Characterizing the Opportunity Space for Sustainable Hydrothermal Valorization of Wet Organic Wastes.

Resource recovery from wet organic wastes can support circular economies by creating financial incentives to produce renewable energy and return nutrients to agriculture. In this study, we characterize the potential for hydrothermal liquefaction (HTL)-based resource recovery systems to advance the economic and environmental sustainability of wastewater sludge, FOG (fats, oils, and grease), food waste, green waste, and animal manure management through the production of liquid biofuels (naphtha, diesel), fertilizers (struvite, ammonium sulfate), and power (heat, electricity). From the waste management perspective, median costs range from -193 $·tonne-1 (FOG) to 251 $·tonne-1 (green waste), and median carbon intensities range from 367 kg CO2 eq·tonne-1 (wastewater sludge) to 769 kg CO2 eq·tonne-1 (green waste). From the fuel production perspective, the minimum selling price of renewable diesel blendstocks are within the commercial diesel price range (2.37 to 5.81 $·gal-1) and have a lower carbon intensity than petroleum diesel (101 kg CO2 eq·MMBTU-1). Finally, through uncertainty analysis and Monte Carlo filtering, we set specific targets (i.e., achieve wastewater sludge-to-biocrude yield >0.440) for the future development of hydrothermal waste management system components. Overall, our work demonstrates the potential of HTL-based resource recovery systems to reduce the costs and carbon intensity of resource-rich organic wastes.

DNA methylation mutants in Physcomitrella patens elucidate individual roles of CG and non-CG methylation in genome regulation.

Cytosine (DNA) methylation in plants regulates the expression of genes and transposons. While methylation in plant genomes occurs at CG, CHG, and CHH sequence contexts, the comparative roles of the individual methylation contexts remain elusive. Here, we present Physcomitrella patens as the second plant system, besides Arabidopsis thaliana, with viable mutants with an essentially complete loss of methylation in the CG and non-CG contexts. In contrast to A. thaliana, P. patens has more robust CHH methylation, similar CG and CHG methylation levels, and minimal cross-talk between CG and non-CG methylation, making it possible to study context-specific effects independently. Our data found CHH methylation to act in redundancy with symmetric methylation in silencing transposons and to regulate the expression of CG/CHG-depleted transposons. Specific elimination of CG methylation did not dysregulate transposons or genes. In contrast, exclusive removal of non-CG methylation massively up-regulated transposons and genes. In addition, comparing two exclusively but equally CG- or CHG-methylated genomes, we show that CHG methylation acts as a greater transcriptional regulator than CG methylation. These results disentangle the transcriptional roles of CG and non-CG, as well as symmetric and asymmetric methylation in a plant genome, and point to the crucial role of non-CG methylation in genome regulation.

Chlorhexidine gluconate bathing in children with cancer or those undergoing hematopoietic stem cell transplantation: A double-blinded randomized controlled trial from the Children's Oncology Group.

BACKGROUND: To the authors' knowledge, information regarding whether daily bathing with chlorhexidine gluconate (CHG) reduces central line-associated bloodstream infection (CLABSI) in pediatric oncology patients and those undergoing hematopoietic stem cell transplantation (HCT) is limited. METHODS: In the current multicenter, randomized, double-blind, placebo-controlled trial, patients aged ≥2 months and <22 years with cancer or those undergoing allogeneic HCT were randomized 1:1 to once-daily bathing with 2% CHG-impregnated cloths or control cloths for 90 days. The primary outcome was CLABSI. Secondary endpoints included total positive blood cultures, acquisition of resistant organisms, and acquisition of cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration. RESULTS: The study was stopped early because of poor accrual. Among the 177 enrolled patients, 174 were considered as evaluable (88 were randomized to the CHG group and 86 were randomized to the control group). The rate of CLABSI per 1000 central line days in the CHG group was 5.44 versus 3.10 in the control group (risk difference, 2.37; 95% confidence interval, 0.05-4.69 [P = .049]). Post hoc conditional power analysis demonstrated a 0.2% chance that the results would have favored CHG had the study fully enrolled. The rate of total positive blood cultures did not differ between groups (risk difference, 2.37; 95% confidence interval, -0.41 to 5.14 [P = .078]). The number of patients demonstrating the new acquisition of resistant organisms did not differ between groups (P = .54). Patients in the CHG group were found to be more likely to acquire cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration (P = .032). CONCLUSIONS: The data from the current study do not support the use of routine CHG bathing in children with cancer or those undergoing allogeneic HCT.

[Project to Reduce Cases of Drug-Resistant Strain Colonization in the Intensive Care Unit Using a Chlorhexidine Gluconate Bath].

BACKGROUND: Drug-resistant strains of bacteria are associated with severe consequences such as bacteremia, shock, and death, and increase hospital stay durations and medical health expenses. Therefore, reducing the spread of drug-resistant strains is a priority concern. PURPOSE: This project was developed to reduce the number of colonization cases of drug-resistant strains and subsequently increase the quality of care provided in our intensive care unit. RESOLUTIONS: In this project, a chlorhexidine gluconate (CHG) bath standard protocol and CHG bath skill checklist were established, education and training courses were planned, a regular bed curtain replacement schedule and sink cleaning protocols were implemented, and regular audits were conducted. RESULTS: Immediately following project implementation (October - December 2018), the average monthly cases of Vancomycin-resistant enterococci colonization decreased from 6.08 to 4.33, and the average monthly cases of multi-drug resistant Acinebacter baumannii colonization decreased from 4.08 to 1.33. Furthermore, between January and July 2019, the average monthly cases of colonization for the abovementioned bacteria numbered 4 and 0.86, respectively, which met the level of reduction targeted in this project. CONCLUSIONS: The results of this project indicate that implementing CHG bed baths is effective in reducing the incidence of drug resistant strain colonization and rate of related infections in patients. CHG bed baths should be applied clinically to improve the quality of intensive care.

A Novel, Widespread qacA Allele Results in Reduced Chlorhexidine Susceptibility in Staphylococcus epidermidis.

Chlorhexidine gluconate (CHG) is a topical antiseptic widely used in health care settings. In Staphylococcus spp., the pump QacA effluxes CHG, while the closely related QacB cannot due to a single amino acid substitution. We characterized 1,050 cutaneous Staphylococcus isolates obtained from 173 pediatric oncology patients enrolled in a multicenter CHG bathing trial. CHG susceptibility testing revealed that 63 (6%) of these isolates had elevated CHG MICs (≥4 µg/ml). Screening of all 1,050 isolates for the qacA/B gene (the same qac gene with A or B allele) by restriction fragment length polymorphism (RFLP) yielded 56 isolates with a novel qacA/B RFLP pattern, qacA/B273 The CHG MIC was significantly higher for qacA/B273 -positive isolates (MIC50, 4 µg/ml; MIC range, 0.5 to 4 µg/ml) than for other qac groups: qacA-positive isolates (n = 559; MIC50, 1 µg/ml; MIC range, 0.5 to 4 µg/ml), qacB-positive isolates (n = 17; MIC50, 1 µg/ml; MIC range, 0.25 to 2 µg/ml), and qacA/B-negative isolates (n = 418, MIC50, 1 µg/ml; MIC range, 0.125 to 2 µg/ml) (P = 0.001). A high proportion of the qacA/B273 -positive isolates also displayed methicillin resistance (96.4%) compared to the other qac groups (24.9 to 61.7%) (P = 0.001). Whole-genome sequencing revealed that qacA/B273 -positive isolates encoded a variant of QacA with 2 amino acid substitutions. This new allele, named qacA4, was carried on the novel plasmid pAQZ1. The qacA4-carrying isolates belonged to the highly resistant Staphylococcus epidermidis sequence type 2 clone. By searching available sequence data sets, we identified 39 additional qacA4-carrying S. epidermidis strains from 5 countries. Curing an isolate of qacA4 resulted in a 4-fold decrease in the CHG MIC, confirming the role of qacA4 in the elevated CHG MIC. Our results highlight the importance of further studying qacA4 and its functional role in clinical staphylococci.

Proceedings from the 2018 International Consensus Meeting on Orthopedic Infections: prevention of periprosthetic shoulder infection.

The Second International Consensus Meeting on Orthopedic Infections was held in Philadelphia, Pennsylvania, in July 2018. Over 800 international experts from all 9 subspecialties of orthopedic surgery and allied fields of infectious disease, microbiology, and epidemiology were assembled to form a consensus workgroup. The following proceedings on the prevention of periprosthetic shoulder infection come from 16 questions evaluated by delegates from the shoulder section.

Current and emerging treatment strategies for children with progressive chiasmatic-hypothalamic glioma diagnosed as infants: a web-based survey.

Treatment of infant hypothalamic chiasmatic glioma (iCHG) is challenging, about 30% of the children progress during chemotherapy. Despite subsequent treatments the 5 year overall-survival rate is only 70%. This study investigates treatment strategies currently applied for progressive iCHG. A web-based questionnaire was sent out to the members of the SIOPE Brain Tumour Group asking for current second and third line strategies at progression during and after the end of first line therapy. The questionnaire was answered by 47 paediatric oncologists from 15 countries. iCHG progressing during first line therapy with carboplatin-vincristine would be considered for treatment with alternative chemotherapy by 17 (36%) and with surgery plus chemotherapy by 27 respondents (58%). Components suggested for second line were vinblastine (62%), cisplatin (34%) and cyclophosphamide (26%). For third line therapy bevacizumab (BVZ) was considered as suitable by respondents in 53% (often with irinotecan 40%) and vinblastine by 34% respectively. Experience with BVZ in CHG is shown by 53% of respondents regarding at least 95 patients (median treated 1-5 patients per respondent at any age) with a median BVZ administration over 12 months. Effectiveness was reported varying between stable disease and regression while complications were rarely stated (proteinuria, hypertension, bleeding). BVZ would be available to 85% of respondents as therapeutic option for iCHG patients. Multiple anti-neoplastic drug regimens are applied for progressive iCHG, partly considered in combination with surgery if safely feasible. BVZ is commonly used at a satisfactory level in third line, mainly combined with irinotecan.

A novel mimovirus encoding ChgA10-19 peptide with PD-L1 induces T cell tolerance and ameliorates the severity of diabetes.

Related studies demonstrate that type 1 diabetes (T1D) is caused by ß-cell antigen specific autoreactive CD8+ T cells. ChgA has recently been identified as the autoantigen in NOD mice and T1D patients. Therefore, attenuating the activation of ChgA specific CD8+ T cells might be a promising target for T1D therapy. The negative co-stimulatory PD-L1 inhibits T cell mediated alloimmunity and induces tolerance. In this experiment, a novel mimovirus encoding ChgA10-19 peptide with PD-L1 was constructed. The NOD.ß2m null HHD mice were administrated with mimovirus transduced DCs. After immunization, the activation and proliferation of CD8+ T cells were detected, diabetes incidence and pancreatic tissue destruction were also analyzed. The results demonstrated that transduced DCs attenuated CD8+ T cell activation and proliferation. In addition, transduced DCs inhibited CD8+ T response to ChgA stimulation, and ameliorated the severity of diabetes. These data suggested that mimovirus transduced DCs might provide novel clues for T1D therapy.

Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients.

Promoter methylation reflects in the inactivation of different genes like O6-methylguanine-DNA methyltransferase DNA repair gene and runt-related transcription factor 3, a known tumor suppressor gene in various cancers such as esophageal cancer. The promoter methylation was evaluated for O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in CpG, CHH, and CHG context (where H is A, T, or C) by next-generation sequencing. The methylation status was correlated with quantitative messenger RNA expression. In addition, messenger RNA expression was correlated with different risk factors like tobacco, alcohol, betel nut consumption, and smoking habit. CpG methylation of O6-methylguanine-DNA methyltransferase promoter had a positive association in the development of esophageal cancer (p < 0.05), whereas runt-related transcription factor 3 promoter methylation showed no significant association (p = 1.0) to develop esophageal cancer. However, the non-CpG methylation, CHH, and CHG were significantly correlated with O6-methylguanine-DNA methyltransferase (p < 0.05) and runt-related transcription factor 3 (p < 0.05) promoters in the development of esophageal cancer. The number of cytosine converted to thymine (C→T) in O6-methylguanine-DNA methyltransferase promoter showed a significant correlation between cases and controls (p < 0.05), but in runt-related transcription factor 3 no such significant correlation was observed. Besides, messenger RNA expression was found to be significantly correlated with promoter hypermethylation of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in the context of CHG and CHH (p < 0.05). The CpG hypermethylation in O6-methylguanine-DNA methyltransferase showed positive (p < 0.05) association, whereas in runt-related transcription factor 3, it showed contrasting negative association (p = 0.23) with their messenger RNA expression. Tobacco, betel nut consumption, and smoking habits were associated with altered messenger RNA expression of O6-methylguanine-DNA methyltransferase (p < 0.05) and betel nut consumption and smoking habits were associated with runt-related transcription factor 3 (p < 0.05). There was no significant association between messenger RNA expression of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 with alcohol consumption (p = 0.32 and p = 0.15). In conclusion, our results suggest that an aberrant messenger RNA expression may be the outcome of CpG, CHG, and CHH methylation in O6-methylguanine-DNA methyltransferase, whereas outcome of CHG and CHH methylation in runt-related transcription factor 3 promoters along with risk factors such as consumption of tobacco, betel nut, and smoking habits in esophageal cancer from Northeast India.

Synthesis of [11C]HG-10-102-01 as a new potential PET agent for imaging of LRRK2 enzyme in Parkinson's disease.

The reference standard (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (HG-10-102-01) and its precursor (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-hydroxyphenyl)(morpholino)methanone (desmethyl-HG-10-102-01) were synthesized from 2,4,5-trichloropyrimide and 3-methoxy-4-nitrobenzoic acid with overall chemical yield 49% in four steps and 14% in five steps, respectively. The target tracer (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-[11C]methoxyphenyl)(morpholino)methanone ([11C]HG-10-102-01) was prepared from the precursor desmethyl-HG-10-102-01 with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 45-55% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370-1110GBq/µmol with a total synthesis time of ∼40-min from EOB.

[Nested melanoma]. / Mélanome en thèques.

BACKGROUND: Nested melanoma in elderly subjects is an entity that has been reported in the literature only since 2012. In this paper, we describe its distinctive clinical, dermatoscopic and histopathological features and compare them to previous published cases, with the aim of highlighting certain specific criteria of this melanoma subtype. CASE REPORT: A 52-year-old man was referred for the presence on his chest of a large suspicious pigmented lesion of irregular shape and colour. Dermatoscopically, the lesion was chaotic and characterized by a black, structureless, eccentric area with some peripheral globules as well as some segmental radial lines. Histopathological examination revealed the presence of an asymmetric lesion with large junctional melanocytic nests showing a focal tendency to gathering and some cytological atypia. A diagnosis of nested melanoma was ultimately made. DISCUSSION: Nested melanoma of the elderly represents a distinct anatomoclinical variant of superficial spreading melanoma. Clinically, the lesion is usually large and occurs in photodamaged skin. We would stress that the "elderly" criterion is not mandatory given the numerous cases reported in people under 60 years. The main dermatoscopic feature is a globular pattern, but several features characteristic of superficial spreading melanoma may also be present. Histological diagnosis may be difficult because of the mainly nested pattern, and the condition may be confused histologically with a benign junctional nevus. But these large junctional nests of different sizes, with bridging and cytonuclear atypias, together with asymmetry of the lesions are the hallmark of this special kind of melanoma.

Impact of Povidone Application to Nares in Addition to Chlorhexidine Bath in Critically Ill Patients on Nosocomial Bacteremia and Central Line Blood Stream Infection.

Nosocomial Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia results in a significant increase in morbidity and mortality in hospitalized patients. We aimed to analyze the impact of applying 10% povidone iodine (PI) twice daily to both nares in addition to chlorhexidine (CHG) bathing on nosocomial (MRSA) bacteremia in critically ill patients. A quality improvement study was completed with pre and post-design. The study period was from January 2018 until February 2020 and February 2021 and June 2021. The control period (from January 2018 to May 2019) consisted of CHG bathing alone, and in the intervention period, we added 10% PI to the nares of critically ill patients. Our primary outcome is rates of nosocomial MRSA bacteremia, and our secondary outcome is central line associated blood stream infection (CLABSI) and potential cost savings. There were no significant differences in rates of MRSA bacteremia in critically ill patients. Nosocomial MRSA bacteremia was significantly lower during the intervention period on medical/surgical areas (MSA). CLABSIs were significantly lower during the intervention period in critically ill patients. There were no Staphylococcus aureus CLABSIs in critical care area (CCA)during the intervention period. The intervention showed potential significant cost savings. The application of 10% povidone iodine twice a day in addition to CHG bathing resulted in a significant decrease in CLABSIs in critically ill patients and a reduction in nosocomial MRSA in the non-intervention areas. Further trials are needed to tease out individual patients who will benefit from the intervention.

Does a Presurgical Antisepsis Protocol Decrease Surgical Site Infections in Young Children?

National standards for surgical site infection (SSI) prevention for children remain elusive. Our institution developed a presurgical antisepsis protocol that included the three components of chlorhexidine gluconate bathing wipes, chlorhexidine gluconate oral rinse, and povidone-iodine nasal swab. This retrospective cohort study examined data from electronic health records to compare SSI rates before and after protocol implementation. We included children aged 2 through 11 years undergoing any surgical procedure with the use of an incision in the OR (N = 1,356). We did not find any difference in the occurrence of SSI before and after the protocol was implemented. Logistic regression showed that an infection present at the time of surgery was the only significant predictor of an SSI. The implementation of a presurgical antisepsis protocol was not associated with SSI rate reduction in this pediatric cohort.

A Randomized Controlled Trial of Povidone-Iodine Versus Chlorhexidine Gluconate With Isopropyl Alcohol for Preoperative Vaginal Antisepsis.

Many surgeons request use of 10% povidone-iodine (PI) for vaginal antisepsis; however, when PI is contraindicated, some surgeons request use of chlorhexidine gluconate (CHG) instead. The purpose of this randomized controlled trial was to determine any significant differences in self-reported symptoms associated with vaginal antisepsis with either 10% PI scrub or 4% CHG with 4% isopropyl alcohol. The control group comprised 62 participants who underwent vaginal antisepsis with the PI product, and the intervention group comprised 58 participants who underwent vaginal antisepsis with the CHG product. Participants completed surveys immediately before surgery, immediately after surgery, and 48 to 72 hours after surgery. No significant differences were found in the reported vaginal symptoms between the two groups for any survey. One participant in the intervention group reported symptoms consistent with an allergic reaction. Additional studies are needed on the use of CHG for vaginal antisepsis.

Pediatric preoperative bathing process: An infection prevention perspective for development of a highly reliable organization.

Surgical site infections are a burden to patients, families and healthcare systems. Preoperative preparation is a crucial part in the multifaceted approach to SSI prevention. Preoperative bathing is a customary procedure that is seemingly straightforward yet challenging to implement. On the basis of best-practices and lived experience, this essay identifies potential barriers and presents several recommendations for improvement of preoperative preventive measures.

The antioxidant, anti-angiogenic, and anticancer impact of chitosan-coated herniarin-graphene oxide nanoparticles (CHG-NPs).

Background: Herniarin, a simple coumarin found in chamomile leaf rosettes is known as the oxidative stress protector. In the current study, herniarin was captured into Graphene oxide nanoparticles and coated with chitosan poly-cationic polymer to be used as a novel bio-compatible nano-drug delivery system and investigate its antioxidant, anti-angiogenic and anti-cancer impacts on human lung A549 cancer cells. Method: The Chitosan-coated Herniarin-Graphene oxide nanoparticles (CHG-NPs) were designed, produced, and characterized utilizing DLS, FESEM, FTIR, and Zeta-potential analysis. The CHG-NPs' antioxidant activity was analyzed by conducting ABTS and DPPH antioxidant assays. The CHG-NPs' anti-angiogenic activity was analyzed by CAM assay and verified by measuring VEGF and VEGFR gene expression levels following their increased treatment doses by applying Q-PCR technique. Finally, the CHG-NPs' cytotoxicity was studied in the human lung A549 cancer cells. Result: The stable (+27.11 mV) 213.6-nm CHG-NPs significantly inhibited the ABTS/DPPH free radicals and exhibited antioxidant activity. The suppressed angiogenesis process in the CAM vessels was observed by detecting the decreased length/number of the vessels. Moreover, the down-regulated VEGF and VEGFR gene expression of the CAM blood vessels following the increased CHG-NPs treatment doses verified the nanoparticles' anti-angiogenic potential. Finally, the CHG-NPs significantly exhibited a selective cytotoxic impact on human A549 cancer cells compared with the normal HFF cell line. Conclusion: The selective cytotoxicity, strong antioxidant activity, and significant anti-angiogenic property of the nano-scaled produced CHG-NPs make it an appropriate anticancer nano-drug delivery system. Therefore, the CHG-NPs have the potential to be used as a selective anti-lung cancer compound.

Best products for skin antisepsis.

BACKGROUND: Skin antiseptics are used for several purposes before surgical procedures, for bathing high-risk patients as a means of reducing central line-associated infections and other health care associated infections. METHODS: A PubMed search was performed to update the evidence on skin antiseptic products and practices. RESULTS: Current guidelines for prevention of surgical site infections (SSIs) recommend preoperative baths or showers with a plain or antimicrobial soap prior to surgery, but do not make recommendations on the timing of baths, the total number of baths needed, or about the use of chlorhexidine gluconate (CGH)-impregnated cloths. Randomized controlled trials have demonstrated that pre-operative surgical hand antisepsis using an antimicrobial soap or alcohol-based hand rub yields similar SSI rates. Other studies have reported that using an alcohol-based hand rub caused less skin irritation, was easier to use, and required shorter scrub times than using antimicrobial soap. Current SSI prevention guidelines recommend using an alcohol-containing antiseptic for surgical site infection. Commonly used products contain isopropanol combined with either CHG or with povidone-iodine. Surgical site preparation protocols for shoulder surgery in men may need to include coverage for anaerobes. Several studies suggest the need to monitor and improve surgical site preparation techniques. Daily bathing of intensive care unit (ICU) patients with a CHG-containing soap reduces the incidence of central line-associated bloodstream infections (CLABSIs). Evidence for a similar effect in non-ICU patients is mixed. Despite widespread CHG bathing of ICU patients, numerous barriers to its effective implementation exist. Measuring CHG levels on the skin is useful for identifying gaps in coverage and suboptimal skin concentrations. Using alcohol-based products with at least 2% CHG for skin preparation prior to central line insertion reduces CLABSIs. CONCLUSIONS: Progress has been made on skin antisepsis products and protocols, but improvements in technique are still needed.

Best practice in the use of peripheral venous catheters: A scoping review and expert consensus.

Background: Peripheral intravenous catheters (PIVCs) are the most commonly used invasive medical device in health care with an overall failure rate of 35-50%. Most complications are non-infectious, but local site and bloodstream infections can also occur. Even if PIVC-related infections are rare, the total number of affected patients and the preponderance of Staphylococcus aureus as related pathogen due to the frequent use of these devices are relevant arguments to implement preventive strategies. The aim of this document is to raise awareness that infections caused by PIVCs are a relevant problem that can be reduced by practice change. Methods: A panel of experts discussed this topic based on evidence and proposed practice points by consensus. Discussion: Despite published evidence-based guidelines, current practice concerning aseptic techniques during insertion and care of PIVCs often are substandard. These devices have become commonplace and tend to be perceived as safe. An overall lack of awareness about the true risks associated with the use of PIVCs results in limited surveillance and prevention efforts. Conclusion: Successful insertion and maintenance bundles in central venous lines are a blueprint to the implementation of adapted bundle strategies in the prevention of PIVC-associated infections. There is a need for studies to specifically investigate infection prevention in PIVCs and to agree on effective and implementable bundles.