Reward mediates the association between engagement in noneating activities and state body dissatisfaction: An ecological momentary assessment study.

OBJECTIVE: Momentary worsening (i.e., greater than one's average levels) of state body dissatisfaction (BD) has been implicated as a proximal risk factor for eating disorder (ED) behaviors in binge-spectrum EDs. Yet, research exploring the prospective association between noneating activities in daily life (e.g., chores, self-care/coping) and momentary state BD remains limited. Understanding the momentary link between engagement in noneating activities and state BD, and pathways through which engagement in said activities influences momentary state BD is critical to informing treatments. The current ecological momentary assessment (EMA) study examined whether (1) engagement in noneating activities at Time 1 prospectively predicted momentary state BD at Time 2 and (2) reward drawn from noneating activities at Time 1 mediates the prospective association between engagement in noneating activities at Time 1 and momentary state BD at Time 2. METHOD: Sixty-six adults with transdiagnostic binge eating completed an EMA protocol over 7-14 days. Participants received six EMA signals per day (total EMA observations = 4038). Multilevel modeling was used to examine the research questions. RESULTS: Engagement in an indoor hobby, outdoor recreation, socializing, and self-care/coping strategies prospectively predicted momentary state BD improvements, while using TV/social media and cooking prospectively predicted momentary state BD worsening. Reward drawn from engagement in these noneating activities mediated the associations. DISCUSSION: If replicated, these findings suggest that increasing the frequency of certain noneating activities and enhancing their rewarding aspects to improve state BD and decrease ED behavior risk during treatment may be worthy of further exploration. PUBLIC SIGNIFICANCE: Momentary worsening of state body dissatisfaction (BD) is a risk factor for eating disorder behaviors in individuals with binge eating. This study found that engaging in certain noneating activities (e.g., socializing) prospectively predicted momentary improvements in state BD, while other noneating activities (e.g., cooking) predicted momentary worsening of state BD. Reward drawn from activities mediated these relations. To improve state BD, treatments should target the frequency of, and reward obtained from these noneating activities.

Prefrontal cortex activation by binge-eating status in individuals with obesity while attempting to reappraise responses to food using functional near infrared spectroscopy.

PURPOSE: Difficulty reappraising drives to consume palatable foods may promote poorer inhibition and binge eating (BE) in adults with obesity, but neural underpinnings of food-related reappraisal are underexamined. METHODS: To examine neural correlates of food-related reappraisal, adults with obesity with and without BE wore a portable neuroimaging tool, functional near-infrared spectroscopy (fNIRS). fNIRS measured activity in the prefrontal cortex while participants watched videos of food and attempt to "resist" the food stimuli (i.e., "consider the negative consequences of eating the food"). RESULTS: Participants (N = 32, 62.5% female; BMI 38.6 [Formula: see text] 7.1; 43.5 [Formula: see text] 13.4 y) had a BMI > 30 kg/m2. Eighteen adults (67.0% female; BMI 38.2 [Formula: see text] 7.6) reported BE (≥ 12 BE-episodes in preceding 3 months). The control group comprised 14 adults who denied BE (64.0% female; BMI 39.2 [Formula: see text] 6.6). Among the entire sample, mixed models showed significant, small hyperactivation during crave and resist compared to watch (relax) condition bilaterally in the medial superior frontal gyrus, dorsolateral areas, and middle frontal gyrus (optodes 5, 7, 9, 10, 11, and 12) in the total sample. No statistically significant differences in neural activation were observed between the BE and control group. Moreover, there were no significant group by condition interactions on neural activation. CONCLUSION: Among adults with obesity, BE status was not linked to differential activation in inhibitory prefrontal cortex areas during a food-related reappraisal task. Future research is needed with larger samples, adults without obesity, and inhibition paradigms with both behavioral and cognitive components. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies. TRIAL REGISTRATION: # NCT03113669, date April 13, 2017.

The effect of weight suppression on eating behavior: Does the intentionality of weight loss matter?

Weight suppression (WS) has been consistently related to eating pathology. The weight loss that produces weight suppression has always been assumed to be intentional, but no study has tested whether unintentional weight loss would also be associated with eating pathology. The current study examined whether the association between WS and eating pathology may be moderated by intentionality of weight loss in a community-based sample of 520 adults. Participants were categorized into low WS (<5% weight loss from highest past weight), intentional, high WS (>5% intentional weight loss), and unintentional, high WS (>5% unintentional weight loss) groups. The intentional WS group reported greater restraint than the unintentional WS and low WS groups, and the low WS group reported greater restraint and more frequent loss-of-control (LOC) eating than those with unintentional WS. Further, WS was positively related to loss-of-control eating frequency only in the intentional WS group, and negatively associated with LOC eating frequency in the low WS group. Additionally, BMI was positively associated with LOC and binge eating frequency and restraint only in the low WS group. Given the relatively high prevalence of substantial but unintended weight loss found in this study, researchers studying weight suppression should consider asking about intentionality of weight loss and analyzing their data with and without unintentional weight suppressors included in the sample.

Patency for autologous vein is superior to cadaveric vein in portal-mesenteric venous reconstruction.

BACKGROUND: Portal venous reconstruction (PVR) is often needed during resection of hepatopancreato-biliary (HPB) malignancies. Primary repair (PR), autologous vein (AV), or cryopreserved cadaveric vein (CCV) are frequently utilized, however relative patency is not well studied. METHODS: All patients undergoing PVR between 2007-2019 at our center were identified. 3-year primary patency (PP), overall survival (OS), and survival-adjusted patency (SAP) were evaluated with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: One-hundred-twenty patients were identified with a median follow-up of 11 months. PR, AV, and CCV reconstruction were used in 28 (23%), 35 (29%), and 57 (48%) patients, respectively, with two (7%), four (11%), and 29 (51%) thromboses, respectively. 3-year PP was greater for both primary repair (90%) and AV (83%) compared to CCV (33%, both p<0.001). On multivariable analysis, CCV had worse 3-year PP (HR 7.89, p=0.005) and SAP (HR 2.09, p=0.02) compared to PR; AV reconstruction had equivalent oncologic and patency-related outcomes to PR (p>0.4 for both comparisons). CONCLUSIONS: Primary patency for PR and AV reconstruction is superior to CCV for PVR during resection of HPB malignancies. AV conduit should be the preferred choice of reconstruction when PR is not achievable. Surgeons should only use CCV when factors preclude PR/AV reconstruction.

Physiologically-based pharmacokinetic model for alectinib, ruxolitinib, and panobinostat in the presence of cancer, renal impairment, and hepatic impairment.

Renal (RIP) and hepatic (HIP) impairments are prevalent conditions in cancer patients. They can cause changes in gastric emptying time, albumin levels, hematocrit, glomerular filtration rate, hepatic functional volume, blood flow rates, and metabolic activity that can modify drug pharmacokinetics. Performing clinical studies in such populations has ethical and practical issues. Using predictive physiologically-based pharmacokinetic (PBPK) models in the evaluation of the PK of alectinib, ruxolitinib, and panobinostat exposures in the presence of cancer, RIP, and HIP can help in using optimal doses with lower toxicity in these populations. Verified PBPK models were customized under scrutiny to account for the pathophysiological changes induced in these diseases. The PBPK model-predicted plasma exposures in patients with different health conditions within average 2-fold error. The PBPK model predicted an area under the curve ratio (AUCR) of 1, and 1.8, for ruxolitinib and panobinostat, respectively, in the presence of severe RIP. On the other hand, the severe HIP was associated with AUCR of 1.4, 2.9, and 1.8 for alectinib, ruxolitinib, and panobinostat, respectively, in agreement with the observed AUCR. Moreover, the PBPK model predicted that alectinib therapeutic cerebrospinal fluid levels are achieved in patients with non-small cell lung cancer, moderate HIP, and severe HIP at 1-, 1.5-, and 1.8-fold that of healthy subjects. The customized PBPK models showed promising ethical alternatives for simulating clinical studies in patients with cancer, RIP, and HIP. More work is needed to quantify other pathophysiological changes induced by simultaneous affliction by cancer and RIP or HIP.

Assessment of microRNA-146a in generalized aggressive periodontitis and its association with disease severity.

BACKGROUND AND OBJECTIVE: MicroRNA-146a (miR-146a) is a small noncoding RNA that plays a critical role in the negative regulation of the innate immune response, and the dysregulation of miR-146a has been associated with several inflammatory disorders. In generalized aggressive periodontitis (GAgP) the degree of clinical inflammation appears to be similar to that of chronic periodontitis, and, in this situation, age of onset and family history are important additional criteria for diagnosis. This study was performed to evaluate the level of miR-146a expressed in gingival tissues of patients with GAgP and its association with disease severity. MATERIAL AND METHODS: Gingival samples from 18 patients with GAgP and 10 healthy subjects were collected and the level of miR-146a and its targets, including necrosis factor-alpha, interleukin-1beta, and interleukin-6, were assessed using real-time PCR. Clinical parameters, including probing depth and clinical attachment loss, were measured and their correlations with the level of miR-146a were determined. RESULTS: Our results demonstrated an elevation in the level of miR-146a expressed in patients with GAgP compared with healthy controls (P < .001), which was directly associated with disease severity (P < .05). Overexpression of miR-146a was accompanied by a reduction in the levels of pro-inflammatory cytokines. CONCLUSIONS: Our findings suggest that there is an association between miR-146a and GAgP and imply that miR-146a may serve as an indicator of periodontal disease severity. However, further studies and additional information are required to confirm this relationship and the precise role of miR-146a in the development and/or progression of periodontitis.

The independent and interacting effects of weight suppression and admission body mass index on treatment weight change in patients with anorexia nervosa or bulimia nervosa.

OBJECTIVE: Weight suppression (WS) and body mass index (BMI) have predicted weight change in individuals with eating disorders, but the interaction between these variables is understudied. Furthermore, WS is usually measured as absolute WS-the numeric difference between current weight and highest past weight-overlooking the potentially important influence of how much a person weighed at their highest historical weight. METHOD: The current study investigated the independent and interacting effects of BMI and two measures of WS at admission on residential treatment weight change. WS measures included absolute WS and the relative WS index, the percentage of total body weight lost from highest past weight. Participants were women with anorexia nervosa (n = 357) or bulimia nervosa (n = 293) who provided complete data, 87% of the eligible treatment sample. RESULTS: In both diagnostic subsamples, BMI, absolute WS, and the relative WS index all significantly predicted weight change. The interaction between BMI and WS predicted weight change, but only when the relative WS index was used. DISCUSSION: Results highlight the potential importance of considering an individual's weight and weight history when predicting their treatment weight change and support the importance of utilizing both methods of calculating WS in future research.

The relationship of weight suppression to treatment outcomes during behavioral weight loss.

Many adults enter behavioral weight loss (BWL) programs at a weight below their highest lifetime weight. The discrepancy between highest lifetime weight and current weight is known as weight suppression (WS). Research has yet to characterize WS during BWL or investigate its relation to weight loss outcomes or treatment acceptability. Adults (N = 272) in a 12-month BWL program were assessed. WS was calculated by subtracting measured baseline weight from self-reported highest lifetime weight. Participants with higher WS lost significantly less weight than those with lower WS during treatment, although they still had clinically meaningful weight losses (e.g., participants with WS above the median: 7.8 kg; participants with WS below the median: 12.0 kg). WS was unrelated to weight losses at 24-month follow-up. Controlling for weight loss, treatment acceptability was unrelated to WS. BWL appears appropriate for those with high WS, but future research should aim to improve outcomes in this group.

Weight Suppression in Eating Disorders: a Research and Conceptual Update.

PURPOSE OF REVIEW: Weight suppression, the discrepancy between an individual's highest past weight at adult height and his or her current weight, is related to many characteristics of individuals with eating disorders. This paper reviews research findings from the past 5 years, draws several implications regarding the mechanism underlying these effects, and proposes new approaches to measuring weight suppression. RECENT FINDINGS: Studies were reviewed under the categories of anorexia nervosa, bulimia nervosa, and mixed or miscellaneous samples, with more studies falling into the last category than in the first two. Recent findings have continued to show that weight suppression is related to a wide variety of biological and behavioral features in both diagnosed and sub-clinical samples. Weight suppression promotes weight gain which is anathema to individuals with eating disorders, putting them in a biobehavioral bind that appears to prolong their disorder. Priorities for future research are to understand the mechanisms underlying the effects of weight suppression, evaluate new ways of defining weight suppression, and study its implications for modifying treatment.

Eating in the absence of hunger is related to loss-of-control eating, hedonic hunger, and short-term weight gain in normal-weight women.

Eating beyond physiological need contributes to obesity onset. Measuring this behavior could help identify those at risk for weight gain. This study measured eating in the absence of hunger (EAH) and its relationship with weight change and self-report measures related to appetite and eating behavior. EAH was assessed in 46 lean young women (69% pre-selected for weight gain proneness) after lunch and defined as the number of calories subsequently consumed from snacks. Participants also completed questionnaires, and their body weights were measured regularly over the next year. Participants consumed a mean 188 calories (±140) during the EAH test. Caloric intake during the EAH test was associated with hedonic hunger (p < .01, R2 = 0.18), loss of control eating (p < .001, R2 = 0.29), and weight gain over two months (p < .01, R2 = 0.19), controlling for baseline body mass index. All were large effect sizes. In contrast, EAH was unrelated to emotional eating, disinhibition, and longer-term weight change. Amount of the test meal eaten in a hungry state was unrelated to these variables. While EAH has mainly been examined in children, these results expand its utility to adults. EAH seems to reflect naturalistic eating behavior, as shown by its relationship with short-term weight gain, drive to overconsume foods, and loss of control over eating. EAH may be a useful test to identify young adults at risk for weight gain and/or disordered eating, and may be a target for intervention.

Conceptualizing body dissatisfaction in eating disorders within a self-discrepancy framework: a review of evidence.

Body dissatisfaction, the negative subjective evaluation of one's body, is associated with many negative psychological and physical health consequences. One conceptualization of body dissatisfaction includes an experience of discrepancy between perceived actual and ideal body shapes. This paper reviews the literature on three facets of body dissatisfaction from the framework of self-discrepancy theory: perceptions of current weight, ideal body weight, and the relative importance of conforming to ideals. We review components of body dissatisfaction among healthy individuals and eating-disordered individuals. We also address the conceptualization's relationship among body dissatisfaction, weight history, and dieting to expand the impact of body dissatisfaction research and to provide more information on the nature and treatment of eating disorders.

The relationship of alcohol use to weight loss in the context of behavioral weight loss treatment.

Despite common wisdom that reducing alcohol intake will facilitate weight loss, little research has examined whether participants in behavioral weight loss treatments actually decrease their alcohol intake, or whether reduced alcohol intake relates to weight loss outcomes in this context. This study examined the relationship of alcohol use to energy intake excluding alcohol and to weight in 283 overweight and obese adults participating in a 26-session behavioral weight loss treatment. The majority of participants consumed low to moderate levels of alcohol at baseline. Participants who consumed alcohol at baseline meaningfully reduced their alcohol intake by end-of-treatment. Alcohol use did not relate to weight at baseline or end-of-treatment when controlling for relevant demographic variables, and change in alcohol use was unrelated to weight change in the overall sample during treatment. However, end-of-treatment alcohol intake did relate to end-of-treatment energy intake excluding alcohol. In addition, behavioral impulsivity and change in alcohol intake interacted to predict weight loss, such that decreases in alcohol intake were associated with greater percent weight loss at end-of-treatment for participants with higher levels of impulsivity. Alcohol consumption may lead to overeating episodes, and highly impulsive individuals may be at risk for increased energy intake during or after episodes of drinking. Therefore, the recommendation to reduce alcohol intake in the context of behavioral weight loss treatment seems warranted, particularly for individuals with high levels of impulsivity.

Microneedles mediated-dermal delivery of Vitamin C: Formulation, characterization, cytotoxicity, and enhancement of stability.

Vitamin C (VIT C) is an antioxidant that prevents skin aging. Although dermal delivery is one of the most effective routes to transport VIT C to the skin, the impact of this route can be limited by the barrier function of the stratum corneum (SC). Additionally, VIT C rapidly oxidized and degraded under light and temperature. Therefore, this study provides an approach to utilizing microneedles (MNs) to improve the dermal delivery of VIT C and enhance its stability by incorporating a stabilizing system of ethylenediaminetetraacetic acid (EDTA) and sodium metabisulfite (Meta) within the MNs. Vitamin C microneedles (VIT C MNs) were fabricated using different biodegradable polymers and various concentrations of EDTA/Meta. VIT C MNs were evaluated for morphology, VIT C content, mechanical properties, dissolution rate, needles' insertion, physicochemical properties, ex vivo permeation, viscosity of VIT C polymeric solutions, cytotoxicity, and stability. The results showed that VIT C MNs were uniform and mechanically strong. The recovery of VIT C in MNs was 88.3-90.0 %. The dissolution rate of MNs was <30 min. The flux of VIT C varied based on the composition of MNs. VIT C MNs demonstrated safety against human dermal fibroblasts. VIT C MNs with EDTA/Meta (0.1/0.3 %) were stable under different storage conditions for two months. In conclusion, VIT C MNs were successfully developed using biodegradable polymers, and the stabilizing system (EDTA/META) provided a stable dermal delivery system for VIT C to protect skin from aging.

Results of external iliac artery reconstruction in avid cyclists.

OBJECTIVE: We report the midterm results of external iliac artery reconstruction in 25 high-performance cyclists. METHODS: Cyclists undergoing arterial reconstruction for symptomatic external iliac arteriopathy at a single institution between October 2004 and August 2010 were identified. With Institutional Review Board approval, data were collected from medical record review and telephone interview. Results were analyzed with χ(2) or independent t-test. RESULTS: Twenty-five patients (31 limbs) underwent operation, which included arterial reconstruction with or without inguinal ligament release. The average patient age at operation was 43.8 ± 5.0 for graft and 35.1 ± 1.9 for patch (P = .08). The average time from competitive cycling until operation was 18.2 ± 5.8 years for graft and 20.0 ± 2.5 for patch repairs (NS). Patients included 14 males and 11 females. There were 23 unilateral and four bilateral arterial reconstructions, including 26 patch angioplasties for localized disease and five interposition grafts for extensive disease; three patients underwent contralateral reconstruction as a separate procedure. Concomitant ipsilateral inguinal ligament release was performed in 25 patients (28 limbs), with contralateral release done in 12 patients (12 limbs). Three patients with isolated ligament release required subsequent arterial intervention. Follow-up averaged 32 months (range, 2-74). Primary patency for all reconstructions was 100%; the four reoperations (five limbs; one bilateral) were for symptom recurrence, two postgraft and two postangioplasty. Three reoperations were for recurrent intimal hyperplasia, one for disease distal to the anastomosis, and one for concomitant atherosclerotic disease. Based on available data, postexercise ankle-brachial indices were improved in 18 of 23 limbs. Seventeen patients completed questions regarding satisfaction: 10 were satisfied or very satisfied (zero graft, 10 patch; P = .25), while four were unsatisfied (three graft, two patch; P = .017, including one patient with both a patch and graft repair). All 20 patients for whom follow-up data were available are still cycling, 10 competitively. Two of the four reoperated patients were unsatisfied; all four are still cycling, one competitively. CONCLUSIONS: External iliac arteriopathy is a disease of prolonged, sustained, and repetitive trauma. Patch angioplasty yields a low rate of reoperation, more satisfied patients, return to competitive activity, and improvement in postexercise ankle-brachial indices. Interposition grafting is associated with slightly older patients, more extensive disease, and less satisfying results. Intimal hyperplasia is the most frequent complication necessitating reoperation. Both the decision to pursue arterial reconstruction and patient expectations must be tempered by the pattern of disease and the potential for unsatisfactory results.

Microemulsions as Lipid Nanosystems Loaded into Thermoresponsive In Situ Microgels for Local Ocular Delivery of Prednisolone.

This study aimed to develop and evaluate thermoresponsive in situ microgels for the local ocular delivery of prednisolone (PRD) (PRD microgels) to improve drug bioavailability and prolong ocular drug residence time. Lipid nanosystems of PRD microemulsions (PRD-MEs) were prepared and evaluated at a drug concentration of 0.25-0.75%. PRD microgels were prepared by incorporating PRD-MEs into 10 and 12% Pluronic® F127 (F127) or combinations of 12% F127 and 1-10% Kolliphor®P188 (F68). PRD microgels were characterized for physicochemical, rheological, and mucoadhesive properties, eye irritation, and stability. Results showed that PRD-MEs were clear, miscible, thermodynamically stable, and spherical with droplet size (16.4 ± 2.2 nm), polydispersity index (0.24 ± 0.01), and zeta potential (-21.03 ± 1.24 mV). The PRD microgels were clear with pH (5.37-5.81), surface tension (30.96-38.90 mN/m), size, and zeta potential of mixed polymeric micelles (20.1-23.9 nm and -1.34 to -10.25 mV, respectively), phase transition temperature (25.3-36 °C), and gelation time (1.44-2.47 min). The FTIR spectra revealed chemical compatibility between PRD and microgel components. PRD microgels showed pseudoplastic flow, viscoelastic and mucoadhesive properties, absence of eye irritation, and drug content (99.3 to 106.3%) with a sustained drug release for 16-24 h. Microgels were physicochemically and rheologically stable for three to six months. Therefore, PRD microgels possess potential vehicles for local ocular delivery.

Formulation and Evaluation of Azithromycin-Loaded Niosomal Gel: Optimization, In Vitro Studies, Rheological Characterization, and Cytotoxicity Study.

Several novel, innovative approaches for improving transdermal delivery of BCS class III drugs have been proposed. Despite their great aqueous solubility, BCS class III drugs have the drawback of limited permeability. The objective of the current work was to screen the suitability of niosomes as a nanocarrier in permeation enhancement of azithromycin (AZM) transdermal delivery. Niosomes were prepared by an ether injection method using a nonionic surfactant (Span 60) and cholesterol at different concentrations. The ζ potential (ZP), polydispersity index (PDI), and particle size (PS) of AZM-loaded niosomes were evaluated. The size of the niosomes was found to vary between 288 and 394 nm. The results revealed that the niosomes prepared in a ratio of 2:1 (Span 60: cholesterol) had larger vesicle sizes, but all of them were characterized by narrow size distributions (PDI <0.95). Niosomal gel was successfully prepared using different polymers. The appearance, pH, viscosity, and ex vivo drug release of niosomal gel formulations were all examined. The flow curves showed that the niosomal gel displayed lower viscosity values than its corresponding conventional gels. Niosomal and conventional gels exhibited a domination of the elastic modulus (G') over the viscous modulus (G″) (G'>G″) in the investigated frequency range (0.1-100 rad/s), indicating stable gels with more solid-like properties. Ex vivo skin permeation studies for the niosomal gel show 90.83 ± 3.19% of drug release in 24 h as compared with the conventional gel showing significantly lower (P < 0.001) drug release in the same duration (1.25 ± 0.12%). Overall, these results indicate that niosomal gel could be an effective transdermal nanocarrier for enhancing the permeability of AZM, a BCS class III drug. In conclusion, this study suggests that transdermal formulations of AZM in the niosomal gel were successfully developed and could be used as an alternative route of administration.

The frequency of transforming growth factor-beta1 gene polymorphisms in a normal southern Iranian population.

Several single nucleotide polymorphisms (SNPs) of the transforming growth factor-beta1 gene (TGFB1) have been reported. Determination of TGFB1 SNPs allele frequencies in different ethnic groups is useful for both population genetic analyses and association studies with immunological diseases. In this study, five SNPs of TGFB1 were determined in 325 individuals from a normal southern Iranian population using polymerase chain reaction-restriction fragment length polymorphism method. This population was in Hardy-Weinberg equilibrium for these SNPs. Of the 12 constructed haplotypes, GTCGC and GCTGC were the most frequent in the normal southern Iranian population. Comparison of genotype and allele frequencies of TGFB SNPs between Iranian and other populations (meta-analysis) showed significant differences, and in this case the southern Iranian population seems genetically similar to Caucasoid populations. However, neighbour-joining tree using Nei's genetic distances based on TGF-beta1 allele frequencies showed that southern Iranians are genetically far from people from the USA, Germany, UK, Denmark and the Czech Republic. In conclusion, this is the first report of the distribution of TGFB1 SNPs in an Iranian population and the results of this investigation may provide useful information for both population genetic and disease studies.

Characterization and effect of metal ions on the formation of the Thermus thermophilus Sco mixed disulfide intermediate.

The Sco protein from Thermus thermophilus has previously been shown to perform a disulfide bond reduction in the CuA protein from T. thermophilus, which is a soluble protein engineered from subunit II of cytochrome ba 3 oxidase that lacks the transmembrane helix. The native cysteines on TtSco and TtCuA were mutated to serine residues to probe the reactivities of the individual cysteines. Conjugation of TNB to the remaining cysteine in TtCuA and subsequent release upon incubation with the complementary TtSco protein demonstrated the formation of the mixed disulfide intermediate. The cysteine of TtSco that attacks the disulfide bond in the target TtCuA protein was determined to be TtSco Cysteine 49. This cysteine is likely more reactive than Cysteine 53 due to a higher degree of solvent exposure. Removal of the metal binding histidine, His 139, does not change MDI formation. However, altering the arginine adjacent to the reactive cysteine in Sco (Arginine 48) does alter the formation of the MDI. Binding of Cu2+ or Cu+ to TtSco prior to reaction with TtCuA was found to preclude formation of the mixed disulfide intermediate. These results shed light on a mechanism of disulfide bond reduction by the TtSco protein and may point to a possible role of metal binding in regulating the activity. IMPORTANCE: The function of Sco is at the center of many studies. The disulfide bond reduction in CuA by Sco is investigated herein and the effect of metal ions on the ability to reduce and form a mixed disulfide intermediate are also probed.

Decubitus ulcers in patients undergoing vascular operations do not influence mortality but affect resource utilization.

BACKGROUND: While it is anticipated that decubitus ulcers are detrimental to outcomes after vascular operations, the contemporary influence of perioperative decubitus ulcers in vascular surgery remains unknown. METHODS: Using the National Impatient Survey, all adult patients who underwent vascular operation were selected. Patients were stratified by the presence or absence (non-decubitus ulcers) of decubitus ulcer. Case-mix adjusted hierarchical mixed-models examined in-hospital mortality, the occurrence of any complication, and discharge disposition. RESULTS: A total of 538,808 cases were analyzed. Decubitus ulcers were most prevalent among Caucasian male Medicare beneficiaries (P < .001). Decubitus ulcer patients also underwent more nonelective vascular operations (P < .001). Wound, infectious, and procedural complications were more common in patients with decubitus ulcers (P < .001). Failure to rescue, defined as mortality after any complication, was more than doubled in decubitus ulcers (non-decubitus ulcers: 1.5%, decubitus ulcers: 3.2%, P < .001). Similarly, unadjusted mortality was also doubled in patients undergoing vascular operation with decubitus ulcers (non-decubitus ulcers: 3%, decubitus ulcers: 6%, P < .001). After risk adjustment among all patients, neither the presence of a decubitus ulcer nor specific ulcer staging increased the adjusted odds of death. Having a decubitus ulcer increased the adjusted odds of discharge to an intermediate care facility (odds ratio 2.9, P < .001). These patients also had 1.6 times the total charges compared to their non-decubitus ulcer cohort (non-decubitus ulcers: $49,460 ± $281 vs decubitus ulcers: $81,149 ± $5,855, P < .001). CONCLUSION: Contrary to common perception, perioperative decubitus ulcer does not adversely affect mortality after vascular operation in patients proceeding to operative intervention. Patients with decubitus ulcers are, however, at higher risk for complications and incur sizeable additional charges.

De-Escalation of Antibiotics Does Not Increase Mortality in Critically Ill Surgical Patients.

BACKGROUND: Overuse of broad-spectrum antibiotics results in microbial resistance and financially is a healthcare burden. Antibiotic de-escalation refers to starting treatment of a presumed infection with broad-spectrum antibiotics and narrowing drug spectrum based on culture sensitivities. A study was designed to evaluate antibiotic de-escalation at a tertiary care center. We hypothesized that antibiotic de-escalation would not be associated with increased patient mortality rates or worsening of the primary infection. METHODS: All infections treated in a single, tertiary care Surgical ICU between August 2009 and December 2011 were reviewed. Antibiotic treatment was classified by skilled reviewers as being either de-escalated or not. Outcomes were evaluated. Univariate statistics were performed (Fisher exact test, Chi-square for categorical data; student t-test for continuous variables). Multivariable logistic regression was completed. RESULTS: A total of 2,658 infections were identified. De-escalation was identified for 995 infections and non-deescalation occurred in 1,663. Patients were similar in age (de-escalated 55 ± 16 y vs. 56 ± 16, p = 0.1) and gender (de-escalated 60% males vs. 58%, p = 0.4). There were substantially greater APACHE II scores in non-deescalated patients (15 ± 8 vs. 14 ± 8, p = 0.03). A greater mortality rate among patients with infections treated without de-escalation was observed compared with those treated with de-escalation (9% vs. 6%, p = 0.002). Total antibiotic duration was substantially longer in the de-escalated group (15 ± 13 d vs. 13 ± 13, p = 0.0001). Multivariable analysis found that de-escalation decreased mortality rates (OR = 0.69; 95%CI, 0.49-0.97; p = 0.04) and high APACHE II score independently increased mortality rates (OR = 1.2; 95%CI, 1.1-1.2; p = 0.0001). Other parameters included were age and infection site. CONCLUSIONS: Antibiotic de-escalation was not associated with increased mortality rates, but the duration of antibiotic use was longer in this group. Greater mortality rates were observed in the non-deescalated group, but this likely owes at least in part to their relatively greater severity of disease classification (APACHE II). Further investigation will help evaluate whether antibiotic de-escalation will improve the quality of patient care.