Efficacy Of Treatment Research Articles

Effects of Transjugular Intrahepatic Portosystemic Shunt on Renal and Pulmonary Function in Hepatic Decompensation with and without Hepatorenal and Hepatopulmonary Syndromes: A Review.

Cirrhosis is often characterized by decreased liver function, ranging from a compensated, typically asymptomatic phase to a decompensated phase characterized by the appearance of ascites or variceal bleeding, and ultimately hepatorenal syndrome (HRS) or hepatopulmonary syndrome (HPS). The latter two complications are associated with a poor prognosis and limited treatment efficacy. In cases of ascites or variceal bleeding resistant to medical therapy, transjugular intrahepatic portosystemic shunt (TIPS) is effective and safe. Shunting blood by TIPS diverts portal blood to the systemic circulation, potentially increasing systemic blood volume and benefiting renal function. However, TIPS could also divert nitric oxide to the systemic circulation, potentially worsening systemic hypotension and perfusion, which could be detrimental to renal function. Available evidence indicates that TIPS often improves renal function in patients with portal hypertension, with or without HRS. No studies have shown persistently decreased renal function after TIPS. However, these data are insufficient to support a recommendation for the use of TIPS specifically for HRS. In patients without pre-existing HPS, TIPS does not appear to significantly affect pulmonary gas exchange. Results of TIPS in HPS have been inconsistent; some studies have shown improvement, but effects were transient. No studies have shown a persistent decline in pulmonary function after TIPS. The evidence supports the need for large randomized controlled trials to investigate the beneficial effects of TIPS for HRS. Similar pulmonary function data are less clear regarding TIPS for HPS. The aim of the current report was to review the literature regarding the effects of TIPS on renal and pulmonary function in hepatic decompensation, with or without the development of HRS or HPS.

Влияние распространенных бактериальных инфекций на индекс фрагментации ДНК сперматозоидов. Обзор литературы

Sperm DNA fragmentation is an important factor in male infertility, miscarriage and unsuccessful ART cycles. The purpose of thisreview wasto summarize and briefly analyze the available data on the effect of common infections of the male genitourinary tract on sperm DNA fragmentation (SDF), the mechanisms of their influence, efficacy and outcomes of treatment. Based on the results of these studies, it can be said that Chlamydia trachomatis, Ureaplasma spp. and Mycoplasma genitalium have a significant effect and lead to a pronounced increase in SDF. The effect of opportunistic bacteria on SDF depends on the type of microorganisms, their diversity and quantity. The presence of certain bacteria is associated with higher levels of ,some are presumably associated with beneficial effects and lower levels of SDF. Candidiasis can presumably affect SDF, but the available data are insufficient for an accurate answer. Treatment ofsuch infectionsleads to a decrease in sperm DNA fragmentation index, an increase in the effectiveness of ART and spontaneous pregnancy rates. Keywords: sperm DNA fragmentation, infection, male infertility, oxidative stress, fertility, semen analysis, sperm, sperm chromatin.

Multi-arm multi-stage survival trial design with arm-specific stopping rule

ABSTRACT Traditional two-arm randomized trial designs have played a pivotal role in establishing the efficacy of medical interventions. However, their efficiency is often compromised when confronted with multiple experimental treatments or limited resources. In response to these challenges, the multi-arm multi-stage designs have emerged, enabling the simultaneous evaluation of multiple treatments within a single trial. In such an approach, if an arm meets efficacy success criteria at an interim stage, the whole trial stops and the arm is selected for further study. However when multiple treatment arms are active, stopping the trial at the moment one arm achieves success diminishes the probability of selecting the best arm. To address this issue, we have developed a group sequential multi-arm multi-stage survival trial design with an arm-specific stopping rule. The proposed method controls the familywise type I error in a strong sense and selects the best promising treatment arm with a high probability.

A Prospective Study on Different Doses of Gammaglobulin Plus Aspirin in the Pediatric Kawasaki Disease and the Impacts on CRP and WBC Levels

Abstract Objective To evaluate the efficacy of different doses of gammaglobulin combined with aspirin in treating pediatric Kawasaki disease and its impact on C-reactive protein (CRP) and white blood cell (WBC) levels. Methods A prospective study was conducted with 150 children (3groups) diagnosed with Kawasaki disease. Group A received a higher dose of intravenous gammaglobulin (2.5 g/kg) combined with aspirin, Group B received a standard dose of intravenous gammaglobulin (2 g/kg) combined with aspirin, and Group C received a lower dose of intravenous gammaglobulin (1 g/kg) combined with aspirin. All groups received oral aspirin therapy (30 mg/kg/day) for a standard duration. The time to symptom improvement, treatment efficacy, laboratory parameters, and adverse reactions were monitored and analyzed. Results Group B showed a shorter time to symptom relief compared to Groups A and C, particularly in fever reduction, mucosal congestion, cervical lymph node enlargement, and limb symptoms. The total effective rate was higher in Group B compared to Groups A and C. Group B showed improvements in WBC, CRP, ESR, and PLT levels. Conclusion Standard-dose intravenous gammaglobulin combined with aspirin was more effective in treating pediatric Kawasaki disease compared to higher and lower doses. The treatment regimen in Group B resulted in shorter time to symptom relief, higher total effective rate, improved biochemical markers. Incidence of adverse reactions was similar among the three groups, demonstrating the safety of standard dosage.

Miniaturized protein profiling permits targeted signaling pathway analysis in individual circulating tumor cells to improve personalized treatment

BackgroundTraditional genomic profiling and mutation analysis of single cells like Circulating Tumor Cells (CTCs) fails to capture post-translational and functional alterations of proteins, often leading to limited treatment efficacy. To overcome this gap, we developed a miniaturized ‘protein analysis on the single cell level’ workflow—baptized ZeptoCTC. It integrates established technologies for single-cell isolation with sensitive Reverse Phase Protein Array (RPPA) analysis, thus enabling the comprehensive assessment of multiple protein expression and activation in individual CTCs.MethodsThe ZeptoCTC workflow involves several critical steps. Firstly, individual cells are labeled and isolated. This is followed by cell lysis and the printing of true single cell lysate preparations onto a ZeptoChip using a modified micromanipulator, CellCelector™. The printed lysates then undergo fluorescence immunoassay RPPA protein detection using a ZeptoReader. Finally, signal quantification is carried out with Image J software, ensuring precise measurement of multiple protein levels.ResultsThe efficacy of ZeptoCTC was demonstrated through various applications. Initially, it was used for measuring EpCAM protein expression, a standard marker for CTC detection, revealing higher levels in single MCF-7 over MDA-MB-231 tumor cells. Furthermore, in Capivasertib (Akt-inhibitor)-treated MCF-7 single cells, ZeptoCTC detected a 2-fold increase in the pAkt/Akt ratio compared to control cells, and confirmed co-performed bulk-cell western blot analysis results. Notably, when applied to individual CTCs from metastasized breast cancer patients, ZeptoCTC revealed significant differences in protein activation levels, particularly in measured pAkt and pErk levels, compared to patient-matched WBCs. Moreover, it successfully differentiated between CTCs from patients with different Akt1 genotypes, highlighting its potential to determine the activation status of druggable cancer driving proteins for individual and targeted treatment decision making.ConclusionsThe ZeptoCTC workflow represents a valuable tool in single cell cancer research, crucial for personalized medicine. It permits detailed analysis of key proteins and their activation status of targeted, cancer-driven signaling pathways in single cell samples, aiding in understanding tumor response, progression, and treatment efficacy beyond bulk analysis. The method significantly advances clinical investigations in cancer, improving treatment precision and effectiveness. The workflow will be applicable to protein analysis on other types of single cells like relevant in stem cell, neuropathology and hemopoietic cell research.

Validation of a deep learning model for automatic detection and quantification of five OCT critical retinal features associated with neovascular age-related macular degeneration

PurposeTo develop and validate a deep learning model for the segmentation of five retinal biomarkers associated with neovascular age-related macular degeneration (nAMD).Methods300 optical coherence tomography volumes from subject eyes with...

Antimalarial Mechanisms and Resistance Status of Artemisinin and Its Derivatives

Artemisinin is an endoperoxide sesquiterpene lactone isolated from Artemisia annua and is often used to treat malaria. Artemisinin’s peroxide bridge is the key structure behind its antimalarial action. Scientists have created dihydroartemisinin, artemether, artesunate, and other derivatives preserving artemisinin’s peroxide bridge to increase its clinical utility value. Artemisinin compounds exhibit excellent efficacy, quick action, and minimal toxicity in malaria treatment and have greatly contributed to malaria control. With the wide and unreasonable application of artemisinin-based medicines, malaria parasites have developed artemisinin resistance, making malaria prevention and control increasingly challenging. Artemisinin-resistant Plasmodium strains have been found in many countries and regions. The mechanisms of antimalarials and artemisinin resistance are not well understood, making malaria prevention and control a serious challenge. Understanding the antimalarial and resistance mechanisms of artemisinin drugs helps develop novel antimalarials and guides the rational application of antimalarials to avoid the spread of resistance, which is conducive to malaria control and elimination efforts. This review will discuss the antimalarial mechanisms and resistance status of artemisinin and its derivatives, which will provide a reference for avoiding drug resistance and the research and development of new antimalarial drugs.

Bisphosphonates and Antibiotics Combination Therapy for Chronic Low Back Pain Associated with Modic Change: A Quasi-Experimental Study

Background: Although effective treatments are still lacking for chronic low back pain (CLBP) associated with Modic changes (MC), in recent years, the efficacy of bisphosphonate and antibiotic treatment has been tested separately with variable success. This study aimed to compare the effectiveness of combined therapy of bisphosphonate and antibiotics versus single-drug therapy in CLBP patients with MC.Methods: This quasi-experimental study was carried out from October 2019 to September 2020 according to 1964 Helsinki declaration among 60 adult CLBP patients with MC (confirmed by magnetic resonant imaging) and randomly allocated in Group-A (n=20): Zoledronic acid (ZA) only, Group-B (n=20): amoxicillin-clavulanate only, and Group-C (n=20): both ZA and amoxicillin-clavulanate. The primary outcomes were measured by the visual analog scale (VAS) and Roland Morris disability questionnaire (RMDQ) at follow-ups after 1 month, 100 days, and 6 months. Per-protocol analysis was performed using SPSS 24.Results: Out of the 60 patients, 43 patients (72%) completed all three follow-ups. The VAS score gradually decreased in all groups after treatment, wherein Group-C patients had the significantly lowest score at the 2nd and 3rd follow-ups (2.87±0.80 and 1.68±0.70, respectively) compared to Group-A (3.40±0.63 and 2.20±0.67, respectively) and Group-B (3.50±0.52 and 2.41±0.66,respectively). In addition, RMDQ also decreased significantly after 1 month compared to pretreatment (p<0.05) in all 3 groups, and this gradual decrement was continued until 6 months of treatment. However, it was reduced more in Group-C (6.26±0.70) than in group-A (6.69±1.40) and Group-B (7.75±1.21) at the end of the 3rd follow-up. Moreover, Group-C patients had the highest satisfaction level and lowest number of days with absence from work score compared to A and B (p<0.05). However, adverse effects were relatively higher in Group-C than A and B (p>0.05).Conclusion: Bisphosphonates and antibiotics combination therapy is more effective than single-drug therapy for CLBP associated with MC.

Exploring the Role of Reactive Oxygen Species in the Pathogenesis and Pathophysiology of Alzheimer’s and Parkinson’s Disease and the Efficacy of Antioxidant Treatment

Exploring the Role of Reactive Oxygen Species in the Pathogenesis and Pathophysiology of Alzheimer’s and Parkinson’s Disease and the Efficacy of Antioxidant Treatment

EMERGENCY ESOPHAGECTOMY FOR ESOPHAGEAL PERFORATION FOLLOWING BALLOON DILATION DUE TO STENOSIS POST-ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ESOPHAGEAL CANCER: A CASE REPORT

Introduction and importance: Esophageal perforation from endoscopic dilation is rare (0.53% to 0.6% incidence) but serious, with mortality rates of 12.5% to 20%. Optimal treatment is debated and depends on the medical facility’s capabilities, patient’s symptoms, extent of perforation, and severity of associated lesions. Treatment options include medical management (fasting, antibiotics), esophageal stenting, surgical closure, or emergency esophagectomy. Early diagnosis and treatment are crucial to reduce mortality and hospital stay. Case presentation: A 49-year-old male with lower third esophageal cancer (stage cT1aN0M0) underwent endoscopic submucosal dissection (ESD) and developed esophageal stenosis. Dilation attempts led to esophageal perforation, necessitating emergency esophagectomy with gastric conduit reconstruction. The patient improved and was discharged on day 10 post-operation without complications. Clinical discussion: Managing esophageal perforation post-endoscopic dilation is complex. This case highlights the importance of rapid recognition and intervention. Esophageal dilation, while effective for stenosis, carries a perforation risk. Treatment decisions must be tailored to individual patients, considering perforation severity, patient’s health, and facility resources. Here, severe perforation and clinical condition warranted emergency esophagectomy. The successful outcome underscores the efficacy of this surgical intervention when performed timely at specialized centers. Conclusion: Emergency esophagectomy with gastric conduit reconstruction for treating esophageal perforation due to stenosis post endoscopic submucosal dissection for esophageal cancer is considered a safe procedure and can be performed at an experienced esophageal surgery center.

Advancing Pediatric Epilepsy Care: Efficacy and Mechanisms of Melatonin Intervention

Advancing Pediatric Epilepsy Care: Efficacy and Mechanisms of Melatonin Intervention

Correlation of gastrointestinal symptom rating scale and frequency scale for the symptoms of gastroesophageal reflux disease with endoscopic findings

Background Gastroesophageal Reflux Disease (GERD) is caused by the reflux of gastric contents into the esophagus and has a 13% global prevalence that is increasing. GERD symptoms negatively impact physical, social, and emotional quality of life. The Frequency Scale for the Symptoms of GERD (FSSG) and the Gastrointestinal Symptom Rating Scale (GSRS) determine the efficacy of treatment but may not correlate with endoscopically estimated esophageal mucosal injury severity. We aimed to probe the correlation between FSSG, GSRS, and esophageal injury severity to evaluate whether these scores can predict GERD severity. Methods A total of 2962 patients who underwent physical examinations, including upper gastrointestinal endoscopy, at the Kyoto Kuramaguchi Medical Center, Japan, were enrolled in this study. Upper gastrointestinal endoscopy was used to diagnose fundic mucosal atrophy, reflux esophagitis based on the Los Angeles (LA) classification, gastroesophageal flap value function (GEFV) based on Hill’s classification, and Barrett’s esophagus. Endoscopic diagnoses were examined for correlations with FSSG and GSRS scores. Results In reflux esophagitis, FSSG and GSRS scores correlated with LA-B and LA-C endoscopic diagnosis but not with LA-M and LA-A endoscopic findings. Multiple regression analysis results were similar. FSSG scores reflected advanced fundic gland mucosal atrophy, while GSRS scores associated with high grade of GEFV. Conclusions This is the first report to examine the correlation between FSSG and GSRS scores and endoscopic findings in a relatively large patient population. Our findings suggest that these scores can diagnose the severity of reflux esophagitis.

Prediction of pathological response and lymph node metastasis after neoadjuvant therapy in rectal cancer through tumor and mesorectal MRI radiomic features

Establishing predictive models for the pathological response and lymph node metastasis in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) based on MRI radiomic features derived from the tumor and mesorectal compartment (MC). This study included 209 patients with LARC who underwent rectal MRI both before and after nCRT. The patients were divided into a training set (n = 146) and a test set (n = 63). Regions of interest (ROIs) for the tumor and MC were delineated on both pre- and post-nCRT MRI images. Radiomic features were extracted, and delta radiomic features were computed. The predictive endpoints were pathological complete response (pCR), pathological good response (pGR), and lymph node metastasis (LNM). Feature selection for various models involved sequentially removing features with a correlation coefficient > 0.9, and features with P-values ≥ 0.05 in univariate analysis, followed by LASSO regression on the remaining features. Logistic regression models were developed, and their performance was evaluated using the area under the receiver operating characteristic curve (AUC). Among the 209 LARC patients, the number of patients achieving pCR, pGR, and LNM were 44, 118, and 40, respectively. The optimal model for predicting each endpoint is the combined model that incorporates pre- and delta-radiomics features for both the tumor and MC. These models exhibited superior performance with AUC values of 0.874 (for pCR), 0.801 (for pGR), and 0.826 (for LNM), outperforming the MRI tumor regression grade (mrTRG) which yielded AUC values of 0.800, 0.715, and 0.603, respectively. The results demonstrate the potential utility of the tumor and MC radiomics features, in predicting treatment efficacy among LARC patients undergoing nCRT.

Development of an antigen-based approach to noninvasively image CAR T cells in real time and as a predictive tool.

CAR T cell therapy has revolutionized the treatment of a spectrum of blood-related malignancies. However, treatment responses vary among cancer types and patients. Accurate monitoring of CAR T cell dynamics is crucial for understanding and evaluating treatment efficacy. Positron emission tomography (PET) offers a comprehensive view of CAR T cell homing, especially in critical organs such as lymphoid structures and bone marrow. This information will help assess treatment response and predict relapse risk. Current PET imaging methods for CAR T require genetic modifications, limiting clinical use. To overcome this, we developed an antigen-based imaging approach enabling whole-body CAR T cell imaging. The probe detects CAR T cells in vivo without affecting their function. In an immunocompetent B cell leukemia model, CAR-PET signal in the spleen predicted early mortality risk. The antigen-based CAR-PET approach allows assessment of CAR T therapy responses without altering established clinical protocols. It seamlessly integrates with FDA-approved and future CAR T cell generations, facilitating broader clinical application.

Clinical efficacy and safety of treatments for exocrine pancreatic insufficiency: A systematic literature review

Introduction: Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis (CF) and chronic pancreatitis (CP). Standard management of EPI includes Pancreatic Enzyme Replacement Therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI. Methods: A systematic literature review was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010–2022; conference proceedings from 2020–2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against pre-defined eligibility criteria. Results: We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n=12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE 1.2] versus Zenpep® 80.9% [SE 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated. Conclusions: This systematic literature review confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes.

Treatment efficacy and patient satisfaction of ustekinumab compared with tumor necrosis factor-alpha inhibitors in Chinese patients with moderate-to-severe psoriasis: a real-world study

Background Ustekinumab is an interleukin (IL)-12/IL-23 inhibitor for the treatment of moderate-to-severe psoriasis. Objective This real-world study compared ustekinumab and tumor necrosis factor-alpha inhibitors (TNFis) in Chinese moderate-to-severe psoriasis patients. Methods Patient health records of 110 moderate-to-severe psoriasis patients initiating or switching biologics were reviewed, with 31 patients receiving ustekinumab (ustekinumab group) and 79 patients receiving TNFis (TNFi group). Results Compared with TNFi group, psoriasis area and severity index (PASI)-75 response rate at month 6 (M6) were elevated (87.1% versus 65.8%, p = 0.026) in the ustekinumab group, whereas the rates at month 1 (M1) and month 3 (M3) and PASI-90 response rates at M1, M3, and M6 only showed an increasing trend (all p > 0.050) in the ustekinumab group than the TNFi group. By subgroup analyses, ustekinumab (versus TNFi) was more effective in patients with biologics therapy history than those without. Compared with the TNFi group, the ustekinumab group had lower dermatology life quality index scores and higher patient satisfaction scores at M3 and M6 (all p < 0.050). Conclusion Chinese moderate-to-severe psoriasis patients treated with ustekinumab have a better treatment response at 6 months with improved quality of life and patient satisfaction after 3–6 months of treatment when compared to TNFi.

Disrupted basolateral amygdala circuits supports negative valence bias in depressive states

Negative bias is an essential characteristic of depressive episodes leading patients to attribute more negative valence to environmental cues. This negative bias affects all levels of information processing including emotional response, attention and memory, leading to the development and maintenance of depressive symptoms. In this context, pleasant stimuli become less attractive and unpleasant ones more aversive, yet the related neural circuits underlying this bias remain largely unknown. By studying a mice model for depression chronically receiving corticosterone (CORT), we showed a negative bias in valence attribution to olfactory stimuli that responds to antidepressant drug. This result paralleled the alterations in odor value assignment we observed in bipolar depressed patients. Given the crucial role of amygdala in valence coding and its strong link with depression, we hypothesized that basolateral amygdala (BLA) circuits alterations might support negative shift associated with depressive states. Contrary to humans, where limits in spatial resolution of imaging tools impair easy amygdala segmentation, recently unravelled specific BLA circuits implicated in negative and positive valence attribution could be studied in mice. Combining CTB and rabies-based tracing with ex vivo measurements of neuronal activity, we demonstrated that negative valence bias is supported by disrupted activity of specific BLA circuits during depressive states. Chronic CORT administration induced decreased recruitment of BLA-to-NAc neurons preferentially involved in positive valence encoding, while increasing recruitment of BLA-to-CeA neurons preferentially involved in negative valence encoding. Importantly, this dysfunction was dampened by chemogenetic hyperactivation of BLA-to-NAc neurons. Moreover, altered BLA activity correlated with durable presynaptic connectivity changes coming from the paraventricular nucleus of the thalamus, recently demonstrated as orchestrating valence assignment in the amygdala. Together, our findings suggest that specific BLA circuits alterations might support negative bias in depressive states and provide new avenues for translational research to understand the mechanisms underlying depression and treatment efficacy.

Evaluation of Chemokines MIG and IP-10 as Immunological Biomarkers of Human Visceral Leishmaniasis: A Systematic Review

Visceral leishmaniasis (VL) is a neglected tropical disease that is potentially fatal when untreated. Current diagnostic methods have limitations that contribute to ongoing transmission and poor prognosis. Thus, new tests are needed to provide quick, accurate diagnoses and evaluate clinical progression and treatment efficacy. The monokine induced by interferon-gamma (MIG) and interferon-gamma-inducible protein 10 (IP-10) has been associated with the host susceptibility to VL with potential diagnostic and prognostic purposes. We performed a systematic review using four search databases (Scopus, PubMed, Web of Science, and MEDLINE) to identify studies assessing MIG and IP-10 as potential biomarkers in patients with VL across various clinical conditions. A total of 13 studies were potentially eligible and included in this review. The articles, in general, reveal that the chemokines MIG and IP-10 are elevated in response to infection by Leishmania spp., acting on the host’s resistance to the development of the disease. They are associated with asymptomatic conditions and after VL treatment, and this relationship can be observed in both immunocompetent and immunocompromised individuals. Consequently, these chemokines hold relevance in the diagnoses and appropriate management of individuals with VL.

A virulence-associated small RNA MTS1338 activates an ABC transporter CydC for rifampicin efflux in Mycobacterium tuberculosis

The efficacy of the tuberculosis treatment is restricted by innate drug resistance of Mycobacterial tuberculosis and its ability to acquire resistance to all anti-tuberculosis drugs in clinical use. A profound understanding of bacterial ploys that decrease the effectiveness of drugs would identify new mechanisms for drug resistance, which would subsequently lead to the development of more potent TB therapies. In the current study, we identified a virulence-associated small RNA (sRNA) MTS1338-driven drug efflux mechanism in M. tuberculosis. The treatment of a frontline antitubercular drug rifampicin upregulated MTS1338 by &amp;gt;4-fold. Higher intrabacterial abundance of MTS1338 increased the growth rate of cells in rifampicin-treated conditions. This fact was attributed by the upregulation of an efflux protein CydC by MTS1338. Gel-shift assay identified a stable interaction of MTS1338 with the coding region of cydC mRNA thereby potentially stabilizing it at the posttranscriptional level. The drug efflux measurement assays revealed that cells with higher MTS1338 abundance accumulate less drug in the cells. This study identified a new regulatory mechanism of drug efflux controlled by an infection-induced sRNA in M. tuberculosis.

Application of hot water and cold air to reduce bacterial contamination on broiler carcasses

Two physical treatments (heat via water bath and cold air) with various temperatures (20/70/75/80°C and − 80/−90°C) and exposure times (20, 30, 40 s) were carried out to identify a decontaminating effect on zoonotic pathogens on broiler carcasses. Subsequently, carcasses were analyzed for thermotolerant Campylobacter (C.), Salmonella, Escherichia (E.). coli and total colony count (TCC). Moreover, for the hot water treatment, qPCR with viable/dead differentiation (v-qPCR) was applied to detect viable but non-culturable cells (VBNC) of Campylobacter, referred to as intact but putatively infectious units (IPIU). Hot water immersion was tested on carcasses inoculated with C. jejuni and Salmonella, while cold air treatment was evaluated for naturally contaminated carcasses of broiler flocks colonized with Campylobacter. For hot water treatment, the statistically significant reducing effect was about 1 log10 CFU/ml for both Salmonella and Campylobacter for 70–80°C and 20/30 s treatments. The effect of heat treatment for Campylobacter was smaller when samples were analyzed with v-qPCR with reductions of 0.5–0.8 log10 IPIU/ml in mean. Cold air treatments at −90°C were effective in reducing the mean contamination level of Campylobacter by 0.4–0.5 log10 CFU/ml at all exposure times (p &amp;lt; 0.05). Hot water treatments showed a decreasing trend on TCC by 0.6–0.9 log10 CFU/ml (p &amp;lt; 0.05). TCC counts were not significantly affected by cold air treatment. For E. coli no statistically significant reductions were observed by hot water treatment. The cold air treatment at −90°C for 20 and 40 s led to a reduction of E. coli by 0.4 and 0.8 log10 CFU/ml (p &amp;lt; 0.05), respectively. Treatment of carcasses with higher bacterial levels tended to show higher reduction. The research demonstrated that the efficacy of physical treatments for decontamination of broiler carcasses was more pronounced for hot water immersion than for cold air exposure. In conclusion, the results shed light on the potential application of these physical treatments in practice to reduce the quantitative load of contaminating pathogens to enhance food safety in the broiler meat production.