Development Of Resistance Research Articles

Intestinal Microbiome and Antimicrobial Resistivity: A Study in Recent Times

The world has recently witnessed a pandemic and is now challenged by continuous environmental changes. Human health is in constant jeopardy with the rise in bacterial, fungal, and viral infections. Antibiotics are the most widely used medication for the treatment of any infection. The urban population does not always maintain a healthy lifestyle due to the fast-paced nature of life. West Bengal the eastern state of India is no exception to this directive. Rampant use of antibiotics and their frequent consumption has widely increased over the years. This is posing a serious threat to the healthy microbiome of the human intestine. It is resulting in a decline of the healthy microbiota and the development of antibiotic resistance. The study aims to understand the effect of antibiotic consumption in the post-COVID scenario on the gut microbiome of the West Bengal population. The population includes both rural and urban as it takes into account the different lifestyles.

Adaptive Resilience: Unraveling the Path of Heavy Metal Tolerance in Multidrug Resistant Pathogens

Co-existence of heavy metal tolerance and antibiotic resistance in bacterial strains pose potential threats to human health and environment. In recent decades, heavy metal pollution has caused selective pressure that leads to the development of multiple drug resistance among bacterial populations. Escherichia coli, Pseudomonas aeruginosa and Staphylococcus cohnii were used in the study. Out of 8 antibiotics tested, it was observed that E.coli was resistant to four, S.cohnii and P. aeruginosa were resistant only to three antibiotics. The isolates were found to grow at high concentration of copper (CuSO4) and varying degrees of chromium (K2Cr2O7) with all the three being sensitive to mercuric chloride (HgCl2). E. coli, S. cohnii and P. aeruginosa were inhibited at 0.84±0.05, 6.79±0.07 and 2.54±0.02 μM ml-1 respectively by chromium salt; similarly, E. coli, S. cohnii and P. aeruginosa had a MIC of 1.56±0.03 μM ml-1, 1.25±0.05 μM ml-1 and 1.56±0.05μM ml-1 and for copper, E. coli, S. cohnii and P. aeruginosa had a MIC of 8.20±0.05, 9.20±0.01, 7.18±0.05μM ml-1 respectively. Further studies were carried out by agarose gel electrophoresis and SDS-PAGE for the characterization of R-plasmid and heavy metal stress protein among the isolated bacteria. The qPCR was used for identification of antimicrobial resistant genes. A phylogenetic study was performed on S. cohnii to understand its evolutionary traits. The results provide insight into the co-occurrence of antibiotic resistance and heavy metal tolerance in clinically important bacterial communities, which may create severe health issues in the coming decades.

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Glyphosate is used as an herbicide in agriculture. At sub-agriculture concentrations, glyphosate-based herbicide inhibits cell proliferation. Glyphosate is a chelating agent that interferes with the metabolic activities in plants thereby adversely affecting its metabolism. The study aimed to determine the glyphosate-induced detrimental changes in SREBP-1c and PPAR-γ mRNA expression in adipose tissue of adult male rats. Adult male Wistar albino rats were divided into 4 groups, each consisting of 6 animals. Group I served as normal control rats; Group II-IV consisted of rats exposed to glyphosate at different concentrations (50, 100, and 250 mg/kg body weight respectively) orally for 16 weeks. After 16 weeks of treatment, the animals were sacrificed, and adipose tissue was dissected out for the assessment of SREBP-1c and PPAR-γ mRNA by real-time PCR using gene-specific down-regulated primers. The results with the p<0.05 level were considered to be statistically significant. The results showed a significant dose-dependent increase (P <0.05) in the expression of SREBP-1c in all the glyphosate-exposed rats compared to control rats and PPAR-γ mRNA expression was found to be significantly reduced in a concentration-dependent manner (P<0.05) compared to normal control animals. The current findings for the first time report that glyphosate had detrimental changes in the expression of transcription factors such as SREBP-1c and PPAR-γ mRNA in adipose tissue and thereby glyphosate may lead to the development of type-2 diabetes or insulin resistance.

Piperine Attenuates Insulin Resistance in Adipocytes by Modulating the Expression of Proinflammatory Signaling Molecules in Experimental Diabetic Wistar Rats

The development of insulin resistance and diabetes in obese people is caused by metabolic inflammation. In adipose tissues in the abdomen, macrophages infiltrate and cause insulin resistance. As a result of the macrophages adopting an M1 polarization, pro-inflammatory cytokines are released. Piperine, known for its potent anti-inflammatory properties, is being studied as a potential treatment for inflammatory diseases. Our findings suggest that piperine, an immunomodulator, can effectively treat obesity-related diabetes.

Field evaluation of the residual efficacy of new generation insecticides for potential use in indoor residual spray programmes in South Africa

BackgroundThe decreasing residual efficacy of insecticides is an important factor when making decisions on insecticide choice for national malaria control programmes. The major challenge to using chemicals for vector control is the selection for the development of insecticide resistance. Since insecticide resistance has been recorded for most of the existing insecticides used for indoor residual spraying, namely, DDT, pyrethroids, organophosphates and carbamates, and new chemicals are necessary for the continued success of indoor residual spraying. The aim of this study was to assess the residual efficacy of Actellic 300CS, SumiShield™ 50WG and Fludora®Fusion by spraying on different wall surfaces.MethodsOne hundred and sixty-eight houses with different wall surface types (mud, cement, painted cement, and tin) which represented the rural house wall surface types in KwaZulu-Natal, South Africa were used to evaluate the residual efficacy of Actellic 300CS, SumiShield 50WG and Fludora®Fusion with DDT as the positive control. All houses were sprayed by experienced spray operators from the Malaria Control Programme. Efficacy of these insecticides were evaluated by contact bioassays against Anopheles arabiensis, a vector species. The residual efficacy of the insecticide formulations was evaluated against a susceptible insectary-reared population of An. arabiensis using WHO cone bioassays.ResultsEffectiveness of the three insecticides was observed up to 12 months post-spray. When assessing the achievement of 100% mortality over time, SumiShield performed significantly better than DDT on mud (OR 2.28, 95% CI 1.72–3.04) and painted cement wall types (OR 3.52, 95% CI 2.36–5.26). On cement wall types, Actellic was found to be less effective than DDT (OR 0.55, 95% CI 0.37–0.82) while Fludora®Fusion was less effective on tin wall types (OR 0.67, 95% CI 0.47–0.95). When compared to the combined efficacy of DDT on mud surfaces, SumiShield applied to each of the mud, cement and painted cement wall types and DDT applied to the cement wall types was found to be significantly more effective. These insecticides usually resulted in 100% mortality for up to 12 months with a delayed mortality period of 96–144 h, depending on the insecticide evaluated and the surface type sprayed.ConclusionField evaluation of these insecticides have shown that Actellic, SumiShield and Fludora®Fusion are suitable replacements for DDT. Each of these insecticides can be used for malaria vector control, requiring just one spray round. These insecticides can be used in rotation or as mosaic spraying.

Experimental evaluation and numerical investigation on the anti-collapse performance of beam-to-column connections in the minor-axis direction

This study examined the effects of structural resistance in both major- and minor-axis directions on the anti-collapse performance of a fully bolted composite frame. Current research in the field has focused predominantly on the anti-collapse performance of H-columns in the major-axis direction, potentially hindering accurate determination of anti-collapse transmission path within a structure. Herein, monotonic static loading experiments were conducted on two substructures in the minor-axis direction: one equipped with welded flange and bolted web connections and the other with fully bolted connections. The ductility development curve, dynamic collapse response curve, and resistance mechanism correlation curve were employed to evaluate the test results. Fully bolted connections exhibited superior nonlinear rotation capacity, which is essential for the development of a structure's catenary resistance The failure mechanisms and resistance development processes of the structures were reproduced using the ABAQUS/Explicit dynamic quasi-static modeling technique. A full-scale finite element model was developed for the frame with fully bolted connections loaded in the minor-axis direction. This research will contribute to the robust design of fully bolted structural frames that considers the effects of the column stiffness, thickness of the splicing cover plate, number of bolt rows, and bolt apertures of flange connections on deformation and resistance to loading in the minor-axis direction.

Clinical audit on management of suspected meningoencephalitis patients at lady reading Hospital, Peshawar

Objective: The purpose of this study was to observe management and empiric treatment of meningitis/encephalitis without doing initial investigation CSF-RE or delaying it, at Department of Emergency Medicine, General Medicine and Neurology wards. Method: It is an observational retrospective study this study was carried out at the General medicine, Neurology and Emergency units from July 2023 to Dec 2023.Total of 54 patients were included. Before conduction of study Ethical Review Committee permission was sought to access patient Data. We studied their hospital stored data on HMIS such as admission Date, start of empiric antibiotics, CT Scans, Blood Culture and CSF-REs. Results: 98% of patients were started on empiric Antibiotics without doing CSF-RE/LP on initial presentation at the hospital. In 64% patients CSF-RE was delayed and subsequently performed. In 34% CSF-RE was never carried out. Conclusion: We did presentations, Information campaigns, to follow standard Guidelines for Suspected meningitis /encephalitis to limit potential side effects, Development of Resistance to Antibiotics and to limit treatment costs.

Access to quality-assured artemisinin-based combination therapy and associated factors among clients of selected private drug outlets in Uganda

BackgroundMalaria treatment in sub-Saharan Africa is faced with challenges including unreliable supply of efficacious agents, substandard medicines coupled with high price of artemisinin-based combinations. This affects access to effective treatment increasing risk of malaria parasite resistance development and adverse drug events. This study investigated access to quality-assured artemisinin-based combination therapy (QAACT) medicines among clients of selected private drug-outlets in Uganda.MethodsThis was a cross sectional study where exit interviews were conducted among clients of private drug outlets in low and high malaria transmission settings in Uganda. This study adapted the World Health Organization/Health Action International (WHO/HAI) standardized criteria. Data was collected using a validated questionnaire. Data entry screen with checks was created in Epi-data ver 4.2 software and data entered in duplicate. Data was transferred to STATA ver 14.0 and cleaned prior to analysis. The analysis was done at 95% level of significance.ResultsA total of 1114 exit interviews were conducted among systematically sampled drug outlet clients. Over half, 54.9% (611/1114) of the participants were males. Majority, 97.2% (1083/1114) purchased an artemisinin-based combination anti-malarial. Most, 55.5% (618/1114) of the participants had a laboratory diagnosis of malaria. Majority, 77.9% (868/1114) of the participants obtained anti-malarial agents without a prescription. Less than a third, 27.7% (309/1114) of the participants obtained a QAACT. Of the participants who obtained QAACT, more than half 56.9% (173/309) reported finding the medicine expensive. The predictors of accessing a QAACT anti-malarial among drug outlet clients include type of drug outlet visited (aPR = 0.74; 95%CI 0.6, 0.91), not obtaining full dose (3-day treatment) of ACT (aPR = 0.49; 95%CI 0.33, 0.73), not finding the ACT expensive (aPR = 1.24; 95%CI 1.03, 1.49), post-primary education (aPR = 1.29; 95%CI 1.07,1.56), business occupation (aPR = 1.24; 95%CI 1.02,1.50) and not having a prescription (aPR = 0.76; 95%CI 0.63, 0.92).ConclusionLess than a third of the private drug outlet clients obtained a QAACT for management of malaria symptoms. Individuals who did not find artemisinin-based combinations to be expensive were more likely to obtain a QAACT anti-malarial. The Ministry of Health needs to conduct regular surveillance to monitor accessibility of QAACT anti-malarial agents under the current private sector copayment mechanism.

The Impact of Inadequate Exposure to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors on the Development of Resistance in Non-Small-Cell Lung Cancer Cells.

Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients treated with EGFR-tyrosine kinase inhibitors (TKIs) inevitably develop resistance through several biological mechanisms. However, little is known on the molecular mechanisms underlying acquired resistance to suboptimal EGFR-TKI doses, due to pharmacodynamics leading to inadequate drug exposure. To evaluate the effects of suboptimal EGFR-TKI exposure on resistance in NSCLC, we obtained HCC827 and PC9 cell lines resistant to suboptimal fixed and intermittent doses of gefitinib and compared them to cells exposed to higher doses of the drug. We analyzed the differences in terms of EGFR signaling activation and the expression of epithelial-mesenchymal transition (EMT) markers, whole transcriptomes byRNA sequencing, and cell motility. We observed that the exposure to low doses of gefitinib more frequently induced a partial EMT associated with an induced migratory ability, and an enhanced transcription of cancer stem cell markers, particularly in the HCC827 gefitinib-resistant cells. Finally, the HCC827 gefitinib-resistant cells showed increased secretion of the EMT inducer transforming growth factor (TGF)-β1, whose inhibition was able to partially restore gefitinib sensitivity. These data provide evidence that different levels of exposure to EGFR-TKIs in tumor masses might promote different mechanisms of acquired resistance.

Composting manure in the poultry farm harbours multidrug-resistance Salmonella

ABSTRACT Salmonella is one of the leading foodborne pathogens that cause gastroenteritis. It is imperative to monitor Salmonella contamination within poultry farms. This study focuses on the prevalence of Salmonella in composting manure at poultry farms a potential and persistent contamination sources. A batch of manure samples (n = 10) were collected from a local poultry farm, and half of the manure samples were detected to be Salmonella-positive. Serotyping results showed four serotypes among different isolated strains, including Typhimurium, Typhi, Newport, and Dublin. Isolates from manure generally demonstrated a high ciprofloxacin resistance and biofilm formation capacity. Multi-drug resistance was found in isolates from organic manure that had been fermented using high-temperature aerobic technology. Our study indicated that composting manure harboured Salmonella and might facilitate the transmission of Salmonella and the development of antimicrobial resistance. Proper composting strategies are needed to reduce the transmission of antimicrobial resistance and Salmonella.

Multidrug-resistant Stenotrophomonas maltophilia in residential aged care facilities: An emerging threat.

Stenotrophomonas maltophilia is a multidrug-resistant (MDR), Gram-negative bacterium intrinsically resistant to beta-lactams, including last-resort carbapenems. As an opportunistic pathogen, it can cause serious healthcare-related infections. This study assesses the prevalence, resistance profiles, and genetic diversity of S. maltophilia isolated from residential aged care facilities (RACFs). RACFs are known for their overuse and often inappropriate use of antibiotics, creating a strong selective environment that favors the development of bacterial resistance. The study was conducted on 73 S. maltophilia isolates recovered from wastewater and facility swab samples obtained from three RACFs and a retirement village. Phenotypic and genotypic assessments of the isolates revealed high carbapenem resistance, exemplifying their intrinsic beta-lactam resistance. Alarmingly, 49.3% (36/73) of the isolates were non-wild type for colistin, with minimum inhibitory concentration values of > 4 mg/L, and 11.0% (8/73) were resistant to trimethoprim-sulfamethoxazole. No resistance mechanisms were detected for either antimicrobial. Genotypic assessment of known lineages revealed isolates clustering with Sm17 and Sm18, lineages not previously reported in Australia, suggesting the potential ongoing spread of MDR S. maltophilia. Lastly, although only a few isolates were biocide tolerant (2.7%, 2/73), their ability to grow in high concentrations (64 mg/L) of triclosan is concerning, as it may be selecting for their survival and continued dissemination.

Associiattiion of Cycllooxygenase 1 ((COX1)) Pollymorphiism att SNP RS1330344 wiitth Aspiiriin Resiisttance iin Pakiisttanii Pattiientts Of Ischemiic Heartt Diisease

Associiattiion of Cycllooxygenase 1 ((COX1)) Pollymorphiism att SNP RS1330344 wiitth Aspiiriin Resiisttance iin Pakiisttanii Pattiientts Of Ischemiic Heartt Diisease

Essential oil from Piper tuberculatum Jacq. (Piperaceae) and its majority compound β-caryophyllene: mechanism of larvicidal action against Aedes aegypti (Diptera: Culicidae) and selective toxicity.

Synthetic insecticides have been the primary approach in controlling Aedes aegypti; however, their indiscriminate use has led to the development of resistance and toxicity to non-target animals. In contrast, essential oils (EOs) are alternatives for vector control. This study investigated the mechanism of larvicidal action of the EO and β-caryophyllene from Piper tuberculatum against A. aegypti larvae, as well as evaluated the toxicity of both on non-target animals. The EO extracted from P. tuberculatum leaves was majority constituted of β-caryophyllene (54.8%). Both demonstrated larvicidal activity (LC50 of 48.61 and 57.20ppm, p < 0.05), acetylcholinesterase inhibition (IC50 of 57.78 and 71.97ppm), and an increase in the production of reactive oxygen and nitrogen species in larvae after exposure to the EO and β-caryophyllene. Furthermore, EO and β-caryophyllene demonstrate no toxicity to non-target animals Toxorhynchites haemorrhoidalis, Anisops bouvieri, and Diplonychus indicus (100% of survival rate), while the insecticide α-cypermethrin was highly toxic (100% of death). The results demonstrate that the EO from P. tuberculatum and β-caryophyllene are important larvicidal agents.

Electrical Resistivity and Phase Evolution of Fe–N Binary System at High Pressure and High Temperature

Partitioning experiments and the chemistry of iron meteorites indicate that the light element nitrogen could be sequestered into the metallic core of rocky planets during core–mantle differentiation. The thermal conductivity and the mineralogy of the Fe–N system under core conditions could therefore influence the planetary cooling, core crystallization, and evolution of the intrinsic magnetic field of rocky planets. Limited experiments have been conducted to study the thermal properties and phase relations of Fe–N components under planetary core conditions, such as those found in the Moon, Mercury, and Ganymede. In this study, we report results from high-pressure experiments involving electrical resistivity measurements of Fe–N phases at a pressure of 5 GPa and temperatures up to 1400 K. Four Fe–N compositions, including Fe–10%N, Fe–6.4%N, Fe–2%N, and Fe–1%N (by weight percent), were prepared and subjected to recovery experiments at 5 GPa and 1273 K. These experiments show that Fe–10%N and Fe–6.4%N form a single hexagonal close-packed phase (ɛ-nitrides), while Fe–2%N and Fe–1%N exhibit a face-centered cubic structure (γ-Fe). In separate experiments, the resistivity data were collected during the cooling after compressing the starting materials to 5 GPa and heating to ~1400 K. The resistivity of all compositions, similar to the pure γ-Fe, exhibits weak temperature dependence. We found that N has a strong effect on the resistivity of metallic Fe under rocky planetary core conditions compared to other potential light elements such as Si. The temperature-dependence of the resistivity also revealed high-pressure phase transition points in the Fe–N system. A congruent reaction, ε ⇌ γ’, occurs at ~673 K in Fe–6.4%N, which is ~280 K lower than that at ambient pressure. Furthermore, the resistivity data provided constraints on the high-pressure phase boundary of the polymorphic transition, γ ⇌ α, and an eutectoid equilibrium of γ’ ⇌ α + ε. The data, along with the recently reported phase equilibrium experiments at high pressures, enable construction of a phase diagram of the Fe–N binary system at 5 GPa.

When Antimicrobial Treatment and Surgical Prophylaxis Collide: A Stewardship Opportunity

Background: In 2002, the Centers for Medicare and Medicaid Services (CMS) in collaboration with the Centers for Disease Control and Prevention (CDC) established the Surgical Infection Prevention (SIP) project for the purposes of developing and standardizing quality improvement measures known to reduce the rates of post-operative surgical site infections (SSIs). Four years later the Surgical Care Improvement Project (SCIP), an expansion of SIP, was published in governmental Specifications Manual for National Inpatient Quality Measures and provided several additional initiatives applicable to the perioperative period. Central to both projects are the assurance of the timeliness, selection, and duration of peri-operative surgical prophylactic antibiotics. In support of this objective, various medical associations, such as the American Society of Health-System Pharmacists (ASHP) and the Infectious Diseases Society of America (IDSA), have developed the Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery. To ensure compliance with quality measures, hospitals are required to report data to the Physicians Quality Reporting System, which is then reviewed by CMS for reimbursement purposes and to measure hospital performance. To maintain optimal standards of care and satisfy all core measures, it is expected that patients undergoing most categories of surgical procedures receive prophylactic antibiotics. We recognized that patients already being administered antimicrobial therapy as treatment for the condition requiring the surgery not uncommonly also were prescribed unwarranted and redundant pre-operative antibiotics. Our study was meant to quantify such antibiotic redundancy, which only risks the development of antimicrobial resistance and adverse events, to bolster our and other hospitals antimicrobial stewardship programs. Methods: A retrospective analysis of computerized hospital records over a one-month period of time (November 2022) was conducted focusing on hospital admissions that involved surgical operative procedures. Only those patients who had received a pre-operative surgical prophylactic antibiotic were included in the analysis. Results: Of the 92 surgeries that fulfilled the inclusion criteria, 38 (41.3%) were performed on patients who were already receiving therapeutic antibiotics for more than 24 hours targeted to treat the infection for which they were undergoing surgery. These included laparoscopic cholecystectomy (24), appendectomy (12), wound debridement (12), and soft tissue incision and drainage procedures (9), comprising nearly 50% of each type of these operations performed during the study time period. Conclusion: These findings demonstrate a clear opportunity to strengthen both our, and presumably other, hospitals antimicrobial stewardship programs. Together with physician education, granting the pharmacy the ability to cancel unnecessary and redundant surgical prophylactic antibiotics would conceivably be of great benefit.

Microbial-mediated conversion of soil organic carbon co-regulates the evolution of antibiotic resistance

The influence of organic carbon on the proliferation of antibiotic resistance genes (ARGs) in the soil has been widely documented. However, it is unclear how soil organic carbon (SOC) interacts with the evolution of antibiotic resistance in bacteria. Here, we examined the variations in ARGs abundance during SOC mineralization and explored the microbiological mechanisms and key metabolic pathways involved in their coevolution. The results showed that the SOC mineralization rate was closely correlated with ARGs abundance (p < 0.05). High organic carbon (OC) mineralization was conducive to the occurrence of multidrug resistance genes. For example, multidrug_transporter and mexB increased 2.26 and 7.83 times from the initial level. The competitor (stress) evolutionary strategy model revealed that higher OC inputs drive environmental microorganisms to evolve from stress tolerant to high resistance and strong adaptation. Meta-genomic and transcriptomic analyses revealed that the conversion process of pyruvate to acetyl-CoA to acetate was the critical metabolic pathway for the co-regulation of antibiotic resistance. Gene deletion validation trials have demonstrated that the key functional genes (ackA and pta) involved in this process can modulate the development of vancomycin and multidrug resistance. This outcome provides a preliminary framework for microbial mechanisms that target the co-regulation of microbial OC conversion and the evolution of antibiotic resistance.

Chromosomal and plasmid-encoded virulence and multidrug resistance of Escherichia coli ST58/24 infecting a 2-year-old sickle cell patient with sepsis in Kampala Uganda, East Africa

Sepsis and drug resistance represent a complex of the most common global causes of mortality in intensive care units (ICUs) especially among patients with comorbidities. Extraintestinal pathogenic Escherichia coli (ExPEC) strains are highly implicated in systemic infections, with multidrug resistance exacerbating the risk of chronic conditions and patient mortality. The diversity of virulence and evolution of multidrug resistance are yet to be fully deciphered. In this work, we aimed at unveiling the pathogens and their genomic determinants of virulence and drug resistance relevant to increased sepsis in a sickle cell child admitted to ICU. From a rectal swab, we isolated a strain of E. coli from the patient and phenotypically tested it against a panel of selected beta lactams, fluoroquinolones, macrolides, aminoglycosides and colistin. We then sequenced the entire genome and integrated multiple bioinformatic pipelines to divulge the virulence and multidrug resistance profiles of the isolate. Our results revealed that the isolate belongs to the sequence type (ST) 58/24, which (ST58), is a known ExPEC. With the use of PathogenFinder, we were able to confirm that this isolate is a human pathogen (p = 0.936). The assembled chromosome and two plasmids encode virulence factors related to capsule (antiphagocytosis), serum survival and resistance, type 6 secretion system (T6SS), multiple siderophores (iron acquisition), and biosynthetic gene clusters for polyketides and nonribosomal peptides exhibiting host cell damaging activity in silico. The genome also harbors multidrug resistance genotypes including extended spectrum beta lactamase (ESBL) genes such as blaTEM-1A/B, sulfonamide resistance genes sul1/2, fluoroquinolone resistance genes dfrA5 and nonsynonymous mutations of the gene pmrB, conferring intrinsic colistin resistance. Conclusively, this pathogen holds the potential to cause systemic infection and might exacerbate sickle cell anemia in the patient. The virulence and multidrug resistance profiles are encoded by both the chromosome and plasmids. Genomic surveillance of pathogens with multidrug resistance among patients with commodities is crucial for effective disease management.

Steadystate: A MATLAB-based routine for determining steady-state friction conditions in the framework of rate-and-state friction analysis

Reliable determination of rate-and-state friction (RSF) parameters depends on achieving steady-state (SS) friction conditions before and after experimental velocity-stepping friction tests. This operation, through nonlinear least squares fitting, is commonly preceded by the removal of any overall slip weakening/hardening after friction velocity steps (VSs) through a sufficiently large window of slip displacement at SS ( = linear detrend). However, to date, the identification of SS and thus the correct linear detrend is dependent on the user, which potentially results in differing RSF outputs from the same data set. Here, we demonstrate that large errors in the determination of the fitted RSF parameters can result if SS conditions are not reached before and after VSs. Such errors can be particularly relevant for materials characterized by long evolution of frictional resistance with slip, such as clay-rich gouge layers, in which identifying SS after VSs is not always obvious. To this end, we propose a methodology to accurately and consistently identify where SS is achieved after VSs. This methodology is coded into a new MATLAB-based routine, steadystate. We show the key features of the methodology, as well as how to use steadystate and read its output. We also illustrate the broad applicability of the approach to friction data with different noise levels and sampling frequencies referenced to slip velocity, by reviewing observations from synthetic data sets and specific examples of experiments from different laboratories involving various sheared materials.

TEMEPHOS RESISTANCE STATUS OF AEDES AEGYPTI POPULATIONS FROM HAVANA, CUBA.

chemical control remains an indispensable alternative to prevent dengue, Zika, and chikungunya outbreaks in Havana, Cuba. The city of Havana requires constant surveillance because of its bioecological characteristics that favor the proliferation of mosquito vectors of these viruses, which constitutes a high risk to the health of its inhabitants. The goal of this study was to determine the impact of the stopping of temephos applications during the 2 years of the COVID-19 pandemic on the level of susceptibility of Ae. aegypti in 5 municipalities of Havana, Cuba. Larval susceptibility was evaluated by bioassays as described by the World Health Organization. All Ae. aegypti populations tested showed high resistance to temephos. The National Control Program of Ae. aegypti in Cuba will need to promote insecticide rotation policies to prevent the evolution of temephos resistance in Havana.

Molecular drilling to combat salmonella typhi biofilm using L-Asparaginase via multiple targeting process

ABSTRACT Objectives Salmonella Typhibiofilm condition is showing as a major public health problem due to the development of antibiotic resistance and less available druggable target proteins. Therefore, we aimed to identify some more druggable targets of S. Typhibiofilm using computational drilling at the genome/proteome level so that the target shortage problem could be overcome and more antibiofilm agents could be designed in the future against the disease. Methods We performed protein–protein docking and interaction analysis between the homological identified target proteins of S.Typhi biofilm and a therapeutic protein L-Asparaginase. Results We have identified some druggable targets CsgD, BcsA, OmpR, CsgG, CsgE, and CsgF in S.Typhi. These targets showed high-binding affinity BcsA (−219.8 Kcal/mol) >csgF (−146.52 Kcal/mol) >ompR (−135.68 Kcal/mol) >CsgE (−134.66 Kcal/mol) >CsgG (−113.81 Kcal/mol) >CsgD(−95.39 Kcal/mol) with therapeutic enzyme L-Asparaginase through various hydrogen-bonds and salt-bridge. We found six proteins of S. Typhi biofilm from the Csg family as druggable multiple targets.  Conclusion This study provides insight into the idea of identification of new druggable targets and their multiple targeting with L-Asparaginase to overcome target shortage in S. Typhibiofilm-mediated infections. Results further indicated that L-Asparaginase could potentially be utilized as an antibiofilm biotherapeutic agent against S.Typhi.