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1.
J Environ Sci (China) ; 147: 498-511, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39003065

ABSTRACT

The land application of livestock manure has been widely acknowledged as a beneficial approach for nutrient recycling and environmental protection. However, the impact of residual antibiotics, a common contaminant of manure, on the degradation of organic compounds and nutrient release in Eutric Regosol is not well understood. Here, we studied, how oxytetracycline (OTC) and ciprofloxacin (CIP) affect the decomposition, microbial community structure, extracellular enzyme activities and nutrient release from cattle and pig manure using litterbag incubation experiments. Results showed that OTC and CIP greatly inhibited livestock manure decomposition, causing a decreased rate of carbon (28%-87%), nitrogen (15%-44%) and phosphorus (26%-43%) release. The relative abundance of gram-negative (G-) bacteria was reduced by 4.0%-13% while fungi increased by 7.0%-71% during a 28-day incubation period. Co-occurrence network analysis showed that antibiotic exposure disrupted microbial interactions, particularly among G- bacteria, G+ bacteria, and actinomycetes. These changes in microbial community structure and function resulted in decreased activity of urease, ß-1,4-N-acetyl-glucosaminidase, alkaline protease, chitinase, and catalase, causing reduced decomposition and nutrient release in cattle and pig manures. These findings advance our understanding of decomposition and nutrient recycling from manure-contaminated antibiotics, which will help facilitate sustainable agricultural production and soil carbon sequestration.


Subject(s)
Anti-Bacterial Agents , Livestock , Manure , Soil Microbiology , Animals , Soil/chemistry , Carbon Sequestration , Carbon/metabolism , Phosphorus , Recycling , Soil Pollutants/metabolism , Cattle , Swine , Nitrogen/analysis , Oxytetracycline
2.
ACS Appl Bio Mater ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980821

ABSTRACT

Sustainable development is the primary key to address global energy challenges. Though the scientific community is engaged in developing efficient ways to not only maximize energy production from natural resources like sun, wind, water, etc. but also to make all the electronic gadgets power efficient, despite all this, the materials used in most of the electronic devices are largely produced using various materials processing techniques and semiconductors, polymers, dielectrics, etc. which again increases the burden on energy and in turn affects the environment. While addressing these challenges, it is very important to explore the possibility to directly, or with minimum processing, utilize the potential of natural resources in the development of electronic devices. Recent articles are focused on the development of herbal electronic devices that essentially implement natural resources, like plants, leaves, etc., either in their raw or extracted form in the device assembly. This review encompasses the recent research developments around herbal electronic devices. Furthermore, herbal electronics has been discussed for several functional applications including electrochromism, energy storage, memresistor, LED, solar cell, water purification, pressure sensor, etc. Moreover, advantages, disadvantages, and challenges encountered in the realization of "herbal electronics" have been discussed at length.

3.
J Vis Exp ; (208)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38975757

ABSTRACT

Gut microbial products are known to act both locally within the intestine and get absorbed into circulation, where their effects can extend to numerous distant organ systems. Short-chain fatty acids (SCFA) are one class of metabolites produced by gut microbes during the fermentation of indigestible dietary fiber. They are now recognized as important contributors to how the gut microbiome influences extra-intestinal organ systems via the gut-lung, gut-brain, and other gut-organ axes throughout the host. SCFAs are absorbed from the colon, through intestinal tissue, into the portal vein (PV). They then pass through the liver, and are consumed in various organs such as the brain, muscle, adipose tissue, and lungs. SCFAs are most easily measured in the expelled fecal material however, more accurate measurements have been obtained from intra-colonic fecal contents. Here we propose that sampling PV and systemic circulating plasma of a single subject may be preferable for studying the absorption, transport, and systemic levels of SCFAs in mice. We present a new technique for efficient blood sampling from the PV and inferior vena cava (IVC) that allows for the collection of relatively large volumes of blood from the portal and systemic circulations. This is accomplished by ligating the PV, thereby allowing for the dilation or enlargement of the PV as it backfills from the mesenteric veins that drain into it. Using this method, we were able to improve the rate of successful collection as well as the total amount of blood collected (up to 0.3 mL from IVC and 0.5 mL from PV).


Subject(s)
Gastrointestinal Microbiome , Portal Vein , Vena Cava, Inferior , Animals , Mice , Portal Vein/metabolism , Gastrointestinal Microbiome/physiology , Vena Cava, Inferior/metabolism , Fatty Acids, Volatile/metabolism , Fatty Acids, Volatile/analysis , Blood Specimen Collection/methods , Male
4.
Res Sq ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38947076

ABSTRACT

Background: The demand for genetic services has outpaced the availability of resources, challenging clinicians untrained in genetic integration into clinical decision-making. The UTHealth Adult Cardiovascular Genomics Certificate (CGC) program trains non-genetic healthcare professionals to recognize, assess, and refer patients with heritable cardiovascular diseases. This asynchronous online course includes 24 modules in three tiers of increasing complexity, using realistic clinical scenarios, interactive dialogues, quizzes, and tests to reinforce learning. We hypothesized that the CGC will increase genomic competencies in this underserved audience and encourage applying genomic concepts in clinical practice. Methods: Required course evaluations include pre- and post-assessments, knowledge checks in each module, and surveys for module-specific feedback. After 6 months, longitudinal feedback surveys gathered data on the long-term impact of the course on clinical practice and conducted focused interviews with learners. Results: The CGC was accredited in September 2022. Principal learners were nurses (24%), nurse practitioners (21%), physicians (16%), and physician assistants. Scores of 283 learners in paired pre- and post-assessments increased specific skills related to recognizing heritable diseases, understanding inheritance patterns, and interpreting genetic tests. Interviews highlighted the CGC's modular structure and linked resources as key strengths. Learners endorsed confidence to use genetic information in clinical practice, such as discussing genetic concepts and risks with patients and referring patients for genetic testing. Learners were highly likely to recommend the CGC to colleagues, citing its role in enhancing heritable disease awareness. Conclusions: The CGC program effectively empowers non-genetic clinicians to master genomic competencies, fostering collaboration to prevent deaths from heritable cardiovascular diseases, and potentially transforming healthcare education and clinical practice.

5.
J Family Med Prim Care ; 13(5): 1868-1874, 2024 May.
Article in English | MEDLINE | ID: mdl-38948591

ABSTRACT

Background: The COVID-19 pandemic resulted in a shift in the way healthcare resources were used. While India faced limited effects in the first COVID wave primarily due to strict lockdown of the county, it was one of the worst affected in the second wave and at one time reported the highest number of daily cases. To address the lack of intensive care units (ICU) beds, the surgical wards of our institute were repurposed to take care of patients requiring supplementary oxygen and other supportive care till either they improved or an ICU bed was available. The medical personnel in charge of the surgical wards were entrusted with the care of patients with support from intensive care support teams (ICST). Aims: We aimed to examine the clinical details of patients admitted in the repurposed orthopaedic wards during the second COVID wave and to evaluate the factors that might affect the clinical outcomes in such patients. Methods: This was a retrospective review of records of patients admitted in the repurposed orthopaedic wards between 16 April 2021 and 20 May 2021. Details related to demography, COVID-19 presentation, COVID-19-related management and clinical course, including transfers to ICUs, and outcomes in terms of either discharge to home or death were recorded. They were analysed using statistical software. Results: One hundred and twenty three patients were treated during the said period. Twenty patients died during treatment, resulting in a mortality rate of 16.3%. Age, gender, RT-PCR status, pre-existing comorbidities, SpO2 at admission, method of supplemental oxygen supply, total leukocyte counts, haemoglobin values, serum C-reactive protein, Lactate dehydrogenase (LDH) and creatinine values had no statistically significant association with death of a patient during treatment. Conclusion: Based on the results, one can state that clinicians of surgical specialities having background knowledge of internal medicine from undergraduate education can manage patients of COVID-19 with support from ICST with reasonable outcomes. In case of future pandemics, surgical wards can be repurposed to tide over exigencies. Additionally, primary care physicians, who are often the first point of contact for patients, can allay their apprehensions adequately in future pandemics, thus preventing widespread panic and burdening of healthcare resources.

6.
bioRxiv ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38948800

ABSTRACT

Cyclophilin A (CypA) promotes HIV-1 infection by facilitating reverse transcription, nuclear entry and by countering the antiviral activity of TRIM5α. These multifunctional roles of CypA are driven by its binding to the viral capsid. Interestingly, recent studies suggest that the HIV-1 capsid lattice enters the nucleus of an infected cell and uncoats just before integration. Therefore, we tested whether CypA-capsid interaction regulates post-nuclear entry steps of infection, particularly integration. First, we challenged CypA-expressing (CypA +/+ ) and CypA-depleted (CypA -/- ) cells with HIV-1 particles and quantified the resulting levels of provirus. Surprisingly, CypA-depletion significantly reduced integration, an effect that was independent of CypA's effect on reverse transcription, nuclear entry, and the presence or absence of TRIM5α. Additionally, cyclosporin A, an inhibitor that disrupts CypA-capsid binding, inhibited HIV-1 integration in CypA +/+ cells but not in CypA -/- cells. Accordingly, HIV-1 capsid mutants (G89V and P90A) deficient in CypA binding were also blocked at integration in CypA +/+ cells but not in CypA -/- cells. Then, to understand the mechanism, we assessed the integration activity of HIV-1 preintegration complexes (PICs) extracted from infected cells. The PICs from CypA -/- cells had lower activity in vitro compared to those from CypA +/+ cells. PICs from cells depleted for CypA and TRIM5α also had lower activity, suggesting that CypA's effect on PIC activity is independent of TRIM5α. Finally, addition of CypA protein significantly stimulated the integration activity of PICs extracted from both CypA +/+ and CypA -/- cells. Collectively, these results suggest that CypA promotes HIV-1 integration, a previously unknown role of this host factor. Importance: HIV-1 capsid interaction with host cellular factors is essential for establishing a productive infection. However, the molecular details of such virus-host interactions are not fully understood. Cyclophilin A (CypA) is the first host protein identified to specifically bind to the HIV-1 capsid. Now it is established that CypA promotes reverse transcription and nuclear entry steps of HIV-1 infection. In this report, we show that CypA promotes HIV-1 integration by binding to the viral capsid. Specifically, our results demonstrate that CypA promotes HIV-1 integration by stimulating the activity of the viral preintegration complex and identifies a novel role of CypA during HIV-1 infection. This new knowledge is important because recent reports suggest that an operationally intact HIV-1 capsid enters the nucleus of an infected cell.

7.
Oral Dis ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950053

ABSTRACT

OBJECTIVES: To describe the epidemiological status of oral cancer (OC) in India along with updates on risk factors, advances and gaps in preventive measures, treatment, costs of care and monitoring. METHODS: Two national estimates of incidence and mortality were cited, one for 2016 by the Global Burden of Disease India Study and one based on projections for 2020 by GLOBOCAN. The National Cancer Registry Project provided local and regional incidence and trends using data from 2012-2016. Scientific literature, reports of the NCRP, the IARC and government press releases were also consulted. RESULTS: Tobacco and areca nut habits are the major risk factors for OC in India. In the 1980s, intervention studies on oral screening, awareness generation and habit cessation in rural areas reduced tobacco use and oral leukoplakia. Lately, adoption of the tobacco control law and mass media communications have resulted in decreased tobacco use. However, the increasing popularity of highly carcinogenic tobacco products containing areca nut, with evasion of their bans, is increasing OC incidence. CONCLUSION: Despite advances in care, there is growing incidence of OC, persisting poor awareness about the need to quit tobacco/areca nut/alcohol use and go for screening. Major efforts are needed to implement preventive activities.

8.
Indian J Public Health ; 68(2): 295-297, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38953821

ABSTRACT

We conducted the study to assess the effect of patient-tailored diet counseling on the nutritional status of chronic respiratory disease (CRD) patients under the pulmonary rehabilitation program from June 2021-May 2022. These patients completed 2 months of patient-tailored diet counseling sessions under the pulmonary rehabilitation program, which consisted of 4-5 interactive diet counseling sessions fortnightly. The pre- and postassessment was done using standardized outcomes: Malnutrition Universal Screening Tool (MUST), body mass index (BMI), and ideal body weight. The study enrolled 110 CRD patients. There was a statistically significant improvement in pre- and postassessment in MUST score, appetite, and unintentional weight loss (P < 0.001). Most of the patient's BMI normalized. In prenutritional assessment, most of the patients were malnourished and in postassessment, the number of malnourished and anemic patients was reduced. This study concludes that nutritional counseling effectively improves nutritional status and anemia.


Subject(s)
Counseling , Hospitals, Teaching , Malnutrition , Nutritional Status , Humans , Female , Male , Middle Aged , Counseling/methods , Malnutrition/diet therapy , Malnutrition/rehabilitation , Body Mass Index , Chronic Disease , Aged , Adult , India , Nutrition Assessment , Anemia/rehabilitation , Anemia/diet therapy
9.
Indian J Public Health ; 68(2): 305-309, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38953824

ABSTRACT

Digital health interventions can overcome geographical barriers and prepare health-care providers for better health outcomes in rural and remote tribal areas, however, it has not been explored among traditional birth attendants (TBAs). A mobile application, "maternal and infant care" (MAI) for capacity building of tribal birth attendants was developed and its quality was evaluated using the Mobile Application Rating Scale for user's interest in and satisfaction with the esthetics, information, and functionality. Thirteen Android user TBAs with the MAI application were piloted with the MARS checklist. Engagement, functionality, esthetics, and information quality; and one subjective quality scale having 29 items were used. The application was found to be entertaining excellent rating (mean score ± standard deviation) (4.00 ± 0.58), and scored high on performance (3.77 ± 0.93); layout design (3.85 ± 0.90); subjective quality (4.23 ± 0.93), however, scored minimum on interest; gestural design; visual appeal, etc. MAI is a user-friendly, culturally acceptable Android app that can be used for the capacity building of frontline workers.


Subject(s)
Midwifery , Mobile Applications , Humans , Female , India , Pregnancy , Infant, Newborn , Infant Care/standards , Adult , Infant , Maternal Health Services/standards , Maternal Health Services/organization & administration
10.
Health Sci Rep ; 7(7): e2215, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38974326

ABSTRACT

Background: Neck pain is one of the most burdensome chronic musculoskeletal problems globally. Impaired proprioception is associated with Chronic Nonspecific neck pain as the structures of the cervical spine are crucial for proprioception and balance. There is a paucity of literature examining objective measures of balance and postural sway in patients with Nonspecific neck pain. Methods: This study was observational and consisted of 126 samples (63 cases and 63 controls who were recruited using convenience sampling. The demographics of the samples were collected and the postural and balance impairment was assessed using Biodex Balance SD. Mean, Median, and SD were obtained and the inferential analysis was done using the Whitney U Test and the level of significance was accepted at p < 0.05. Results: The subjects with neck pain showed had a lower static stability index, static sway index, static stability index- forward backward and static sway index lateral scores than the normal counterparts. There are significant differences in the overall static stability index, (p < 0.001). There was a significant difference in static sway index(p = 0.003), and static stability index lateral (p = 0.004). There was no significant difference for static sway index forward and backward (p = 0.550) and lateral sway index (p = 0.711). Conclusion: Subjects with neck pain showed had a lower static stability index, static sway index, static stability index- forward backward and static sway index lateral scores than the normal counterparts and there was a significant difference between the static sway and static stability index in forward and backward directions as well as in lateral direction. These findings may help to assess the specific balance parameters and address the underlying causes of balance issues in patients with neck pain and also provide a comprehensive care to the patients. Clinical Trial Registration: The trial was registered with CTRI India with registration number: CTRI/2022/07/044222.

11.
J Extracell Biol ; 3(7): e158, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38966868

ABSTRACT

Analysis of single extracellular vesicles (EVs) has the potential to yield valuable label-free information on their morphological structure, biomarkers and therapeutic targets, though such analysis is hindered by the lack of reliable and quantitative measurements of the mechanical properties of these compliant nanoscale particles. The technical challenge in mechanical property measurements arises from the existing tools and methods that offer limited throughput, and the reported elastic moduli range over several orders of magnitude. Here, we report on a flow-based method complemented by transmission electron microscopy (TEM) imaging to provide a high throughput, whole EV deformation analysis for estimating the mechanical properties of liposarcoma-derived EVs as a function of their size. Our study includes extracting morphological data of EVs from a large dataset of 432 TEM images, with images containing single to multiple EVs, and implementing the thin-shell deformation theory. We estimated the elastic modulus, E = 0.16 ± 0.02 MPa (mean±SE) for small EVs (sEVs; 30-150 nm) and E = 0.17 ± 0.03 MPa (mean±SE) for large EVs (lEVs; >150 nm). To our knowledge, this is the first report on the mechanical property estimation of LPS-derived EVs and has the potential to establish a relationship between EV size and EV mechanical properties.

12.
Ann Surg Oncol ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969849

ABSTRACT

BACKGROUND: Questions have been raised as to an increased risk of local recurrence with breast-conserving surgery (BCS) post NAC highlighting the uncertainty around optimal margin width in this patient population. We examined the association between margin status and local recurrence-free survival (LRFS) in patients who underwent BCS following NAC. METHODS: We performed a retrospective cohort study of adult female patients with stage I-III breast cancer who underwent NAC followed by BCS between 2012 and 2021 at two cancer centers. Margins were categorized as "close" if they were < 1 mm. RESULTS: The full cohort included 544 patients with a median age of 53 years (interquartile range [IQR] 44-64). Pathologic complete response (pCR) was achieved in 41.2% of the overall cohort (n = 224). Of the 320 with residual disease, 29.4% (n = 94) had at least one close margin, and 10.9% (n = 35) had ≥2 close margins. Median follow-up was 55 months (IQR 32-83); 4.8% had an ipsilateral breast recurrence (n = 26). Patients with pCR had a higher 5-year LRFS than those with residual disease (98.0% vs. 91.6%, p = 0.02). There was no difference in 5-year LRFS between the margin categories (clear vs. 1 close margin vs. ≥2 close margins) in those with residual disease (92.2% vs. 88.9% vs. 92.9%) (p = 0.78). CONCLUSIONS: In patients undergoing BCS post-NAC, those who achieved pCR had a significantly higher LRFS compared with those with residual disease at the time of surgery, but LRFS was not associated with margin width nor the number of close margins.

13.
World J Radiol ; 16(6): 221-231, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38983840

ABSTRACT

BACKGROUND: The hemodynamic alterations seen in liver cirrhosis lead to renal vasoconstriction, ultimately causing acute kidney injury (AKI). The renal resistive index (RRI) is the most common Doppler ultrasound variable for measuring intrarenal vascular resistance. AIM: To evaluate the association of the RRI with AKI in patients with liver cirrhosis and to identify risk factors for high RRI. METHODS: This was a prospective observational study, where RRI was measured using Doppler ultrasound in 200 consecutive hospitalized patients with cirrhosis. The association of RRI with AKI was studied. The receiver operating characteristic (ROC) curve analysis was utilized to determine discriminatory cut-offs of RRI for various AKI phenotypes. Multivariate analysis was conducted to determine the predictors of high RRI. RESULTS: The mean patient age was 49.08 ± 11.68 years, with the majority (79.5%) being male; the predominant etiology of cirrhosis was alcohol (39%). The mean RRI for the study cohort was 0.68 ± 0.09, showing a progressive increase with higher Child-Pugh class of cirrhosis. Overall, AKI was present in 129 (64.5%) patients. The mean RRI was significantly higher in patients with AKI compared to those without it (0.72 ± 0.06 vs 0.60 ± 0.08; P < 0.001). A total of 82 patients (41%) had hepatorenal syndrome (HRS)-AKI, 29 (22.4%) had prerenal AKI (PRA), and 18 (13.9%) had acute tubular necrosis (ATN)-AKI. The mean RRI was significantly higher in the ATN-AKI (0.80 ± 0.02) and HRS-AKI (0.73 ± 0.03) groups than in the PRA (0.63 ± 0.07) and non-AKI (0.60 ± 0.07) groups. RRI demonstrated excellent discriminatory ability in distinguishing ATN-AKI from non-ATN-AKI (area under ROC curve: 93.9%). AKI emerged as an independent predictor of high RRI (adjusted odds ratio [OR]: 11.52), and high RRI independently predicted mortality among AKI patients (adjusted OR: 3.18). CONCLUSION: In cirrhosis patients, RRI exhibited a significant association with AKI, effectively differentiated between AKI phenotypes, and predicted AKI mortality.

14.
Cureus ; 16(6): e61971, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38984008

ABSTRACT

Anomalous origin of the left main coronary artery (LMCA) from the right sinus of Valsalva (RSV) is a rare congenital anomaly that can cause myocardial ischemia, ventricular arrhythmia, and sudden cardiac death. We report the case of a 74-year-old male with a history of hyperlipidemia and hypertension who presented with non-ST elevation myocardial infarction (NSTEMI). On coronary angiogram, the patient was found to have LMCA originating from the RSV and a 90% stenosis of the left anterior descending (LAD) artery. The patient subsequently underwent computed tomography angiography (CTA) to assess the course of the LMCA, which was found to be intramyocardial with no compression. The echocardiogram reported a reduced ejection fraction (EF) of 40% and wall motion abnormalities in the anterior wall. The patient had a successful staged percutaneous coronary intervention (PCI). The patient on follow-up reported no symptoms and EF improved to 50%. Anomalous origin of the LMCA from the RSV is a rare but potentially life-threatening congenital anomaly. Once the course of the anomalous artery is established, immediate reperfusion using PCI is being increasingly used in place of surgical unroofing, noting a change in clinical practice. Further research is needed to determine the optimal treatment for this anomaly and to improve the long-term outcomes of affected individuals.

15.
World J Virol ; 13(2): 92586, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38984084

ABSTRACT

BACKGROUND: Rotavirus is a highly contagious virus responsible for a significant burden of acute gastroenteritis, particularly among infants and young children worldwide, however, vaccination against this viral agent is available. Several studies have hypothesized that rotavirus vaccination has been linked to lower rates of antibiotic resistance. AIM: To assess the relationship between rotavirus vaccination and antibiotic resistance. METHODS: The present systematic review was tailored based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Several electronic databases (PubMed/MEDLINE, Scopus and Web of Science) were searched independently by two investigators in order to retrieve relevant publications published until April 2023 that investigated the aforementioned research question. RESULTS: The comprehensive database search identified a total of 91 records. After the duplicates were removed (n = 75), we screened the titles and abstracts of 16 potentially eligible publications. After the irrelevant records were excluded (n = 5), we screened the full texts of 11 manuscripts. Finally, 5 studies were entered into the qualitative and quantitative analysis. CONCLUSION: In conclusion, all the studies support the idea that vaccinations can reduce the need for antibiotic prescriptions which could potentially contribute to mitigating antibiotic resistance. However, to fully comprehend the mechanisms of antibiotic resistance, enhance treatment guidelines, and consider diverse demographic situations, further research is necessary to use evidence-based strategies to fight antibiotic misuse and resistance.

16.
Horm Res Paediatr ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38986456

ABSTRACT

INTRODUCTION: Thyroid dyshormonogenesis (TDH) is a sub-group of congenital hypothyroidism with recessive inheritance resulting from disease causing variants in thyroid hormone biosynthesis pathway genes, like DUOX2, TG, TPO, SLC5A5, SLC26A4, IYD, DUOXA2, SLC26A7 and SECISBP2. Thyroid peroxidase (TPO) is a crucial enzyme involved in thyroid hormone biosynthesis and is one of the frequently mutated genes in patients with TDH. The purpose of the study is to describe the insilico and functional characterization of novel variants in TPO gene identified in patients with thyroid dyshormonogenesis. METHODS: We performed exome sequencing in Indian patients with TDH. In the current study, we describe the results of patients with TPO gene mutations. Exome sequencing results were further analysed by sanger sequencing, computational studies and invitro functional studies such as immunofluorescence and enzyme assay. RESULTS: We identified nine biallelic disease-causing variants in the TPO gene in twelve patients from nine unrelated Indian families. Eight of the nine variants were novel. No recurrent variants were identified. Computational analysis of six missense variants showed that these amino acid substitutions caused changes in non-covalent interactions with the adjacent residues that may affect the TPO protein structure and function. In-vitro experimental data using immunofluorescence assay showed that these variants did not affect the plasma membrane localization of the TPO protein but caused significant loss of TPO enzymatic activity compared to wild type. CONCLUSION: Our study revealed multiple novel pathogenic variants in TPO gene in Indian patients, thereby expanding the genotype spectrum. Functional studies helped us to reveal the pathogenicity of the missense variants.

17.
J Appl Microbiol ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38986507

ABSTRACT

AIM: Colistin serves as the drug of last resort for combating numerous multidrug-resistant (MDR) Gram-negative infections. Its efficacy is hampered by the prevalent issue of colistin resistance, which severely limits treatment options for critically ill patients. Identifying resistance genes is crucial for controlling resistance spread, with horizontal gene transfer being the primary mechanism among bacteria. This study aimed to assess the prevalence of plasmid-mediated mcr genes associated with colistin resistance in Gram-negative bacteria, utilizing both genotypic and phenotypic tests. METHODS AND RESULTS: The clinical isolates (n=913) were obtained from a tertiary care center in Chennai, India. Colistin resistance was seen among Gram-negative isolates. These strains underwent screening for mcr-1, mcr-3, mcr-4, and mcr-5 genes via conventional PCR. Additionally, mcr-positive isolates were confirmed through Sanger sequencing and phenotypic testing. The bacterial isolates predominantly comprised Klebsiella pneumoniae (62.43%), Escherichia coli (19.71%), Pseudomonas aeruginosa (10.73%), Acinetobacter baumannii (4.81%), along with other species. All isolates exhibited multidrug resistance to three or more antibiotic classes. Colistin resistance, determined via broth microdilution (BMD) using CLSI guidelines, was observed in 13.08% of the isolates studied. Notably, mcr-5 was detected in K. pneumoniae in PCR, despite their absence in Sanger sequencing and phenotypic tests (including the combined-disk test, colistin MIC in the presence of EDTA, and Zeta potential assays). This finding underscores the importance of employing multiple diagnostic approaches to accurately identify colistin resistance mechanisms. CONCLUSION AND IMPACT: The study highlights a concerning prevalence of colistin resistance among Enterobacterales, especially those producing carbapenemase, thereby impacting mortality rates. Nonetheless, further investigations are warranted to elucidate common mechanisms of colistin resistance and to evaluate the efficacy of screening techniques in detecting isolates carrying mcr genes responsible for enzyme-mediated lipopolysaccharide (LPS) modification.

18.
Lung India ; 41(4): 307-317, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38953196

ABSTRACT

INTRODUCTION: Pneumococcal diseases pose a significant public health concern in India, with substantial morbidity and mortality, with the elderly and those with coexisting medical conditions being most at risk. Pneumococcus was also seen to be one of the main reasons for co-infection, pneumonia and complications in COVID. Current guidelines recommend vaccination for specific adult populations, but there is a lack of uniformity and guidance on risk stratification, prioritisation and optimal timing. METHODS: Nation Against Pneumococcal Infections - Expert Panel Opinion (NAP-EXPO) is a panel convened to review and update recommendations for adult pneumococcal vaccination in India. The panel of 23 experts from various medical specialties engaged in discussions and evidence-based reviews, discussed appropriate age for vaccination, risk stratification for COPD and asthma patients, vaccination strategies for post-COVID patients, smokers and diabetics, as well as methods to improve vaccine awareness and uptake. OUTCOME: The NAP-EXPO recommends the following for adults: All healthy individuals 60 years of age and above should receive the pneumococcal vaccine; all COPD patients, regardless of severity, high-risk asthma patients, post-COVID cases with lung fibrosis or significant lung damage, should be vaccinated with the pneumococcal vaccine; all current smokers and passive smokers should be educated and offered the pneumococcal vaccine, regardless of their age or health condition; all diabetic individuals should receive the pneumococcal vaccine, irrespective of their diabetes control. Strategies to improve vaccine awareness and uptake should involve general practitioners (GPs), primary health physicians (PHPs) and physicians treating patients at high risk of pneumococcal disease. Advocacy campaigns should involve media, including social media platforms. CONCLUSION: These recommendations aim to enhance pneumococcal vaccination coverage among high-risk populations in India in order to ensure a reduction in the burden of pneumococcal diseases, in the post-COVID era. There is a need to create more evidence and data to support the recommendations that the vaccine will be useful to a wider range of populations, as suggested in our consensus.

19.
Stress Biol ; 4(1): 33, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38981936

ABSTRACT

Global crop production is severely affected by environmental factors such as drought, salinity, cold, flood etc. Among these stresses, drought is one of the major abiotic stresses reducing crop productivity. It is expected that drought conditions will further increase because of the increasing global temperature. In general, viruses are seen as a pathogen affecting the crop productivity. However, several researches are showing that viruses can induce drought tolerance in plants. This review explores the mechanisms underlying the interplay between viral infections and the drought response mechanisms in plants. We tried to address the molecular pathways and physiological changes induced by viruses that confer drought tolerance, including alterations in hormone signaling, antioxidant defenses, scavenging the reactive oxygen species, role of RNA silencing and miRNA pathway, change in the expression of several genes including heat shock proteins, cellulose synthase etc. Furthermore, we discuss various viruses implicated in providing drought tolerance and examine the range of plant species exhibiting this phenomenon. By applying current knowledge and identifying gaps in understanding, this review aims to provide valuable insights into the complex dynamics of virus-induced drought tolerance in plants, paving the way for future research directions and practical applications in sustainable agriculture.

20.
Cureus ; 16(6): e62545, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39022523

ABSTRACT

Progressive multifocal leukoencephalopathy (PML) is a rare, demyelinating infectious disease of the central nervous system, primarily affecting immunosuppressed individuals, such as those with acquired immunodeficiency syndrome (AIDS) or undergoing immunosuppressive therapy. The causative agent is the dormant John Cunningham (JC) polyomavirus, which reactivates in immunocompromised patients. PML is diagnosed through clinical observations, imaging, and polymerase chain reaction (PCR) analysis, detecting JC virus deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF). Here, we report a case of a 42-year-old male, recently diagnosed with human immunodeficiency virus (HIV), who presented with slurred speech, difficulty articulating, tingling in both feet, difficulty walking, and significant weight loss. Examination revealed absent reflexes, coordination impairment, and diminished vibration sense. Blood tests showed anemia, elevated D-dimer, and HIV-1 positivity with a low CD4 count. CSF analysis indicated a lymphocytic profile with elevated protein and marginally increased adenosine deaminase (ADA). Autoantibody testing was positive for antinuclear antibodies (ANA), but CSF culture and India ink staining were negative. Magnetic resonance imaging (MRI) of the brain revealed hyperintense lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images in the left peritrigonal and parietal white matter, suggesting demyelination. The diagnosis of PML was confirmed by a positive JC virus PCR result from the CSF. The patient was started on combination antiretroviral therapy (cART) and supportive measures to improve immune status. This case underscores the importance of considering PML in patients with new-onset neurological symptoms and immunosuppression.

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