UNASSIGNED: Buruli ulcer (BU) can lead to disfiguring ulcers and permanent disability. The 2030 World Health Organization (WHO) road map for Neglected Tropical Diseases (NTDs) calls for major scaling up in diagnosis and management to eliminate disability due to the disease. Current treatment for BU is with daily oral rifampicin (10mg/kg dose) and clarithromycin (15mg/kg dose) for eight weeks, combined with standard gauze wound dressings. Dialkylcarbamoyl chloride (DACC)-coated dressings have been shown to irreversibly bind bacteria on wound surfaces resulting in their removal when dressings are changed. This trial aims to determine whether combining a high-dose oral rifampicin regimen with DACC dressings can improve the rate of wound healing relative to standard-dose oral rifampicin combined with DACC dressings.
UNASSIGNED: This is an individual, multi-centre Phase 3 randomised controlled trial, which will be conducted in three clinical sites in Ghana. The primary outcome measure will be the mean time to clearance of viable mycobacteria. Cost and health-related quality of life data will be collected, and a cost-effectiveness analysis will be performed.
UNASSIGNED: The findings from this trial could lead to a change in how BU is treated. A shorter but more efficacious regimen would lead to improved treatment outcomes and potentially substantial financial and economic savings.
UNASSIGNED: Pan African Clinical Trials Repository (registration number; PACTR202011867644311). Registered on 30 th November 2020.
Buruli ulcer (BU), caused by Mycobacterium ulcerans, manifests clinically as a wound or swelling. There are several approaches for managing this condition. One is the availability of two antibiotics, usually rifampicin in combination with clarithromycin, that can be used to treat the disease. Rifampicin is thought to be the most important of these two drugs. Scientists have found out that a higher dose of rifampicin is safe and may help improve healing outcome and shorten the duration of treatment. Individuals with BU wounds also go through wound dressing procedures at their hospitals and health centres. Commonly, wounds are dressed using Vaseline gauze and bandages. However, it has been observed that some affected individuals heal faster than others even with the antibiotic treatment. Some still have living organisms in their wounds many weeks after the antibiotic treatment. There is a new dressing material called DACC which is believed to permanently bind bacteria on the wound surface leading to their removal when the dressings are changed. This may be a good way to treat and prevent infection without the use of more drugs. This study aims to determine whether combining a high-dose oral rifampicin regimen with DACC dressings can improve the rate of wound healing relative to standard-dose oral rifampicin combined with DACC dressings. Furthermore, cost and health-related quality of life data will be collected and a cost-effectiveness analysis will be performed. The findings from this trial could lead to a change in how BU is treated. A shorter but more efficacious regimen would lead to improved treatment outcomes and potentially substantial financial and economic savings.

UNASSIGNED: Wound dressings that inactivate or sequestrate microorganisms, such as those with a hydrophobic, bacteria-binding dialkylcarbamoyl chloride (DACC) surface, can reduce the risk of clinical infections. This \'passive\' bioburden control, avoiding bacterial cell wall disruption with associated release of bacterial endotoxins aggravating inflammation, is advantageous in hard-to-heal wounds. Hence, the full scope of DACC dressings, including the potential impact of higher inoculum densities, increased protein load and different pH on antibacterial activity, needs to be evaluated.
UNASSIGNED: The Japanese Industrial Standard (JIS) L 1902 challenge test was used to evaluate the antimicrobial activity of the DACC-coated dressing against several World Health Organization (WHO)-prioritised wound pathogens (e.g., meticillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, microorganisms with extended-spectrum beta-lactamases and Acinetobacter baumannii), the effect of repeated bacterial challenge in an adverse wound environment, and antimicrobial performance at wound-related pH.
UNASSIGNED: High antibacterial activity of the DACC-coated dressing against the WHO-prioritised bacteria strains by its irreversible binding and inhibition of growth of bound bacteria was confirmed using JIS L 1902. At increased inoculation densities, compared to standard conditions, the DACC-coated dressing still achieved strong-to-significant antibacterial effects. Augmenting the media protein content also affected antibacterial performance; a 0.5-1 log reduction in antibacterial activity was observed upon addition of 10% fetal calf serum. The pH did not influence antibacterial performance. The DACC-coated dressing also sustained antibacterial activity over subsequent reinfection steps.
UNASSIGNED: It can be assumed that the DACC-coated dressing exerts beneficial effects in controlling the wound bioburden, reducing the overall demand placed on antibiotics, without using antimicrobial substances.

According to the inhibition deficit hypothesis, the ability to inhibit unwanted or irrelevant thoughts and behaviors decreases with age, which can have a significant impact on cognitive and emotional processing. However, studies examining inhibition and age have shown mixed results, with some studies finding a decrease in inhibitory control as individuals age, while others have found no relationship. The goal of this proof-of-concept study was to examine the underlying neural mechanisms that may explain why some older adults are better than others at inhibitory control by investigating the relationship between resting-state functional connectivity (rsFC) of the salience network, a network critical for detecting and focusing attention toward relevant stimuli while ignoring irrelevant information in the environment, and a behavioral measure of inhibitory control (Stroop Task interference score) in a sample of 65 healthy older individuals (ages 65+). Results revealed no direct effect of age on Stroop performance; however, there was an indirect effect of age on Stroop performance through rsFC. These results suggest that rsFC of the salience network may be an important factor to consider when it comes to understanding individual differences in inhibitory control behavior among older adults.

BACKGROUND: Surgical site infection in vascular surgery has a reported incidence of up to 19%. A novel method of reducing this rate of infection is dressings coated with dialkylcarbamoylchloride (DACC), a hydrophobic wound contact layer that binds bacteria and removes them from the wound bed. Early research has suggested that DACC-coated wound dressings are effective in reducing surgical site infection when applied to wounds healing by primary intention post-operatively, therefore this trial aims to assess the feasibility of producing high-quality evidence assessing this theory.
METHODS: Patients undergoing clean or clean-contaminated vascular surgery will be randomised to have their surgical wounds dressed with a DACC-coated dressing or a non-coated occlusive absorbent post-operative dressing. All other aspects of their peri-operative care will be standardised or carried out in line with hospital policy. Wound assessments will be carried out between day 5-7, day 30 (± 3 days) and 6 months post-operatively (± 7 days) by a blinded assessor using the ASEPSIS scoring tool. Quality of life data using EQ-5D and SF-36, resource use and mortality data will also be collected. This feasibility trial will dictate the conduct of a full-scale trial through the collection of data on recruitment and retention rates, and fitness-for-purpose of the follow-up arrangements.
CONCLUSIONS: Surgical site infections are now the second most common hospital acquired infections with a significant cost implication. The aim of the DRESSINg trial is to investigate the effectiveness of a novel preventative measure at reducing wound infections post-surgery and will provide robust evidence to support or deny its use.
BACKGROUND: Clinicaltrials.gov identifier: NCT02992951, Registered 12/12/16. REC Reference: 16/LO/2135.

Chronic low back pain (CLBP) is highly prevalent, with a substantial psychosocial burden. Pain has both sensory and affective components. The latter component is a significant driver of disability and psychiatric comorbidity but is often inadequately treated. Previously we reported that noninvasive transcranial direct current stimulation (tDCS) may modulate pain-associated affective distress. Here we tested whether 10 daily tDCS sessions aimed to inhibit the left dorsal anterior cingulate cortex (dACC), a region strongly implicated in the affective component of pain, would produce selective reduction in pain-related symptoms.
In this multisite, double-blinded, randomized placebo-controlled trial (RCT), 21 CLBP patients received 10 weekday sessions of 2-mA active tDCS or sham (20 minutes/session). A cathodal electrode was placed over FC1 (10-20 electroencephalography coordinates), and an identical anodal return electrode was placed over the contralateral mastoid. Participants rated pain intensity, acceptance, interference, disability, and anxiety, plus general anxiety and depression.
Regression analysis noted significantly less pain interference (P =0.002), pain disability (P =0.001), and depression symptoms (P =0.003) at six-week follow-up for active tDCS vs sham. Omnibus tests suggested that these improvements were not merely due to baseline (day 1) group differences.
To our knowledge, this is the first double-blinded RCT of multiple tDCS sessions targeting the left dACC to modulate CLBP\'s affective symptoms. Results are encouraging, including several possible tDCS-associated improvements. Better-powered RCTs are needed to confirm these effects. Future studies should also consider different stimulation schedules, additional cortical targets, high-density multi-electrode tDCS arrays, and multimodal approaches.

Cognitive flexibility is the ability to switch rapidly between multiple goals. By using a task-switching paradigm, the present study investigated how positive emotion affected cognitive flexibility and the underlying neural mechanisms. After viewing pictures of different emotional valence (positive, negative, or neutral), participants discriminated whether a target digit in a specific color was odd or even. After a series of trials, the color of target stimuli was changed, i.e., the switch condition. Switch costs were measured by the increase of reaction times (RTs) in the switch trials compared to those in the repeat trials. Behavior results indicated that switch costs significantly decreased in the positive emotional condition, and increased in the negative emotional condition, compared with those in the neutral condition. Imaging data revealed enhanced activation in the dorsal anterior cingulate cortex (dACC) in switch trials than those in repeat trials. Moreover, the interaction between emotion (positive, negative, neutral) and trial type (repeat vs. switch) was significant. For switch trials, the activation of dACC decreased significantly in the positive condition, while increased significantly in the negative condition compared to neutral condition. By contrast, for repeat trials, no significant difference was observed for the activation of dACC among three emotional conditions. Our results showed that positive emotions could increase the cognitive flexibility and reduce the conflict by decreasing the activation of dACC.

Recent research has found that individuals with posttraumatic stress disorder (PTSD) exhibit an impaired memory of fear extinction compounded by deficient functional activation of key nodes of the fear network including the amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC). Research has shown these regions are sexually dimorphic and activate differentially in healthy men and women during fear learning tasks. To explore biological markers of sex differences following exposure to psychological trauma, we used a fear learning and extinction paradigm together with functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) to assess 31 individuals with PTSD (18 women; 13 men) and 25 matched trauma-exposed healthy control subjects (13 women; 12 men). Whereas no sex differences appeared within the trauma-exposed healthy control group, both psychophysiological and neural activation patterns within the PTSD group indicated deficient recall of extinction memory among men and not among women. Men with PTSD exhibited increased activation in the left rostral dACC during extinction recall compared with women with PTSD. These findings highlight the importance of tracking sex differences in fear extinction when characterizing the underlying neurobiological mechanisms of PTSD psychopathology.