Subjective feelings associated with expectations and rewards during risky decision-making in impulse control disorder.

Impulse Control Disorder (ICD) in Parkinson's disease is a behavioral addiction induced by dopaminergic therapies, but otherwise unclear etiology. The current study investigates the interaction of reward processing variables, dopaminergic therapy, and risky decision-making and subjective feelings in patients with versus without ICD. Patients with (n = 18) and without (n = 12) ICD performed a risky decision-making task both 'on' and 'off' standard-of-care dopaminergic therapies (the task was performed on 2 different days with the order of on and off visits randomized for each patient). During each trial of the task, participants choose between two options, a gamble or a certain reward, and reported how they felt about decision outcomes. Subjective feelings of 'pleasure' are differentially driven by expectations of possible outcomes in patients with, versus without ICD. While off medication, the influence of expectations about risky-decisions on subjective feelings is reduced in patients with ICD versus without ICD. While on medication, the influence of expected outcomes in patients with ICD versus without ICD becomes similar. Computational modeling of behavior supports the idea that latent decision-making factors drive subjective feelings in patients with Parkinson's disease and that ICD status is associated with a change in the relationship between factors associated with risky behavior and subjective feelings about the experienced outcomes. Our results also suggest that dopaminergic medications modulate the impact expectations have on the participants' subjective reports. Altogether our results suggest that expectations about risky decisions may be decoupled from subjective feelings in patients with ICD, and that dopaminergic medications may reengage these circuits and increase emotional reactivity in patients with ICD.

Use of Quantitative Electroencephalography to Inform Age- and Sex-Related Differences in NMDA Receptor Function Following MK-801 Administration.

Sex- and age-related differences in symptom prevalence and severity have been widely reported in patients with schizophrenia, yet the underlying mechanisms contributing to these differences are not well understood. N-methyl-D-aspartate (NMDA) receptor hypofunction contributes to schizophrenia pathology, and preclinical models often use NMDA receptor antagonists, including MK-801, to model all symptom clusters. Quantitative electroencephalography (qEEG) represents a translational approach to measure neuronal activity, identify targetable biomarkers in neuropsychiatric disorders and evaluate possible treatments. Abnormalities in gamma power have been reported in patients with schizophrenia and correspond to psychosis and cognitive impairment. Further, as gamma power reflects cortical glutamate and GABA signaling, it is highly sensitive to changes in NMDA receptor function, and NMDA receptor antagonists aberrantly increase gamma power in rodents and humans. To evaluate the role of sex and age on NMDA receptor function, MK-801 (0.03-0.3 mg/kg, SC) was administered to 3- and 9-month-old male and female Sprague-Dawley rats that were implanted with wireless EEG transmitters to measure cortical brain function. MK-801-induced elevations in gamma power were observed in 3-month-old male and female and 9-month-old male rats. In contrast, 9-month-old female rats demonstrated blunted maximal elevations across a wide dose range. Importantly, MK-801-induced hyperlocomotor effects, a common behavioral screen used to examine antipsychotic-like activity, were similar across all groups. Overall, sex-by-age-related differences in gamma power support using qEEG as a translational tool to evaluate pathological progression and predict treatment response across a heterogeneous population.

Subsecond fluctuations in extracellular dopamine encode reward and punishment prediction errors in humans.

In the mammalian brain, midbrain dopamine neuron activity is hypothesized to encode reward prediction errors that promote learning and guide behavior by causing rapid changes in dopamine levels in target brain regions. This hypothesis (and alternatives regarding dopamine's role in punishment-learning) has limited direct evidence in humans. We report intracranial, subsecond measurements of dopamine release in human striatum measured, while volunteers (i.e., patients undergoing deep brain stimulation surgery) performed a probabilistic reward and punishment learning choice task designed to test whether dopamine release encodes only reward prediction errors or whether dopamine release may also encode adaptive punishment learning signals. Results demonstrate that extracellular dopamine levels can encode both reward and punishment prediction errors within distinct time intervals via independent valence-specific pathways in the human brain.

Valence-partitioned learning signals drive choice behavior and phenomenal subjective experience in humans.

How the human brain generates conscious phenomenal experience is a fundamental problem. In particular, it is unknown how variable and dynamic changes in subjective affect are driven by interactions with objective phenomena. We hypothesize a neurocomputational mechanism that generates valence-specific learning signals associated with 'what it is like' to be rewarded or punished. Our hypothesized model maintains a partition between appetitive and aversive information while generating independent and parallel reward and punishment learning signals. This valence-partitioned reinforcement learning (VPRL) model and its associated learning signals are shown to predict dynamic changes in 1) human choice behavior, 2) phenomenal subjective experience, and 3) BOLD-imaging responses that implicate a network of regions that process appetitive and aversive information that converge on the ventral striatum and ventromedial prefrontal cortex during moments of introspection. Our results demonstrate the utility of valence-partitioned reinforcement learning as a neurocomputational basis for investigating mechanisms that may drive conscious experience.

Computational reinforcement learning, reward (and punishment), and dopamine in psychiatric disorders.

In the DSM-5, psychiatric diagnoses are made based on self-reported symptoms and clinician-identified signs. Though helpful in choosing potential interventions based on the available regimens, this conceptualization of psychiatric diseases can limit basic science investigation into their underlying causes. The reward prediction error (RPE) hypothesis of dopamine neuron function posits that phasic dopamine signals encode the difference between the rewards a person expects and experiences. The computational framework from which this hypothesis was derived, temporal difference reinforcement learning (TDRL), is largely focused on reward processing rather than punishment learning. Many psychiatric disorders are characterized by aberrant behaviors, expectations, reward processing, and hypothesized dopaminergic signaling, but also characterized by suffering and the inability to change one's behavior despite negative consequences. In this review, we provide an overview of the RPE theory of phasic dopamine neuron activity and review the gains that have been made through the use of computational reinforcement learning theory as a framework for understanding changes in reward processing. The relative dearth of explicit accounts of punishment learning in computational reinforcement learning theory and its application in neuroscience is highlighted as a significant gap in current computational psychiatric research. Four disorders comprise the main focus of this review: two disorders of traditionally hypothesized hyperdopaminergic function, addiction and schizophrenia, followed by two disorders of traditionally hypothesized hypodopaminergic function, depression and post-traumatic stress disorder (PTSD). Insights gained from a reward processing based reinforcement learning framework about underlying dopaminergic mechanisms and the role of punishment learning (when available) are explored in each disorder. Concluding remarks focus on the future directions required to characterize neuropsychiatric disorders with a hypothesized cause of underlying dopaminergic transmission.

Pregestational oxycodone exposure does not impact future maternal care or drug preference in the postpartum mouse.

Females are uniquely sensitive to drugs of abuse at specific points in their reproductive cycle. Females' endogenous opioid system contributes to both reward-related processes and maternally relevant physiological functions, yet less is known about how adolescent opioid exposure impacts females' future behavior, ranging from parental caregiving to opioid preference. The present study explores 2 questions: (a) are there sex differences in response to adolescent oxycodone exposure, spontaneous withdrawal, and oxycodone preference in adulthood, and (b) to what extent does this pregestational opioid exposure alter females' future maternal caregiving behavior? Female and male mice received 12d of oxycodone or saline injections during mid/late adolescence, and drug was then withheld. Some females were then mated and experienced a drug-free pregnancy. Following parturition, females' maternal behavior and motivation were assessed. All mice then underwent a place conditioning procedure to assess the incentive value of oxycodone during adulthood. Mice displayed similar behavioral responses to oxycodone (e.g., sensitization) and patterns of withdrawal behaviors, independent of sex. Mice showed strong group preferences for the oxycodone-paired chamber, and the strength of these preferences did not differ by sex or maternal status. Postpartum females' maternal behavior and motivation were also similar despite adolescent drug history. Together, results did not suggest overt sex differences in response to adolescent oxycodone exposure and that, in females, a range of motivated behaviors may be relatively resilient to such perturbations during adolescence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Factors contributing to racial differences in gait mechanics differ by sex.

BACKGROUND: Racial differences in gait mechanics have been recently reported, but we don't know what factors may drive differences in gait and whether these factors are innate or modifiable. The answers to those questions will inform both basic research and clinical interventions and outcomes. RESEARCH QUESTION: Do anthropometric, strength, and health status measures explain racial differences in gait between African Americans (AA) and white Americans (WA)? METHODS: Venous blood samples, anthropometric measures, lower extremity strength, and an assessment of health status were collected from 92 participants (18-30 years old) as part of an Institutional Review Board-approved study. 3D motion capture and force plate data were recorded during 7 walking trials at set regular (1.35 m/s) and fast (1.6 m/s) speeds. Racial differences in gait were identified at both speeds. Correlations between anthropometric, strength, and health status independent variables and outcome measures were computed after stratifying data by sex. Stepwise linear regression models evaluated whether the inclusion of anthropometric, strength, and health status independent variables explained racial effects. RESULTS: In males, no racial differences in gait were explained by independent variables. Q-angle and ankle dorsiflexion strength accounted for racial differences in self-selected walking speed in females. Racial differences in ankle plantarflexion angle were explained by ankle plantarflexion strength differences. SIGNIFICANCE: Factors that explain racial differences in gait in females were both innate and modifiable. These data make clear that it is important to include racially diverse normative gait databases in research studies. These results also identify potential intervention targets aimed at reducing racial health disparities.

Partial mGlu5 Negative Allosteric Modulator M-5MPEP Demonstrates Antidepressant-Like Effects on Sleep Without Affecting Cognition or Quantitative EEG.

Selective negative allosteric modulators (NAMs) targeting the metabotropic glutamate receptor subtype 5 (mGlu5) demonstrate anxiolytic-like and antidepressant-like effects yet concern regarding adverse effect liability remains. Functional coupling of mGlu5 with ionotropic N-methyl-D-aspartate receptors (NMDARs) represents a potential mechanism through which full inhibition leads to adverse effects, as NMDAR inhibition can induce cognitive impairments and psychotomimetic-like effects. Recent development of "partial" mGlu5 NAMs, characterized by submaximal but saturable levels of blockade, may represent a novel development approach to broaden the therapeutic index of mGlu5 NAMs. This study compared the partial mGlu5 NAM, M-5MPEP, with the full mGlu5 NAM, VU0424238 on sleep, cognition, and brain function alone and in combination with a subthreshold dose of the NMDAR antagonist, MK-801, using a paired-associates learning (PAL) cognition task and electroencephalography (EEG) in rats. M-5MPEP and VU0424238 decreased rapid eye movement (REM) sleep and increased REM sleep latency, both putative biomarkers of antidepressant-like activity. Neither compound alone affected accuracy, but 30 mg/kg VU0424238 combined with MK-801 decreased accuracy on the PAL task. Using quantitative EEG, VU0424238, but not M-5MPEP, prolonged arousal-related elevations in high gamma power, and, in combination, VU0424238 potentiated effects of MK-801 on high gamma power. Together, these studies further support a functional interaction between mGlu5 and NMDARs that may correspond with cognitive impairments. Present data support further development of partial mGlu5 NAMs given their potentially broader therapeutic index than full mGlu5 NAMs and use of EEG as a translational biomarker to titrate doses aligning with therapeutic versus adverse effects.

Cues play a critical role in estrous cycle-dependent enhancement of cocaine reinforcement.

While preclinical work has aimed to outline the neural mechanisms of drug addiction, it has overwhelmingly focused on male subjects. There has been a push in recent years to incorporate females into existing addiction models; however, males and females often have different behavioral strategies, making it important to not only include females, but to develop models that assess the factors that comprise female drug addiction. Traditional self-administration models often include light or tone cues that serve as discriminative stimuli and/or consequent stimuli, making it nearly impossible to disentangle the effects of cue learning, the cues themselves, and acute effects of psychostimulant drugs. To disentangle the interaction between drug-associated cues and the consummatory and appetitive responding driven by cocaine, we have developed a new behavioral procedure that combines Pavlovian-instrumental transfer with behavioral economic analysis. This task can be completed within a single session, allowing for studies looking at estrous cycle stage-dependent effects in intact cycling females, something that has been difficult in the past. In this study, we found no differences in self-administration across the estrous cycle in the absence of cues; however, when cues were introduced, the cues that acquired value during estrus-but not during diestrus or in males-increased motivation. Cues paired during estrus also increased c-fos expression to a greater extent in striatal regions, an effect that may underlie the observed increases in seeking induced by these cues, even weeks later. Together, these data suggest that fundamental differences in the motivational properties of psychostimulant drugs between males and females are complex and are driven primarily by the interaction between drug-associated stimuli and drug effects.

Burst-suppression ratio underestimates absolute duration of electroencephalogram suppression compared with visual analysis of intraoperative electroencephalogram.

BACKGROUND: Machine-generated indices based on quantitative electroencephalography (EEG), such as the patient state index (PSI™) and burst-suppression ratio (BSR), are increasingly being used to monitor intraoperative depth of anaesthesia in the endeavour to improve postoperative neurological outcomes, such as postoperative delirium (POD). However, the accuracy of the BSR compared with direct visualization of the EEG trace with regard to the prediction of POD has not been evaluated previously. METHODS: Forty-one consecutive patients undergoing non-cardiac, non-intracranial surgery with general anaesthesia wore a SedLine ® monitor during surgery and were assessed after surgery for the presence of delirium with the Confusion Assessment Method. The intraoperative EEG was scanned for absolute minutes of EEG suppression and correlated with the incidence of POD. The BSR and PSI™ were compared between patients with and without POD. RESULTS: Visual analysis of the EEG by neurologists and the SedLine ® -generated BSR provided a significantly different distribution of estimated minutes of EEG suppression ( P =0.037). The Sedline ® system markedly underestimated the amount of EEG suppression. The number of minutes of suppression assessed by visual analysis of the EEG was significantly associated with POD ( P =0.039), whereas the minutes based on the BSR generated by SedLine ® were not associated with POD ( P =0.275). CONCLUSIONS: Our findings suggest that SedLine ® (machine)-generated indices might underestimate the minutes of EEG suppression, thereby reducing the sensitivity for detecting patients at risk for POD. Thus, the monitoring of machine-generated BSR and PSI™ might benefit from the addition of a visual tracing of the EEG to achieve a more accurate and real-time guidance of anaesthesia depth monitoring and the ultimate goal, to reduce the risk of POD.

A new Caenorhabditis elegans model of human huntingtin 513 aggregation and toxicity in body wall muscles.

Expanded polyglutamine repeats in different proteins are the known determinants of at least nine progressive neurodegenerative disorders whose symptoms include cognitive and motor impairment that worsen as patients age. One such disorder is Huntington's Disease (HD) that is caused by a polyglutamine expansion in the human huntingtin protein (htt). The polyglutamine expansion destabilizes htt leading to protein misfolding, which in turn triggers neurodegeneration and the disruption of energy metabolism in muscle cells. However, the molecular mechanisms that underlie htt proteotoxicity have been somewhat elusive, and the muscle phenotypes have not been well studied. To generate tools to elucidate the basis for muscle dysfunction, we engineered Caenorhabditis elegans to express a disease-associated 513 amino acid fragment of human htt in body wall muscle cells. We show that this htt fragment aggregates in C. elegans in a polyglutamine length-dependent manner and is toxic. Toxicity manifests as motor impairment and a shortened lifespan. Compared to previous models, the data suggest that the protein context in which a polyglutamine tract is embedded alters aggregation propensity and toxicity, likely by affecting interactions with the muscle cell environment.

Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery.

INTRODUCTION: Postoperative delirium is common in older patients. Despite its prognostic significance, the pathophysiology is incompletely understood. Although many risk factors have been identified, no reversible factors, particularly ones potentially modifiable by anaesthetic management, have been identified. The goal of this prospective cohort study was to investigate whether intraoperative hypotension was associated with postoperative delirium in older patients undergoing major non-cardiac surgery. METHODS: Study subjects were patients >65 years of age, undergoing major non-cardiac surgery, who were enrolled in an ongoing prospective observational study of the pathophysiology of postoperative delirium. Intraoperative blood pressure was measured and predefined criteria were used to define hypotension. Delirium was measured by the Confusion Assessment Method on the first two postoperative days. Data were analysed using t-tests, two-sample proportion tests and ordered logistic regression multivariable models, including correction for multiple comparisons. RESULTS: Data from 594 patients with a mean age of 73.6 years (sd 6.2) were studied. Of these 178 (30%) developed delirium on day 1 and 176 (30%) on day 2. Patients developing delirium were older, more often female, had lower preoperative cognitive scores, and underwent longer operations. Relative hypotension (decreases by 20, 30, or 40%) or absolute hypotension [mean arterial pressure (MAP)<50 mm Hg] were not significantly associated with postoperative delirium, nor was the duration of hypotension (MAP<50 mm Hg). Conversely, intraoperative blood pressure variance was significantly associated with postoperative delirium. DISCUSSION: These results showed that increased blood pressure fluctuation, not absolute or relative hypotension, was predictive of postoperative delirium.

Pilot clinical trial of gabapentin to decrease postoperative delirium in older patients.

In this randomized pilot clinical trial, the authors tested the hypothesis that using gabapentin as an add-on agent in the treatment of postoperative pain reduces the occurrence of postoperative delirium. Postoperative delirium occurred in 5/12 patients (42%) who received placebo vs 0/9 patients who received gabapentin, p = 0.045. The reduction in delirium appears to be secondary to the opioid-sparing effect of gabapentin.

Nitrous oxide does not change the incidence of postoperative delirium or cognitive decline in elderly surgical patients.

BACKGROUND: Postoperative delirium and cognitive decline are common in elderly surgical patients after non-cardiac surgery. Despite this prevalence and clinical importance, no specific aetiological factor has been identified for postoperative delirium and cognitive decline. In experimental setting in a rat model, nitrous oxide (N(2)O) produces neurotoxic effect at high concentrations and in an age-dependent manner. Whether this neurotoxic response may be observed clinically has not been previously determined. We hypothesized that in the elderly patients undergoing non-cardiac surgery, exposure to N(2)O resulted in an increased incidence of postoperative delirium than would be expected for patients not receiving N(2)O. METHODS: Patients who were >or=65 yr of age, undergoing non-cardiac surgery and requiring general anaesthesia were randomized to receive an inhalational agent and either N(2)O with oxygen or oxygen alone. A structured interview was conducted before operation and for the first two postoperative days to determine the presence of delirium using the Confusion Assessment Method. RESULTS: A total of 228 patients were studied with a mean (range) age of 73.9 (65-95) yr. After operation, 43.8% of patients developed delirium. By multivariate logistic regression, age [odds ratio (OR) 1.07; 95% confidence interval (CI) 1.02-1.26], dependence on performing one or more independent activities of daily living (OR 1.54; 95% CI 1.01-2.35), use of patient-controlled analgesia for postoperative pain control (OR 3.75; 95% CI 1.27-11.01) and postoperative use of benzodiazepine (OR 2.29; 95% CI 1.21-4.36) were independently associated with an increased risk for postoperative delirium. In contrast, the use of N(2)O had no association with postoperative delirium. CONCLUSIONS: Exposure to N(2)O resulted in an equal incidence of postoperative delirium when compared with no exposure to N(2)O.

Effects of colonoscopy on intracranial pressure: observation in a large animal model.

BACKGROUND AND STUDY AIMS: Increased intra-abdominal pressure has been associated with increased intracranial pressure. Bowel insufflation during colonoscopy may increase the intra-abdominal pressure. It was hypothesized that colonoscopy may be associated with intracranial pressure elevation subsequent to an elevation in intra-abdominal pressure. MATERIALS AND METHODS: Colonoscopy was carried out in seven anesthetized pigs, and the colonoscope was advanced up to 60 cm from the anal verge. Insufflation was used to allow safe advancement of the colonoscope and to allow visualization of the colon, in the same way as in the procedure performed in humans. Intra-abdominal pressure was measured by determining the hydrostatic pressure in the urinary bladder. A subarachnoid screw was used to monitor intracranial pressure. The mean arterial blood pressure and intra-abdominal venous pressure were directly monitored via the femoral vessel access; all parameters were recorded before and during colonoscopy. RESULTS: A statistically significant elevation in intracranial pressure was demonstrated during colonoscopy. The average increase in intracranial pressure was 3.1 mm Hg. The intra-abdominal pressure and intra-abdominal venous pressure were also significantly elevated during the procedure. CONCLUSIONS: Colonoscopy may increase intracranial pressure due to an increase in intra-abdominal pressure. This may have clinical implications when colonoscopy is conducted in patients with brain pathology associated with high intracranial pressure.

Reduced employment in caregivers of frail elders: impact of ethnicity, patient clinical characteristics, and caregiver characteristics.

BACKGROUND: Without family caregivers, many frail elders who live at home would require nursing home care. However, providing care to frail elders requires a large time commitment that may interfere with the caregiver's ability to work. Our goal was to determine the patient and caregiver characteristics associated with the reduction of employment hours in caregivers of frail elders. METHODS: This was a cross-sectional study of 2806 patients (mean age 78, 73% women, 29% African American, 12% Hispanic, 54% with dementia) with at least one potentially working caregiver (defined as one who is either currently employed or who would have been employed if they had not been providing care) and their 4592 potentially working caregivers. Patients were enrollees at 11 sites of the Program of All-Inclusive Care for the Elderly (PACE). Social workers interviewed patients and caregivers at the time of PACE enrollment. Caregivers were asked if they had reduced the hours they worked or had stopped working to care for the patient. Nurses interviewed patients and caregivers to assess independence in activities of daily living (ADLs) and the presence of behavioral disturbances. Comorbid conditions were assessed by physicians during enrollment examinations. RESULTS: A total of 604 (22%) of the 2806 patients had at least one caregiver who either reduced the number of hours they worked or quit working to care for the patient. Patient characteristics independently associated with a caregiver reducing hours or quitting work were ethnicity, 95% confidence interval [CI] 1.14-1.78 for African American;, 95% CI 1.43-2.52 for Hispanic), ADL function below the median (, 95% CI 1.44-2.15), a diagnosis of dementia (, 95% -2.17 if associated with a behavioral disturbance;, 95% CI 1.06-1.63 if not associated with a behavioral disturbance), or a history of stroke (OR = 1.42, 95% CI 1.16-1.73). After controlling for these patient characteristics, caregiver characteristics associated with reducing work hours included being the daughter or daughter-in-law of the patient (OR = 1.69, 95% CI 1.37-2.08) and living with the patient (OR = 4.66, 95% CI 3.65-5.95 if no other caregiver lived at home, OR = 2.53, 95% CI 2.03-3.14 if another caregiver lived at home). CONCLUSIONS: Many caregivers reduce the number of hours they work to care for frail elderly relatives. The burden of reduced employment is more likely to be incurred by the families of ethnic minorities and of patients with specific clinical characteristics. Daughters and caregivers who live with the patient are more likely to reduce work hours than other caregivers. Future research should examine the impact of lost caregiver employment on patients' families and the ways in which the societal responsibility of caring for frail elders can be equitably shared.

Tungsten oxo salicylate complexes from tungsten hexachloride reactions systems.

Tungsten hexachloride is a potent halogen-transfer agent, capable of reacting directly with salicylic acid to generate a tungsten oxo fragment and salicoyl chloride. As a result, oxo complexes dominate the chemistry of tungsten(VI) salicylates. Both mono- and disalicylate substituted tungsten oxo complexes are accessible. The Brønsted free acid W(=O)Cl(Hsal)(sal) complex is a sparingly soluble, presumably polymeric material that can be dissolved in THF. The THF adduct has been characterized by NMR spectroscopy, although an X-ray crystallographic study indicates that the product cocrystallizes with a structurally analogous d(1) WCl(2)(Hsal.THF)(sal) byproduct. The remaining chloride ligand in W(=O)Cl(Hsal)(sal) is replaced by a bridging oxo unit when the reaction contains a significant excess of salicylic acid. The product "linear" oxo bridged ditungsten complex, [W(=O)(Hsal)(sal)](2)O, forms intramolecular hydrogen bonds, accounting for its high solubility in noncoordinating solvents. An X-ray study shows that the intramolecular Hsal.sal hydrogen bonding in this complex accommodates a more linear W-O-W arrangement than does a previously observed class of isostructural diolate derivatives. Tungsten oxo tetrachloride, formed in the initial reaction between salicylic acid and WCl(6), also reacts with the salicoyl chloride byproduct to generate tungsten salicoylate (OAr-2-COCl) complexes.

Structural diversity in a family of copper(I) thioether complexes.

Copper(I) complexes of the tridentate thioether ligands [PhB(CH(2)SCH(3))(3)] (abbreviated PhTt), [PhB(CH(2)SPh)(3)] (PhTt(Ph)), [PhB(CH(2)S(t)()Bu)(3)] (PhTt(t)()(Bu)), and [PhB(CH(2)S(p)()Tol)(3)] (PhTt(p)()(Tol)) and bidentate thioether ligands [Ph(2)B(CH(2)SCH(3))(2)] (Ph(2)Bt), [Et(2)B(CH(2)SCH(3))(2)] (Et(2)Bt), and [Ph(2)B(CH(2)SPh)(2)] (Ph(2)Bt(Ph)) have been prepared and characterized. The solution and solid state structures are highly sensitive to the identity of the borato ligand employed. Ligands possessing the smaller (methylthio)methyl donors, [PhTt] and [Ph(2)Bt], yielded tetrameric species, [(PhTt)Cu](4) and [(Ph(2)Bt)Cu](4), containing both terminal and bridging thioether ligation. The ligands containing the larger (arylthio)methyl groups, [PhTt(Ph)] and [PhTt(p)()(Tol)], form monomeric [PhTt(Ar)]Cu(NCCH(3)) in solution and one-dimensional extended structures in the solid state. Each complex type reacted cleanly with acetonitrile, pyridine, or triphenylphosphine generating the corresponding four-coordinate monomer, of which [PhTt(Ph)]Cu(PPh(3)), [PhTt(p)()(Tol)]Cu(PPh(3)), and [Et(2)Bt]Cu(PPh(3))(2) have been structurally characterized.

Measurement properties of Skindex-16: a brief quality-of-life measure for patients with skin diseases.

BACKGROUND: An accurate, sensitive, but brief quality-of-life outcomes measure is needed for studies of dermatologic care. OBJECTIVE: To construct a single-page version of Skindex (a dermatologic quality-of-life instrument) that would have two new features compared with the current 29-item version: (1) fewer items to which a majority of patients choose the same response, and (2) measurement of bother rather than frequency of patient experiences. METHODS: Random samples of patients waiting for dermatology appointments in clinics of Veterans Affairs hospitals and in private dermatology practices completed questionnaires; 692 patients responded to the parent instrument and 541 additional patients responded to the brief version. Reproducibility, internal consistency reliability, validity, and responsiveness of the brief version of Skindex were determined. RESULTS: For 16 items of the current 29-item version (55%), more than 50% of patients responded "Never." After an explicit process of item analysis and elimination, a single-page 16-item version was composed that asks patients about bother from their experiences; responses are reported as three scales, Symptoms, Emotions, and Functioning. For 6 items of the 16-item version (38%), more than 50% of patients responded "Never." Scale scores were reproducible after 72 hours (r = 0.88-0.90) and were internally reliable (Cronbach's alpha = 0.86-0.93). The instrument demonstrated both content and construct validity: Most patients' responses to an open-ended question about their skin disease was addressed by the items; patients with inflammatory dermatoses had higher scores than those with isolated lesions; and in an exploratory principal axes factor analysis with an oblique rotation, 74% of the common variance was explained by three factors that correlated with the a priori scales. Mean scale scores stayed the same or changed in the expected direction in patients who reported that their skin was the same or had improved. CONCLUSION: This brief single-page version of Skindex accurately and sensitively measures how much patients are bothered by their skin conditions.