Conectar
by Paige K. Marty, Balaji Pathakumari, Thomas M. Cox, Virginia P. Van Keulen, Courtney L. Erskine, Maleeha Shah, Mounika Vadiyala, Pedro Arias-Sanchez, Snigdha Karnakoti, Kelly M. Pennington, Elitza S. Theel, Cecilia S. Lindestam Arlehamn, Tobias Peikert, Patricio Escalante
Clinical prediction of nontuberculous mycobacteria lung disease (NTM-LD) progression remains challenging. We aimed to evaluate antigen-specific immunoprofiling utilizing flow cytometry (FC) of activation-induced markers (AIM) and IFN-γ enzyme-linked immune absorbent spot assay (ELISpot) accurately identifies patients with NTM-LD, and differentiate those with progressive from nonprogressive NTM-LD. A Prospective, single-center, and laboratory technician-blinded pilot study was conducted to evaluate the FC and ELISpot based immunoprofiling in patients with NTM-LD (n = 18) and controls (n = 22). Among 18 NTM-LD patients, 10 NTM-LD patients were classified into nonprogressive, and 8 as progressive NTM-LD based on clinical and radiological features. Peripheral blood mononuclear cells were collected from patients with NTM-LD and control subjects with negative QuantiFERON results. After stimulation with purified protein derivative (PPD), mycobacteria-specific peptide pools (MTB300, RD1-peptides), and control antigens, we performed IFN-γ ELISpot and FC AIM assays to access their diagnostic accuracies by receiver operating curve (ROC) analysis across study groups. Patients with NTM-LD had significantly higher percentage of CD4+/CD8+ T-cells co-expressing CD25+CD134+ in response to PPD stimulation, differentiating between NTM-LD and controls. Among patients with NTM-LD, there was a significant difference in CD25+CD134+ co-expression in MTB300-stimulated CD8+ T-cells (pby Md. Abu Raihan, Md. Saiful Islam, Shariful Islam, A. F. M. Mahmudul Islam, Khandaker Tanveer Ahmed, Tania Ahmed, Md. Nahidul Islam, Shamsunnahar Ahmed, Mysha Samiha Chowdhury, Dipto Kumar Sarker, Anika Bushra Lamisa
BackgroundEscalating antibiotic resistance presents a notable worldwide dilemma, pointing a large involvement of general population. The objective of this study was to assess knowledge, attitudes, and practices regarding the utilization of antibiotics among Bangladeshi residents.
MethodsA cross-sectional study, conducted from January 01 to April 25, 2022, included 1,947 Bangladeshi adults with a history of antibiotic use, via online surveys and face-to-face interviews using a pretested semi-structured questionnaire. Descriptive statistics, Chi-square tests, and multivariate linear regression models were employed.
ResultsMean scores for knowledge, attitudes, and practices were 6.59±1.20, 8.34±1.19, and 12.74±2.59, with correct rates of 73.22%, 92.67%, and 57.91%. Positive predictors for knowledge included being unmarried (β = 0.10, p = 0.001), higher education (College: β = 0.09, p = 0.025; Bachelor: β = 0.22, p Conclusions
Participants exhibited adequate knowledge and positive attitudes but lagged behind in proper practice of antibiotic use. Proper initiatives should be tailored to enhance prudent antibiotic use and mitigate the risk of antimicrobial resistance.
by Gorantla V. Raghuram, Kavita Pal, Gaurav Sriram, Afzal Khan, Ruchi Joshi, Vishalkumar Jadhav, Sushma Shinde, Alfina Shaikh, Bhagyeshri Rane, Harshada Kangne, Indraneel Mittra
Metastatic dissemination following successful treatment of the primary tumour remains a common cause of death. There is mounting evidence that therapeutic interventions themselves may promote development of metastatic disease. We earlier reported that cell-free chromatin particles (cfChPs) released from dying cancer cells are potentially oncogenic. Based on this observation we hypothesized that therapeutic interventions may lead to the release of cfChPs from therapy induced dying cancer cells which could be carried via the blood stream to distant organs to transform healthy cells into new cancers that would masquerade as metastasis. To test this hypothesis, we generated xenografts of MDA-MB-231 human breast cancer cells in severe combined immune-deficient mice, and using immuno-fluorescence and FISH analysis looked for cfChPs in their brain cells. We detected multiple human DNA signals representing cfChPs in nuclei of brain cells of mice which co-localized with eight human onco-proteins. No intact MDA-MB-231 cells were detected. The number of co-localizing human DNA and human c-Myc signals increased dramatically following treatment with chemotherapy, localized radiotherapy or surgery, which could be prevented by concurrent treatment with three different cfChPs deactivating agents. These results suggest that therapeutic interventions lead to the release cfChPs from therapy induced dying cancer cells carrying oncogenes and are transported via the blood stream to brain cells to potentially transform them to generate new cancers that would appear as metastases. cfChPs induced metastatic spread of cancer is preventable by concurrent treatment with agents that deactivate cfChPs.by Sabina Marasini, Sudim Sharma, Anjali Joshi, Surakshya Kunwar, Roshan Kumar Mahato, Archana Shrestha, Biraj Karmacharya
BackgroundInappropriate use of antimicrobials is a global public health issue, particularly in developing countries, including Nepal, where over-the-counter sales and self-medication of antimicrobials are common.
ObjectivesTo explore knowledge, perceptions, and practices of antimicrobials and their resistance among medicine dispensers and community members in Nepal.
MethodsThe study was conducted in three rural and five urban municipalities of the Kavrepalanchok district from May 2021 to August 2021. Data were collected using two qualitative approaches: In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs). Data were analyzed using thematic analysis that combined deductive and inductive approaches to identify codes under pre-specified themes.
ResultsA total of 16 In-depth interviews with medicine dispensers and 3 focus group discussions with community members were conducted. Knowledge regarding antimicrobial resistance varied among dispensers. Those with a prior educational background in pharmacy often had good knowledge about the causes and consequences of antimicrobial resistance. Meanwhile, consumers were less aware of antimicrobial resistance. Community members perceived antimicrobials as effective medicines but not long-term solution for treating diseases. They reported that dispensing without a prescription was common and that both consumers and dispensers were responsible for the inappropriate use of antimicrobials. On the contrary, several dispensers said that self-medication was common among the consumers, especially among more educated groups. The medicine dispensers and consumers expressed concerns about the weak enforcement of policies regarding pharmacy drug use and dispensing practices.
ConclusionPromoting and strengthening the appropriate use of antimicrobials among medicine dispensers and community members is crucial. Bold policies and collective implementation of regulations could help combat antimicrobial resistance.
by Özgür İlke Ulusoy, Nidambur Vasudev Ballal, Rajkumar Narkedamalli, Nuran Ulusoy, Krishna Prasad Shetty, Alexander Maniangat Luke
This study aimed to evaluate the dislodgement resistance and structural changes of different mineral trioxide aggregate cements (MTA) like Pro-Root MTA, Ortho MTA, and Retro MTA after exposure to sodium hypochlorite (NaOCl), NaOCl-Ethylenediaminetetraacetic acid (EDTA), 1-hydroxyethylidene-1, 1-bisphosphonate (Dual Rinse HEDP), and NaOCl-Maleic acid (MA). The root canal spaces of 150 dentine slices were obturated using tricalcium silicate cements and divided into 3 groups (n = 50): Group1: ProRoot MTA, Group2: Retro MTA, and Group3: Ortho MTA. The samples in each group were further subdivided into four experimental (n = 10) and one control groups (n = 10): 2.5% NaOCl-17% EDTA, Dual Rinse HEDP, 2.5% NaOCl-7% Maleic acid, 2.5% NaOCl, distilled water (control). The dislodgement resistance and structural changes of cements were measured. Use of DR HEDP resulted in higher dislodgement resistance compared to17% EDTA and 7% MA in the samples obturated with Ortho MTA and Pro-Root MTA (pby Harikrishnan Vijayakumar Sreelatha, Hamza Palekkodan, Ansar Fasaludeen, Lissy K. Krishnan, Klas S. P. Abelson
Usage and reporting of analgesia in animal models of spinal cord injury (SCI) have been sparse and requires proper attention. The majority of experimental SCI research uses rats as an animal model. This study aimed to probe into the effects of some commonly used regimens with NSAIDs and opioids on well-being of the rats as well as on the functional outcome of the model. This eight-week study used forty-two female Wistar rats (Crl: WI), randomly and equally divided into 6 treatment groups, viz. I) tramadol (5mg/kg) and buprenorphine (0.05mg/kg); II) carprofen (5mg/kg) and buprenorphine (0.05mg/kg); III) carprofen (5mg/kg); IV) meloxicam (1mg/kg) and buprenorphine (0.05mg/kg); V) meloxicam (1mg/kg); and VI) no analgesia (0.5 ml sterile saline). Buprenorphine was administered twice daily whereas other treatments were given once daily for five days post-operatively. Injections were given subcutaneously. All animals underwent dental burr-assisted laminectomy at the T10-T11 vertebra level. A custom-built calibrated spring-loaded 200 kilodynes force deliverer was used to induce severe SCI. Weekly body weight scores, Rat Grimace Scale (RGS), and dark-phase home cage activity were used as markers for well-being. Weekly Basso Beattie and Bresnahan (BBB) scores served as markers for functionality together with Novel Object Recognition test (NOR) at week 8 and terminal histopathology using area of vacuolisation and live neuronal count from the ventral horns of spinal cord. It was concluded that the usage of analgesia improved animal wellbeing while having no effects on the functional aspects of the animal model in comparison to the animals that received no analgesics.by Divya Kumar, Waqas Hameed, Bilal Iqbal Avan
BackgroundMost empirically researched interventions for postpartum depression (PPD) tend to target mothers’ depression alone. Harmful effects of PPD on physical and mental health of both mother and child has led researchers to investigate the impact of interventions on PPD and child outcomes together. So far, the evidence is limited regarding how these interventions compare with those focusing only on mothers’ depression. This review compares the effectiveness of PPD-improving interventions focusing only on mothers with those focusing on mother and child together.
MethodsNine electronic databases were searched. Thirty-seven studies evaluating mother-focused (n = 30) and mother-child focused interventions (n = 7) were included. Under each category, three theoretical approaches—psychological, psychosocial and mixed—were compared using standardized qualitative procedures. The review’s primary outcome was maternal PPD.
ResultsA higher proportion of mother-focussed interventions [20/30 (66.7%)] brought significant reduction in PPD outcomes as compared to a lower proportion of mother-child focused interventions [4/7 (57.14%)]. Mother-focused mixed approaches [3/3 (100%)] performed better in improving PPD than psychological [16/24 (67%)] or psychosocial approaches [1/3 (33.3%)] alone. Amongst mother-child focused interventions, psychosocial approaches performed well with two-thirds demonstrating positive effects on PPD.
ConclusionThe evidence strongly favors mother-focused interventions for improving PPD with mixed interventions being more effective. Psychosocial approaches performed better with PPD once child-related elements were added, and also seemed best for child outcomes. Psychological approaches were most practiced and effective for PPD, irrespective of the intervention’s focus. Further trials are needed to unpack intervention components that improve PPD and increase uptake, especially in lower-and middle-income countries.
by Mo Ahamad Khan, Ismail Celik, Haris M. Khan, Mohammad Shahid, Anwar Shahzad, Sachin Kumar, Bilal Ahmed
The quorum sensing mechanism relies on the detection and response to chemical signals, termed autoinducers, which regulate the synthesis of virulence factors including toxins, enzymes, and biofilms. Emerging therapeutic strategies for infection control encompass approaches that attenuate quorum-sensing systems. In this study, we evaluated the antibacterial, anti-quorum sensing, and anti-biofilm activities of Psidium guajava L. methanolic leaf extracts (PGME). Minimum Inhibitory Concentrations (MICs) of PGME were determined as 500 μg/ml for C. violaceum and 1000 μg/ml for P. aeruginosa PAO1. Significantly, even at sub-MIC concentrations, PGME exhibited noteworthy anti-quorum sensing properties, as evidenced by concentration-dependent inhibition of pigment production in C. violaceum 12742. Furthermore, PGME effectively suppressed quorum-sensing controlled virulence factors in P. aeruginosa PAO1, including biofilm formation, pyoverdin, pyocyanin, and rhamnolipid production, with concentration-dependent inhibitory effects. Phytochemical analysis utilizing GC-MS revealed the presence of compounds such as alpha-copaene, caryophyllene, and nerolidol. In-silico docking studies indicated a plausible mechanism for the observed anti-quorum sensing activity, involving favorable binding and interactions with QS-receptors, including RhlR, CviR’, LasI, and LasR proteins. These interactions were found to potentially disrupt QS pathways through suppression of AHL production and receptor protein blockade. Collectively, our findings propose PGME as a promising candidate for the treatment of bacterial infections. Its attributes that mitigate biofilm development and impede quorum-sensing mechanisms highlight its potential therapeutic value.by Bushra Jamil, Divya Nair, Pruthu Thekkur, Neelofar Laeeq, Anum Adil, Mohammed Khogali, Rony Zachariah, Selma Dar Berger, Srinath Satyanarayana, Ajay M. V. Kumar, Aaron Bochner, Amanda McClelland, Razia Fatima, Anthony D. Harries
IntroductionScreening household contacts of TB patients and providing TB preventive therapy (TPT) is a key intervention to end the TB epidemic. Global and timely implementation of TPT in household contacts, however, is dismal. We adapted the 7-1-7 timeliness metric designed to evaluate and respond to infectious disease outbreaks or pandemics, and assessed the feasibility, enablers and challenges of implementing this metric for screening and management of household contacts of index patients with bacteriologically-confirmed pulmonary TB in Karachi city, Pakistan.
MethodsWe conducted an explanatory mixed methods study with a quantitative component (cohort design) followed by a qualitative component (descriptive design with focus group discussions).
ResultsFrom January-June 2023, 92% of 450 index patients had their household contacts line-listed within seven days of initiating anti-TB treatment (“first 7”). In 84% of 1342 household contacts, screening outcomes were ascertained within one day of line-listing (“next 1”). In 35% of 256 household contacts eligible for further evaluation by a medical officer (aged ≤5 years or with chest symptoms), anti-tuberculosis treatment, TPT or a decision for no drugs was made within seven days of symptom screening (“second 7”). The principal reason for not starting anti-tuberculosis treatment or TPT was failure to consult a medical officer: only 129(50%) of 256 contacts consulted a medical officer. Reasons for poor performance in the “second 7” component included travel costs to see a medical officer, loss of daily earnings and fear of a TB diagnosis. Field staff reported that timeliness metrics motivated them to take prompt action in household contact screening and TPT provision and they suggested these be included in national guidelines.
ConclusionsField staff found “7-1-7” timeliness metrics to be feasible and useful. Integration of these metrics into national guidelines could improve timeliness of diagnosis, treatment and prevention of TB within households of index patients.
by Umesh Kumar Garg, Nitish Mathur, Rahul Sahlot, Pradeep Tiwari, Balram Sharma, Aditya Saxena, Raj Kamal Jainaw, Laxman Agarwal, Shalu Gupta, Sandeep Kumar Mathur
BackgroundAsian-Indians show thin fat phenotype, characterized by predominantly central deposition of excess fat. The roles of abdominal subcutaneous fat (SAT), intra-peritoneal adipose tissue, and fat depots surrounding the vital organs (IPAT-SV) and liver fat in insulin resistance (IR), type-2 diabetes (T2D) and metabolic syndrome (MetS) in this population are sparsely investigated.
Aims and objectivesAssessment of liver fat, SAT and IPAT-SV by MRI in subjects with T2D and MetS; and to investigate its correlation with IR, specifically according to different quartiles of HOMA-IR.
MethodsEighty T2D and the equal number of age sex-matched normal glucose tolerant controls participated in this study. Abdominal SAT, IPAT-SV and liver fat were measured using MRI. IR was estimated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).
ResultsT2D and MetS subjects have higher quantity liver fat and IPAT-SV fat than controls (P = 9 x 10−4 and 4 x 10−4 for T2D and 10−4 and 9 x 10−3 for MetS subjects respectively). MetS subjects also have higher SAT fat mass (P = 0.012), but not the BMI adjusted SAT fat mass (P = 0.48). Higher quartiles of HOMA-IR were associated with higher BMI, W:H ratio, waist circumference, and higher liver fat mass (ANOVA Test P = 0.020, 0.030, 2 x 10−6 and 3 x 10−3 respectively with F-values 3.35, 3.04, 8.82, 4.47 respectively). In T2D and MetS subjects, HOMA-IR showed a moderately strong correlation with liver fat (r = 0.467, P −5 and r = 0.493, P −7), but not with SAT fat and IPAT-SV. However, in MetS subjects IPAT-SV fat mass showed borderline correlation with IR (r = 0.241, P r = 0.13, P = 0.26). In non-T2D and non-MetS subjects, no such correlation was seen. On analyzing the correlation between the three abdominal adipose compartment fat masses and IR according to its severity, the correlation with liver fat mass becomes stronger with increasing quartiles of HOMA-IR, and the strongest correlation is seen in the highest quartile (r = 0.59, P −3). On the other hand, SAT fat mass tended to show an inverse relation with IR with borderline negative correlation in the highest quartile (r = -0.284, P P = 0.07).
ConclusionIn individuals suffering from T2D and MetS, IR shows a trend towards positive and borderline negative correlation with liver fat and SAT fat masses respectively. The positive trend with liver fat tends to become stronger with increasing quartile of IR. Therefore, these findings support the theory that possibly exhaustion of protective compartment’s capacity to store excess fat results in its pathological deposition in liver as ectopic fat.
by Ajaya Basnet, Basanta Tamang, Mahendra Raj Shrestha, Lok Bahadur Shrestha, Junu Richhinbung Rai, Rajendra Maharjan, Sushila Dahal, Pradip Shrestha, Shiba Kumar Rai
IntroductionThe lack of standardized methods for detecting biofilms continues to pose a challenge to microbiological diagnostics since biofilm-mediated infections induce persistent and recurrent infections in humans that often defy treatment with common antibiotics. This study aimed to evaluate diagnostic parameters of four in vitro phenotypic biofilm detection assays in relation to antimicrobial resistance in aerobic clinical bacterial isolates.
MethodsIn this cross-sectional study, bacterial strains from clinical samples were isolated and identified following the standard microbiological guidelines. The antibiotic resistance profile was assessed through the Kirby-Bauer disc diffusion method. Biofilm formation was detected by gold standard tissue culture plate method (TCPM), tube method (TM), Congo red agar (CRA), and modified Congo red agar (MCRA). Statistical analyses were performed using SPSS version 17.0, with a significant association considered at p Result
Among the total isolates (n = 226), TCPM detected 140 (61.95%) biofilm producers, with CoNS (9/9) (p Conclusion
It is suggested that TM be used for biofilm detection, after TCPM. Unlike MCRA, black pigmentation in colonies formed on CRA declined with time. MDR- and XDR-biofilm formers were frequent among the clinical isolates.
by Abarna Nadeshkumar, Gitanjali Sathiadas, Shalini Sri Ranganathan
IntroductionOral liquid dosage forms remain popular in several middle income countries. The accuracy of liquid dosage form dosing depends on the accuracy and availability of measuring devices. Lack of quality oral liquid measuring devices will lead to medication errors. Hence there is an urgent need to describe the quality of manufacturer supplied measuring devices enclosed with paediatric oral liquid dosage forms currently registered in Sri Lanka.
MethodologyStandards for measuring devices were developed after a detailed literature search. Multidisciplinary panel rated each standard for the necessity criteria on a 9 point Likert scale. Standards with overall panel median score of ≥ 7 with agreement were selected. A cross-sectional study was done. All the measuring devices, labels and instructions enclosed with the registered products were assessed against the standards developed. Three volumes of liquid antibacterials were measured using the enclosed measuring device. Accuracy of the volumes was measured.
ResultsOf the total products (n = 202) only 126 were packed with a dosing device. Around quarter of the oral liquid dosage forms (n = 36) did not have a measuring device. More than half of the measuring devices aligned with all the standards developed. Out of 44 oral liquid paediatric antimicrobials measuring cups (n = 25, 56.8%, 95% CI: 41%-72%) were enclosed more and less error was seen with measuring cups.
ConclusionThe quality of oral liquid measuring devices were not satisfactory. Quality could be further improved if the regulatory body request the manufactures/importers to adhere to the standards developed. Correct volumes were not measured using the measuring devices provided with the liquid antimicrobial agents
by Sukanya G. Gakare, Jay M. Bhatt, Kishore Kumar S. Narasimhan, Shashank M. Dravid
In this study, we investigated the role of glutamate delta 1 receptor (GluD1) in oligodendrocyte progenitor cell (OPC)-mediated myelination during basal (development) and pathophysiological (cuprizone-induced demyelination) conditions. Initially, we sought to determine the expression pattern of GluD1 in OPCs and found a significant colocalization of GluD1 puncta with neuron-glial antigen 2 (NG2, OPC marker) in the motor cortex and dorsal striatum. Importantly, we found that the ablation of GluD1 led to an increase in the number of myelin-associated glycoprotein (MAG+) cells in the corpus callosum and motor cortex at P40 without affecting the number of NG2+ OPCs, suggesting that GluD1 loss selectively facilitates OPC differentiation rather than proliferation. Further, deletion of GluD1 enhanced myelination in the corpus callosum and motor cortex, as indicated by increased myelin basic protein (MBP) staining at P40, suggesting that GluD1 may play an essential role in the developmental regulation of myelination during the critical window period. In contrast, in cuprizone-induced demyelination, we observed reduced MBP staining in the corpus callosum of GluD1 KO mice. Furthermore, cuprizone-fed GluD1 KO mice showed more robust motor deficits. Collectively, our results demonstrate that GluD1 plays a critical role in OPC regulation and myelination in normal and demyelinating conditions.by Farhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar
The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. “Prodigiosin NRPS”, among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 μg/mL and 7.81 to 31.25 μg/mL respectively. At concentration 500 μg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 μg/mL pigment where 125 μg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.
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