Increasing evidence points to a pivotal role of immune processes in the pathogenesis of Alzheimer disease, which is the most prevalent neurodegenerative and dementia-causing disease of our time. Multiple lines of information provided by experimental, epidemiological, neuropathological and genetic studies suggest a pathological role for innate and adaptive immune activation in this disease. Here, we review the cell types and pathological mechanisms involved in disease development as well as the influence of genetics and lifestyle factors. Given the decade-long preclinical stage of Alzheimer disease, these mechanisms and their interactions are driving forces behind the spread and progression of the disease. The identification of treatment opportunities will require a precise understanding of the cells and mechanisms involved as well as a clear definition of their temporal and topographical nature. We will also discuss new therapeutic strategies for targeting neuroinflammation, which are now entering the clinic and showing promise for patients.

Eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are two biologically active omega-3 polyunsaturated fatty acids (n-3 PUFA), acquired by nutrition and incorporated in cell membranes' phospholipids, thus playing a crucial role in human health and homeostasis. Due to their potential cardioprotective, anti-inflammatory, and anti-arrhythmic actions, n-3 PUFA emerge as an interesting therapeutic option for cardiac surgery (CS) patients. The aim of this review was to assess the effects of perioperative administration of n-3 PUFA in CS patients. A comprehensive literature search was conducted in order to identify prospective cohort studies and randomized controlled trials (RCT) reporting on the perioperative effects of n-3 PUFA among adult patients undergoing CS. A total of 31 articles, published between 1995 and 2022, including 10 543 patients, met the inclusion criteria. There seems to be a beneficial effect of n-3 PUFA supplementation for arrhythmias such as in Postoperative Atrial Fibrillation (POAF), reduction of Intensive Care Unit Length of Stay (ICULOS) & Hospital Length of Stay (HLOS), reduction in postoperative ventilation time, in inotropic demand, in postoperative fatigue, as well as in overall morbidity and mortality. Moreover, n-3 PUFA increase antioxidant potential, attenuate oxidative stress and inflammation with subsequent significant reduction in myocardial ischemia/reperfusion (I/R) injury, thus promoting early metabolic recovery of the heart after elective CS leading to improved myocardial protection. They represent a readily available and cost-effective strategy that could improve the outcome of patients undergoing CS, by reducing the risks of serious cardiovascular adverse events (AE), both peri- and post-operatively.

The prevalence of multidrug-resistant (MDR) ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, represents a critical global public health challenge. In response, mRNA vaccines offer an adaptable and scalable platform for immunotherapy against ESKAPE pathogens by encoding specific antigens that stimulate B-cell-driven antibody production and CD8+ T-cell-mediated cytotoxicity, effectively neutralizing these pathogens and combating resistance. This review examines recent advancements and ongoing challenges in the development of mRNA vaccines targeting MDR ESKAPE pathogens. We explore antigen selection, the nuances of mRNA vaccine technology, and the complex interactions between bacterial infections and antibiotic resistance. By assessing the potential efficacy of mRNA vaccines and addressing key barriers to their paraclinical implementation, this review highlights the promising function of mRNA-based immunization in combating MDR ESKAPE pathogens.

Acinetobacter baumannii is associated with multidrug-resistant infections in healthcare settings, with fluoroquinolones such as ciprofloxacin being currently ineffective. Clinical isolates largely harbor mutations in the GyrA and TopoIV fluoroquinolone targets, as well as mutations that increase expression of drug resistance-nodulation-division (RND) efflux pumps. Factors critical for maintaining fitness levels of pump overproducers are uncharacterized despite their prevalence in clinical isolates. We, here, identify proteins that contribute to the fitness of fluoroquinolone-resistant (FQR) strains overexpressing three known RND systems using high-density insertion mutagenesis. Overexpression of the AdeFGH efflux pump caused hypersensitization to defects in outer membrane homeostatic regulation, including lesions that reduced lipooligosaccharide (LOS) biosynthesis and blocked production of the major A. baumannii porin. In contrast, AdeAB pump hyperexpression, in the absence of elevated adeC expression (the outer membrane component of the pump), was relatively tolerant to loss of these functions, consistent with the outer membrane protein being the primary disruptive component. Surprisingly, overexpression of proton-transporting efflux pumps had little impact on cytosolic pH, consistent with a compensatory response to pump activity. The most striking transcriptional changes were associated with AdeFGH pump overexpression, including the activation of the phenylacetate (PAA) degradation regulon. Disruption of the PAA pathway resulted in cytosolic acidification and defective expression of genes involved in protection from oxidative stress. These results indicate that RND efflux pump overproduction is compensated by maintenance of outer membrane integrity in A. baumannii to facilitate fitness of FQR isolates.IMPORTANCEAcinetobacter baumannii is a pathogen that often causes multidrug-resistant infections in healthcare settings, presenting a threat to the efficacy of known therapeutic interventions. Fluoroquinolones such as ciprofloxacin are currently ineffective against a majority of clinical A. baumannii isolates, many of which express pumps that remove this antibiotic class from within the bacterium. Three of these pumps can be found in most clinical isolates, with one of the three often hyperproduced at all times. In this study, we identify proteins that are necessary for the fitness of pump hyperproducers. The identified proteins are necessary to stabilize the outer membrane and allow the cytoplasm to tolerate the accumulation of ions as a consequence of excess pump activity. These results point to strategies for developing therapies that combine known antibiotics with drugs that target proteins important for survival of strains hyper-expressing efflux pumps.

The quality and safety of fish products are crucial because poorly handled fish products can result in foodborne illnesses, spoilage, and economic losses. Data on the nutritional and microbiological quality of fish products in Ethiopia, especially in Lake Tana, is limited. This study assessed the proximate composition and microbial quality of raw and open sun-dried fish products in Lake Tana. Using the standard procedures, 60 fish tissue samples were collected and analyzed for proximate composition and microbial quality. The open sun-dried fish had significantly higher ash (10.08% ± 1.98%), fat (6.01% ± 1.59%), protein (48.76% ± 8.55%), water activity (0.7358 ± 0.0368) and salt contents (5.89% ± 3.17%) compared to the raw fish (p < 0.05). A significant difference was observed between raw and dried fish in aerobic mesophilic bacteria, Staphylococcus aureus, yeast and mold counts (p < 0.05). The mean total and fecal coliform counts were not significantly different between the raw and dried fish (p > 0.05). In raw fish, 16.6% and 83.3% of samples had total coliforms and fecal coliforms exceeding the recommended limits, respectively. Both raw and dried fish samples tested positive for Salmonella and Shigella spp. There was a strong positive correlation between water activity and microbial load (r = 0.756, p < 0.05) and also between moisture content and microbial load (r = 0.786, p < 0.05). Most of the assessed raw and sun-dried fish samples were above the international microbial specification limits, which need attention to ensure the safety of fish consumers.

To investigate which fluoroquinolone is safer when combined with bedaquiline for tuberculosis treatment by using the FDA Adverse Event Reporting System (FAERS) database.

We selected data from the first quarter (Q1) of 2013 to the second quarter (Q4) of 2024 from the FDA FAERS database for disproportionality analysis. Signal detection was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM).

This study analyzed 12, 303, 879 reports from the FAERS database, including 722 reports related to the combination of bedaquiline and levofloxacin (with 2,723 adverse events) and 573 reports related to the combination of bedaquiline and moxifloxacin (with 2,233 adverse events). For the bedaquiline-levofloxacin regimen, these reports were categorized into 100 preferred terms (PTs) and 24 System Organ Classification (SOCs). The three most common SOCs were hepatobiliary disorders (n = 128, ROR 5.79, PRR 5.56, IC 2.48, EBGM 5.56), blood and lymphatic system disorders (n = 217, ROR 5.04, PRR 4.72, IC 2.24, EBGM 4.71), and metabolism and nutrition disorders (n = 185, ROR 3.44, PRR 3.27, IC 1.71, EBGM 3.27). In terms of PTs, the three strongest signals were portal fibrosis (ROR 330.64), hepatitis C RNA increased (ROR 301.24), and toxic optic neuropathy (ROR 238.11). Reports of prolonged QT interval on ECG (125 cases) and anemia (130 cases) were significantly more frequent than other PTs. For the bedaquiline-moxifloxacin regimen, these reports were categorized into 85 preferred terms (PTs) and 24 System Organ Classification (SOCs). The three most common SOCs were hepatobiliary disorders (n = 141, ROR 7.9, PRR 7.47, IC 2.9, EBGM 7.46), ear and labyrinth disorders (n = 40, ROR 4.03, PRR 3.97, IC 1.99, EBGM 3.97), and cardiac disorders (n = 141, ROR 3.08, PRR 2.95, IC 1.56, EBGM 2.95). The three strongest PT signals were chronic pyelonephritis (ROR 563.29), bronchopleural fistula (ROR 314.86), and toxic neuropathy (ROR 187.11). Prolonged QT interval on ECG (152 cases) remained the most frequently reported PT. In both treatment regimens, individuals under 45 years of age experienced a higher frequency and variety of AEs, indicating the need for enhanced monitoring. For those over 45, particular attention should be given to ECG changes, especially in men. Finally, some PTs with extremely high signal strength, such as chronic pyelonephritis (ROR 563.29), hepatitis C RNA increased (ROR 301.24), and bronchopleural fistula (ROR 301.24), may represent rare adverse events associated with the combination of bedaquiline-fluoroquinolone.

Our study suggests that the safety profile of bedaquiline combined with moxifloxacin does not appear superior to that of bedaquiline combined with levofloxacin in terms of cardiac, hepatic, and neurological effects. Therefore, in the BPaLM regimen, considering the substitution of moxifloxacin with levofloxacin may be worthwhile if their efficacy is proven to be similar. Increased monitoring may be required for individuals under 45 years of age and male MDR-TB patients.

As the global trend for healthy eating grows, firms are emphasising dairy functional foods (DFFs). This study looks into the relationship between consumer attitudes and readiness to consume DFFs, taking into account how a healthy lifestyle might both motivate and deter people from using them. Hungary was chosen because consumer behaviour towards functional foods is under-researched in comparison to Western Europe. Data were generated using a survey questionnaire from 313 respondents. The results of Partial Least Squares (PLS) analysis revealed that consumer attitudes had a considerable influence on the desire to consume DFFs. Furthermore, the motivators and barriers had a direct influence on willingness through the consumer attitudes that serve as mediators. These findings show the need for targeting consumer attitudes and lifestyle characteristics in order to increase the market acceptance of DFFs.

Acinetobacter baumannii is associated with multidrug resistant (MDR) infections in healthcare settings, with fluoroquinolones such as ciprofloxacin being currently ineffective. Clinical isolates largely harbor mutations in the GyrA and TopoIV fluoroquinolone targets, as well as mutations that increase expression of drug resistance-nodulation-division (RND) efflux pumps. Factors critical for maintaining fitness levels of pump overproducers are uncharacterized despite their prevalence in clinical isolates. We here identify proteins that contribute to the fitness of FQR strains overexpressing three known RND systems using high-density insertion mutagenesis. Overexpression of the AdeFGH efflux pump caused hypersensitization to defects in outer membrane homeostatic regulation, including lesions that reduced LOS biosynthesis and blocked production of the major A. baumannii porin. In contrast, AdeAB pump hyperexpression, in the absence of elevated adeC expression (the outer membrane component of the pump), was relatively tolerant to loss of these functions, consistent with the outer membrane protein being the primary disruptive component. Surprisingly, overexpression of proton-transporting efflux pumps had little impact on cytosolic pH, consistent with a compensatory response to pump activity. The most striking transcriptional changes were associated with AdeFGH pump overexpression, including the activation of the phenylacetate (PAA) degradation regulon. Disruption of the PAA pathway resulted in cytosolic acidification and defective expression of genes involved in protection from oxidative stress. These results indicate that RND efflux pump overproduction is compensated by maintenance of outer membrane integrity in A. baumannii to facilitate fitness of FQR isolates.

The scarcity of blood for transfusion purposes has been widely acknowledged. Surgical therapeutic processes, war zones, and post-disaster treatments demand a huge amount of blood. Modern-day laboratories also require blood for bioengineering experimentation. Therefore, an artificially devised solution capable of mimicking the blood functions from biological and engineering relevance would be a noteworthy discovery of contemporary science. The experience drawn from discarded century-old blood substitutes has led us to technologically more advanced present-day solutions, which are better at carrying out the physiological functions of blood. Aiming at safety, stability, non-toxicity, and compatibility in terms of immuno-response, a remarkable number of substitutes are being tried to mimic the physiological properties and functions of red blood cells, platelets, plasma, and white blood cells. Despite significant efforts and time devoted, for transfusion, no product so far has been able to replace natural blood. This article puts together the important developments in blood substitutes that have evolved over the years, including substitutes for clinical as well as engineering requirements. It also points out the recent endeavors of synthesizing blood cells through modern synthetic routes. It has been highlighted that none of the blood substitutes have achieved the required efficacy so that they can be used in vivo. Finally, the emerging trends and future research needs have been stressed upon.

To determine the prevalence and risk factors of sleep bruxism (SB) in adults with primary snoring (PS).

This study included 292 adults with PS (140 males, 152 females; mean age ± standard deviation = 42.8 ± 12.2 years; mean body mass index ± standard deviation = 26.7 ± 4.7 kg/m2) without previous treatment for snoring. SB was diagnosed based on the frequency of the biomarker of SB: rhythmic masticatory muscle activity (SB when rhythmic masticatory muscle activity ≥ 2 episodes/h). Logistic regression was performed, with SB as the dependent variable and with age, sex, body mass index, and sleep- and respiratory-related polysomnographic parameters as the independent variables to identify the risk factors for SB.

The prevalence of SB was 44.6% in adults with PS. Younger age (odds ratio = 0.965 [0.944, 0.987]) and shorter total sleep time (odds ratio = 0.760 [0.609, 0.948]) significantly increased the risk of SB (P < .05).

SB is highly prevalent in adults with PS. Younger age and shorter sleep time are significant risk factors for SB in adults with PS.

Registry: onderzoekmetmensen.nl; Name: A Large Sample Polysomnographic Study on Sleep Bruxism; URL: https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON19947; Identifier: NL8516.

Li D, Lobbezoo F, Hilgevoord AAJ, de Vries N, Aarab G. Prevalence and risk factors of sleep bruxism in adults with primary snoring: a large-scale polysomnographic study. J Clin Sleep Med. 2024;20(8):1331-1337.

Mobile phone-based SMS text message reminders have the potential to improve colorectal cancer screening participation rates.

This study assessed the effectiveness and acceptability of adding targeted SMS text message reminders to the standard procedure for those who picked up but did not return their screening kit at the pharmacy within 14 days in a colorectal cancer screening program in Catalonia, Spain.

We performed a randomized control trial among individuals who picked up a fecal immunochemical test (FIT) kit for colorectal cancer screening at the pharmacy but did not return it within 14 days. The intervention group (n=4563) received an SMS text message reminder on the 14th day of kit pick up and the control group (n=4806) received no reminder. A 30-day reminder letter was sent to both groups if necessary. The main primary outcome was the FIT completion rate within 30, 60, and 126 days from FIT kit pick up (intention-to-treat analysis). A telephone survey assessed the acceptability and appropriateness of the intervention. The cost-effectiveness of adding an SMS text message reminder to FIT completion was also performed.

The intervention group had higher FIT completion rates than the control group at 30 (64.2% vs 53.7%; P<.001), 60 (78.6% vs 72.0%; P<.001), and 126 (82.6% vs 77.7%; P<.001) days. Participation rates were higher in the intervention arm independent of sex, age, socioeconomic level, and previous screening behavior. A total of 339 (89.2%) interviewees considered it important and useful to receive SMS text message reminders for FIT completion and 355 (93.4%) preferred SMS text messages to postal letters. We observed a reduction of US $2.4 per participant gained in the intervention arm for invitation costs compared to the control arm.

Adding an SMS text message reminder to the standard procedure significantly increased FIT kit return rates and was a cost-effective strategy. SMS text messages also proved to be an acceptable and appropriate communication channel for cancer screening programs.

ClinicalTrials.gov NCT04343950; https://www.clinicaltrials.gov/study/NCT04343950.

RR2-10.1371/journal.pone.0245806.

SUMMARYInfectious bacteria have both intrinsic and acquired mechanisms to combat harmful biocides that enter the cell. Through adaptive pressures, many of these pathogens have become resistant to many, if not all, of the current antibiotics used today to treat these often deadly infections. One prominent mechanism is the upregulation of efflux systems, especially the resistance-nodulation-cell division class of exporters. These tripartite systems consist of an inner membrane transporter coupled with a periplasmic adaptor protein and an outer membrane channel to efficiently transport a diverse array of substrates from inside the cell to the extracellular space. Detailed mechanistic insight into how these inner membrane transporters recognize and shuttle their substrates can ultimately inform both new antibiotic and efflux pump inhibitor design. This review examines the structural basis of substrate recognition of these pumps and the molecular mechanisms underlying multidrug extrusion, which in turn mediate antimicrobial resistance in bacterial pathogens.

A new polyether sulfone (PES) membrane modified with manganese-aluminum layered double hydroxide (Mn-Al LDH) was prepared and utilized in the membrane micro-solid phase extraction (M-µSPE) of acrylamide for the first time. The analyses were conducted using HPLC-UV. The extraction efficiency of the PES membrane was enhanced two-fold with the addition of LDH. The fabricated LDH@PES was characterized using ATR-FTIR, SEM, XRD, and nitrogen adsorption/desorption isotherms. The specific surface area, average pore diameter, thickness, cross-sectional channels, and LDH particle size of the LDH@PES membrane were determined. The extraction key factors including membrane composition, desorption conditions, sample pH, and salt concentration were studied. The method was validated by determining the limit of detection, the limit of quantification, linear range, r2, matrix effect, enrichment factor, and precision. Extraction recoveries ranged from 87.4 to 103.5% with RSD < 5.9%. Finally, the method's green features were assessed with the AGREE protocol. This is the first report on the application of LDH@PES for microfiltration/extraction of acrylamide in various chocolate and cocoa products.

Aggression has multiple benefits and is often coupled with other behaviors ("behavioral syndromes"). The level of aggressiveness is influenced by an adaptive benefit-cost ratio suggesting that benefits should outweigh the costs of aggression. Here, we assess if several behaviors are coupled in two behaviorally different populations (aggressive, peaceful) of the high-elevation ant Tetramorium alpestre. For three weeks, we collected colony fragments and analyzed boldness, exploring, foraging, and risk-taking behaviors. We hypothesized that the aggressive population is bolder, more explorative and risk-prone, and forages more food than the peaceful population. To test whether (a) the combination of experiments and parameters used yields a good setup, (b) populations differ behaviorally, and (c) populations display behavioral syndromes, we assessed (a) the frequency of repeatable behaviors of each experiment, (b) the behavioral means among populations, and (c) the behavioral repeatability, respectively. We found that (a) boldness and exploring were most repeatable and represent a good experimental setup, (b) the aggressive population was bolder and more explorative and risk-prone than the peaceful population, (c) boldness and exploring behaviors were highly repeatable in both populations, thus corroborating our hypothesis. The results suggest that boldness, exploring, and risk-taking but not foraging are presumably coupled with aggression and indicate the presence of behavioral syndromes in this ant. Under specific ecological conditions, aggression may be coupled with other behaviors and important for finding food. Aggression is probably adaptive in T. alpestre, possibly indicating that selection favors aggression at least partially, which may counteract the complete loss of intraspecific aggression.

This paper presents the results of experimental investigation of the mechanical characteristics of 3D-printed acrylonitrile butadiene styrene (ABS) and its modifications reinforced with different types of short-fiber fillers: carbon, glass, and basalt. Elastic modulus, tensile and bending strength, as well as fracture toughness were determined in series of mechanical tests for samples produced with different manufacturing parameters, such as nozzle diameter and infill angle. It was found that the use of ABS filament reinforced with the short fibers can significantly improve the mechanical properties of 3D-printed devices when the infill angle is oriented along the vector of the applied load. In such a case, the elastic modulus and tensile strength can be increased by more than 1.7 and 1.5 times, respectively. The use of a larger nozzle diameter led to the growth of tensile strength by an average of 12.5%. When the macroscopic load is applied along the normal to the printed layers, the addition of short fibers does not give much gain in mechanical properties compared to pure ABS, which was confirmed by both standard tensile and fracture toughness tests. The surface of the fractured samples was examined using scanning electronic microscopy, which allowed us to make conclusions on the type of defects as well as on the level of adhesion between the polymeric matrix and different types of short fibers.

Phytoremediation is widely considered as a cost-effective method for managing heavy metal soil pollution. Leersia hexandra Swartz shows a promising potential for the remediation of heavy metals pollution, including chromium (Cr), copper (Cu), and nickel (Ni). It is vital to understand the physiological and biochemical responses of L. hexandra to Ni stress to elucidate the mechanisms underlying Ni tolerance and accumulation. Here, we examined the metabolic and transcriptomic responses of L. hexandra exposed to 40 mg/L Ni for 24 h and 14 d. After 24-h Ni stress, gene expression of glutathione metabolic cycle (GSTF1, GSTU1 and MDAR4) and superoxide dismutase (SODCC2) was significantly increased in plant leaves. Furthermore, after 14-d Ni stress, the ascorbate peroxidase (APX7), superoxide dismutase (SODCP and SOD1), and catalase (CAT) gene expression was significantly upregulated, but that of glutathione metabolic cycle (EMB2360, GSTU1, GSTU6, GSH2, GPX6, and MDAR2) was downregulated. After 24-h Ni stress, the differentially expressed metabolites (DEMs) were mainly flavonoids (45%) and flavones (20%). However, after 14-d Ni stress, the DEMs were mainly carbohydrates and their derivatives (34%), amino acids and derivatives (15%), and organic acids and derivatives (8%). Results suggest that L. hexandra adopt distinct time-dependent antioxidant and metal detoxification strategies likely associated with intracellular reduction-oxidation balance. Novel insights into the molecular mechanisms responsible for Ni tolerance in plants are presented.

Gram-negative bacterial members of the Resistance Nodulation and cell Division (RND) superfamily form tripartite efflux pump systems that span the cell envelope. One of the intriguing features of the multiple drug efflux members of this superfamily is their ability to recognize different classes of antibiotics, dyes, solvents, bile salts, and detergents. This review provides an overview of the molecular mechanisms of multiple drug efflux catalysed by the tripartite RND efflux system AcrAB-TolC from Eschericha coli. The determinants for sequential or simultaneous multiple substrate binding and efflux pump inhibitor binding are discussed. A comparison is made with the determinants for substrate binding of AdeB from Acinetobacter baumannii, which acts within the AdeABC multidrug efflux system. There is an apparent general similarity between the structures of AcrB and AdeB and their substrate specificity. However, the presence of distinct conformational states and different drug efflux capacities as revealed by single-particle cryo-EM and mutational analysis suggest that the drug binding and transport features exhibited by AcrB may not be directly extrapolated to the homolog AdeB efflux pump.

This quality improvement project is aimed to increase pain free hospital implementation from 21.7 to 80% at Wallaga University Referral Hospital (WURH) from January 1, 2023 to June 30, 2023.

Hospital based interventional study was conducted at WURH. The Plan- Do-Study-Act (PDSA) cycle was used to test change ideas. A fishbone diagram and a driver diagram were used to identify root causes and address them. Major interventions included training of health professionals, initiation of pain as fifth vital sign, policy and protocol development, and conducting regular supportive supervision.

Upon completion of the project, overall pain-free hospital implementation increased from baseline 21.7-88.7%. Implementation of pain as 5th the vital sign was increased from 15.4 to 92.3%. Regular audits of pain assessment and management increased from 27.3 to 81.8%. Two standardized treatment protocols or chronic and acute pains were developed from baseline zero. A focal person for Pain-free hospital implementation was assigned. More than 85% of healthcare providers were trained in pain assessment and management.

Compliance with pain-free hospital implementations was significantly improved in the study area. This was achieved through the application of multidimensional change ideas related to health professionals, standardized guidelines and protocols, supplies, and leadership. Therefore, we recommend providing regular technical updates & conducting a frequent clinical audit on pain management.

Acinetobacter baumannii is a nosocomial pathogen often associated with multidrug resistance (MDR) infections. Fluoroquinolone resistance (FQR) due to drug target site mutations and elevated expression of RND drug transporters is common among clinical isolates. We describe here a CRISPRi platform that identifies hypomorphic mutations that preferentially altered drug sensitivity in RND pump overproducers. An sgRNA library against essential genes of A. baumannii was constructed with single and double nucleotide mutations that produced titratable knockdown efficiencies and introduced into multiple strain backgrounds. Other than nusG depletions, there were few candidates in the absence of drug treatment that showed lowered fitness specifically in strains overexpressing clinically relevant RND efflux pumps AdeAB, AdeIJK, or AdeFGH. In the presence of ciprofloxacin, the hypomorphs causing hypersensitivity were predicted to result in outer membrane dysfunction, to which the AdeFGH overproducer appeared particularly sensitive. Depletions of either the outer membrane assembly BAM complex, LOS biogenesis proteins, or Lpt proteins involved in LOS transport to the outer membrane caused drug hypersensitivity in at least two of the three pump overproducers. On the other hand, depletions of translation-associated proteins, as well as components of the proton-pumping ATP synthase pump resulted in fitness benefits for at least two pump-overproducing strains in the presence of the drug. Therefore, pump overproduction exacerbated stress caused by defective outer membrane integrity, while the efficacy of drug resistance in efflux overproducers was enhanced by slowed translation or defects in ATP synthesis linked to the control of proton movement across the bacterial membrane.

Multidrug Resistance mechanisms in microorganisms confer the slackness of the existing drugs, leading to added difficulty in treating infections. As a consequence, efficient novel drugs and innovative therapies to treat MDR infections are necessarily required. One of the primary contributors to the emergence of multidrug resistance in gram-negative bacteria has been identified as the efflux pumps. These transporter efflux pumps reduce the intracellular concentration of antibiotics and aid bacterial survival in suboptimal low antibiotic concentration environments that may cause treatment failure. The reversal of this resistance via inhibition of the efflux mechanism is a promising method for increasing the effectiveness of antibiotics against multidrug-resistant pathogens. Such EPI, in combination with antibiotics, can make it easier to reintroduce traditional antibiotics into clinical practice. This review mostly examines efflux-mediated multidrug resistance in critical gram-negative bacterial pathogens and EPI of plant origin that have been reported over previous decades.

Acinetobacter baumannii-calcoaceticus complex (ABC) causes severe infections that are difficult to treat due to pre-existing antibiotic resistance. Sulbactam-durlobactam (SUL-DUR) is a targeted β-lactam/β-lactamase inhibitor combination antibiotic designed to treat serious infections caused by Acinetobacter, including multidrug- and carbapenem-resistant strains. In a recent global surveillance study of 5,032 ABC clinical isolates collected from 2016 to 2021, less than 2% of ABC isolates had SUL-DUR MIC values >4 µg/mL. Molecular characterization of these isolates confirmed the primary drivers of resistance are metallo-β-lactamases or penicillin-binding protein 3 (PBP3) mutations, as previously described. In addition, this study shows that certain common PBP3 variants, such as A515V, are insufficient to confer sulbactam resistance and that the efflux of durlobactam by AdeIJK is likely to play a role in a subset of strains.

Concerns exist that widespread use of antiseptic or disinfectant biocides could contribute to the emergence and spread of multidrug-resistant bacteria. To investigate this, we performed transposon-directed insertion-site sequencing (TraDIS) on the multidrug-resistant pathogen, Acinetobacter baumannii, exposed to a panel of ten structurally diverse and clinically relevant biocides. Multiple gene targets encoding cell envelope or cytoplasmic proteins involved in processes including fatty acid biogenesis, multidrug efflux, the tricarboxylic acid cycle, cell respiration and cell division, were identified to have effects on bacterial fitness upon biocide exposure, suggesting that these compounds may have intracellular targets in addition to their known effects on the cell envelope. As cell respiration genes are required for A. baumannii fitness in biocides, we confirmed that sub-inhibitory concentrations of the biocides that dissipate membrane potential can promote A. baumannii tolerance to antibiotics that act intracellularly. Our results support the concern that residual biocides might promote antibiotic resistance in pathogenic bacteria.

The need for consistency in analytical method development reinforces the dependence of pharmaceutical product development and manufacturing on robust analytical data. The Analytical Quality by Design (AQbD), akin to the product Quality by Design (QbD) endows a high degree of confidence to the method quality developed. AQbD involves the definition of the analytical target profile as starting point, followed by the identification of critical method variables and critical analytical attributes, supported on risk assessment and design of experiment tools for the establishment of a method operable design region and control strategy of the method. This systematic approach moves away from reactive troubleshooting to proactive failure reduction. The objective of this review is to highlight the elements of the AQbD framework and provide an overview of their implementation status in various analytical methods used in the pharmaceutical field. These methodologies include but are not limited to, high-performance liquid chromatography, UV-Vis spectrophotometry, capillary electrophoresis, supercritical fluid chromatography, and high-performance thin-layer chromatography. Finally, a critical appraisal is provided to highlight how regulators have encouraged AQbD principles application to boost the prevention of method failures and a better understanding of the method operable design region (MODR) and control strategy, ultimately resulting in cost-effectiveness and regulatory flexibility.

In Peru, insect consumption, as a nutritional complement or as the main source in the diet, is limited to the regions of our the central jungle where Atta sexdens ants are consumed. An energy bar based on Andean grains with Atta sexdens ant flour was formulated. The ants were obtained from the department of San Martin, district of Rioja, province of Rioja. Four different formulations were prepared with different Atta sexdens ant flour concentrations: 13%, 17%, 20%, and 23%. Moisture, total fat, ash, proteins, fiber, carbohydrates, instrumental texture, and organoleptic analysis (taste, texture, and color) were performed. The developed cereal energy bar presented a 10 g protein content in 100 g of the final product. Acceptability was evaluated in adolescents and young adult populations. The developed cereal bars presented a high protein content, adequate organoleptic properties and high acceptability.

Introduction Both osteoporosis and osteopenia are prevalent public health concerns worldwide and can lead to debilitating bone fractures. This study aimed to assess the efficacy of Asthiposhak® Tablets in individuals with Asthikshaya (osteopenia) by measuring changes in the bone mineral density (BMD) score before and after the intervention, specifically between visit 1 (baseline) and visit 8 (after 180 days of treatment). Methods The single-arm study involved the screening of participants for Asthikshaya (osteopenia) using baseline investigations, which included a bone mineral density (BMD) assessment through a dual-energy X-ray absorptiometry (DEXA) scan. A total of 36 participants were enrolled in the study, who took two Asthiposhak Tablets three times a day with lukewarm water, for a period of 180 days. Safety assessments, along with evaluations of BMD (DEXA Scan), Ayurvedic Symptom Score, and serum biochemical markers, were conducted through blood investigations. Efficacy and safety data were analyzed using 'intention-to-treat' analysis. Descriptive statistics were used to express data in percentages, mean ± SD, or median (IQR). Data at different intervals were compared using paired t-tests or Wilcoxon signed-rank tests. One-way analysis of variance (ANOVA) with Bonferroni correction tested the significance between visits for the Ayurvedic Symptom Score, and Friedman's two-way analysis of variance by ranks measured differences in vital parameters. The significance level used was p<0.05. Results Out of the initially recruited 36 participants, 30 successfully completed the study, consisting of 12 males and 18 females, with an age range of 40 to 70 years and a mean age of 51.33 years. After 180 days of treatment with Asthiposhak Tablets, a statistically significant (p<0.05) improvement in hip and spine BMD (T-score) was observed. Additionally, significant reductions in the mean Total Ayurvedic Symptom Score were noted at both 90 and 180 days of treatment compared to day 0. Moreover, the levels of bone-specific alkaline phosphatase and osteocalcin, serum bone markers, showed statistically significant (p<0.05) reduction after 180 days of treatment compared to day 0. Importantly, all safety variables, including laboratory investigations, remained within the normal range following the 180-day treatment with Asthiposhak Tablets. Conclusion Asthiposhak Tablets exhibited significant efficacy in enhancing both BMD (T-score) and Ayurvedic Symptom Score, thereby substantiating their osteoprotective potential in individuals with Asthikshaya (osteopenia). Furthermore, the tablets were found to reduce the levels of biochemical markers, such as serum bone-specific alkaline phosphatase and osteocalcin, suggesting their anti-resorptive action.

Vat photopolymerization (VPP) is an effective additive manufacturing (AM) process known for its high dimensional accuracy and excellent surface finish. It employs vector scanning and mask projection techniques to cure photopolymer resin at a specific wavelength. Among the mask projection methods, digital light processing (DLP) and liquid crystal display (LCD) VPP have gained significant popularity in various industries. To upgrade DLP and LCC VPP into a high-speed process, increasing both the printing speed and projection area in terms of the volumetric print rate is crucial. However, challenges arise, such as the high separation force between the cured part and the interface and a longer resin refilling time. Additionally, the divergence of the light-emitting diode (LED) makes controlling the irradiance homogeneity of large-sized LCD panels difficult, while low transmission rates of near ultraviolet (NUV) impact the processing time of LCD VPP. Furthermore, limitations in light intensity and fixed pixel ratios of digital micromirror devices (DMDs) constrain the increase in the projection area of DLP VPP. This paper identifies these critical issues and provides detailed reviews of available solutions, aiming to guide future research towards developing a more productive and cost-effective high-speed VPP in terms of the high volumetric print rate.

The WHO Non-Communicable Diseases Kit (NCDK) was developed to support care for non-communicable diseases (NCDs) in humanitarian settings. Targeting primary healthcare, each kit contains medicines and supplies that are forecasted to meet the needs of 10,000 people for 3 months. This study aimed to evaluate the NCDK deployment process, contents, usage and limitations, and to explore its acceptability and effectiveness among healthcare workers (HCWs) in South Sudan.

This mixed-method observational study captured data from pre-and-post NCDK deployment. Six data collection tools included: (i) contextual analysis, (ii) semi-structured interviews, in addition to surveys measuring/assessing (iii) healthcare workers' knowledge about NCDs, and healthcare workers' perceptions of: (iv) health facility infrastructure, (v) pharmaceutical supply chain, and (vi) NCDK content. The pre- and post-deployment evaluations were conducted in four facilities (October-2019) and three facilities (April-2021), respectively. Descriptive statistics were used for quantitative data and content analysis for open-ended questions. A thematic analysis was applied on interviews findings and further categorized into four predetermined themes.

Compared to baseline, two of the re-assessed facilities had improved service availability for NCDs. Respondents described NCDs as a growing problem that is not addressed at a national level. After deployment, the same struggles were intensified with the COVID-19 pandemic. The delivery process was slow and faced delays associated with several barriers. After deployment, poor communications and the "push system" of inventories were commonly perceived by stakeholders, leading to expiry/disposal of some contents. Despite being out-of-stock at baseline, at least 55% of medicines were found to be unused post-deployment and the knowledge surveys demonstrated a need for improving HCWs knowledge of NCDs.

This assessment further confirmed the NCDK role in maintaining continuity of care on a short-term period. However, its effectiveness was dependent on the health system supply chain in place and the capacity of facilities to manage and treat NCDs. Availability of medicines from alternative sources made some of the NCDK medicines redundant or unnecessary for some health facilities. Several learnings were identified in this assessment, highlighting barriers that contributed to the kit underutilization.

Natural weathering test at two different European climatic zones were conducted to investigate simultaneously both, the fungal colonisation and weathering process of Scots pine wood (Pinus sylvestris L.). The hypothesis was that the wood performing differently in various climate conditions might affect fungal infestation. The colour changes, wettability, and glossiness were measured as indicators of weathering progress of wood together with an assessment of fungal diversity. Different intensities in weathering, occupancy, and colonisation of fungi on wooden surface were detected. A higher number of fungal species was found on wood exposed to the warm temperate climates compared to subarctic or boreal climates. The dominant fungal species in both locations were from the genera Cladosporium and Aureobasidium.

Acceptability of digital mental health interventions is a significant predictor of treatment-seeking behavior and engagement. However, acceptability has been conceptualized and operationalized in various ways, which decreases measurement precision and leads to heterogeneous conclusions about acceptability. Standardized self-report measures of acceptability have been developed, which have the potential to ameliorate these problems, but none have demonstrated evidence for validation among Black communities, which limits our understanding of attitudes toward these interventions among racially minoritized groups with well-documented barriers to mental health treatment.

This study aims to examine the psychometric validity and reliability of one of the first and most widely used measures of acceptability, the Attitudes Towards Psychological Online Interventions Questionnaire, among a Black American sample.

Participants (N=254) were recruited from a large southeastern university and the surrounding metropolitan area and completed the self-report measure via a web-based survey. A confirmatory factor analysis using mean and variance adjusted weighted least squares estimation was conducted to examine the validity of the underlying hierarchical 4-factor structure proposed by the original authors of the scale. An alternative, hierarchical 2-factor structure model and bifactor model were examined for comparative fit.

The findings indicated that the bifactor model demonstrated a superior fit (comparative fit index=0.96, Tucker-Lewis index=0.94, standardized root mean squared residual=0.03, and root mean square error of approximation=0.09) compared with both 2- and 4-factor hierarchical structure models.

The findings suggest that, within a Black American sample, there may be greater utility in interpreting the Attitudes Towards Psychological Online Interventions Questionnaire subscales as attitudinal constructs that are distinct from the global acceptability factor. The theoretical and practical implications for culturally responsive measurements were explored.

Production of metals stands for 40% of all industrial greenhouse gas emissions, 10% of the global energy consumption, 3.2 billion tonnes of minerals mined, and several billion tonnes of by-products every year. Therefore, metals must become more sustainable. A circular economy model does not work, because market demand exceeds the available scrap currently by about two-thirds. Even under optimal conditions, at least one-third of the metals will also in the future come from primary production, creating huge emissions. Although the influence of metals on global warming has been discussed with respect to mitigation strategies and socio-economic factors, the fundamental materials science to make the metallurgical sector more sustainable has been less addressed. This may be attributed to the fact that the field of sustainable metals describes a global challenge, but not yet a homogeneous research field. However, the sheer magnitude of this challenge and its huge environmental effects, caused by more than 2 billion tonnes of metals produced every year, make its sustainability an essential research topic not only from a technological point of view but also from a basic materials research perspective. Therefore, this paper aims to identify and discuss the most pressing scientific bottleneck questions and key mechanisms, considering metal synthesis from primary (minerals), secondary (scrap), and tertiary (re-mined) sources as well as the energy-intensive downstream processing. Focus is placed on materials science aspects, particularly on those that help reduce CO₂ emissions, and less on process engineering or economy. The paper does not describe the devastating influence of metal-related greenhouse gas emissions on climate, but scientific approaches how to solve this problem, through research that can render metallurgy fossil-free. The content is considering only direct measures to metallurgical sustainability (production) and not indirect measures that materials leverage through their properties (strength, weight, longevity, functionality).

Bacterial resistance to antibiotics has been long recognized as a priority to address for human health. Among all micro-organisms, the so-called multi-drug resistant (MDR) bacteria, which are resistant to most, if not all drugs in our current arsenal, are particularly worrisome. The World Health Organization has prioritized the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) pathogens, which include four Gram-negative bacterial species. In these bacteria, active extrusion of antimicrobial compounds out of the cell by means of 'molecular guns' known as efflux pumps is a main determinant of MDR phenotypes. The resistance-nodulation-cell division (RND) superfamily of efflux pumps connecting the inner and outer membrane in Gram-negative bacteria is crucial to the onset of MDR and virulence, as well as biofilm formation. Thus, understanding the molecular basis of the interaction of antibiotics and inhibitors with these pumps is key to the design of more effective therapeutics. With the aim to contribute to this challenge, and complement and inspire experimental research, in silico studies on RND efflux pumps have flourished in recent decades. Here, we review a selection of such investigations addressing the main determinants behind the polyspecificity of these pumps, the mechanisms of substrate recognition, transport and inhibition, as well as the relevance of their assembly for proper functioning, and the role of protein-lipid interactions. The journey will end with a perspective on the role of computer simulations in addressing the challenges posed by these beautifully complex machineries and in supporting the fight against the spread of MDR bacteria.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons and neuromuscular impairment leading to complete paralysis, respiratory failure and premature death. The pathogenesis of the disease is multifactorial and noncell-autonomous involving the central and peripheral compartments of the neuromuscular axis and the skeletal muscle. Advanced clinical trials on specific ALS-related pathways have failed to significantly slow the disease. Therapy with stem cells from different sources has provided a promising strategy to protect the motor units exerting their effect through multiple mechanisms including neurotrophic support and excitotoxicity and neuroinflammation modulation, as evidenced from preclinical studies. Several phase I and II clinical trial of ALS patients have been developed showing positive effects in terms of safety and tolerability. However, the modest results on functional improvement in ALS patients suggest that only a coordinated effort between basic and clinical researchers could solve many problems, such as selecting the ideal stem cell source, identifying their mechanism of action and expected clinical outcomes. A promising approach may be stem cells selected or engineered to deliver optimal growth factor support at multiple sites along the neuromuscular pathway. This review covers recent advances in stem cell therapies in animal models of ALS, as well as detailing the human clinical trials that have been done and are currently undergoing development.

Pathogen inactivation is a strategy to improve the safety of transfusion products. The only pathogen reduction technology for blood products currently approved in the US utilizes a psoralen compound, called amotosalen, in combination with UVA light to inactivate bacteria, viruses, and protozoa. Psoralens have structural similarity to bacterial multidrug efflux pump substrates. As these efflux pumps are often overexpressed in multidrug-resistant pathogens, we tested whether contemporary drug-resistant pathogens might show resistance to amotosalen and other psoralens based on multidrug efflux mechanisms through genetic, biophysical, and molecular modeling analysis. The main efflux systems in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa are tripartite resistance-nodulation-cell division (RND) systems, which span the inner and outer membranes of Gram-negative pathogens, and expel antibiotics from the bacterial cytoplasm into the extracellular space. We provide evidence that amotosalen is an efflux substrate for the E. coli AcrAB, Acinetobacter baumannii AdeABC, and P. aeruginosa MexXY RND efflux pumps. Furthermore, we show that the MICs for contemporary Gram-negative bacterial isolates for these species and others in vitro approached and exceeded the concentration of amotosalen used in the approved platelet and plasma inactivation procedures. These findings suggest that otherwise safe and effective inactivation methods should be further studied to identify possible gaps in their ability to inactivate contemporary, multidrug-resistant bacterial pathogens. IMPORTANCE Pathogen inactivation is a strategy to enhance the safety of transfused blood products. We identify the compound, amotosalen, widely used for pathogen inactivation, as a bacterial multidrug efflux substrate. Specifically, experiments suggest that amotosalen is pumped out of bacteria by major efflux pumps in E. coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. Such efflux pumps are often overexpressed in multidrug-resistant pathogens. Importantly, the MICs for contemporary multidrug-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, Burkholderia spp., and Stenotrophomonas maltophilia isolates approached or exceeded the amotosalen concentration used in approved platelet and plasma inactivation procedures, potentially as a result of efflux pump activity. Although there are important differences in methodology between our experiments and blood product pathogen inactivation, these findings suggest that otherwise safe and effective inactivation methods should be further studied to identify possible gaps in their ability to inactivate contemporary, multidrug-resistant bacterial pathogens.

The paper has two objectives. The first one examines whether informing women about the benefits and adverse effects of breast cancer screening could have an effect on three variables: their knowledge, the importance women attach to the future consequences of their current decisions (time perspective), and the degree to which women are worried about developing breast cancer (worry). The second one examines whether these three variables affect their intention to participate in the screening, either directly or indirectly through their feeling of regret if they do not attend the screening (anticipated regret); through their values and the support they receive in making their decisions (decisional conflict); and, through the perceived acceptability and benefits of the screening programme (attitude).

Partial least squares-structural equation modelling (PLS-SEM) is used to analyse both objectives and to differentiate between direct, indirect, and moderating effects, due to the incorporation in the model of the three mediating variables (anticipated regret, decisional conflict, and attitude) and a moderating variable (educational level).

Information affects knowledge (objective variable), but not the behavioural variables (time perspective and worry). On the other hand, the level of knowledge has no direct or indirect effect on intention, but behavioural variables do affect it through the mediating variables.

The variables of the planned behaviour theory are relevant to understand women's decisions and to be able to take appropriate health policy measures. Doing so, the processes of personalised screening would improve, or there would be the incorporation of shared decision-making in this context; these being demands associated with the most recent goals achieved in health programmes in many countries.

In the pathogenesis of inflammatory bowel disease (IBD), the advanced glycation end product receptor (RAGE) has been involved. IBD is classified into Chron's disease (CD) and ulcerative colitis (UC). The promoter gene of the RAGE gene was discovered to have had unique polymorphisms that increased its transcriptional activity. This study, therefore, used a systematic review and meta-analysis to examine the relationship between the RAGE gene polymorphism and the risk of IBD.

Databases such as PubMed, Scopus, and Cochrane library were searched to identify the relationship between RAGE gene polymorphisms and IBD susceptibility. We identified three Single Nucleotide Polymorphism (SNPs) (RAGE-429T/C, 374T/A, and G82S). The data were analyzed by RevMan 5.4.

Four studies (932 cases/1366 controls) were included. The findings showed no relationship between RAGE -429T/C and -G82S polymorphisms and the risk of IBD in all genetic models significantly. TT genotype of RAGE -374T/A polymorphisms was related to increased CD risk (OR=1.37; 95%CI=1.04-1.81; P=0.02), while TA genotype was determined to be a protective factor (OR=0.75; 95%CI=0.57-0.99; P=0.04). In UC, A allele of RAGE -374T/A was related to increase risk (OR=1.26; 95%CI=1.04-1.53; P=0.02), while T allele was determined to decrease risk (OR=0.79; 95%CI= 0.65-0.96; P=0.02).

Our findings demonstrated that TT genotype and A allele of RAGE -374T/A polymorphisms were related to CD and UC risks, respectively, while the TA genotype and T allele possibly had a protective effect. RAGE -429T/C and RAGE -G82S polymorphisms were not related to increased IBD risk.

This study examined the origins and evolution of the AdeABC, AdeFGH and AdeIJK efflux pumps in the Acinetobacter genus, including human and animal pathogens and species from non-clinical environments.

Comparative genome analyses were performed using the reference sequences for 70 Acinetobacter species to identify putative orthologs of AdeABC, AdeFGH and AdeIJK and their regulators. Sequence similarities and the genomic locations of coding sequences were correlated with phylogeny to infer modes of evolution. Intraspecies variation was assessed in species of interest using up to 236 complete genome sequences. Mutants overproducing adeIJK in A. baylyi were examined to identify regulators of this system in a non A. baumannii species.

The results indicate that adeIJK has been a stable part of Acinetobacter genomes since the genesis of this genus, whereas adeABC and adeFGH were carried by less than half of the species, but showed some lineage specificity. The organisation and local genetic contexts of adeABC loci were particularly variable to the sub-species level, suggesting frequent recombination. Cognate regulatory systems were almost always found in the genomes of species encoding pumps. Mutations in adeN, which encodes a repressor of adeIJK, were selected by antibiotic exposure in A. baylyi, similar to previous findings in pathogenic lineages.

The multidrug efflux capacity of clinical Acinetobacter strains stems from accessory and core genetic features. AdeIJK is likely to have ancient core function(s) that have promoted its maintenance, whereas recent antibiotic use may be driving the evolution of the AdeABC pump.

Brand loyalty is seen as a repeat purchase and the ability to recommend services or products. Telecommunication service providers require loyal customers to stay in business. The current study examines the impact of brand function and corporate image on customer loyalty in the telecommunication industry. The research employed a total of 971 responses from an anonymous online survey of telecommunication customers in Africa, Europe, and North America. Employing partial least squares, the study examined the relationships between brand function, corporate image, and loyalty. The result showed that brand function and corporate image have a significant positive effect on customer satisfaction. In addition, a machine learning algorithm was used to model the best prediction for consumer recommendations of products and services provided by their telecommunication service provider to friends and family.

Mining is a vital part of the global, and many national, economies. Mining also has the potential to drive extensive land cover change, including deforestation, with impacts reaching far from the mine itself. Understanding the amount of deforestation associated with mining is important for conservationists, governments, mining companies, and consumers, yet accurate quantification is rare. We applied statistical matching, a quasi-experimental methodology, along with Bayesian hierarchical generalized linear models to assess the impact on deforestation of new mining developments in Zambia from 2000 to present. Zambia is a globally significant producer of minerals and mining contributes ~ 10% of its gross domestic product and ~ 77% of its exports. Despite extensive deforestation in mining impacted land, we found no evidence that any of the 22 mines we analysed increased deforestation compared with matched control sites. The extent forest lost was therefore no different than would likely have happened without the mines being present due to other drivers of deforestation in Zambia. This suggests previous assessments based on correlative methodologies may overestimate the deforestation impact of mining. However, mining can have a range of impacts on society, biodiversity, and the local environment that are not captured by our analysis.

We apply a tracer model linked with a 3D circulation model to simulate transport and fate of water-soluble persistent substances in the Black Sea that do not bioaccumulate to a considerable extent. The model uses specified degradation time and identical concentrations in the rivers to build a correlation between average concentration in the basin and half-life (DT50). The average concentration in certain sub-regions of the Black Sea can be estimated using an exponential dependence of DT50, if DT50 and concentration in rivers are known. Averaging is performed on the simulations from 2000 to 2019 with real atmospheric forcing and river runoff. A well-defined seasonal cycle is evident for the average shelf concentration, while the average concentration in the deep region does not show a pronounced seasonal cycle or inter-annual variations. With the help of the existing observational data, we estimate DT50 and concentration in the rivers for carbamazepine, sulfamethoxazole and terbuthylazine. Atrazine and simazine are believed to have accumulated in the basin for a long time due to their widespread use in the past and the slow rate of degradation in the marine environment.

Extensive growth of industries leads to uncontrolled ammonia releases to environment. This can result in significant degradation of the aquatic ecology as well as significant health concerns for humans. Knowing the mechanism of ammonia elimination is the simplest approach to comprehending it. Ammonia has been commonly converted to less hazardous substances either in the form of nitrate or nitrogen gas. Ammonia has been converted into nitrite by ammonia-oxidizing bacteria and further reduced to nitrate by nitrite-oxidizing bacteria in aerobic conditions. Denitrification takes place in an anoxic phase and nitrate is converted into nitrogen gas. It is challenging to remove ammonia by employing technologies that do not incur particularly high costs. Thus, this review paper is focused on biofilm reactors that utilize the nitrification process. Many research publications and patents on biofilm wastewater treatment have been published. However, only a tiny percentage of these projects are for full-scale applications, and the majority of the work was completed within the last few decades. The physicochemical approaches such as ammonia adsorption, coagulation-flocculation, and membrane separation, as well as conventional biological treatments including activated sludge, microalgae, and bacteria biofilm, are briefly addressed in this review paper. The effectiveness of biofilm reactors in removing ammonia was compared, and the microbes that effectively remove ammonia were thoroughly discussed. Overall, biofilm reactors can remove up to 99.7% ammonia from streams with a concentration in range of 16-900 mg/L. As many challenges were identified for ammonia removal using biofilm at a commercial scale, this study offers future perspectives on how to address the most pressing biofilm issues. This review may also improve our understanding of biofilm technologies for the removal of ammonia as well as polishing unit in wastewater treatment plants for the water reuse and recycling, supporting the circular economy concept.

To determine the clinical relevance of the effects that Massage-Therapy (MT) and Abdominal-Hypopressive-Gymnastics (AHG) and the combination of both procedures have on the disability, pain intensity, quality of life, and lumbar mobility of patients with chronic nonspecific low back pain (CNSLBP).

A randomized controlled-trial with parallel-groups, concealed allocation, assessor blinding, and intention-to-treat analysis was carried out. The sample included 60 adults with CNSLBP. The participants received MT (n = 20), AHG (n = 20), or MT + AHG (n = 20). Each group received 8 interventions.