Search

Background: Retromuscular sublay (RMS) technique for repair of ventral hernias has gained popularity due to lower risk of recurrence and wound complications. Robotic approaches to RMS have been shown to decrease hospital stay; however, previous studies have failed to show a significant reduction in wound morbidity. Utilizing the Abdominal Core Health Quality Collaborative (ACHQC) database, this study sought to determine the effect of robotic approach on wound morbidity, while specifically focusing on a high-risk population. Methods: A retrospective review of elective robotic and open RMS repairs in the ACHQC database was performed. Patients deemed to be high-risk for wound complications were included: adult patients with BMI greater than 35 and who were either current smokers or diabetics. A propensity score match was then done to balance covariates between the two groups. Main outcomes of concern were surgical site occurrences (SSO), surgical site infections (SSI), and surgical site occurrence requiring procedural intervention (SSOPI) at 30-day follow-up. Results: A total of 917 patients met inclusion criteria. After propensity score matching, 211 patients matched for each approach. There was no difference in overall SSO (18% for Open vs 23% for Robotic, p = 0.23). Open repair was associated with higher rates of SSI (4% vs 1%, p = 0.032) and SSOPI (9% SSOPI vs 3%, p < 0. 015). As seen in previous studies, there was a higher rate of seroma associated with Robotic RMS repair (87% vs 48%, p < 0.001) in patients that developed an SSO. Conclusions: In this analysis, a robotic approach was associated with decreased rates of SSI and SSOPI in obese patients who were either current smokers or diabetics. In effort to reduce wound morbidity and the associated physical and economic costs, robotic approach for retromuscular ventral hernia repair should be considered in this patient population. [ABSTRACT FROM AUTHOR]

Introduction: Robotic extended totally extraperitoneal hernia (eTEP) repair is a novel technique for minimally invasive ventral hernia repair with retromuscular placement of mesh. This study aimed to evaluate the learning curve for robotic eTEP hernia repair using risk-adjusted cumulative sum (RA-CUSUM) analysis for two general surgeons—one with dedicated fellowship training in robotic eTEP technique (surgeon 2) and another without robotic eTEP-specific training (surgeon 1). Methods: We conducted a retrospective analysis of 98 patients undergoing robotic eTEP hernia repair from July 2020 to February 2022 for two surgeons. RA-CUSUM method was applied to the overall operative time (OT) in minutes, adjusting for transversus abdominis release (TAR). Results: Figures 3 (surgeon 1) and 4 (surgeon 2) illustrate the three phases in the RA-CUSUM graphs of OT. For surgeon 1, the cases for each phase were determined: phase 1 (1 to 12), phase 2 (13 to 24), and phase 3 (25 to 51). For surgeon 2, the three phases were similarly determined as 1 to 8, 9 to 32, and 33 to 47, respectively. A significant (p = 0.017) difference existed for the OTs between phases 1 (262 ± 69) and 3 (192 ± 63.0) for surgeon 1. OT compared to the risk-adjusted value stabilized after case 12 and decreased after case 24 for surgeon 1; it began to decrease after case 8 for surgeon 2. Conclusions: The initial learning curve for surgeon 1 reached its plateau after 12 cases, shorter than comparable studies. This was likely due to the surgeon's intentional focus on learning this technique through courses, proctoring, and active mentorship. The flat learning curve seen in surgeon 2's series illustrates the value of experience gained during fellowship training. Our data support that, given the right resources and support, a short learning curve for eTEP is attainable for community surgeons without prior training in the technique. [ABSTRACT FROM AUTHOR]

Rationale: Little is known about how acute and chronic alcohol exposure may alter the in vivo membrane properties of neurons. Objectives: We employed neurite orientation dispersion and density imaging (NODDI) to examine acute and chronic effects of alcohol exposure on neurite density. Methods: Twenty-one healthy social drinkers (CON) and thirteen nontreatment-seeking individuals with alcohol use disorder (AUD) underwent a baseline multi-shell diffusion magnetic resonance imaging (dMRI) scan. A subset (10 CON, 5 AUD) received dMRI during intravenous infusions of saline and alcohol during dMRI. NODDI parametric images included orientation dispersion (OD), isotropic volume fraction (ISOVF), and corrected intracellular volume fraction (cICVF). Diffusion tensor imaging metrics of fractional anisotropy and mean, axial, and radial diffusivity (FA, MD, AD, RD) were also computed. Average parameter values were extracted from white matter (WM) tracts defined by the Johns Hopkins University atlas. Results: There were group differences in FA, RD, MD, OD, and cICVF, primarily in the corpus callosum. Both saline and alcohol had effects on AD and cICVF in WM tracts proximal to the striatum, cingulate, and thalamus. This is the first work to indicate that acute fluid infusions may alter WM properties, which are conventionally believed to be insensitive to acute pharmacological challenges. It also suggests that the NODDI approach may be sensitive to transient changes in WM. The next steps should include determining if the effect on neurite density differs with solute or osmolality, or both, and translational studies to assess how alcohol and osmolality affect the efficiency of neurotransmission. [ABSTRACT FROM AUTHOR]

Purpose: eHealth and mHealth approaches are increasingly used to support cancer survivors. This review aimed to examine adherence, acceptability and satisfaction with Internet-based self-management programmes for post-surgical cancer rehabilitation and to identify common components of such interventions. Methods: Nine electronic databases were searched from inception up to February 15, 2020, for relevant quantitative and qualitative studies evaluating Internet-based cancer rehabilitation interventions. Studies were required to include an exercise or physical activity–based self-management intervention and a measure of adherence, acceptability or user satisfaction with the programme. Two independent reviewers performed all data extraction and quality assessment procedures. Data were synthesized using a narrative approach. Results: Six hundred ninety-six potential papers were identified and screened. Eleven met the inclusion criteria. Interventions had wide variations in levels of adherence, but the majority were reported as being acceptable to the users. Increased acceptability and user satisfaction were associated with interventions which were seen as time and cost-efficient, requiring acquisition of minimal or no new skills, which used coherent language, or which provided tailored information. The majority contained behaviour change components such as goal setting. Conclusions: Despite high levels of heterogeneity between studies, Internet-based approaches may be an acceptable method for the delivery of self-management interventions in post-surgical cancer rehabilitation. Implications for Cancer Survivors: There is a need for further studies exploring factors associated with increased user engagement and usage of digital interventions in cancer rehabilitation settings. These findings should be used to help develop interventions prior to testing their effectiveness in adequately powered randomized controlled trials. [ABSTRACT FROM AUTHOR]

Rationale: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication.Objectives: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian-conditioned stimuli in fMRI when subjects were not intoxicated.Methods: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (conditioned stimulus; CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS−) infusion at matched rates. On day 2, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS−, and an irrelevant symbol.Results: CS+ elicited stronger activation than CS− in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS−] activation. Delay-tolerant choice and [CS+ > CS−] activation in right inferior parietal cortex were positively related.Conclusions: Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations. [ABSTRACT FROM AUTHOR]

Rationale: Although striatal dopamine (DA) is important in alcohol abuse, the nature of DA release during actual alcohol drinking is unclear, since drinking includes self-administration of both conditioned flavor stimuli (CS) of the alcoholic beverage and subsequent intoxication, the unconditioned stimulus (US). Objectives: Here, we used a novel self-administration analog to distinguish nucleus accumbens (NAcc) DA responses specific to the CS and US. Methods: Right-handed male heavy drinkers ( n = 26) received three positron emission tomography (PET) scans with the D/D radioligand [C]raclopride (RAC) and performed a pseudo self-administration task that separately administered a flavor CS of either a habitually consumed beer or the appetitive control Gatorade®, concomitant with the US of ethanol intoxication (0.06 g/dL intravenous (IV) administration) or IV saline. Scan conditions were Gatorade flavor + saline (Gat&Sal), Gatorade flavor + ethanol (Gat&Eth), and beer flavor + ethanol (Beer&Eth). Results: Ethanol (US) reduced RAC binding (inferring DA release) in the left (L) NAcc [Gat&Sal > Gat&Eth]. Beer flavor (CS) increased DA in the right (R) NAcc [Gat&Eth > Beer&Eth]. The combination of beer flavor and ethanol (CS + US), [Gat&Sal > Beer&Eth], induced DA release in bilateral NAcc. Self-reported intoxication during scanning correlated with L NAcc DA release. Relative to saline, infusion of ethanol increased alcoholic drink wanting. Conclusions: Our findings suggest lateralized DA function in the NAcc, with L NAcc DA release most reflecting intoxication, R NAcc DA release most reflecting the flavor CS, and the conjoint CS + US producing a bilateral NAcc response. [ABSTRACT FROM AUTHOR]

Reprogrammed glucose metabolism as a result of increased glycolysis and glucose uptake is a hallmark of cancer. Here we show that cancer cells can suppress glucose uptake by non-tumour cells in the premetastatic niche, by secreting vesicles that carry high levels of the miR-122 microRNA. High miR-122 levels in the circulation have been associated with metastasis in breast cancer patients, and we show that cancer-cell-secreted miR-122 facilitates metastasis by increasing nutrient availability in the premetastatic niche. Mechanistically, cancer-cell-derived miR-122 suppresses glucose uptake by niche cells in vitro and in vivo by downregulating the glycolytic enzyme pyruvate kinase. In vivo inhibition of miR-122 restores glucose uptake in distant organs, including brain and lungs, and decreases the incidence of metastasis. These results demonstrate that, by modifying glucose utilization by recipient premetastatic niche cells, cancer-derived extracellular miR-122 is able to reprogram systemic energy metabolism to facilitate disease progression. [ABSTRACT FROM AUTHOR]

Rationale: Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement. Objective: Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure. Methods: Twenty-two family history-positive (FHP; age = 22.7 years, SD = 1.9) and 18 family history-negative (FHN; age = 23.7, SD = 1.8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60 mg/dL, and once during infusion of placebo saline. An independent reference group ( n = 13, age = 23.7, SD = 1.8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to 'Go' trials that carried no need for inhibition [Inh > Go]. Results: FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh > Go] activation in FHN subjects but not in FHP subjects. Within this right frontal cortical region, stop-signal reaction time also correlated negatively with [Inh > Go] activation, suggesting that the [Inh > Go] activity was related to inhibitory behavior. Conclusions: The results are consistent with the low level of response theory (Schuckit, J Stud Alcohol 55:149-158, ; Quinn and Fromme, Alcohol Clin Exp Res 35:1759-1770, ), with FHP being less sensitive to alcohol's effects. [ABSTRACT FROM AUTHOR]

Rationale: Individuals learn associations between alcohol's sensory properties and intoxication, with such conditioned stimuli (CS) becoming involved in craving and relapse. However, these CS also carry idiosyncratic associations. Objectives: This study aimed to test brain responses to novel CS conditioned with alcohol intoxication. Methods: Fourteen heavy drinkers (age 24.9 ± 3.2) performed a reaction time task with embedded novel geometric CS and were told only that the task was to measure alcohol's effect on speed. Rapid intravenous alcohol infusion (the unconditioned stimulus; UCS) began with the appearance of a CS+, using pharmacokinetic modeling to increment breath alcohol by ~18 mg% in 200 s per each of six CS-UCS pairings. Placebo-saline infusion with CS− used the same infusion parameters in same-day randomized/counterbalanced sessions. The next morning subjects, connected to inactive intravenous pumps, underwent functional magnetic resonance imaging (fMRI) of the same task with mixed brief presentations of CS+, CS−, and irrelevant CS and were told that alcohol could be infused at any time during imaging. Results: CS− responses were significantly greater than those of CS+ in medial frontal cortex. Notably, CS+ responses were negative, suggesting reduced neural activity. Negative activity was most pronounced in early scans, extinguishing with time. As subjects were told that alcohol could be administered in fMRI, a CS+ without alcohol is similar to a negative prediction error, with associated reduced frontal activity during withheld reward. Conclusions: Novel stimuli relatively free of demand characteristics can be classically conditioned to intermittent brain exposure of even low alcohol concentrations, permitting imaging studies of conditioned alcohol expectancies. [ABSTRACT FROM AUTHOR]

Purpose: In studies where [C]raclopride (RAC) positron emission tomography (PET) is used to assess changes in striatal dopamine, it is important to control for cognitive states, such as drug craving, that could alter dopamine levels. In cigarette smokers, transdermal nicotine patches (TNP) can control nicotine craving, but the effects of nicotine patches on RAC binding are unknown. Thus, we sought to determine the test-retest reliability of RAC binding in the presence of nicotine patches. Methods: Eleven male smokers were scanned twice with RAC on separate days while wearing TNP. Results: Across the striatum, test-retest variability was 7.63 ± 5.88; percent change in binding potential was 1.11 ± 9.83; and the intraclass correlation coefficient was 0.91 ( p < 0.0001). Conclusion: Baseline RAC binding is highly reproducible in smokers wearing nicotine patches. This suggests that TNP are an acceptable method for controlling cigarette craving during studies that utilize RAC to examine changes in dopamine. [ABSTRACT FROM AUTHOR]

Lithium aluminosilicate inorganic polymers were synthesised from dehydroxylated kaolin-type clay (halloysite) by the conventional method under highly alkaline conditions with lithium hydroxide or lithium silicate solutions of two different Li2O/SiO2 molar ratios. Variants were also developed of a solid-state synthesis method involving the thermal reaction of dehydroxylated halloysite with LiOH followed by hydration of the product. The molar compositions of the materials prepared by all three methods (SiO2/Al2O3 = 2.41–3.27, Li2O/SiO2 = 0.30–0.61, and H2O/Li2O = 9.33–10.40) fall within the range of compositions previously reported to produce viable geopolymers. Curing at 40 °C produces solid samples of varying viability depending on the amount of synthesis water. The cured materials are not characteristically X-ray amorphous, but contain the lithium zeolites Li-ABW and fibrous Li-EDI, the latter in the materials synthesised by solid-state reaction. The 27Al and 29Si MAS NMR spectra of the cured materials contain narrow resonances more characteristic of zeolites than of inorganic polymers. Heating the synthesised products at <800 °C produces β-eucryptite, LiAlSiO4. In a further series of thermal reactions, β-spodumene, LiAlSi2O6 is formed at 900 °C, decomposing at 1100 °C to form additional β-eucryptite. At 1275 °C, β-spodumene reappears in the samples of higher silica content. Judicious manipulation of the composition and thermal treatment of the Li-zeolites formed in these lithium aluminosilicate syntheses could make them useful precursors to β-eucryptite and β-spodumene ceramics. [ABSTRACT FROM AUTHOR]

A new synthesis method is described to produce aluminosilicate inorganic polymers by direct reaction of aluminium hydroxide with amorphous silica under alkaline conditions. XRD and 27Al and 29Si MAS NMR spectroscopy suggest that the reaction mechanism involves the dissolution of the aluminium hydroxide in the alkali. The best results are obtained with more reactive gibbsite of small particle size and X-ray amorphous ρ-alumina containing 5-fold coordinated Al, and with compositions in the previously reported optimum range (SiO2: Al2O3 = 3.0, M2O: SiO2 = 0.34, H2O: M2O = 9.4). Unreacted aluminium hydroxide occurs where there is insufficient silica for complete inorganic polymer formation but the reaction is less sensitive to variations in the K2O: Al2O3 and K2O: SiO2 ratios. Zeolite formation was not observed in any of the present samples. More complex alumina sources such as thermally activated hydrotalcite can also be used to form an inorganic polymer, but under the alkaline synthesis conditions the unused alumina reacts with the poorly crystalline MgO present to re-form hydrotalcite, presumably containing atmospheric carbonate as the interlayer anion. This synthesis method can also potentially be extended to hydroxides other than those of aluminium. [ABSTRACT FROM AUTHOR]

Acute alcohol effects may differ in social drinkers with a positive family history of alcohol use disorders (FHP) compared to FH negative (FHN) controls. To investigate whether FHP subjects prefer higher levels of brain alcohol exposure than do FHN controls. Twenty-two young healthy nondependent social drinkers participated in two identical sessions of computer-assisted self-infusion of ethanol (CASE); the first for practicing the procedures, the second to test hypotheses. All 12 FHP (four women) and ten FHN (three women) participants received a priming exposure, increasing arterial blood alcohol concentration (aBAC) to 30 mg% at 10 min and decreasing it to 15 mg% at 25 min. A 2-h self-administration period followed, during which only the subjects could increase their aBAC by pressing a button connected to a computer controlling the infusion pump. Infusion rate profiles were calculated instantaneously to increase aBAC by precisely 7.5 mg% within 2.5 min after each button press, followed by a steady descent. Subjects were instructed to produce the same alcohol effects as they would do at a weekend party. The mean and maximum aBAC during the self-administration period and the number of alcohol requests (NOAR) were significantly higher in the FHP vs. FHN participants. This is the first laboratory experiment demonstrating higher alcohol self-administration in FHP compared to FHN subjects. A practice session increases the sensitivity of CASE experiments for detection of subtle differences in human alcohol self-administration. [ABSTRACT FROM AUTHOR]

The additive genetic heritability of both monopolar and bipolar EEG spectral power in a sample of 305 non-twin sibships comprising 690 individuals (age range 7–65) was estimated in order to investigate their regional variation. The heritabilities of the bipolar EEG spectral power ranged from 0.10 to 0.63 in 38 electrode-pairs, and those of monopolar power ranged from 0.23 to 0.68 in 19 electrodes in six frequency bands from theta to high beta. The bipolar data shows significantly greater topographic variation compared to that of the monopolar data. The mean of bivariate genetic correlations were consistently lower for the bipolar data and the coefficients of variation consistently higher when compared to those of the monopolar data for each of the frequency bands. The results from the bipolar derivations are in greater accord with genetic findings in brain anatomy and show the possibility of multiple genetic sources for the phenotypic variability of EEG activity. [ABSTRACT FROM AUTHOR]

We report genetic linkage and association findings which implicate the gene encoding the muscarinic acetylcholine receptor M2 ( CHRM2) in the modulation of a scalp-recorded electrophysiological phenotype. The P3 (P300) response was evoked using a three-stimulus visual oddball paradigm and a phenotype that relates to the energy in the theta band (4–5 Hz) was analyzed. Studies have shown that similar electrophysiological measures represent cognitive correlates of attention, working memory, and response selection; a role has been suggested for the ascending cholinergic pathway in the same functions. The results of our genetic association tests, combined with knowledge regarding the presence of presynaptic cholinergic M2 autoreceptors in the basal forebrain, indicate that the cognitive processes required by the experiment may in part be mediated by inhibitory neural networks. These findings underscore the utility of electrophysiology and neurogenetics in the understanding of cognitive function and the study of brain-related disorders. [ABSTRACT FROM AUTHOR]

Signal transducer and activator of transcription 3 (STAT3), normally activated by Janus kinase (JAK) in response to cytokine stimulation, has been shown to have oncogenic potential. In addition to JAK, recent data suggest that STAT3 can also be activated by other proteins such as the aberrant fusion protein, NPM-ALK, which is expressed in a subset of systemic anaplastic large cell lymphoma (ALCL). In this study, we investigated the possible role of JAK in activating STAT3 in ALCL using two ALK-positive ALCL cell lines, Karpas 299 and SU-DHL-1. At the steady state, JAK3 showed detectable tyrosine phosphorylation by immunoprecipitation. Treatment with AG490, a JAK inhibitor, decreased but did not completely abrogate tyrosine phosphorylation of JAK3 and STAT3 in a concentration-dependent manner. Similar results were obtained using two other inhibitors of JAK3, WHI-P131 and WHI-P154. These biochemical changes were associated with apoptosis in both cell lines that was coupled with activation of caspase 3 and decreased bcl-xL and bcl-2. Cell cycle analysis revealed a decrease in the S?phase, which may be attributed to cyclin D3 downregulation and p21waf1 upregulation. Importantly, the tyrosine kinase activity of NPM-ALK, as assessed by an in vitro assay, decreased with increasing concentrations of AG490. Our findings highlight the importance of JAK3 in activating STAT3 in ALCL, and that NPM-ALK-mediated activation of STAT3 is influenced by the functional status of JAK3.Oncogene (2003) 22, 5399-5407. doi:10.1038/sj.onc.1206849 [ABSTRACT FROM AUTHOR]

The correlational association from 19 electrode sites between peak amplitude and latency for the P3(00) event-related brain potential (ERP) for n=80 homogeneous subjects was assessed using a simple auditory discrimination task. The correlation strength varied systematically across scalp topography in different ways for the various ERP components. For the target stimuli, P3 amplitude and latency were negatively correlated and most tightly coupled over the frontal-central and right medial/lateral recording sites. In contrast, the N1 produced negative correlations that were strongest over the left and right central/lateral locations; P2 demonstrated a positive correlation that was strongest frontally and centrally; N2 demonstrated a positive correlations that was strongest over the central and parietal sites. ERPs from the standard stimuli produced generally similar patterns for the P3 and P2 components, with only weak or no reliable effects observed for the N1 and N2 potentials. Taken together, the findings suggest that analysis of amplitude/latency correlational relationships can provide information about ERP component generation. Theoretical implications are discussed. [ABSTRACT FROM AUTHOR]