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1.
Front Microbiol ; 15: 1387628, 2024.
Article in English | MEDLINE | ID: mdl-38725678

ABSTRACT

Marburg virus disease (MVD) presents a significant global health threat, lacking effective antivirals and with current supportive care offering limited therapeutic options. This mini review explores the emerging landscape of novel antiviral strategies against MVD, focusing on promising therapeutics currently in the development pipeline. We delve into direct-acting antiviral approaches, including small molecule inhibitors targeting viral entry, replication, and assembly, alongside nucleic acid antisense and RNA interference strategies. Host-targeting antivirals are also considered, encompassing immune modulators like interferons and cytokine/chemokine modulators, broad-spectrum antivirals, and convalescent plasma and antibody-based therapies. The paper then examines preclinical and clinical development for the novel therapeutics, highlighting in vitro and in vivo models for antiviral evaluation, safety and efficacy assessments, and the critical stages of clinical trials. Recognizing the challenges of drug resistance and viral escape, the mini review underscores the potential of combination therapy strategies and emphasizes the need for rapid diagnostic tools to optimize treatment initiation. Finally, we discuss the importance of public health preparedness and equitable access to these promising therapeutics in achieving effective MVD control and global health security. This mini review presents a comprehensive overview of the burgeoning field of MVD antivirals, highlighting the potential of these novel approaches to reshape the future of MVD treatment and prevention.

2.
Int J Biol Macromol ; 269(Pt 2): 132068, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38719001

ABSTRACT

Pullulan was used as the wall material for microencapsulation of L. plantarum CRD7 by spray drying, while isomalto-oligosaccharides (IMO) was used as prebiotic. Also, the effect of different thermal protectants on survival rate during microencapsulation was evaluated. Taguchi orthogonal array design showed that pullulan at 14 % concentration, IMO at 30 % concentration and whey protein isolate at 20 % rate were the optimized wall material, prebiotic and thermal protectant, respectively for microencapsulation of L. plantarum. FESEM images revealed that the spray-dried encapsulates were fibrous similar to those produce by electrospinning, while fluorescence microscopy ascertained that most of the probiotic cells were alive and intact after microencapsulation. The adsorption-desorption isotherm was of Type II and the encapsulate had specific surface area of 1.92 m2/g and mean pore diameter of 15.12 nm. The typical amide II and III bands of the bacterial proteins were absent in the FTIR spectra, suggestive of adequate encapsulation. DSC thermogram showed shifting of melting peaks to wider temperature range due to interactions between the probiotic and wall materials. IMO at 30 % (w/w) along with WPI at 20 % concentration provided the highest storage stability and the lowest rate of cell death of L. plantarum after microencapsulation. Acid and bile salt tolerance results confirmed that microencapsulated L. plantarum could sustain the harsh GI conditions with >7.5 log CFU/g viability. After microencapsulation, L. plantarum also possessed the ability to ferment milk into curd with pH of 4.62.

3.
Cureus ; 16(4): e58031, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38738040

ABSTRACT

Mitral annular calcification (MAC) is relatively common in clinical practice. Females are more often affected than males. Patients with end-stage renal disease have MAC relatively more commonly than the general population. Patients with MAC often develop conduction system disturbances, including advanced atrioventricular blocks. They are also more likely to develop various arrhythmias, including atrial fibrillation. Caseous mitral annulus calcification is a variant of MAC that often looks like a cardiac tumor on an echocardiogram and needs to be differentiated.

4.
Virus Genes ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38739246

ABSTRACT

The Newcastle disease virus (NDV) affects wild and domesticated bird species, including commercial poultry. Although the diversity of NDV in domestic chickens is well documented, limited information is available about Newcastle disease (ND) outbreaks in other bird species. We report an annotated sequence of NDV/Vulture/Borjuri/01/22, an avirulent strain of NDV reported from Borjuri, Northeast India, in Himalayan Griffon vulture. The complete genome is 15,186 bases long with a fusion protein (F) cleavage site 112GRQGR↓L117. The phylogenetic analysis based on the F protein gene and the whole genome sequence revealed that the isolate from the vulture belongs to genotype II, sharing significant homology with vaccine strain LaSota. The study highlights the possible spillover of the virus from domestic to wild species through the food chain.

5.
Sci Rep ; 14(1): 8865, 2024 04 17.
Article in English | MEDLINE | ID: mdl-38632307

ABSTRACT

Breast cancer, a global health concern predominantly affecting women, recorded 2.3 million new cases and 685,000 deaths in 2020. Alarmingly, projections suggest that by 2040, there could be over 3 million new cases and 1 million deaths. To assess breast cancer prevalence in 24 rural villages within a 60 km radius of NIMS Hospital, Tala Mod, Jaipur, Rajasthan, North India 303,121. A study involving 2023 participants conducted initial screenings, and positive cases underwent further tests, including ultrasound, mammography, and biopsy. SPSSv28 analysed collected data. Among 2023 subjects, 3 screened positive for breast lumps. Subsequent clinical examination and biopsy identified 1 normal case and 2 with breast cancer, resulting in a prevalence proportion of 0.0009 or 98 per 100,000. This study helps fill gap in breast cancer prevalence data for rural Rajasthan. The results highlight a concerning prevalence of breast cancer in the rural area near NIMS hospital, emphasizing the urgent need for increased awareness, early detection, and better healthcare access. Challenges like limited resources, awareness programs, and delayed diagnosis contribute to this high incidence. To address this, comprehensive approach is necessary, including improved screening programs and healthcare facilities in rural areas. Prioritizing rural healthcare and evidence-based strategies can reduce the burden of breast cancer and improve health outcomes.


Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/pathology , Rural Population , Prevalence , Early Detection of Cancer , Mass Screening , India
6.
Ann Diagn Pathol ; 71: 152303, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38636337

ABSTRACT

Philadelphia (Ph) chromosome (9;22)(q34;q11) comprises 90-95 % of chronic myeloid leukemia (CML), while 5-10 % of CML have translocations involving three or more chromosomes. The outcome of treating patients harbouring complex Ph-positive cytogenetics with tyrosine kinase inhibitors (TKI) is unclear. In the present systematic review, we aim to summarise the response of patients with complex Ph-positive cytogenetics to treatment with TKI therapy. We collated all available literature from databases such as PubMed, Google Scholar, Web of Science database, Cochrane library, Scopus and Embase (up until January 31st, 2024), which describe cases of patients with CML, harbouring complex Ph-positive variations (three and four-way translocations), and summarised their response to TKI therapy. The studies were screened for the following criteria: documented TKI intervention and outcome (whether CR was achieved). Studies that did not report the same, were excluded. Additionally, we report a case from our center of a 55-year-old patient with CML, positive for the Ph-chromosome, harbouring a three-way translocation involving chromosome 15 i.e. 46XX, t(9;15;22) (q34;p11;q11). Identification of BCR::ABL and involvement of chromosome 15 was carried out using conventional cytogenetics, fluorescence in situ hybridization (FISH), and quantitative PCR (qPCR). Based on the inclusion criteria, a total of 15 studies were included from which a total of 87 cases were covered. Overall, we identified 38 unique complex three- and four-way translocations across 87 Ph-positive cases and found that 85 patients with complex Ph-positive cytogenetics achieved complete remission upon treatment and did not appear to have a lesser response to TKI therapy.

7.
Eur J Pharmacol ; 972: 176584, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38621507

ABSTRACT

Primary hypertension is a multiplex and multifactorial disease influenced by various strong components including genetics. Extensive research such as Genome-wide association studies and candidate gene studies have revealed various single nucleotide polymorphisms (SNPs) related to hypertension, providing insights into the genetic basis of the condition. This review summarizes the current status of SNP research in primary hypertension, including examples of hypertension-related SNPs, their location, function, and frequency in different populations. The potential clinical implications of SNP research for primary hypertension management are also discussed, including disease risk prediction, personalized medicine, mechanistic understanding, and lifestyle modifications. Furthermore, this review highlights emerging technologies and methodologies that have the potential to revolutionize the vast understanding of the basis of genetics in primary hypertension. Gene editing holds the potential to target and correct any kind of genetic mutations that contribute to the development of hypertension or modify genes involved in blood pressure regulation to prevent or treat the condition. Advances in computational biology and machine learning enable researchers to analyze large datasets and identify complex genetic interactions contributing to hypertension risk. In conclusion, SNP research in primary hypertension is rapidly evolving with emerging technologies and methodologies that have the potential to transform the knowledge about genetic basis related to the condition. These advances hold promise for personalized prevention and treatment strategies tailored to an individual's genetic profile ultimately improving patient outcomes and reducing healthcare costs.


Subject(s)
Hypertension , Polymorphism, Single Nucleotide , Humans , Hypertension/genetics , Genetic Predisposition to Disease , Animals , Genome-Wide Association Study , Precision Medicine/methods , Biomarkers/metabolism
8.
J Pharm Bioallied Sci ; 16(Suppl 1): S415-S417, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595357

ABSTRACT

Objective: Primary brain injuries, which are the result of severe head trauma and cannot be prevented, are always catastrophic and fatal. Yet, if diagnostic and therapeutic steps are taken promptly after a craniocerebral injury, further brain insults may be prevented and the victim's death can be avoided within 24 hours. Materials and Methods: Source of data, sample size, inclusion criteria, exclusion criteria, statistical methods. Results: One hundred individuals with confirmed cumputer tomography (CT) scan results of severe head trauma participated in this analysis. Seventy men and thirty women accounted for the total number of patients. The research included 70% men and 30% women. The M/F ratio is 2.3:1. Males between the ages of 21 and 30 (a total of 21 patients) had the highest rate of head injury in our analysis. Males had a lower incidence overall, with nine cases in the 0-10 age range, 11 cases in the 11-20 age range, five cases in the 41-50 age range, three cases in the 51-60 age range, and four cases in patients older than 61. Similarly, eight of the female patients were in the 21-30 age range. There were also four patients between the ages of 0 and 10, four between the ages of 11 and 20, two between the ages of 41 and 50, five between the ages of 51 and 60, and three among those older than 61. Summary and Conclusion: Men were more likely than women to sustain a head injury. The majority of the study population consisted of patients between the ages of 21 and 30 and 31 and 40. Injuries were found to most often occur in car crashes.

9.
J Pharm Bioallied Sci ; 16(Suppl 1): S663-S665, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595469

ABSTRACT

Background: This study aims to explore the connection between obstructive sleep apnea (OSA) and temporomandibular joint disorders (TMD) through a case-control investigation. OSA is a sleep-related breathing disorder that affects breathing during sleep, whereas TMD involves pain and dysfunction in the jaw joint. Understanding any potential association between these two conditions could contribute to improved diagnostic and therapeutic approaches. Materials and Methods: A total of 50 participants were included in both the OSA group and the control group. Participants with diagnosed OSA constituted the OSA group, whereas individuals without OSA formed the control group. TMD symptoms were assessed using standardized diagnostic criteria. Statistical analysis was performed to compare the prevalence of TMD symptoms between the two groups. Results: In the OSA group, 36 out of 50 participants exhibited TMD symptoms, whereas in the control group, 18 out of 50 participants displayed such symptoms. The calculated P value was found to be 0.023, indicating a statistically significant association between OSA and TMD. Conclusion: The findings of this study suggest a notable association between OSA and TMD. Individuals with OSA are more likely to experience TMD symptoms compared to those without OSA. This underscores the importance of considering TMD symptoms in individuals with OSA and vice versa for a comprehensive approach to diagnosis and management.

10.
Sci Rep ; 14(1): 7657, 2024 04 01.
Article in English | MEDLINE | ID: mdl-38561353

ABSTRACT

The present study was conducted to assess the impact of non-encapsulated, air-dried microencapsulated, and lyophilized microencapsulated probiotics in indigenous cattle calves (Bos indicus). Twenty-four (5-7 days old) indigenous cattle calves were selected and assigned into four groups, with six calves in each as follows: control (CON), fed milk and basal diet alone, and treatment groups supplemented with non-encapsulated (NEC), air-dried microencapsulated (AEC) and lyophilized microencapsulated (LEC) probiotic L. reuteri SW23 at 108 CFU/head/day in skim milk as a carrier provided for 60 days. The animals were divided into four groups, adopting a complete randomized design, and the effects were considered significant at p ≤ 0.05. Probiotics supplementation increased (p < 0.05) body weight gain (kg), average daily gain, and structural growth measurements in calves of all treatment groups. Dry matter intake (g/d), feed conversion efficiency, and fecal counts of Lactobacilli and Bifidobacteria were also increased in the treatment groups compared to CON. The fecal consistency index was highest in CON (0.70 ± 0.03), followed by NEC (0.68 ± 0.01), AEC (0.66 ± 0.02), and LEC (0.65 ± 0.02). Fecal pH and ammonia levels were reduced (p < 0.05) in the probiotic-fed groups compared to CON, with a concomitant increase in fecal lactate, acetate, and propionate levels. In addition, cell-mediated and humoral immunity were significantly increased in supplemented groups as compared to CON. Thus, it can be concluded that supplementation of the probiotics in microencapsulated/non-encapsulated forms to neonatal calves had a variety of positive effects on their health, including better performance, improved gut health, and a lower fecal consistency index. Moreover, among all supplemented groups, the lyophilized microencapsulated group outperformed air-dried microencapsulated and non-microencapsulated groups in terms of ADG, DMI, and gut health.


Subject(s)
Limosilactobacillus reuteri , Probiotics , Animals , Cattle , Animal Feed/analysis , Body Weight , Diet/veterinary , Dietary Supplements , Lactic Acid , Probiotics/pharmacology , Weaning
12.
Free Radic Biol Med ; 219: 184-194, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38636716

ABSTRACT

Hematopoietic stem cells (HSCs) replenish blood cells under steady state and on demand, that exhibit therapeutic potential for Bone marrow failures and leukemia. Redox signaling plays key role in immune cells and hematopoiesis. However, the role of reactive nitrogen species in hematopoiesis remains unclear and requires further investigation. We investigated the significance of inducible nitric oxide synthase/nitric oxide (iNOS/NO) signaling in hematopoietic stem and progenitor cells (HSPCs) and hematopoiesis under steady-state and stress conditions. HSCs contain low levels of NO and iNOS under normal conditions, but these increase upon bone marrow stress. iNOS-deficient mice showed subtle changes in peripheral blood cells but significant alterations in HSPCs, including increased HSCs and multipotent progenitors. Surprisingly, iNOS-deficient mice displayed heightened susceptibility and delayed recovery of blood progeny following 5-Fluorouracil (5-FU) induced hematopoietic stress. Loss of quiescence and increased mitochondrial stress, indicated by elevated MitoSOX and MMPhi HSCs, were observed in iNOS-deficient mice. Furthermore, pharmacological approaches to mitigate mitochondrial stress rescued 5-FU-induced HSC death. Conversely, iNOS-NO signaling was required for demand-driven mitochondrial activity and proliferation during hematopoietic recovery, as iNOS-deficient mice and NO signaling inhibitors exhibit reduced mitochondrial activity. In conclusion, our study challenges the conventional view of iNOS-derived NO as a cytotoxic molecule and highlights its intriguing role in HSPCs. Together, our findings provide insights into the crucial role of the iNOS-NO-mitochondrial axis in regulating HSPCs and hematopoiesis.


Subject(s)
Fluorouracil , Hematopoiesis , Hematopoietic Stem Cells , Mitochondria , Nitric Oxide Synthase Type II , Nitric Oxide , Signal Transduction , Animals , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type II/genetics , Hematopoietic Stem Cells/metabolism , Mice , Mitochondria/metabolism , Fluorouracil/pharmacology , Hematopoiesis/genetics , Nitric Oxide/metabolism , Regeneration , Mice, Knockout , Bone Marrow/metabolism , Mice, Inbred C57BL
13.
Sci Rep ; 14(1): 7447, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38548782

ABSTRACT

This paper proposes a circularly polarized ultra-thin flexible antenna with a flexible rectifier and power management unit (PMU) for smartwatch/wristband applications. The flexible antenna is compact (0.17λ0 × 0.20λ0 × 0.0004λ0) and has a stepped ground plane. A parasitic element is used at the substrate bottom to reduce the specific absorption rate (SAR) and enhance the gain up to 3.2 dBi, at the resonating frequency of WLAN/Wi-Fi (2.45 GHz). The SAR of the proposed design is also analysed at the resonating frequency, and it satisfies the guidelines of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and IEEE C95.1-2019 human safety standards. An impedance matching circuit is used between the antenna and the RF energy harvester to improve conversion efficiency. Polarization mismatch is avoided with the help of circular polarization, achieved by tuning stubs of size 0.02λ0 × 0.044λ0. The integration of the antenna and rectenna results in a good conversion efficiency of 78.2% at - 5 dBm of input power with a load resistance of 2 KΩ. The availability of RF signals allows the user to charge the smartwatch/wristband by connecting the PMU circuit with the RF energy harvester.

14.
Hum Mol Genet ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38538568

ABSTRACT

The Northeastern region of India is considered a gateway for modern humans' dispersal throughout Asia. This region is a mixture of various ethnic and indigenous populations amalgamating multiple ancestries. One reason for such amalgamation is that, South Asia experienced multiple historic migrations from various parts of the world. A few examples explored genetically are Jews, Parsis and Siddis. Ahom is a dynasty that historically migrated to India during the 12th century. However, this putative migration has not been studied genetically at high resolution. Therefore, to validate this historical evidence, we genotyped autosomal data of the Modern Ahom population residing in seven sister states of India. Principal Component and Admixture analyses haave suggested a substantial admixture of the Ahom population with the local Tibeto-Burman populations. Moreover, the haplotype-based analysis has linked these Ahom individuals mainly with the Kusunda (a language isolated from Nepal) and Khasi (an Austroasiatic population of Meghalaya). Such unexpected presence of widespread population affinities suggests that Ahom mixed and assimilated a wide variety of Trans-Himalayan populations inhabiting this region after the migration. In summary, we observed a significant deviation of Ahom from their ancestral homeland (Thailand) and extensive admixture and assimilation with the local South Asian populations.

15.
J Surg Oncol ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38436618

ABSTRACT

BACKGROUND AND OBJECTIVES: The role of cell-free DNA (cfDNA) in operable nonsmall cell lung cancer (NSCLC) is unclear. This study was aimed to evaluate the feasibility for identification of cfDNA in pleural lavage fluid and its correlation with plasma in resectable NSCLCs. METHODS: Consecutively resected NSCLCs were evaluated for cfDNA levels in preoperative plasma (PLS1), intraoperative pleural-lavage (PLV) and postoperative (at 1 month) plasma sample (PLS2). CfDNA was isolated and measured quantitatively by qPCR in a TaqMan probe-detection approach using the human ß-actin gene as the amplifying target. RESULTS: All (n = 34) except one were negative for malignant cells in PLV cytology. CfDNA could be isolated from all the three samples (PLS1, PLV, and PLS2) successfully in each patient. The median cfDNA levels in PLS1, PLV and PLS2 were 118 ng/mL (IQR 61-158), 167 ng/mL (IQR 59.9-179.9) and 103 ng/mL (IQR 66.5-125.4) respectively. The median follow-up was 34.1 months (IQR 25.2-41.6). A significant overall-survival (OS) and disease-free survival (DFS) were recorded for patients with cfDNA level cut-offs at 125, 170, and 100 ng/mL, respectively for PLS1, PLV, and PLS2. Patients with raised cfDNA in PLS1 (>125 ng/mL) and PLV (>170 ng/mL) had significantly poorer 2-year OS, p = 0.005 and p = 0.012, respectively. The hazards (OS) were also higher for those with raised cfDNA in PLV (HR = 5.779, 95% CI = 1.162-28.745, p = 0.032). PLV (>170 ng/mL) had increased pleural recurrences (p = 0.021) and correlated significantly with poorer DFS at 2-years (p = 0.001) with increased hazards (HR = 9.767, 95% CI = 2.098-45.451, p = 0.004). Multivariable analysis suggested higher cfDNA in PLV as a poor prognostic factor for both OS and DFS. CONCLUSIONS: Among patients with operable NSCLC, it is feasible to identify cfDNA in pleural lavage and correlate PLV cfDNA with pleural recurrences and outcomes.

16.
Expert Opin Drug Metab Toxicol ; 20(4): 181-195, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38480460

ABSTRACT

INTRODUCTION: Pharmacokinetic parameters assessment is a critical aspect of drug discovery and development, yet challenges persist due to limited training data. Despite advancements in machine learning and in-silico predictions, scarcity of data hampers accurate prediction of drug candidates' pharmacokinetic properties. AREAS COVERED: The study highlights current developments in human pharmacokinetic prediction, talks about attempts to apply synthetic approaches for molecular design, and searches several databases, including Scopus, PubMed, Web of Science, and Google Scholar. The article stresses importance of rigorous analysis of machine learning model performance in assessing progress and explores molecular modeling (MM) techniques, descriptors, and mathematical approaches. Transitioning to clinical drug development, article highlights AI (Artificial Intelligence) based computer models optimizing trial design, patient selection, dosing strategies, and biomarker identification. In-silico models, including molecular interactomes and virtual patients, predict drug performance across diverse profiles, underlining the need to align model results with clinical studies for reliability. Specialized training for human specialists in navigating predictive models is deemed critical. Pharmacogenomics, integral to personalized medicine, utilizes predictive modeling to anticipate patient responses, contributing to more efficient healthcare system. Challenges in realizing potential of predictive modeling, including ethical considerations and data privacy concerns, are acknowledged. EXPERT OPINION: AI models are crucial in drug development, optimizing trials, patient selection, dosing, and biomarker identification and hold promise for streamlining clinical investigations.


Subject(s)
Artificial Intelligence , Computer Simulation , Drug Development , Machine Learning , Pharmacokinetics , Precision Medicine , Humans , Drug Design , Drug Development/methods , Drug Discovery/methods , Models, Biological , Models, Molecular , Pharmaceutical Preparations/metabolism , Pharmaceutical Preparations/administration & dosage , Pharmacogenetics , Precision Medicine/methods , Reproducibility of Results
17.
Sci Rep ; 14(1): 5264, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38438596

ABSTRACT

We present a temporary keyword search over sensitive and confidential health data in a cloud environment. The cloud constitutes a semi-trusted domain, making it necessary for data owners to secure their data before outsourcing it through techniques like encryption. Attribute-based keyword search techniques tend to perform a search operation using a search token generated by an authorized user. These search tokens can lead to serious privacy threats, as they can extract all ciphertexts that may have been generated along with their keyword. Therefore, restricting search tokens to extract ciphertexts generated within a time interval is a more promising solution. In this paper, we present a novel ciphertext policy fine-grained temporary keyword that prevents the misuse of these search tokens. Further, it mitigates the risk of insider threats within healthcare organizations by limiting the window of opportunity for unauthorized access to minimum. To assess the security, our proposed scheme is formally proven to be secure against Selectively Chosen Keyword Attacks in the generic bilinear group model. Additionally, we demonstrate that the encryption algorithm's complexity is linear in relation to the number of attributes. Our scheme's significance and practicality are revealed by the performance evaluation.

18.
ASAIO J ; 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38483812

ABSTRACT

Physical therapy (PT) benefits for critically ill patients are well recognized; however, little data exist on PT in patients receiving temporary mechanical circulatory support. In this single-center retrospective study (February 2017-January 2022), we analyzed 37 patients who received an axillary Impella device (Abiomed, Danvers, MA) and PT to "prehabilitate" them before durable left ventricular assist device (dLVAD) implantation. The Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility tool assessed the functional status at different points during admission. Immediately after Impella placement, the median AM-PAC score was 12.7 (interquartile range [IQR], 9-15), and the scores continued to significantly increase to 18.4 (IQR, 16-23) before dLVAD and up to 20.7 (IQR, 19-24) at discharge, indicating improved independence. No PT-related complications were reported. Thus, we hypothesize that critically ill patients initially deemed equivocal candidates may safely participate in PT while maximizing functional activities before dLVAD placement.

19.
Exp Appl Acarol ; 92(4): 809-833, 2024 May.
Article in English | MEDLINE | ID: mdl-38448756

ABSTRACT

To study the acaricide resistance status and possible mechanisms of action in conferring resistance to commonly used acaricides (deltamethrin and coumaphos), Hyalomma anatolicum ticks were collected from 6 dairy farms of Hisar and Charkhi Dadri districts of Haryana. By using standard larval packet test, H. anatolicum tick larvae of Charkhi Dadri isolates were found to be susceptible (100% mortality) to both the acaricides. Level-I resistance against coumaphos was recorded from four isolates, whereas, level-II was observed in only one isolate, collected from Hisar. One isolates (Kaimri) from Hisar also showed level-I resistance against deltamethrin. Biochemically, the ticks having higher values of resistance factor (RF) against coumaphos were found to possess increased enzymatic activity of α-esterase, ß-esterase, glutathione-S-transferase (GST) and mono-oxygenase enzymes, whereas, the monoamine oxidase did not show any constant trend. However, the RF showed a statistical significant correlation with GST only. Native PAGE analysis of H. anatolicum ticks revealed the presence of nine types of esterases (EST-1 h to EST-9 h) by using napthyl acetate as substrate. In the inhibitory assay, esterases were found to be inhibited by PMSF, indicating the presence of serine residue at catalytic triad. The partial cds of carboxylesterase and domain II of sodium channel genes were sequenced to determine any proposed mutations in resistant isolates of H. anatolicum ticks, however, no mutations were observed in either gene, indicating that increased expression of detoxification enzymes as a possible mechanism for resistance development, in the current study.


Subject(s)
Acaricides , Coumaphos , Ixodidae , Nitriles , Pyrethrins , Animals , Pyrethrins/pharmacology , Nitriles/pharmacology , Acaricides/pharmacology , Ixodidae/drug effects , Ixodidae/genetics , Ixodidae/physiology , Coumaphos/pharmacology , Larva/growth & development , Larva/drug effects , India , Drug Resistance/genetics , Insecticide Resistance/genetics , Female , Esterases/metabolism , Esterases/genetics
20.
J Gen Virol ; 105(2)2024 02.
Article in English | MEDLINE | ID: mdl-38376490

ABSTRACT

Reactive oxygen species (ROS) accumulation inside the cells instigates oxidative stress, activating stress-responsive genes. The viral strategies for promoting stressful conditions and utilizing the induced host proteins to enhance their replication remain elusive. The present work investigates the impact of oxidative stress responses on Newcastle disease virus (NDV) pathogenesis. Here, we show that the progression of NDV infection varies with intracellular ROS levels. Additionally, the results demonstrate that NDV infection modulates the expression of oxidative stress-responsive genes, majorly sirtuin 7 (SIRT7), a NAD+-dependent deacetylase. The modulation of SIRT7 protein, both through overexpression and knockdown, significantly impacts the replication dynamics of NDV in DF-1 cells. The activation of SIRT7 is found to be associated with the positive regulation of cellular protein deacetylation. Lastly, the results suggested that NDV-driven SIRT7 alters NAD+ metabolism in vitro and in ovo. We concluded that the elevated expression of NDV-mediated SIRT7 protein with enhanced activity metabolizes the NAD+ to deacetylase the host proteins, thus contributing to high virus replication.


Subject(s)
Newcastle disease virus , Sirtuins , Animals , NAD , Newcastle disease virus/genetics , Oxidative Stress , Reactive Oxygen Species , Sirtuins/genetics , Chickens , Cell Line
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