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1.
Chemosphere ; 364: 143129, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39159762

RESUMEN

In this study, we investigated the interaction between arsenate (AsV) and phosphate (PO43-) in freshwater phytoplankton using single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS). This study aimed to elucidate the influence of varying PO43- concentrations on arsenic (As) uptake and distribution at the single-cell level, providing insights into intraspecies diversity. Two species of freshwater phytoplanktons, Scenedesmus acutus and Pediastrum duplex, were cultured under different concentrations of PO43- and AsV in a controlled laboratory environment. Scenedesmus acutus, a species with strong salt tolerance, and Pediastrum duplex, known for its weak salt tolerance, were selected based on their contrasting behaviors in previous studies. SC-ICP-MS revealed non-uniform uptake of As by individual phytoplankton cells, with distinct variations in response to PO43- availability. Arsenic uptake by both species declined with a high PO43- level after 7 days of exposure. However, after 14 days, As uptake increased in S. acutus with higher PO43- concentrations, but decreased in P. duplex. Moreover, our findings revealed differences in cell morphology and membrane integrity between the two species in response to AsV and various PO43- concentrations. S. acutus maintained cell integrity under all experimental culture conditions, whereas P. duplex experienced cell lysis at elevated AsV and PO43- concentrations. This study highlights the varying responses of freshwater phytoplankton to changes in AsV and PO43- levels and underscores the advantages of SC-ICP-MS over conventional ICP-MS in providing detailed, cellular level insights. These findings are crucial for understanding and managing As pollution in aquatic ecosystems.


Asunto(s)
Arseniatos , Agua Dulce , Espectrometría de Masas , Fosfatos , Fitoplancton , Contaminantes Químicos del Agua , Arseniatos/metabolismo , Fitoplancton/metabolismo , Fitoplancton/efectos de los fármacos , Fosfatos/metabolismo , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/análisis , Scenedesmus/metabolismo , Scenedesmus/efectos de los fármacos , Análisis de la Célula Individual/métodos , Arsénico/metabolismo
2.
Microbiol Spectr ; 12(10): e0397423, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39162545

RESUMEN

The increasing clinical significance of Mycobacterium abscessus is owed to its innate high-level, broad-spectrum resistance to antibiotics and therefore rapidly evolves as an important human pathogen. This warrants the identification of novel targets for aiding the discovery of new drugs or drug combinations to treat M. abscessus infections. This study is inspired by the drug-hypersensitive profile of a mutant M. abscessus (U14) with transposon insertion in MAB_1915. We validated the role of MAB_1915 in intrinsic drug resistance in M. abscessus by constructing a selectable marker-free in-frame deletion in MAB_1915 and complementing the mutant with the same or extended version of the gene and then followed by drug susceptibility testing. Judging by the putative function of MAB_1915, cell envelope permeability was studied by ethidium bromide accumulation assay and susceptibility testing against dyes and detergents. In this study, we established genetic evidence of the role of MAB_1915 in intrinsic resistance to rifampicin, rifabutin, linezolid, clarithromycin, vancomycin, and bedaquiline. Disruption of MAB_1915 has also been observed to cause a significant increase in cell envelope permeability in M. abscessus. Restoration of resistance is observed to depend on at least 27 base pairs upstream of the coding DNA sequence of MAB_1915. MAB_1915 could therefore be associated with cell envelope permeability, and hence its role in intrinsic resistance to multiple drugs in M. abscessus, which presents it as a novel target for future development of effective antimicrobials to overcome intrinsic drug resistance in M. abscessus. IMPORTANCE: This study reports the role of a putative fadD (MAB_1915) in innate resistance to multiple drugs by M. abscessus, hence identifying MAB_1915 as a valuable target and providing a baseline for further mechanistic studies and development of effective antimicrobials to check the high level of intrinsic resistance in this pathogen.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Mycobacterium abscessus/efectos de los fármacos , Mycobacterium abscessus/genética , Antibacterianos/farmacología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Humanos , Farmacorresistencia Bacteriana Múltiple/genética , Claritromicina/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Vancomicina/farmacología , Linezolid/farmacología , Diarilquinolinas/farmacología , Rifampin/farmacología , Elementos Transponibles de ADN
3.
Cureus ; 16(4): e57774, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38716020

RESUMEN

BACKGROUND: The incidence of traumatic vertebral artery injury (VAI) associated with cervical spine trauma varies widely in published trauma series. The primary aim of this study was to determine the incidence of traumatic VAI in patients who suffered cervical spine injuries by means of routine magnetic resonance imaging, and the secondary objective was to identify any associations with injury mechanism, level of injury, and neurologic injury severity.  Materials and methods: A retrospective review was conducted on 96 patients who suffered cervical spine fracture dislocation with or without an associated spinal cord injury (SCI) in Indian Spinal Injuries Center (ISIC), New Delhi, India from January 2013 to April 2023. Cervical magnetic resonance imaging (MRI) was used to diagnose VAI. Patient's age, sex, cervical injury level, mechanism of injury, neurologic level of injury, association with foraminal fracture, facet dislocation, and clinical sequelae of vertebral artery injury were analyzed. RESULTS: In this study, of 96 patients who met the inclusion criteria, 18 patients (18.75%) had VAI on the MRI study. Thirteen (72.22%) of the eighteen patients had right-sided injuries, four (22.22%) had left-sided injuries, and one (5.55%) had bilateral injuries. There was an associated SCI in every VAI patient. VAI was significantly more common in patients who had ASIA A (61%, n = 11) and ASIA B (22%, n = 4) injuries, and no VAI was noted in neurologically intact patients (p<0.001). The incidence of VAI was higher in the flexion distraction type of injury (n = 12, 66%). The most commonly involved cervical spine injury level was C5-C6 (27%, n = 5), followed by 22% (n = 4) at C4-C5 and C6-C7 levels. About 27.8% (n = 5) of VAI was associated with foraminal fractures, and 72% (n = 13) of VAI was associated with facet dislocations, of which 44% (n = 8) were bifacetal and 28% (n = 5) were unifacetal dislocations. On clinical symptoms, only one (5.56%) patient had a headache, and 17 (94.4%) had no clinical features due to VAI. CONCLUSION: The incidence of traumatic vertebral artery disease is not very uncommon and requires careful and meticulous screening and management. Otherwise, complications like pseudoaneurysm, neurologic deficit, late-onset hemorrhage, infarction, and death can happen. Mostly, it is associated with high-velocity injuries and neurological injuries. MRI can be used as a good screening tool, which can be aided by a CT angiogram or digital subtraction angiography for confirmation. Proper pre-operative evaluation of vascular injury in cervical spine fracture dislocation is very important for patient counseling, patient management, and surgical planning.

4.
Plant Dis ; 108(7): 2000-2005, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38213118

RESUMEN

The reniform nematode (Rotylenchulus reniformis Linford and Oliveira) adversely impacts the quality and quantity of sweetpotato storage roots. Management of R. reniformis in sweetpotato remains a challenge because host plant resistance is not available, fumigants are detrimental to the environment and health, and crop rotation is not effective. We screened a core set of 24 sweetpotato plant introductions (PIs) against R. reniformis. Four PIs were resistant, and 10 were moderately resistant to R. reniformis, suggesting these PIs can serve as sources of resistance for sweetpotato resistance breeding programs. PI 595869, PI 153907, and PI 599386 suppressed 83 to 89% egg production relative to the susceptible control 'Beauregard', and these PIs were employed in subsequent experiments to determine if their efficacy against R. reniformis can be further increased by applying nonfumigant nematicides oxamyl, fluopyram, and fluensulfone. A 34 to 93% suppression of nematode reproduction was achieved by the application of nonfumigant nematicides, with oxamyl providing the best suppression followed by fluopyram and fluensulfone. Although sweetpotato cultivars resistant to R. reniformis are currently not available and there is a need for the development of safer yet highly effective nonfumigant nematicides, results from the current study suggest that complementing host plant resistance with nonfumigant nematicides can serve as an important tool for effective and sustainable nematode management.


Asunto(s)
Antinematodos , Ipomoea batatas , Enfermedades de las Plantas , Ipomoea batatas/parasitología , Animales , Antinematodos/farmacología , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/prevención & control , Resistencia a la Enfermedad , Tylenchoidea/efectos de los fármacos , Tylenchoidea/fisiología , Interacciones Huésped-Parásitos/efectos de los fármacos
5.
J Med Chem ; 67(3): 1914-1931, 2024 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-38232131

RESUMEN

Decaprenylphosphoryl-ß-d-ribose oxidase (DprE1) is a promising target for treating tuberculosis (TB). Currently, most novel DprE1 inhibitors are discovered through high-throughput screening, while computer-aided drug design (CADD) strategies are expected to promote the discovery process. In this study, with the aid of structure-based virtual screening and computationally guided design, a series of novel scaffold N-(1-(6-oxo-1,6-dihydropyrimidine)-pyrazole) acetamide derivatives with significant antimycobacterial activities were identified. Among them, compounds LK-60 and LK-75 are capable of effectively suppressing the proliferation of Mtb with MICMtb values of 0.78-1.56 µM, comparable with isoniazid and much superior to the phase II candidate TBA-7371 (MICMtb = 12.5 µM). LK-60 is also the most active DprE1 inhibitor derived from CADD so far. Further studies confirmed their high affinity to DprE1, good safety profiles to gut microbiota and human cells, and synergy effects with either rifampicin or ethambutol, indicating their broad potential for clinical applications.


Asunto(s)
Mycobacterium tuberculosis , Humanos , Antituberculosos/farmacología , Oxidorreductasas de Alcohol , Pirazoles/farmacología , Acetamidas/farmacología , Proteínas Bacterianas
6.
BMC Res Notes ; 16(1): 303, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37908017

RESUMEN

Improved sanitation is indispensable to human health. However, lack of access to improved sanitation remains one of the most daunting public health challenges of the twenty-first century in Bangladesh. The aim of the study was to describe the trends in access to improved sanitation facilities following the inequity gap among households in different socioeconomic groups in Bangladesh. Data from the Bangladesh Demographic and Health Survey (BDHS) 2007, 2011, 2014, and 2017-18 were extracted for this study. Inequity in access to improved sanitation was calculated using rich-poor ratio and concentration index to determine the changes in inequity across the time period. In Bangladesh, the proportion of households with access to improved sanitation increased steadily from 25.4% to 45.4% between 2007 and 2014, but slightly decreased to 44.0% in 2017-18. Age, educational status, marital status of household head, household wealth index, household size, place of residence, division, and survey year were significantly associated with the utilisation of improved sanitation. There is a pro-rich situation, which means that utilisation of improved sanitation was more concentrated among the rich across all survey years (Concentration Index ranges: 0.40 to 0.27). The government and other relevant stakeholders should take initiatives considering inequity among different socioeconomic groups to ensure the use of improved sanitation facilities for all, hence achieving universal health coverage.


Asunto(s)
Composición Familiar , Saneamiento , Humanos , Bangladesh , Factores Socioeconómicos , Encuestas y Cuestionarios
7.
Pharmaceuticals (Basel) ; 16(11)2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-38004430

RESUMEN

The World Health Organization (WHO) reports that tuberculosis (TB) is one of the top 10 leading causes of global mortality. The increasing incidence of multidrug-resistant TB highlights the urgent need for an intensified quest to discover innovative anti-TB medications In this study, we investigated four new derivatives from the quinoxaline-2-carboxylic acid 1,4-dioxide class. New 3-methylquinoxaline 1,4-dioxides with a variation in substituents at positions 2 and 6(7) were synthesized via nucleophilic aromatic substitution with amines and assessed against a Mycobacteria spp. Compound 4 showed high antimycobacterial activity (1.25 µg/mL against M. tuberculosis) and low toxicity in vivo in mice. Selection and whole-genomic sequencing of spontaneous drug-resistant M. smegmatis mutants revealed a high number of single-nucleotide polymorphisms, confirming the predicted mode of action of the quinoxaline-2-carboxylic acid 1,4-dioxide 4 as a DNA-damaging agent. Subsequent reverse genetics methods confirmed that mutations in the genes MSMEG_4646, MSMEG_5122, and MSMEG_1380 mediate resistance to these compounds. Overall, the derivatives of quinoxaline-2-carboxylic acid 1,4-dioxide present a promising scaffold for the development of innovative antimycobacterial drugs.

8.
J Nematol ; 55(1): 20230025, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37284001

RESUMEN

Meloidogyne enterolobii is a highly aggressive quarantine pathogen which threatens the multibillion-dollar tobacco industry and is not manageable with the currently available management methods in tobacco. There is currently no known host plant resistance in tobacco and previous studies have shown that the lower level of the currently recommended rate of non-fumigant nematicides does not provide satisfactory management of M. enterolobii. The current study was conducted with the hypothesis that M. enterolobii can be better managed using a single soil application of the maximum allowed rate of non-fumigant nematicides. Treatments involved three non-fumigant chemical nematicides (oxamyl, fluopyram, and fluensulfone), a biological nematicide derived from Burkholderia, and a non-treated control. Fluensulfone significantly suppressed the nematode reproduction relative to the control, the suppression being 71% for eggs and 86% for the second stage juveniles (J2). Fluopyram also suppressed nematode reproduction, although this was statistically insignificant, with the suppression being 26% and 37% for eggs and J2, respectively. Oxamyl significantly suppressed J2 (80%), but not eggs (50%) in relation to the control. The most significant reduction of disease severity was achieved by the application of fluensulfone (64%), followed by oxamyl (54%) and fluopyram (48%). Except for fluensulfone, which significantly reduced the root biomass, none of the nematicides significantly impacted root and shoot biomass. The biological nematicide did not significantly affect nematode reproduction, pathogenicity, or disease severity. The results from the current study suggest that while the non-fumigant nematicides provided a good level of the nematode suppression, more research is needed to improve the efficacy of non-fumigant nematicides through employing better application methods or finding better chemistries.

9.
Cureus ; 15(2): e35235, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36825073

RESUMEN

Background For the treatment of unstable thoracolumbar fractures, this study compared the results of short-segment fixation with fracture level inclusion (SSFIFL) with long-segment pedicle fixation (LSPF). Methodology In this prospective case series study conducted from January 2015 to January 2019, 80 patients with partial spinal cord lesions were investigated. For the comparison, two groups of 40 patients each were chosen and treated with SSFIFL and LSPF. The outcomes were measured using pre and postoperative radiological parameters and clinical parameters. The radiographic variables included the kyphotic angle with loss of correction, kyphotic deformation, and the Beck index. Mean blood loss, operative time, and cost-effectiveness were also examined for clinical indicators such as the American Spinal Injury Association Impairment Scale, Visual Analog Scale (VAS), and Oswestry Disability Index (ODI). Results There were no substantial variations between the groups regarding age or gender, trauma etiology, fracture level, or fracture pattern. Between the two categories, there appeared to be no notable change in radiological indicators such as kyphotic angle, kyphotic deformation, and Beck index at the end of follow-up (p = 0.120, 0.360, and 0.776, respectively). Both groups had similar neurological outcomes (p = 0.781). In terms of ODI and VAS, statistically, there was no discernible difference (p = 0.567 and 0.161, respectively). In this study, however, there was less surgical time, blood loss, and implant cost (p = 0.05). Conclusions When fracture level is included in a short-segment fixation, the radiological and clinical results are comparable to long-segment posterior fixation. Ultimately, this treatment has proven to be not only a motion segment-saving procedure but also cost-effective.

10.
Cureus ; 15(2): e34787, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36777970

RESUMEN

Background Though there is ongoing controversy regarding the best treatment option for cervical spine dislocation (CSD), anterior cervical surgery with direct decompression is becoming widely accepted. However, managing all cases of subaxial CSD entirely by a single anterior approach is rarely seen in the published literature. Methods The study comprised patients with subaxial CSD who underwent surgical stabilization utilizing a single anterior approach. Most of the CSD was reduced and anterior cervical discectomy and fusion (ACDF) were performed. Anterior cervical corpectomy and fusion (ACCF) were done in unreduced dislocations. The patient's neurological condition, radiological findings, and functional outcomes were assessed. SPSS version 25.0 (IBM Corp., Armonk, NY) was used for statistical analysis. Results The total number of operated cases was 64, with an average of 42 months of follow-up. The mean age was 34.50±11.92 years. The most prevalent level of injury was C5/C6 (57.7%). Reduction was achieved in 92.2% of cases; only 7.8% of patients needed corpectomy. The typical operative time was 84.25±9.55 minutes, with an average blood loss of 112.12±25.27 ml. All cases except complete spinal cord injury (CSI) were improved neurologically (87.63%). The mean Neck Disability Index (NDI) was 11.14±11.43, and the pre-operative mean visual analog score (VAS) was finally improved to 2.05±0.98 (P<0.05). In all cases, fusion was achieved. The most common complication was transient dysphagia (23.4%). After surgery, no patient developed or aggravated a neurological impairment. Implant failure was not observed at the final follow-up except for two cases where screws were pulled out partially. Conclusion Based on the results of this study, a single anterior approach is a safe and effective procedure for subaxial CSD treatment with favorable radiological, neurological, and functional outcomes.

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