Chlorhexidine-alcohol versus iodine-alcohol for surgical site skin preparation in an elective arthroplasty (ACAISA) study: a cluster randomized controlled trial.

OBJECTIVES: Surgical site skin preparation is an effective method to prevent wound complications. The optimal agent has not been established, and guidelines contain conflicting recommendations. METHODS: The aim of alcoholic chlorhexidine or alcoholic iodine skin antisepsis (ACAISA) was to assess the efficacy of surgical site skin preparation with 0.5% chlorhexidine gluconate (w/v) in 70% ethanol (v/v) to 1% iodine (w/v) in 70% ethanol (v/v). This was a cluster randomized, controlled, single-centre, assessor-blinded, superiority trial in patients undergoing elective hip or knee arthroplasty. Each surgeon had a set operating day and the unit of randomization was the day of surgery. The primary outcome was superficial wound complication, defined as a composite endpoint of superficial incisional surgical site infection and/or clinically significant wound ooze in the 30 days following arthroplasty. The secondary outcome was any surgical site infection, including prosthetic joint infection. Outcome ascertainment was undertaken by an independent verification panel. The primary analysis was intention-to-treat, performed at the individual level. Taking into account the clustering effect, analysis of primary and secondary outcomes was undertaken at the level of the surgeon. RESULTS: A total of 780 participants were included; 390 participants were allocated chlorhexidine-alcohol and 390 participants were allocated iodine-alcohol. There was no difference in superficial wound complications: 19 (4.9%) versus 15 (3.8%) respectively (OR 1.28; 95%CI 0.62, 2.63; p 0.50). There was an increased odds of surgical site infection in the chlorhexidine-alcohol group compared to iodine-alcohol: 12 (3.1%) versus four (1.0%) respectively (OR 3.06; 95%CI 1.26, 7.46; p 0.014). The odds of prosthetic joint infection were also increased in the chlorhexidine-alcohol arm compared with iodine-alcohol: seven (1.8%) versus two (0.5%) respectively (OR 3.55; 95%CI 1.20, 10.44; p 0.022). CONCLUSIONS: No difference was observed in the primary outcome of superficial wound complications when chlorhexidine-alcohol and iodine-alcohol were compared. However, on a secondary analysis, iodine-alcohol had greater efficacy than chlorhexidine-alcohol for preventing surgical site infection. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614000177651.

Large variations in the practice patterns of surgical antiseptic preparation solutions in patients with open and closed extremity fractures: a cross-sectional survey.

Background: Surgically-managed fractures, particularly open fractures, are associated with high rates of surgical site infections (SSIs). To reduce the risk of an SSI, orthopaedic surgeons routinely clean open fracture wounds in the emergency department (ED) and then apply a bandage to the open wound. Prior to the surgical incision, it is standard practice to prepare the fracture region with an antiseptic skin solution as an additional SSI prevention strategy. Multiple antiseptic solutions are available. Objectives: To explore the variation in practice patterns among orthopaedic surgeons regarding antiseptic solution use in the ED and antiseptic preparatory techniques for fracture surgery. Methods: We developed a 27-item survey and surveyed members of several orthopaedic associations. Results: Two hundred and-ten surveys were completed. 71.0% of respondents irrigate the open wound and skin in the ED, primarily with saline alone (59.7%) or iodine-based solutions (32.9%). 90.5% of responders indicated that they dress the open wound in the ED, with 41.0% applying a saline-soaked bandage and 33.7% applying an iodine-soaked dressing (33.7%). In their surgical preparation of open fractures, 41.0% of respondents used an iodine-based solution, 26.7% used a chlorhexidine gluconate (CHG)-based solution, and 31.4% used a combination of the two. In closed fractures, 43.8% of respondents used a CHG-based solution, 28.1% used an iodine-based solution, and 27.1% used a combination. Despite theoretical concerns about the use of alcohol in open wounds, 51.4% used alcohol-based solutions or alcohol alone during skin preparation of open fractures. Conclusions: A lack of consensus exists regarding use of antiseptic surgical preparation solutions for fractures. High-quality clinical research is needed to assess the effectiveness of different surgical antiseptic preparation solutions on patient outcomes in fracture populations.

Adhesive arachnoiditis following inadvertent epidural injection of 2% chlorhexidine in 70% alcohol-partial recovery over the ensuing eight years.

We report a case of serious neurologic injury due to inadvertent epidural injection of 8 ml of the antiseptic 2% chlorhexidine in 70% alcohol during a procedure aimed to relieve the pain of labour. This resulted in immediate severe back pain, progressive tetraparesis and sphincter dysfunction caused by damage to the spinal cord and nerve roots. Subacute hydrocephalus necessitated drainage, but cranial nerve and cognitive function were spared. Magnetic resonance imaging documented marked abnormality of the spinal cord and surrounding leptomeninges. In the ensuing eight years, there has been clinical and electrophysiological evidence of partial recovery, but neurologic deficit remains severe.

Supraclavicular Brachial Plexus Neurolysis for a Malignant Peripheral Nerve Sheath Tumor: A Case Report.

The perineural administration of alcohol or phenol results in protein denaturation and, consequently, neurolysis. This can produce long-lasting analgesia, with a duration of 3-6 months. Although neurolytic blocks for the brachial plexus have been described in multiple review articles and textbooks, they are rarely performed. As such, little is known about the efficacy and adverse effect profile of this commonly described treatment. In this article, we report the outcomes of a patient who underwent a left brachial plexus neurolytic block for the management of upper limb pain arising from a malignant peripheral nerve sheath tumor.

Re-exposure to nicotine-associated context from adolescence enhances alcohol intake in adulthood.

Alcohol and nicotine are the two most commonly-abused substances and are often used together. Nicotine enhances alcohol-drinking behaviors in humans and in animals, and was suggested to enhance the reinforcing properties of other reinforcers. Here, we show that nicotine-associated environment, rather than nicotine itself, enhances alcohol intake in rats. Adolescent rats received repeated intermittent injections of nicotine (0.4 mg/kg, i.p., 5 injections, every 3rd day) or saline. The injection was paired with their home cage, or with the subsequent alcohol self-administration context. Rats were then trained to self-administer 20% alcohol. Nicotine given in the home cage did not alter subsequent alcohol intake. However, pairing nicotine with the operant chamber during adolescence led to a long-lasting increased alcohol self-administration in adulthood, compared to nicotine pre-treatment in other contexts. This effect persisted 3 months after nicotine cessation, in a relapse test after abstinence. Furthermore, re-exposure to the nicotine-associated context in adult rats led to a decrease in glial cell line-derived neurotrophic factor (Gdnf) mRNA expression in the ventral tegmental area, an effect that leads to increased alcohol consumption, as we have previously reported. Our findings suggest that retrieval of nicotine-associated contextual memories from adolescence may gate alcohol intake in adulthood, with a possible involvement of GDNF.

Dose considerations for alcohol-based hand rubs.

BACKGROUND: Manufacturers' recommended dosages for alcohol-based hand rubs are typically determined by measuring product efficacy using a model protocol such as EN 1500; however, anecdotal reports and informal observation suggests that in many cases users self-titrate to much lower doses in real-world application. AIM: To examine the interdependence of alcohol-based hand-rub volume on in-vivo efficacy using the EN 1500 standard test method, on drying time on users' hands, and on their perceptions of acceptability. METHODS: Three formulations were studied using EN 1500 and a modification of this method. The modification used volumes ranging from 0.5 to 3.0 mL and 30 s application. Drying times were recorded and user acceptability was established using a three-point scale (too long, OK, or too short). Dying times were analysed in relation to hand surface area. FINDINGS: The drying time for all three products increased as a function of volume. The drying time displayed a positive association with volume and a negative association with hand surface area. The optimum volume for user acceptability was between 1.5 and 2 mL, yielding a drying time of between 20 and 30 s. CONCLUSION: Whereas EN 1500 is appropriate for establishing the efficacy of a hygienic hand-rub formulation compared to a benchmark, it does not reflect actual in-use conditions or the likely clinical effectiveness of the product. In particular, it fails to address the need to optimize the volume of application and user acceptability of the product.

Modulatory role of Pterocarpus santalinus against alcohol-induced liver oxidative/nitrosative damage in rats.

Pterocarpus santalinus, a traditional medicinal plant has shown protective mechanisms against various complications. The aim of the present study is to evaluate therapeutic efficacy of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced oxidative/nitrosative stress leading to hepatotoxicity. In-vitro studies revealed that PSE possess strong DPPH (1,1-diphenyl-2-picryl hydrazyl) and nitric oxide radical scavenging activity. For in vivo studies male albino Wistar rats were treated with 20% alcohol (5g/kg b.wt/day) and PSE (250mg/kg b.wt/day) for 60days. Results showed that alcohol administration significantly altered plasma lipid profile with marked increase in the levels of plasma transaminases (ALT and AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (γGT). Moreover, lipid peroxides, nitric oxide (NOx) levels in plasma and liver were increased with increased iNOS protein expression in liver was noticed in alcohol administered rats and these levels were significantly brought back close to normal level by PSE administration except iNOS protein expression. Alcohol administration also decreased the content of reduced glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione-s transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) in liver, which were significantly enhanced by administration of PSE. The active compounds pterostilbene, lignan and lupeols present in PSE might have shown protection against alcohol-induced hepatic damage by possibly reducing the rate of lipid peroxidation, NOx levels and increasing the antioxidant defence mechanism in alcohol administered rats. Both biochemical and histopathological results in the alcohol-induced liver damage model emphasize beneficial action of PSE as a hepatoprotective agent.

Exposure to chronic alcohol accelerates development of wall stress and eccentric remodeling in rats with volume overload.

Chronic alcohol abuse is one of the leading causes of dilated cardiomyopathy (DCM) in the United States. Volume overload (VO) also produces DCM characterized by left ventricular (LV) dilatation and reduced systolic and diastolic function, eventually progressing to congestive heart failure. For this study, we hypothesized that chronic alcohol exposure would exacerbate cardiac dysfunction and remodeling due to VO. Aortocaval fistula surgery was used to induce VO, and compensatory cardiac remodeling was allowed to progress for either 3days (acute) or 8weeks (chronic). Alcohol was administered via chronic intermittent ethanol vapor (EtOH) for 2weeks before the acute study and for the duration of the 8week chronic study. Temporal alterations in LV function were assessed by echocardiography. At the 8week end point, pressure-volume loop analysis was performed by LV catheterization and cardiac tissue collected. EtOH did not exacerbate LV dilatation (end-systolic and diastolic diameter) or systolic dysfunction (fractional shortening, ejection fraction) due to VO. The combined stress of EtOH and VO decreased the eccentric index (posterior wall thickness to end-diastolic diameter ratio), increased end-diastolic pressure (EDP), and elevated diastolic wall stress. VO also led to increases in posterior wall thickness, which was not observed in the VO+EtOH group, and wall thickness significantly correlated with LV BNP expression. VO alone led to increases in interstitial collagen staining (picrosirius red), which while not statistically significant, tended to be decreased by EtOH. VO increased LV collagen I protein expression, whereas in rats with VO+EtOH, LV collagen I was not elevated relative to Sham. The combination of VO and EtOH also led to increases in LV collagen III expression relative to Sham. Rats with VO+EtOH had significantly lower collagen I/III ratio than rats with VO alone. During the acute remodeling phase of VO (3days), VO significantly increased collagen III expression, whereas this effect was not observed in rats with VO+EtOH. In conclusion, chronic EtOH accelerates the development of elevated wall stress and promotes early eccentric remodeling in rats with VO. Our data indicate that these effects may be due to disruptions in compensatory hypertrophy and extracellular matrix remodeling in response to volume overload.

Sources of variation of transthyretin in healthy subjects in East and Southeast Asia: Clinical and experimental evidence for the effect of alcohol on transthyretin metabolism.

BACKGROUND: Although transthyretin (TTR), a negative acute phase protein, is recognized as one of the nutrition assessment proteins, factors affecting serum TTR concentrations than nutritional state in healthy subjects have not been well understood. We investigated the sources of variation of serum TTR concentrations in healthy subjects. METHODS: Serum samples of 3511 healthy volunteers (2055 of Japanese subjects and 1456 of other East and Southeast Asian subjects) were collected. We measured serum TTR concentrations in addition to routine blood examinations in each sample, and assessed the relationship between each serum TTR concentrations and the clinical indices such as age, sex, body mass index (BMI), smoking, and level of daily alcohol consumption. We also investigated the direct alcohol effect of TTR expression by assessing TTR mRNA and protein levels in vivo and in vitro experiments. RESULTS: Mean TTR concentrations of males were prominently higher than those of females. Multiple regression analysis revealed that serum TTR concentrations increased with age, BMI, and the level of daily alcohol consumption after adjustment for a slight regional difference. Moreover, TTR expression was up-regulated by alcohol treatment through hepatocyte nuclear factor 4α (HNF-4α) in vitro and in vivo experiments. CONCLUSIONS: Sex, aging, BMI, and the level of daily alcohol consumption may be the factors affecting serum TTR concentrations in healthy subjects.

The Combined Impact of Surgical Team Education and Chlorhexidine 2% Alcohol on the Reduction of Surgical Site Infection following Cardiac Surgery.

BACKGROUND: The use of 2% chlorhexidine in 70% alcohol (CHG) has been associated with reduction in catheter-related bloodstream infections and surgical site infection (SSI) in general surgery. Also, improved awareness of best practice from the perspective of the operative team is likely to result in reductions in SSI rates. METHODS: This is an ambispective cohort study of patients undergoing elective cardiac surgery. Between January 2010 and December 2010, patients underwent surgical preparation using Alcohol Povidone Iodine (API). Between January 2011 and December 2011, the surgical team received education and switched to CHG for surgical preparation. Univariate analysis was performed to identify the impact of known risk factors for SSI. A logistic regression model was then fit to estimate the effect of education and CHG in the reduction of SSI in 2011, controlling for known SSI risk factors. RESULTS: There was a substantial reduction in overall SSI rate in 2011 following staff education and the introduction of CHG. The overall unadjusted SSI rate was 4.67% versus 2.08% (p<0.05) for 2010 and 2011 respectively. Using a logistic regression model, the combined effect of education and CHG in 2011 was a 63% reduction in SSI in cardiothoracic surgery (OR 0.37, 95% CI: 0.17-0.83, p=0.016), controlling for age, major co-morbidities, and SSI risk factors. CONCLUSIONS: Using CHG as pre-operative antiseptic in cardiothoracic surgery in a risk-adjusted cohort with education of the surgical team is associated with significantly lower SSI infection rates when compared with API. Emphasis must be placed on the multifactorial approach required to prevent postoperative wound infections.

Surgical site infections, occurrence, and risk factors, before and after an alcohol-based handrub intervention in a general surgical department in a rural hospital in Ujjain, India.

BACKGROUND: This study set out to determine occurrence of and risk factors for surgical site infections (SSIs) before and after implementation of an alcohol-based handrub (ABHR) intervention in general surgery wards in a rural, tertiary care hospital in India. METHODS: Patients who underwent surgery between October 2010 and August 2011 (preintervention period) or September 2011 and August 2013 (intervention period) in the department of surgery were included. ABHR was introduced in September 2011. SSI was defined as per the Centers for Disease Control and Prevention guidelines. Comparison of SSI rate between the 2 periods was performed using analysis of variance. Risk factors were determined using multiple logistic regression models. RESULTS: Incidence of SSI was 5% (36/720) and 6.5% (103/1,581) respectively, showing nonsignificant difference (P = .5735). The risk factor common for SSI in both periods was the duration of surgery (OR = 2.6 vs OR = 1.96, pre- and intervention periods, respectively). Risk factors in the intervention period were being a woman (OR = 2.18), renal disease (OR = 3.61), diabetes (OR = 4.43), smoking (OR = 2.14), preoperative hospitalization (<3 vs >15 days; OR = 3.22), and previous hospitalization (OR = 3.5). Compared with other studies, the amount of ABHR used in our study was low. CONCLUSION: The amount of ABHR used might not be sufficient to interrupt the chain of contamination of microorganisms; therefore, continuation of the intervention and surveillance is recommended.

A new aliphatic alcohol and cytotoxic chemical constituents from Acorus gramineus rhizomes.

A new aliphatic alcohol, (2R,6R)-oct-7-ene-2,6-diol (1), and seven other known compounds (2-8) were isolated from Acorus gramineus rhizomes. The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including 2D NMR, HR-MS, and the modified Mosher's method. Compounds 3-8 displayed consistent antiproliferative activities against the cell lines tested with IC50 values ranging from 7 to 48 µm.

R-modafinil attenuates nicotine-taking and nicotine-seeking behavior in alcohol-preferring rats.

(±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long-Evans rats. As Long-Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long-Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine's effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans.

Chronic alcohol exposure exacerbates inflammation and triggers pancreatic acinar-to-ductal metaplasia through PI3K/Akt/IKK.

Pancreatic acinar-to-ductal metaplasia (ADM) has been identified as an initiating event that can progress to pancreatic intraepithelial neoplasia (PanIN) or pancreatic ductal adenocarcinoma (PDAC). Acini transdifferentiation can be induced by persistent inflammation. Notably, compelling evidence has emerged that chronic alcohol exposure may trigger an inflammatory response of macrophages/monocytes stimulated by endotoxins. In the present study, we aimed to evaluate the role of inflammation induced by chronic alcohol and lipopolysaccharide (LPS) exposure in the progression of pancreatic ADM, as well as to elucidate the possible mechanisms involved. For this purpose, cultured macrophages were exposed to varying doses of alcohol for 1 week prior to stimulation with LPS. Tumor necrosis factor-α (TNF-α) and regulated upon activation, normal T cell expression and secreted (RANTES) expression were upregulated in the intoxicated macrophages with activated nuclear factor-κB (NF-κB). Following treatment with the supernatant of intoxicated macrophages, ADM of primary acinar cells was induced. Furthermore, the expression of TNF-α and RANTES, as well as the phosphatidylinositol-3-kinase (PI3K)/protein kinase B(Akt)/inhibitory κB kinase (IKK) signaling pathway have been proven to be involved in the ADM of acinar cells. Moreover, Sprague-Dawley (SD) rats were employed to further explore the induction of pancreatic ADM by chronic alcohol and LPS exposure in vivo. At the end of the treatment period, a number of physiological parameters, such as body weight, liver weight and pancreatic weight were reduced in the exposed rats. Plasma alcohol concentrations and oxidative stress levels in the serum, as well as TNF-α and RANTES expression in monocytes were also induced following chronic alcohol and LPS exposure. In addition, pancreatic ADM was induced through the PI3K/Akt/IKK signaling pathway by the augmented TNF-α and RANTES expression levels in the exposed rats. Overall, we characterized the link between inflammation induced by chronic alcohol and LPS exposure and pancreatic ADM. However, the mechanisms behind the induction of pancreatic ADM warrant further investigation.

Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration.

Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.

Phosphodiesterase 10A regulates alcohol and saccharin self-administration in rats.

A history of stress produces increases in rodent relapse-like alcohol self-administration behavior and regional brain gene expression of phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate/cyclic guanosine monophosphate-inhibiting enzyme. Here, we tested the hypothesis that administration of TP-10, a specific PDE10A inhibitor, would reduce alcohol self-administration in conditions predisposing to elevated self-administration. TP-10 administration dose-dependently (0.562, 1.0 mg/kg; subcutaneously) reduced relapse-like alcohol self-administration regardless of stress history enhancement of relapse-like behavior. TP-10 also reduced alcohol self-administration in genetically alcohol-preferring rats, as well as in alcohol-non-dependent and -dependent rats. Effective systemic TP-10 doses did not alter alcohol pharmacokinetics, significantly reduce motor activity or intrabout operant response speed, or promote a conditioned place aversion. TP-10 also reduced saccharin self-administration, suggesting a general role for PDE10A in the self-administration of reinforcing substances. PDE10A inhibition in the dorsolateral striatum, but not the nucleus accumbens, reduced alcohol self-administration. Taken together, the results implicate dorsolateral striatum PDE10A in facilitating alcohol intake and support further investigation of PDE10A systems in the pathophysiology and potential treatment of substance use disorders.

Orphan nuclear receptor Errγ induces C-reactive protein gene expression through induction of ER-bound Bzip transmembrane transcription factor CREBH.

The orphan nuclear receptor estrogen-related receptor-γ (ERRγ) is a constitutively active transcription factor regulating genes involved in several important cellular processes, including hepatic glucose metabolism, alcohol metabolism, and the endoplasmic reticulum (ER) stress response. cAMP responsive element-binding protein H (CREBH) is an ER-bound bZIP family transcription factor that is activated upon ER stress and regulates genes encoding acute-phase proteins whose expression is increased in response to inflammation. Here, we report that ERRγ directly regulates CREBH gene expression in response to ER stress. ERRγ bound to the ERRγ response element (ERRE) in the CREBH promoter. Overexpression of ERRγ by adenovirus significantly increased expression of CREBH as well as C-reactive protein (CRP), whereas either knockdown of ERRγ or inhibition of ERRγ by ERRγ specific inverse agonist, GSK5182, substantially inhibited ER stress-mediated induction of CREBH and CRP. The transcriptional coactivator PGC1α was required for ERRγ mediated induction of the CREBH gene as demonstrated by the chromatin immunoprecipitation (ChIP) assay showing binding of both ERRγ and PGC1α on the CREBH promoter. The ChIP assay also revealed that histone H3 and H4 acetylation occurred at the ERRγ and PGC1α binding site. Moreover, chronic alcoholic hepatosteatosis, as well as the diabetic obese condition significantly increased CRP gene expression, and this increase was significantly attenuated by GSK5182 treatment. We suggest that orphan nuclear receptor ERRγ directly regulates the ER-bound transcription factor CREBH in response to ER stress and other metabolic conditions.

Alcohol injection for Morton's neuroma: a five-year follow-up.

BACKGROUND: Although many treatment modalities are available for Morton's neuroma (MN), studies looking at the long-term effectiveness of most forms of treatment are scarce. The injection of MN with alcohol has gained popularity over the past 10 years with widespread media coverage. Many surgeons have anecdotally questioned the long-term effectiveness of this treatment. We reviewed a cohort of patients at an average 5-year follow-up to assess the medium-term results of alcohol injection. METHODS: We used the modified Johnson score and visual analogue scales to assess 45 of the original cohort of patients with an average follow-up of 61 months (range, 33-73 months). Any complications from the procedure were also noted. RESULTS: Our results indicated that by 5 years, 16 of 45 patients had undergone surgical treatment and a further 13 patients had return of symptoms. Only 29% (13/45) remained symptom free. The visual analog scale and modified Johnson scores showed statistically significant deterioration in patients' symptoms at 5 years following alcohol injection. CONCLUSION: Injection with alcohol sclerosant for MN has been marketed as a definitive management option comparable to surgical excision. Our investigation illustrated that although short-term results are encouraging, alcohol injection does not offer permanent resolution of symptoms for most patients and can be associated with considerable morbidity. Our investigation provides the only long-term data for alcohol injection treatment of MN. LEVEL OF EVIDENCE: Level II, prospective case series.

Evaluation with a focus on both the antimicrobial efficacy and cumulative skin irritation potential of chlorhexidine gluconate alcohol-containing preoperative skin preparations.

BACKGROUND: Important characteristics for ideal skin preparations include long-lasting antimicrobial efficacy and low potential for skin irritation. METHODS: A total of 55 healthy adult subjects were enrolled to evaluate the antimicrobial effects of 3 test formulations applied to inguinal, abdominal, and antecubital sites at post-treatment time points of 30 seconds, 72 hours, and 7 days. To investigate skin irritation potential, the 3 formulations were tested in a 21-day repeat-insult patch test conducted on the skin of the backs of 23 healthy subjects. RESULTS: The mean log(10) reduction (MLR) at 7 days post-treatment produced by a 79% vol/vol ethanol containing 1% wt/vol chlorhexidine gluconate (1% CHG-EtOH) applied to abdominal sites was significantly superior to that produced by a 10% povidone-iodine solution (2.45 MLR vs 0.90 MLR; P < .05). The 1% CHG-EtOH and a 70% vol/vol isopropanol containing 2% wt/vol CHG (2% CHG-IPA) provided statistically equivalent persistence at 72 hours and 7 days post-treatment. The 1% CHG-EtOH had less skin irritation potential than the 2% CHG-IPA and the 10% povidone-iodine solution, although the differences were not statistically significant (P > .05). CONCLUSION: Considering its persistent effect and low skin irritation potential, the 1% CHG-EtOH preparation is expected to perform well in surgical site preparation to reduce the risk of surgery- and catheter-related bloodstream infection.

Comparison of virucidal activity of alcohol-based hand sanitizers versus antimicrobial hand soaps in vitro and in vivo.

Three ethanol-based sanitizers were compared with three antimicrobial liquid soaps for their efficacy to inactivate polio-, adeno-, vaccinia- and bovine viral diarrhoea virus (BVDV) as well as feline calicivirus (FCV) and murine norovirus (MNV) as surrogates for human norovirus in a suspension test. Additionally, sanitizers and soaps were examined against MNV in a modified fingerpad method. All sanitizers sufficiently inactivated the test viruses in the suspension test whereas two soaps were active only against vaccinia virus and BVDV. In the modified fingerpad test a povidone-iodine-containing soap was superior to the sanitizers whereas the other two soaps showed no activity.