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Veterinary and Animal Science Sep 2024The emergence of serovars that produce extended-spectrum beta-lactamase and exhibit multi-drug resistance (MDR) poses a substantial global threat, contributing to...
The emergence of serovars that produce extended-spectrum beta-lactamase and exhibit multi-drug resistance (MDR) poses a substantial global threat, contributing to widespread foodborne illnesses and presenting an alarming issue for public health. This study specifically concentrated on the isolation and identification of ESBL-resistant genes ( ) and the antibiogram profiling of serovars found in goat meat samples procured from retail outlets in Bangladesh. During the research in the Sylhet district of Bangladesh, researchers gathered a total of 210 samples of goat meat from 13 different Upazilas. Primarily, cultural and biochemical methods were used for isolation of bacteria from the selected samples. serovars Typhimurium and Enteritidis, along with three ESBL-resistant genes, were identified through polymerase chain reactions (PCRs). The disk diffusion test was used to determine antimicrobial susceptibilities. Out of 210 samples analysed, spp was detected in 18.10 % (38 out of 210), with Enteritidis and Typhimurium found in 9.05 % (19 out of 210) and 5.24 % (11 out of 210) of the samples, respectively. A total of 72.73 % (8/11) of Enteritidis and 100 % (19/19) of Typhimurium isolates were positive by Multidrug-resistant patterns. The positive outcomes were found of Typhimurium tested 63.16 % (12 out of 19) for the gene and 21.05 % (4/19) for the gene. The study proposes that the retail goat meat market channel could be a prominent transmission way of ESBL-producing MDR serovars, representing a significant public health hazard.
PubMed: 38947184
DOI: 10.1016/j.vas.2024.100367 -
Research Square Jun 2024Nutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes and various...
Nutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes and various obesity-related morbidities. Among different metabolic regulatory signals, cytosolic Ca plays pivotal roles in metabolic regulation, including glycolysis, gluconeogenesis, and lipolysis. Recently, intercellular calcium waves (ICWs), the propagation of Ca signaling through tissues, have been found in different systems to coordinate multicellular responses. Nevertheless, our understanding of how ICWs are modulated and operate within living organisms remains limited. In this study, we explore the real-time dynamics, both in organ culture and free-behaving animals, of ICWs in larval and adult adipose tissues. We identified Adipokinetic hormone (AKH), the fly functional homolog of mammalian glucagon, as the key factor driving Ca activities in adipose tissue. Interestingly, we found that AKH, which is released in a pulsatile manner into the circulating hemolymph from the AKH-producing neurosecretory cells (APCs) in the brain, stimulates ICWs in the larval fat by a previously unrecognized gap-junction-independent mechanism to promote lipolysis. In the adult fat body, however, gap-junction-dependent random ICWs are triggered by a presumably uniformly diffused AKH. This highlights the stage-specific interplay of hormone secretion, extracellular diffusion, and intercellular communication in the regulation of Ca dynamics. Additionally, we discovered that specific dietary amino acids activate the APCs, leading to increased intracellular Ca and subsequent AKH secretion. Altogether, our findings identify that dietary amino acids regulate the release of AKH peptides from the APCs, which subsequently stimulates novel gap-junction-independent ICWs in adipose tissues, thereby enhancing lipid metabolism.
PubMed: 38947048
DOI: 10.21203/rs.3.rs-4493132/v1 -
MedRxiv : the Preprint Server For... Jun 2024Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative....
IMPORTANCE
Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. Distributed white matter (WM) impairments in individuals with heroin use disorder (iHUD) have been associated with increased drug craving, a reliable predictor of treatment outcomes. However, little is known about the extent of whole-brain structural connectivity changes with inpatient treatment and abstinence in iHUD.
OBJECTIVE
To assess WM microstructure and associations with drug craving changes with inpatient treatment in iHUD (effects of time/re-scan compared to controls; CTL).
DESIGN
Longitudinal cohort study (12/2020-09/2022) where iHUD and CTL underwent baseline magnetic resonance imaging (MRI#1) and follow-up (MRI#2) scans, (mean interval of 13.9 weeks in all participants combined).
SETTING
The iHUD and CTL were recruited from urban inpatient treatment facilities and surrounding communities, respectively.
PARTICIPANTS
Thirty-four iHUD (42.1yo; 7 women), 25 age-/sex-matched CTL (40.5yo; 9 women).
INTERVENTION
Between scans, inpatient iHUD continued their medically-assisted treatment and related clinical interventions. CTL participants were scanned at similar time intervals.
MAIN OUTCOMES AND MEASURES
Changes in white matter diffusion metrics [fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivities (RD)] in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance).
RESULTS
Main findings showed HUD-specific WM microstructure changes encompassing mostly frontal major callosal, projection, and association tracts, characterized by increased FA (.949<1- p<.986) and decreased MD (.949<1-p<.997) and RD (.949<1-p<.999). The increased FA (r=- 0.72, p<.00001) and decreased MD (r=0.69, p<.00001) and RD (r=0.67, p<.0001) in the genu and body of the corpus callosum and the left anterior corona radiata in iHUD were correlated with a reduction in baseline craving (.949<1-p<.999). No other WM correlations with outcome variables reached significance.
CONCLUSIONS AND RELEVANCE
Our findings suggest whole-brain normalization of structural connectivity with inpatient medically-assisted treatment in iHUD encompassing recovery in frontal WM pathways implicated in emotional regulation and top-down executive control. The association with decreases in baseline craving further supports the relevance of these WM markers to a major symptom in drug addiction, with implications for monitoring clinical outcomes.
KEY POINTS
Does white matter (WM) microstructure change with medication-assisted treatment in individuals with heroin use disorder (iHUD)? In this longitudinal cohort study, diffusion MRI was acquired in 34 inpatient iHUD and 25 healthy controls (CTL) twice, separated by a mean of 13.9 weeks. We found HUD- specific WM microstructure changes with time, characterized by increased anisotropy and decreased diffusivity in fronto-striatal WM pathways. These changes were correlated with decreased baseline drug craving with treatment. Frontal WM changes and associated drug craving decreases suggest brain-behavior recovery with inpatient treatment in iHUD, potentially contributing to reduced drug use and sustained abstinence.
PubMed: 38946983
DOI: 10.1101/2024.06.10.24308719 -
Research Square Jun 2024Despite advancements, the prevalence of HIV-associated neurocognitive impairment remains at approximately 40%, attributed to factors like pre-cART (combination...
Despite advancements, the prevalence of HIV-associated neurocognitive impairment remains at approximately 40%, attributed to factors like pre-cART (combination antiretroviral therapy) irreversible brain injury. People with HIV (PWH) treated with cART do not show significant neurocognitive changes over relatively short follow-up periods. However, quantitative neuroimaging may be able to detect ongoing subtle microstructural changes. This study aimed to investigate the sensitivity of tensor-valued diffusion encoding in detecting such changes in brain microstructural integrity in cART-treated PWH. Additionally, it explored relationships between these metrics, neurocognitive scores, and plasma levels of neurofilament light (NFL) chain and glial fibrillary acidic protein (GFAP). Using MRI at 3T, 24 PWH and 31 healthy controls underwent cross-sectional examination. The results revealed significant variations in b-tensor encoding metrics across white matter regions, with associations observed between these metrics, cognitive performance, and blood markers of neuronal and glial injury (NFL and GFAP). Moreover, a significant interaction between HIV status and imaging metrics was observed, particularly impacting total cognitive scores in both gray and white matter. These findings suggest that b-tensor encoding metrics offer heightened sensitivity in detecting subtle changes associated with axonal injury in HIV infection, underscoring their potential clinical relevance in understanding neurocognitive impairment in PWH.
PubMed: 38946952
DOI: 10.21203/rs.3.rs-4482269/v1 -
Molecular Therapy. Methods & Clinical... Jun 2024Alpha-mannosidosis is caused by a genetic deficiency of lysosomal alpha-mannosidase, leading to the widespread presence of storage lesions in the brain and other...
Alpha-mannosidosis is caused by a genetic deficiency of lysosomal alpha-mannosidase, leading to the widespread presence of storage lesions in the brain and other tissues. Enzyme replacement therapy is available but is not approved for treating the CNS, since the enzyme does not penetrate the blood-brain barrier. However, intellectual disability is a major manifestation of the disease; thus, a complimentary treatment is needed. While enzyme replacement therapy into the brain is technically feasible, it requires ports and frequent administration over time that are difficult to manage medically. Infusion of adeno-associated viral vectors into the cerebrospinal fluid is an attractive route for broadly targeting brain cells. We demonstrate here the widespread post-symptomatic correction of the globally distributed storage lesions by infusion of a high dose of AAV1-feline alpha-mannosidase (fMANB) into the CSF via the cisterna magna in the gyrencephalic alpha-mannosidosis cat brain. Significant improvements in clinical parameters occurred, and widespread global correction was documented pre-mortem by non-invasive magnetic resonance imaging. Postmortem analysis demonstrated high levels of MANB activity and reversal of lysosomal storage lesions throughout the brain. Thus, CSF treatment by adeno-associated viral vector gene therapy appears to be a suitable complement to systemic enzyme replacement therapy to potentially treat the whole patient.
PubMed: 38946937
DOI: 10.1016/j.omtm.2024.101272 -
Neuro-oncology Advances 2024Primary CNS lymphoma (PCNSL) and glioblastoma (GBM) both represent frequent intracranial malignancies with differing clinical management. However, distinguishing PCNSL...
BACKGROUND
Primary CNS lymphoma (PCNSL) and glioblastoma (GBM) both represent frequent intracranial malignancies with differing clinical management. However, distinguishing PCNSL from GBM with conventional MRI can be challenging when atypical imaging features are present. We employed advanced dMRI for noninvasive characterization of the microstructure of PCNSL and differentiation from GBM as the most frequent primary brain malignancy.
METHODS
Multiple dMRI metrics including Diffusion Tensor Imaging, Neurite Orientation Dispersion and Density Imaging, and Diffusion Microstructure Imaging were extracted from the contrast-enhancing tumor component in 10 PCNSL and 10 age-matched GBM on 3T MRI. Imaging findings were correlated with cell density and axonal markers obtained from histopathology.
RESULTS
We found significantly increased intra-axonal volume fractions (V-intra and intracellular volume fraction) and microFA in PCNSL compared to GBM (all < .001). In contrast, mean diffusivity (MD), axial diffusivity (aD), and microADC (all < .001), and also free water fractions (V-CSF and V-ISO) were significantly lower in PCNSL (all < .01). Receiver-operating characteristic analysis revealed high predictive values regarding the presence of a PCNSL for MD, aD, microADC, V-intra, ICVF, microFA, V-CSF, and V-ISO (area under the curve [AUC] in all >0.840, highest for MD and ICVF with an AUC of 0.960). Comparative histopathology between PCNSL and GBM revealed a significantly increased cell density in PCNSL and the presence of axonal remnants in a higher proportion of samples.
CONCLUSIONS
Advanced diffusion imaging enables the characterization of the microstructure of PCNSL and reliably distinguishes PCNSL from GBM. Both imaging and histopathology revealed a relatively increased cell density and a preserved axonal microstructure in PCNSL.
PubMed: 38946879
DOI: 10.1093/noajnl/vdae093 -
Neuro-oncology Advances 2024The treatment timing and choice after neurosurgical resection in patients with newly diagnosed diffuse low-grade glioma (DLGG) remain controversial. Indeed, the effect...
BACKGROUND
The treatment timing and choice after neurosurgical resection in patients with newly diagnosed diffuse low-grade glioma (DLGG) remain controversial. Indeed, the effect of such treatments must be balanced with the possible side effects. This study evaluated the feasibility of longitudinal exhaustive quality of life (QoL) and neuropsychological assessments in patients with DLGG receiving first-line temozolomide.
METHODS
QoL, neurocognition, and psychological disorders were assessed prospectively until disease progression, using testing, clinician-reported, and self-reported questionnaires. The primary endpoint was the participation and adherence to this complete assessment at (before temozolomide initiation), months 6 and 12 of treatment, and month 6 post-treatment. The QoL and neuropsychological changes over time also were described.
RESULTS
Twenty-six of the twenty-nine eligible patients were enrolled (participation rate: 89.7%, 95% CI: 72.6-97.8). The adherence rate was 95.7% (95% CI: 78.1-99.9; = 23 because 3 patients progressed in the first 12 months of treatment). Up to month 6 post-treatment, QoL and fatigue remained stable (EORTC QLQC30 and BN20, MFI-20); some specific symptoms were transitory. Both subjective (FACT-Cog) and objective (Z-scores of neurocognitive tests) neurocognitive outcomes remained stable or tended to improve. The percentage of patients with severe depression (BDI-II), anxiety (STAI-Y), or anger (STAXI-II) was stable over time.
CONCLUSIONS
This prospective study demonstrated the feasibility of an exhaustive and longitudinal evaluation of QoL, neurocognition, and psychological disorders, with high acceptability by patients with DLGG undergoing chemotherapy. First-line temozolomide seems to have limited short-term effects on QoL and neurocognition. These findings must be confirmed in the long term and in a larger cohort.
PubMed: 38946878
DOI: 10.1093/noajnl/vdae084 -
RSC Advances Jun 2024Halogen-halogen interactions play a pivotal role in the formation and stability of supramolecular assemblies. Herein, we investigate the assembly dynamics and...
Halogen-halogen interactions play a pivotal role in the formation and stability of supramolecular assemblies. Herein, we investigate the assembly dynamics and dissociation pathways of linear supramolecular polymers based on pillar[5]arene-mediated by guest halogen-halogen interactions (C-X × X-C) in both the solution and solid states. The structure of the solid-state supramolecular assembly was determined by single-crystal X-ray diffraction analysis. The binding affinities of four different 1,4-dihalobutane guests with pillar[5]arene were investigated by H NMR spectroscopic titration and isothermal titration calorimetry (ITC). The formation of the halogen-bonded linear supramolecular polymer in solution was demonstrated using diffusion-ordered spectroscopy (DOSY) and ITC. Our findings highlight the dependence of the dissociation process on halogen nature within the encapsulated guest, revealing that the process is entropically driven (Δ = 27.12 kJ mol) and enthalpically disfavored (Δ = 9.99 kJ mol). Moreover, the disassembly of supramolecular polymers promoted by N-containing compounds was investigated using H NMR spectroscopy and ITC, revealing that the process is driven both enthalpically (Δ = -2.64 kJ mol) and entropically (Δ = 15.70 kJ mol). Notably, the data suggest the formation of N⋯I bonding interactions at both ends of the inclusion guest, elucidating the intricate interplay of halogen interactions and host-guest chemistry in supramolecular polymer systems.
PubMed: 38946765
DOI: 10.1039/d4ra03769c -
RSC Advances Jun 2024With the aim to resolve the problem of water pollution, we herein propose a new photocatalyst based on metal-organic frameworks (MOFs), called La-doped MIL-88B(Fe)-NH...
With the aim to resolve the problem of water pollution, we herein propose a new photocatalyst based on metal-organic frameworks (MOFs), called La-doped MIL-88B(Fe)-NH (MIL-88B((1 - )Fe/La)-NH), which was designed and employed for the photocatalytic reduction of Cr(vi) in aqueous solutions. MIL-88B((1-)Fe/La)-NH materials with different values were synthesized a one-pot solvothermal method. Their characteristics were investigated using various techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), Brunauer-Emmett-Teller (BET) analysis, Fourier-transform infrared (FT-IR) spectroscopy and ultraviolet-visible diffuse reflectance spectroscopy (UV-vis DRS). We found that compared to pristine MIL-88B(Fe)-NH with a photocatalytic efficiency of 67.08, MIL-88B((1 - )Fe/La)-NH materials with = 0.010, 0.025 and 0.050 exhibit excellent photocatalytic efficiencies reaching 88.21, 81.19 and 80.26%, respectively, after only 30 minutes of irradiation at a small catalyst dosage of 0.2 g L. These La-doped MIL-88B(Fe)-NH photocatalysts can work well under mild conditions (pH = 6). Furthermore, they are robust-can be recycled for at least four consecutive runs without any activity loss. This novel material is promising for the photocatalytic degradation of pollutants.
PubMed: 38946761
DOI: 10.1039/d4ra03351e -
CNS Neuroscience & Therapeutics Jul 2024Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its...
OBJECTIVE
Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its infrequency, there is limited research on its characteristics.
METHODS
This study aims to present three cases of WD of MCPs following pontine infarction and to analyze the prognosis, clinical manifestations, and neuroimaging features by amalgamating our cases with previously reported ones.
RESULTS
The cohort consisted of 25 cases, comprising 18 men and 7 women aged 29 to 77 years (mean age: 66.2 years). The majority of patients (94%) exhibit risk factors for cerebrovascular disease, with hypertension being the primary risk factor. Magnetic resonance imaging (MRI) can detect WD of MCPs within a range of 21 days to 12 months following pontine infarction. This degeneration is characterized by bilateral symmetric hyperintensities on T2/FLAIR-weighted images (WI) lesions in the MCPs. Moreover, restricted diffusion, with hyperintensity on diffusion-weighted imaging (DWI) and low apparent diffusion coefficient (ADC) signal intensity may be observed as early as 21 days after the infarction. Upon detection of WD, it was observed that 20 patients (80%) remained asymptomatic during subsequent clinic visits, while four (16%) experienced a worsening of pre-existing symptoms.
CONCLUSIONS
These findings underscore the importance of neurologists enhancing their understanding of this condition by gaining fresh insights into the neuroimaging characteristics, clinical manifestations, and prognosis of individuals with WD of bilateral MCPs.
Topics: Humans; Male; Female; Middle Aged; Aged; Adult; Wallerian Degeneration; Pons; Brain Stem Infarctions; Middle Cerebellar Peduncle; Magnetic Resonance Imaging; Neuroimaging
PubMed: 38946709
DOI: 10.1111/cns.14828