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1.
Proc Natl Acad Sci U S A ; 121(11): e2310044121, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38446857

ABSTRACT

We present a comprehensive study on the non-invasive measurement of hippocampal perfusion. Using high-resolution 7 tesla arterial spin labeling (ASL) data, we generated robust perfusion maps and observed significant variations in perfusion among hippocampal subfields, with CA1 exhibiting the lowest perfusion levels. Notably, these perfusion differences were robust and already detectable with 50 perfusion-weighted images per subject, acquired in 5 min. To understand the underlying factors, we examined the influence of image quality metrics, various tissue microstructure and morphometric properties, macrovasculature, and cytoarchitecture. We observed higher perfusion in regions located closer to arteries, demonstrating the influence of vascular proximity on hippocampal perfusion. Moreover, ex vivo cytoarchitectonic features based on neuronal density differences appeared to correlate stronger with hippocampal perfusion than morphometric measures like gray matter thickness. These findings emphasize the interplay between microvasculature, macrovasculature, and metabolic demand in shaping hippocampal perfusion. Our study expands the current understanding of hippocampal physiology and its relevance to neurological disorders. By providing in vivo evidence of perfusion differences between hippocampal subfields, our findings have implications for diagnosis and potential therapeutic interventions. In conclusion, our study provides a valuable resource for extensively characterizing hippocampal perfusion.


Subject(s)
Arteries , Benchmarking , Perfusion , Hippocampus/diagnostic imaging , Magnetic Resonance Imaging
2.
J Neurosci ; 44(23)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839341

ABSTRACT

The hippocampus is a brain structure that plays key roles in a variety of cognitive processes. Critically, a wide range of neurological disorders are associated with degeneration of the hippocampal microstructure, defined as neurons, dendrites, glial cells, and more. Thus, the hippocampus is a key target for methods that are sensitive to these microscale properties. Diffusion MRI is one such method, which can noninvasively probe neural architecture. Here we review the extensive use of diffusion MRI to capture hippocampal microstructure in both health and disease. The results of these studies indicate that (1) diffusion tensor imaging is sensitive but not specific to the hippocampal microstructure; (2) biophysical modeling of diffusion MRI signals is a promising avenue to capture more specific aspects of the hippocampal microstructure; (3) use of ultra-short diffusion times have shown unique laminar-specific microstructure and response to hippocampal injury; (4) dispersion of microstructure is likely abundant in the hippocampus; and (5) the angular richness of the diffusion MRI signal can be leveraged to improve delineation of the internal hippocampal circuitry. Overall, extant findings suggest that diffusion MRI offers a promising avenue for characterizing hippocampal microstructure.


Subject(s)
Diffusion Magnetic Resonance Imaging , Hippocampus , Hippocampus/diagnostic imaging , Humans , Diffusion Magnetic Resonance Imaging/methods , Animals
3.
J Neurochem ; 168(4): 397-413, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37864501

ABSTRACT

The basal forebrain cholinergic neurons provide acetylcholine to the cortex via large projections. Recent molecular imaging work in humans indicates that the cortical cholinergic innervation is not uniformly distributed, but rather may disproportionately innervate cortical areas relevant to supervisory attention. In this study, we therefore reexamined the spatial relationship between acetylcholinergic modulation and attention in the human cortex using meta-analytic strategies targeting both pharmacological and non-pharmacological neuroimaging studies. We found that pharmaco-modulation of acetylcholine evoked both increased activity in the anterior cingulate and decreased activity in the opercular and insular cortex. In large independent meta-analyses of non-pharmacological neuroimaging research, we demonstrate that during attentional engagement these cortical areas exhibit (1) task-related co-activation with the basal forebrain, (2) task-related co-activation with one another, and (3) spatial overlap with dense cholinergic innervations originating from the basal forebrain, as estimated by multimodal positron emission tomography and magnetic resonance imaging. Finally, we provide meta-analytic evidence that pharmaco-modulation of acetylcholine also induces a speeding of responses to targets with no apparent tradeoff in accuracy. In sum, we demonstrate in humans that acetylcholinergic modulation of midcingulo-insular hubs of the ventral attention/salience network via basal forebrain afferents may coordinate selection of task relevant information, thereby facilitating cognition and behavior.


Subject(s)
Acetylcholine , Attention , Humans , Cognition/physiology , Neuroimaging , Cholinergic Agents/pharmacology
4.
Chemistry ; 30(19): e202303369, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38258609

ABSTRACT

We demonstrate supramolecular polymerization and formation of 1D nanofiber of azobenzene based organogelator (AZO-4) in cyclic hydrocarbon solvents (toluene and methylcyclohexane). The AZO-4 exhibits J- and H-type aggregates in toluene: MCH (9 : 1) and MCH: toluene (9 : 1) respectively. The type of aggregate was governed by the geometry of the solvents used in the self-assembly process. The J-type aggregates with high thermal stability in toluene is due to the enhanced interaction of AZO-4 π- surface with the toluene π-surface, whereas H-aggregate with moderate thermal stability in MCH was due to the interruption of the cyclic hydrocarbon in van der Waals interactions of peripheral chains of AZO-4 molecule. The light induced reversible photoisomerization is observed for both J- and H-aggregates. The macroscopic property revealed spontaneous and strong gelation in toluene preferably due to the strong interactions of the AZO-4 nanofibers with the toluene solvent molecules compared to the MCH. The rheological measurements revealed thixotropic nature of the gels by step-strain experiments at room temperature. The thermodynamic parameter (ΔHm) of gel-to-sol transition was determined for all the gels to get more insight into the gelation property. Furthermore, the phase selective gelation property was extended to the oil spill recovery application using diesel/water and petrol/water mixture.

5.
Theor Appl Genet ; 137(6): 136, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38764078

ABSTRACT

KEY MESSAGE: Different kinship and resistance to cotton leaf curl disease (CLCuD) and heat were found between upland cotton cultivars from China and Pakistan. 175 SNPs and 82 InDels loci related to yield, fiber quality, CLCuD, and heat resistance were identified. Elite alleles found in Pakistani accessions aided local adaptation to climatic condition of two countries. Adaptation of upland cotton (Gossypium hirsutum) beyond its center of origin is expected to be driven by tailoring of the genome and genes to enhance yield and quality in new ecological niches. Here, resequencing of 456 upland cotton accessions revealed two distinct kinships according to the associated country. Fiber quality and lint percentage were consistent across kinships, but resistance to cotton leaf curl disease (CLCuD) and heat was distinctly exhibited by accessions from Pakistan, illustrating highly local adaption. A total of 175 SNP and 82 InDel loci related to yield, fiber quality, CLCuD and heat resistance were identified; among them, only two overlapped between Pakistani and Chinese accessions underscoring the divergent domestication and improvement targets in each country. Loci associated with resistance alleles to leaf curl disease and high temperature were largely found in Pakistani accessions to counter these stresses prevalent in Pakistan. These results revealed that breeding activities led to the accumulation of unique alleles and helped upland cotton become adapted to the respective climatic conditions, which will contribute to elucidating the genetic mechanisms that underlie resilience traits and help develop climate-resilient cotton cultivars for use worldwide.


Subject(s)
Gossypium , Polymorphism, Single Nucleotide , Gossypium/genetics , Pakistan , China , Disease Resistance/genetics , Plant Diseases/genetics , INDEL Mutation , Adaptation, Physiological/genetics , Genome, Plant , Alleles , Plant Breeding , Cotton Fiber , Phenotype
6.
J Chem Phys ; 161(6)2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39136661

ABSTRACT

A reduced pressure glow discharge is produced by passing a high-power pulsed DC source of 0-500 W with a frequency of 50 Hz across two parallel disk electrodes. A hydrogen peroxide aqueous solution is used as a flowing gas for discharge generation. Optical emission spectroscopy is employed to diagnose the discharge generated at a reduced pressure of 0.2 mbar with an electrode gap of 4 cm. The spectra are recorded at a power density of 9.4 mW/cm3 and typically lie in the visible wavelength range of 380-880 nm. The spectra are analyzed using the line intensity ratio method to estimate electron temperature and density. The results indicated that the electron temperature and density are, respectively, 0.87 eV and 6.4 × 1014 cm-3.

7.
Plant Cell Rep ; 43(3): 65, 2024 Feb 10.
Article in English | MEDLINE | ID: mdl-38341396

ABSTRACT

Microplastic pollution has emerged as a critical global environmental issue due to its widespread distribution, persistence, and potential adverse effects on ecosystems and human health. Although research on microplastic pollution in aquatic environments has gained significant attention. However, a limited literature has summarized the impacts of microplastic pollution the agricultural land and human health. Therefore, In the current review, we have discussed how microplastic(s) affect the microorganisms by ingesting the microplastic present in the soil, alternatively affecting the belowground biotic and abiotic components, which further elucidates the negative effects on the above-ground properties of the crops. In addition, the consumption of these crops in the food chain revealed a potential risk to human health throughout the food chain. Moreover, microplastic pollution has the potential to induce a negative impact on agricultural production and food security by altering the physiochemical properties of the soil, microbial population, nutrient cycling, and plant growth and development. Therefore, we discussed in detail the potential hazards caused by microplastic contamination in the soil and through the consumption of food and water by humans in daily intake. Furthermore, further study is urgently required to comprehend how microplastic pollution negatively affects terrestrial ecosystems, particularly agroecosystems which drastically reduces the productivity of the crops. Our review highlights the urgent need for greater awareness, policy interventions, and technological solutions to address the emerging threat of microplastic pollution in soil and plant systems and mitigation strategies to overcome its potential impacts on human health. Based on existing studies, we have pointed out the research gaps and proposed different directions for future research.


Subject(s)
Metals, Heavy , Microplastics , Humans , Microplastics/toxicity , Soil/chemistry , Plastics , Ecosystem , Metals, Heavy/toxicity , Crops, Agricultural
8.
Eur Spine J ; 33(1): 133-154, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37926719

ABSTRACT

PURPOSE: Cervical Spondylotic Myelopathy (CSM) is a degenerative condition that leads to loss of cervical spinal cord (CSC) integrity. Various spinal cord Magnetic Resonance Imaging (MRI) methods can identify and characterize the extent of this damage. This systematic review aimed to evaluate the diagnostic, biomarker, and predictive utilities of different spinal cord MRI methods in clinical research studies of CSM. The aim was to provide a comprehensive understanding of the progress in this direction for future studies and effective diagnosis and management of CSM. METHODS: A comprehensive literature search was conducted on PubMed and EMBASE from 2010 to 2022 according to PRISMA guidelines. Studies with non-human subjects, less than 3T magnetic field strength, non-clinical design, or not quantitatively focusing on the structural integrity of CSC were excluded. The extracted data from each study included demographics, disease severity, MRI machine characteristics, quantitative metrics, and key findings in terms of diagnostic, biomarker, and predictive utilities of each MRI method. The risk of bias was performed using the guide from AHRQ. The quality of evidence was assessed separately for each type of utility for different MRI methods using GRADE. RESULTS: Forty-seven studies met the inclusion criteria, utilizing diffusion-weighted imaging (DTI) (n = 39), magnetization transfer (MT) (n = 6), MR spectroscopy (n = 3), and myelin water imaging (n = 1), as well as a combination of MRI methods (n = 12). The metric fractional anisotropy (FA) showed the highest potential in all facets of utilities, followed by mean diffusivity. Other promising metrics included MT ratio and intracellular volume fraction, especially in multimodal studies. However, the level of evidence for these promising metrics was low due to a small number of studies. Some studies, mainly DTI, also reported the usefulness of spinal cord MRI in mild CSM. CONCLUSIONS: Spinal cord MRI methods can potentially facilitate the diagnosis and management of CSM by quantitatively interrogating the structural integrity of CSC. DTI is the most promising MRI method, and other techniques have also shown promise, especially in multimodal configurations. However, this field is in its early stages, and more studies are needed to establish the usefulness of spinal cord MRI in CSM.


Subject(s)
Spinal Cord Diseases , Spondylosis , Humans , Diffusion Tensor Imaging/methods , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/etiology , Spinal Cord Diseases/pathology , Spinal Cord/pathology , Magnetic Resonance Imaging , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/pathology , Biomarkers , Spondylosis/complications , Spondylosis/diagnostic imaging , Spondylosis/pathology
9.
Spinal Cord ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39354176

ABSTRACT

STUDY DESIGN: Cross-sectional study. OBJECTIVES: This study's goal is to report whether Magnetization Transfer Ratio (MTR) can evaluate the severity of white matter (WM) injury in degenerative cervical myelopathy (DCM). SETTING: Laureate Institute of Brain Research, USA; Department of Neurosurgery, University of Oklahoma Health Sciences Center, USA. METHODS: 27 DCM patients were aged-matched with 20 healthy controls (HC) and categorized into treatment groups based on modified Japanese Orthopedic Association (mJOA) severity (11 mild and 16 moderate/severe). Regional and tract MTRs were extracted from the two vertebral levels containing maximum compression within magnetization transfer images. MTR differences between groups were assessed using a one-way ANOVA or Kruskal-Wallis test. The association between MTR and mJOA measures was evaluated using Spearman's correlation. RESULTS: Significant decreases in MTR were found between HC and moderate/severe groups in the overall (p = 0.0065) and ventral (p = 0.0009) WM regions; and ventral corticospinal (p = 0.0101), ventral reticulospinal (p = 0.0084), spinal lemniscus (p = 0.0079), and fasciculus cuneatus (p = 0.0219) tracts. The spinal lemniscus MTR also significantly decreased between HC and mild groups (p = 0.038). Ventral reticulospinal tract MTR correlated with upper (r = 0.439; p = 0.022) and lower (r = 0.386; p = 0.047) limb motor mJOA scores. CONCLUSIONS: Significant tract-based MTR changes and correlations align with known DCM symptoms, are demonstrated to be lost at the regional level, and display the inhomogeneous compressive damage occurring within DCM spinal cords.

10.
Instr Course Lect ; 73: 651-664, 2024.
Article in English | MEDLINE | ID: mdl-38090931

ABSTRACT

Multiple approaches for instrumentation of the upper cervical spine have evolved to treat atlantoaxial instability which, until the 20th century, was largely considered to be inoperable and managed nonsurgically with immobilization. Surgeons set out to provide safe and effective approaches in a clearly dangerous and technically complex anatomic region. It is important to provide a historical analysis of the evolution of techniques that have shaped C1-C2 instrumentation, and how the diligent efforts of surgeons to improve the biomechanical stability and fusion rates of their constructs eventually led to the prevailing Harms technique. This technique is explored by describing its surgical steps, alternative techniques, and associated outcomes. For successful instrumentation of the atlantoaxial joint, a comprehensive understanding of spinal biomechanics, surgical techniques, and anatomic variations is imperative for surgeons to develop a tailored plan for each patient's individual pathology and anatomy.


Subject(s)
Atlanto-Axial Joint , Joint Instability , Spinal Fusion , Humans , Spinal Fusion/methods , Bone Screws , Cervical Vertebrae/surgery , Atlanto-Axial Joint/surgery , Joint Instability/surgery
11.
Surgeon ; 22(5): e164-e170, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38789384

ABSTRACT

BACKGROUND AND OBJECTIVES: Acute appendicitis is one of the most commonly encountered surgical emergencies on a global level. Due to the requirement of an immediate clinical diagnosis and the presence of limited resources, clinicians and diagnosticians refer to scoring systems to diagnose this condition, among which Alvarado and Tzanakis scoring systems are widely used. This meta-analysis aims to compare the diagnostic accuracy of these two systems. METHODS: We searched PubMed, Google Scholar, and SCOPUS databases. All studies that reported diagnostic parameters of Alvarado and Tzanakis scores in patients with suspected acute appendicitis were selected. Diagnostic values such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were extracted from the selected studies and statistical analysis was performed with Meta Disc 1.4 software. Quality assessment of the selected studies was performed using the QUADAS-2 and QUADAS-C tools. Fourteen studies were included in our meta-analysis which enrolled 2235 patients. RESULTS: The overall sensitivity of the Tzanakis score was calculated as 0.86 (95% CI; 0.84-00.87) while the specificity was 0.73 (95% CI; 0.69-0.78). In addition, the area under the curve (AUC) was 0.9261 (SE; 0.0169) and the diagnostic Odds Ratio (OR) was 22.52 (95% CI; 9.47-53.56). The pooled sensitivity of Alvarado score was 0.67 (95% CI; 0.65-0.69) and the specificity was 0.74 (95% CI; 0.69-0.79). Moreover, the area under the curve (AUC) of the Alvarado score was 0.7389 (SE; 0.0489) and the diagnostic Odds Ratio was 4.92 (95% CI; 2.48-9.75). INTERPRETATION AND CONCLUSION: The Tzanakis scoring system has a higher sensitivity, area under the curve, and diagnostic odds ratio when compared to the Alvarado score. However, the Alvarado score has a marginally better specificity making it more reliable in excluding acute appendicitis.


Subject(s)
Appendicitis , Humans , Acute Disease , Appendicitis/diagnosis , Appendicitis/surgery , Sensitivity and Specificity
12.
J Relig Health ; 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38581542

ABSTRACT

The purpose of the study was to construct and validate a Belief in Divine Retribution Scale for the Pakistani Muslim population. The process of construction and validation was completed by following standardized guidelines for scale construction (Boateng et al., 2018). The present study was carried out in four phases. In phase I, the task of item generation was completed through literature review and interviews (inductive and deductive approaches). Phase II aimed at exploration of factor structure. Exploratory factor analysis was carried out on a sample of seven hundred Muslim participants. Data for EFA were collected through a purposive sampling technique, which comprised both men (n = 339) and women (n = 361) with an age range of 18 to 69 years. Results of EFA revealed a two-factor structure with a cumulative variance of 42.59 and with a Cronbach alpha reliability of .83. To confirm the obtained factor structure, Phase III was carried out on a sample of three hundred Muslim participants. The results of CFA confirmed the two-dimensional factor structure with a good model fit to the data. Phase IV provided evidence of convergent and discriminant validity of the scale. Moreover, data for validation were collected from an independent sample (N = 204). Finally, the results of validation revealed that there exists a significant positive correlation of Belief in Divine Retribution Scale with Belief in Just World Scale, which provided evidence of convergent validity. However, there exists a non-significant correlation of Belief in Divine Retribution Scale with Religious Practice Subscale of Short Muslim Practice and Belief Scale, and it provided evidence of discriminant validity. Implications along with limitations and suggestions for future research have also been mentioned.

13.
Int J Cancer ; 152(11): 2410-2423, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36602287

ABSTRACT

Breast cancer (luminal and triple-negative breast cancer [TNBC]) is the most common cancer among women in India and worldwide. Altered sphingolipid levels have emerged as a common phenomenon during cancer progression. However, these alterations are yet to be translated into robust diagnostic and prognostic markers for cancer. Here, we present the quantified sphingolipids of tumor and adjacent-normal tissues from patients of luminal (n = 70) and TNBC (n = 42) subtype from an Indian cohort using targeted liquid chromatography mass spectrometry. We recorded unique sphingolipid profiles that distinguished luminal and TNBC tumors in comparison to adjacent normal tissue by six-sphingolipid signatures. Moreover, systematic comparison of the profiles of luminal and TNBC tumors provided a unique five-sphingolipid signature distinguishing the two subtypes. We further identified key sphingolipids that can stratify grade II and grade III tumors of luminal and TNBC subtype as well as their lymphovascular invasion status. Therefore, we provide the right evidence to develop these candidate sphingolipids as widely acceptable marker/s capable of diagnosing luminal vs TNBC subtype of breast cancer, and predicting the disease severity by identifying the tumor grade.


Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Triple Negative Breast Neoplasms/pathology , Breast Neoplasms/pathology , Sphingolipids , Neoplasm Recurrence, Local , Receptors, Estrogen , Receptors, Progesterone , Biomarkers, Tumor/analysis
14.
Plant Cell Physiol ; 64(6): 686-699, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37036744

ABSTRACT

Reactive oxygen species (ROS) are highly reactive molecules, generated by nicotinamide adenine dinucleotide phosphate oxidases encoded by respiratory burst oxidase homologs. The functions of the OsRbohs gene family in rice are diverse and poorly understood. OsRbohI was recently identified as a newly evolved gene in the rice OsRbohs gene family. However, the function of OsRbohI in regulating rice growth is not yet reported. In this study, our results indicate that knockout (KO) OsRbohI mutants showed significantly shorter shoot and primary roots, along with lower ROS content than the control lines, whereas the overexpression (OE) lines displayed contrasting results. Further experiments showed that the abnormal length of the shoot and root is mainly caused by altered cell size. These results indicate that OsRbohI regulates rice shoot and root growth through the ROS signal. More importantly, RNA-seq analysis and jasmonic acid (JA) treatment demonstrated that OsRbohI regulates rice growth via the JA synthesis and signaling pathways. Compared with the control, the results showed that the KO mutants were more sensitive to JA, whereas the OE lines were less sensitive to JA. Collectively, our results reveal a novel pathway in which OsRbohI regulates rice growth and development by affecting their ROS homeostasis through JA synthesis and signaling pathway.


Subject(s)
Oryza , Plant Proteins , Plant Proteins/genetics , Plant Proteins/metabolism , Oryza/metabolism , Reactive Oxygen Species/metabolism , Plant Roots/metabolism , Oxylipins/pharmacology , Oxylipins/metabolism , Cyclopentanes/pharmacology , Cyclopentanes/metabolism , Signal Transduction , Growth and Development , Gene Expression Regulation, Plant
15.
Hum Brain Mapp ; 44(16): 5485-5503, 2023 11.
Article in English | MEDLINE | ID: mdl-37615057

ABSTRACT

The hippocampus is classically divided into mesoscopic subfields which contain varying microstructure that contribute to their unique functional roles. It has been challenging to characterize this microstructure with current magnetic resonance based neuroimaging techniques. In this work, we used diffusion magnetic resonance imaging (dMRI) and a novel surface-based approach in the hippocampus which revealed distinct microstructural distributions of neurite density and dispersion, T1w/T2w ratio as a proxy for myelin content, fractional anisotropy, and mean diffusivity. We used the neurite orientation dispersion and density imaging (NODDI) model optimized for grey matter diffusivity to characterize neurite density and dispersion. We found that neurite dispersion was highest in the cornu ammonis (CA) 1 and subiculum subfields which likely captures the large heterogeneity of tangential and radial fibres, such as the Schaffer collaterals, perforant path, and pyramidal neurons. Neurite density and T1w/T2w were highest in the subiculum and CA3 and lowest in CA1, which may reflect known myeloarchitectonic differences between these subfields. Using a simple logistic regression model, we showed that neurite density, dispersion, and T1w/T2w measures were separable across the subfields, suggesting that they may be sensitive to the known variability in subfield cyto- and myeloarchitecture. We report macrostructural measures of gyrification, thickness, and curvature that were in line with ex vivo descriptions of hippocampal anatomy. We employed a multivariate orthogonal projective non-negative matrix factorization (OPNNMF) approach to capture co-varying regions of macro- and microstructure across the hippocampus. The clusters were highly variable along the medial-lateral (proximal-distal) direction, likely reflecting known differences in morphology, cytoarchitectonic profiles, and connectivity. Finally, we show that by examining the main direction of diffusion relative to canonical hippocampal axes, we could identify regions with stereotyped microstructural orientations that may map onto specific fibre pathways, such as the Schaffer collaterals, perforant path, fimbria, and alveus. These results highlight the value of combining in vivo dMRI with computational approaches for capturing hippocampal microstructure, which may provide useful features for understanding cognition and for diagnosis of disease states.


Subject(s)
Diffusion Tensor Imaging , White Matter , Humans , Diffusion Tensor Imaging/methods , Diffusion Magnetic Resonance Imaging/methods , Neuroimaging/methods , Hippocampus/diagnostic imaging , Hippocampus/pathology , Gray Matter , Neurites/pathology , White Matter/pathology
16.
Clin Genet ; 104(1): 142-144, 2023 07.
Article in English | MEDLINE | ID: mdl-36843358

ABSTRACT

IDDBCS is a heterogeneous genetic syndrome with diverse clinical features including Intellectual disability and epilepsy. Using WES, Sanger sequencing, we identified a novel nonsense variant in the PHF21A gene responsible for IDDBCS syndrome. The patient has diverse and overlapping clinical phenotypes. The identified variant leads to abnormal secondary and tertiary structure of the protein and, consequently, affects its function.


Subject(s)
Craniofacial Abnormalities , Epilepsy , Intellectual Disability , Humans , Intellectual Disability/genetics , Epilepsy/genetics , Syndrome , Phenotype , Craniofacial Abnormalities/genetics , Histone Deacetylases/genetics
17.
J Surg Res ; 284: 237-244, 2023 04.
Article in English | MEDLINE | ID: mdl-36599285

ABSTRACT

Small non-coding RNAs (sncRNAs) are defined by being less than 200 nucleotides (nt) in length, and consequently, have been divided into many different subclasses including mature microRNA (miRNA), small interfering RNA (siRNA), piwi-interacting RNA (piRNA), protein functional effector sncRNA (pfeRNA), precursor miRNA (pre-miRNA), small nucleolar RNA (snoRNA), 5S ribosome RNA (5SrRNA), 5.8SrRNA, and small nuclear RNA (snRNA). Except for the class of pfeRNAs, the discovery, identification, biogenesis, characterization, and function of other sncRNAs have been well documented. Herein, we provide a review, written especially for clinicians, of the least understood class of functional sncRNAs, the pfeRNAs, focusing on their initial discovery, identification, unique features, function, as well as their exciting clinical translational potential.


Subject(s)
MicroRNAs , RNA, Small Untranslated , RNA, Small Untranslated/genetics , RNA, Small Untranslated/metabolism , MicroRNAs/genetics , RNA, Small Interfering/genetics , Piwi-Interacting RNA
18.
Nicotine Tob Res ; 25(Suppl_1): S84-S93, 2023 07 28.
Article in English | MEDLINE | ID: mdl-37506235

ABSTRACT

INTRODUCTION: Cigars are currently the second-highest-used combustible tobacco product among U.S. adults, but knowledge about health effects of premium cigars versus other cigar subtype use is limited. AIMS AND METHODS: This study analyzed the biospecimen data (n = 31 875) from Waves 1-5 of the Population Assessment of Tobacco and Health Study, collected during 2013-2019. Multivariable generalized estimation equations, accounting for within-person clustering, were conducted to examine differences in urine biomarkers of exposure (BOE) from five classes of harmful and potentially harmful constituents along with a biomarker of oxidative stress (urine 8-isoprostane) among exclusive users of premium cigars versus other exclusive cigar subtypes (ie, non-premium large cigars, cigarillos, and filtered cigars), cigarettes, and non-tobacco users. RESULTS: In comparison to non-tobacco users, exclusive premium cigar users had higher geometric mean concentrations of the nicotine metabolite cotinine (5.8 vs. 0.5ng/mg, p < .0001), tobacco-specific nitrosamine (TSNA) (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL): 7.8 vs. 1.3pg/mg, p < .0001), and volatile organic compound (VOC) (N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA, acrylonitrile): 4.7 vs. 1.6ng/mg, p < .0001). Exclusive premium cigar users were less likely to be daily users than other tobacco user groups and had comparable BOEs with exclusive non-premium large cigar users but generally lower BOEs than exclusive cigarillo, filtered cigar, and cigarette smokers. Daily exclusive premium cigar users had similar nicotine and TSNA exposure but lower exposure to polycyclic aromatic hydrocarbons and volatile organic compounds than exclusive cigarillo and filtered cigar users. CONCLUSIONS: Premium cigar use exhibits different exposure to toxicants from other cigar subtype users. Regulations of premium cigars need to formalize product definition and take the population's health effects into consideration. IMPLICATIONS: This population study provides important information on BOE and potential harm with premium cigar use and its potential health effects. At present, premium cigars appear to pose a relatively low overall population health risk due to low frequency of use. However, future regulation of other tobacco products might change the landscape of premium cigar use and alter the overall health impact.


Subject(s)
Nitrosamines , Tobacco Products , Adult , Humans , Nicotine/adverse effects , Nicotine/urine , Smoking/epidemiology , Smoking/urine , Biomarkers/urine , Nitrosamines/urine , Oxidative Stress
19.
Nicotine Tob Res ; 25(5): 975-982, 2023 04 06.
Article in English | MEDLINE | ID: mdl-36507903

ABSTRACT

INTRODUCTION: This study sought to examine reasons for youth e-cigarette use in association with vaping patterns and cessation behaviors. AIMS AND METHODS: A national representative sample of current (past 30-day) e-cigarette users in grades 6-12 was analyzed using the National Youth Tobacco Survey (NYTS), conducted from January to March 2020. An exploratory oblique factor analysis using a rotated pattern matrix to select salient variable-factor relationships yielded four subscales related to reasons for youth e-cigarette use. Multivariate logistic regressions were performed to assess the associations of each subscale with vaping patterns (frequent e-cigarette use, dual use of e-cigarettes and other tobacco products) and vaping cessation behaviors (intention to quit vaping and past-year quit attempts). RESULTS: The 2020 NYTS sampled 180 schools with 1769 current e-cigarette users. Four main reasons for vaping were identified through factor analysis, including (1) replacing cigarettes, (2) product characteristics [eg, flavors, concealability, and vape tricks], (3) family/friend use, and (4) curiosity. Curiosity was associated with lower odds of frequent e-cigarette use (adjusted odds ratio [AOR] = 0.5, p < .0001) and dual use of e-cigarettes and other tobacco products (AOR = 0.6, p = .01) but higher odds of intention to quit (AOR = 1.2, p = .26) and past year quit attempts (AOR =1.5, p = .01). Vaping due to product characteristics was associated with higher odds of frequent e-cigarette use (AOR = 1.7, p < .0001) and lower odds of intention to quit (AOR = 0.3, p < .0001) and past year quit attempts (AOR = 0.9, p = .01). CONCLUSIONS: Adolescents vape for various reasons that follow distinct patterns and user characteristics. Overall, interventions tailored to address heterogeneous reasons for vaping may help optimize the reduction in youth e-cigarette use. IMPLICATIONS: E-cigarettes have surpassed cigarettes and become the most commonly used tobacco product by US youths. Adolescents choose to vape for different reasons. This study examined reasons for youth e-cigarette use and their associations with vaping patterns and cessation behaviors. The product characteristics factor (eg, flavors, concealability, and vape tricks) was associated with more frequent e-cigarette use and lower odds of cessation behaviors, suggesting a need for flavor bans and product design regulation.


Subject(s)
Electronic Nicotine Delivery Systems , Tobacco Products , Vaping , Humans , Adolescent , Vaping/epidemiology , Smokers , Nicotiana
20.
Dig Dis Sci ; 68(1): 284-290, 2023 01.
Article in English | MEDLINE | ID: mdl-35467310

ABSTRACT

INTRODUCTION: Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has been shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics. Seven days of antibiotics are generally recommended but very few studies have compared antibiotic duration to clinical outcomes in current available scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on patient outcomes. METHODS: We conducted a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010 to 2018. Patients were divided into three cohorts based on duration of antibiotic administration for prophylaxis: 1-3 days of antibiotics, 4-6 days of antibiotics and 7 days or more of antibiotics. Rates of infection diagnosis within 30 days, rebleeding, and mortality were compared between the three groups with Chi square, Fisher Exact and Kruskall-Wallace tests. Multivariable analysis was conducted to evaluate independent risk factors for infection. RESULTS: Medical charts of 980 patients with cirrhosis and upper GI bleeding during the study period were reviewed. A total of 303 with upper gastrointestinal bleeding were included in the final sample, of these 243 patients received antibiotics for prophylaxis and were included for analysis. Seventy-seven patients received antibiotic therapy for 3 days or less, 69 patients for 4-6 days, and 97 patients longer than 6 days. The three groups were well matched in demographic and clinical variables. Twenty-seven patients developed infections within 30 days of bleeding. MELD-Na score at presentation and presence of ascites were associated with infection within 30 days. Rates of infection were not statistically different between the three antibiotic groups (p = 0.78). In the thirty days following the GI bleed, pneumonia was the most diagnosed infection (eleven patients) followed by urinary tract infections (eight patients). Four patients developed spontaneous bacterial peritonitis and three were diagnosed with bacteremia. There was no difference in time to infection (Kruskall Wallace test p = 0.75), early re-bleeding (p = 0.81), late re-bleeding (p = 0.37) and in-hospital mortality (p = 0.94) in the three groups. Six patients in the cohort developed C. Difficile infection; no patient in the short antibiotic group developed C. Difficile infection. CONCLUSION: Short course of antibiotics for prophylaxis (3 days) appears safe and adequate for prophylaxis in patients with cirrhosis with upper gastrointestinal bleeding if there is no active infection.


Subject(s)
Bacterial Infections , Clostridioides difficile , Humans , Antibiotic Prophylaxis , Retrospective Studies , Gastrointestinal Hemorrhage/prevention & control , Gastrointestinal Hemorrhage/complications , Anti-Bacterial Agents/therapeutic use , Liver Cirrhosis
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