days after the cultures were prepared, the resting potentials reached a maximum value of -72 millivolts. The cells were electrically excitable; spikes exhibited a slow upstroke, a fast downstroke, a discrete threshold, a large overshoot, and a brief undershoot. Repetitive firing was induced by a maintained depolarizing current. A positive relation was observed between transmembrane currents and resting potential. Voltage-current relations were nonrectifying for subthreshold current injections. Since these cells had not been treated with any specific activation factors, the electrical activity recorded is evidence for the presence of voltage-dependent inward and outward currents in the membranes of mature macrophages. The electrical signals generated by these cells may be useful for the assay of sensor and effector functions of macrophages, such as chemotaxis, receptor-ligand interactions, and phagocytosis.

Evidence that phentolamine is not an inhibitor of extraneuronal uptake.

1. Tracheal segments from guinea-pigs pretreated with 6-hydroxydopamine were incubated in isoprenaline at 37 degrees C for 5 min in the absence or presence of phentolamine. Catechol-O-methyl transferase was inhibited by 100 mumol l-1 U-0521. Tissues were prepared for fluorescence histochemistry and accumulated isoprenaline in trachealis smooth muscle cells (fluorescence) was measured by microphotometry. 2. Phentolamine, in concentrations up to 100 mumol l-1, had no effect on isoprenaline fluorescence. 3. It is concluded that phentolamine does not inhibit extraneuronal uptake in concentrations used to block alpha-adrenoceptors in isolated tissue experiments. Thus, is can be present in experiments designed to examine the effects of extraneuronal uptake inhibitor drugs on beta-adrenoceptor-mediated responses.