Category: Nevin Manimala

J Mol Neurosci. 2023 Feb 6. doi: 10.1007/s12031-023-02103-4. Online ahead of print.

ABSTRACT

Regardless of shifts in levels of individual transcripts, it remains elusive whether natural variability in cell-specific transcriptomes within the cerebral cortex is limited in aggregate. It is also unclear whether cortical cell-specific transcriptomes might change dynamically in absence of cell number changes. Total variation in neuron- and glia-specific in-aggregate transcriptomes could be identified in a model-free way via glia-neuron ratio approach, by univariate median-to-median ratios comparing integral levels of cell-specific transcripts within a tissue sample. When deleterious, regenerative or developmental events affecting cortical cell numbers were subtle, median-to-median ratios demonstrated within-group variability not exceeding <20-25% in most cases. These levels of total variability might be explained in part by limited (~5-10%) circadian and stress-induced shifts in cell-specific cortical transcriptomes. Relevant in-aggregate transcriptomic alterations were identified after shifts in cell numbers induced by well-validated deleterious events including ischemia, traumatic injury, microglia’s activation/depletion or specific mutations. Cortical median-to-median ratios also follow naturally occurring changes in the numbers of excitatory, inhibitory neurons and glial cells during perinatal brain development. These findings characterize cortical cell-specific transcriptomes as subjects to circadian shifts and lifetime events, urging the importance of reporting full details on an origin of any transcriptomic sample collected in vivo.

PMID:36745298 | DOI:10.1007/s12031-023-02103-4

MAGMA. 2023 Feb 6. doi: 10.1007/s10334-022-01058-8. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the origin of compartment size overestimation in double diffusion encoding MRI (DDE) in vivo experiments in the human corticospinal tract. Here, the extracellular space is hypothesized to be the origin of the DDE signal. By exploiting the DDE sensitivity to pore shape, it could be possible to identify the origin of the measured signal. The signal difference between parallel and perpendicular diffusion gradient orientation can indicate if a compartment is regular or eccentric in shape. As extracellular space can be considered an eccentric compartment, a positive difference would mean a high contribution to the compartment size estimates.

MATERIALS AND METHODS: Computer simulations using MISST and in vivo experiments in eight healthy volunteers were performed. DDE experiments using a double spin-echo preparation with eight perpendicular directions were measured in vivo. The difference between parallel and perpendicular gradient orientations was analyzed using a Wilcoxon signed-rank test and a Mann-Whitney U test.

RESULTS: Simulations and MR experiments showed a statistically significant difference between parallel and perpendicular diffusion gradient orientation signals ([Formula: see text]).

CONCLUSION: The results suggest that the DDE-based size estimate may be considerably influenced by the extra-axonal compartment. However, the experimental results are also consistent with purely intra-axonal contributions in combination with a large fiber orientation dispersion.

PMID:36745290 | DOI:10.1007/s10334-022-01058-8

Ir J Med Sci. 2023 Feb 6. doi: 10.1007/s11845-023-03284-y. Online ahead of print.

ABSTRACT

BACKGROUND: People with serious mental illness exhibit higher morbidity and mortality rates of chronic diseases than the general population.

AIMS: The aim of this study was to establish a dedicated clinic for patients with chronic mental illness to monitor physical health and quality of life in accordance with best practice guidelines.

METHODS: Patients were invited to attend the clinic. The following areas were examined: personal and family history of cardiovascular disease, diet, exercise, and smoking. Mental state examination, waist circumference, BP, pulse, ECG and BMI. Laboratory tests including U + E, LFTs, HbA1c, Lipid profile and other tests as appropriate such as serum lithium. AIMS scale, HoNOS and WHOQOL-BREF scales as additional indicators of global health.

RESULTS: A total of 80 patients attended during 3.5 years of clinic. Mean age was 54.9 years (SD: 13.81) at first contact and 45% were females. Mean years in the service was 19.66 (SD: 11.54) and mean number of previous hospital admissions was 4.4 (SD: 5.63). Metabolic syndrome was present in 42% at first assessment. A statistically significant improvement was found for the psychological domain of the WHOQOL-BREF and the HoNOs, particularly at third assessment. (β = 4.64, Wald x² = 7.38, df:1, p = 0.007, CI:1.3-8.1, β = – .889, Wald x² = 4.08, df:1, p = 0.043, CI: – 1.752 to – .026) respectively.

CONCLUSION: The results show a high prevalence of physical health conditions in this cohort, some of which represent a new diagnosis. This implicates better allocation of existing resources for screening and early detection, and potential to run joint clinics with primary care.

PMID:36745285 | DOI:10.1007/s11845-023-03284-y

J Egypt Public Health Assoc. 2023 Feb 6;98(1):1. doi: 10.1186/s42506-023-00129-5.

ABSTRACT

BACKGROUND: Research shows that trust in government is associated with the acceptance of COVID-19 vaccination. However, there is no empirical evidence suggesting the pathway by which this association is formed. This study examines how dimensional attitudes towards vaccination explain the relationship between mistrust in government and COVID-19 vaccination acceptance.

METHODS: The study was an online cross-sectional survey involving 1026 adults (of which 58.9% are female) resident in Nigeria with a mean age of 26.09 (±8.46) years. Data were collected using structured questionnaires assessing the level of mistrust in government, dimensional attitudes towards vaccination, and acceptance to be vaccinated for COVID-19. Structural equation modeling was used to analyze data.

RESULTS: Results show that 56.8% of participants mistrust the government, while COVID-19 vaccination acceptance rate was 28.2%. Mistrust in government was significantly associated with low acceptance of COVID-19 vaccination. Furthermore, mistrust in the government was predictive of negative attitudes towards COVID-19 vaccination which include worries about unforeseen future effects of vaccines, mistrust of vaccine benefits (MVB), concerns about commercial profiteering (CCP), and preference for natural immunity. The outcomes of indirect effect analyses indicated that mistrust in government was associated with high mistrust in vaccine benefits (MVB) and increased concerns about commercial profiteering (CCP), which in turn lead to low acceptance of COVID-19 vaccination.

CONCLUSIONS: Mistrust in the government was high and was coupled with low vaccination acceptance. It is important to initiate culturally relevant awareness programs aiming at combating false notions about COVID-19 vaccination such as MVB and CCP arising from mistrust in government.

PMID:36745270 | DOI:10.1186/s42506-023-00129-5

Ann Surg Oncol. 2023 Feb 6. doi: 10.1245/s10434-023-13149-4. Online ahead of print.

NO ABSTRACT

PMID:36745260 | DOI:10.1245/s10434-023-13149-4

Amino Acids. 2023 Feb 6. doi: 10.1007/s00726-023-03241-0. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is accepted as a form of progressive dementia. Cholinergic systems are commonly affected in AD. Neurokinin 3 receptor (NK3R) is involved in learning memory-related processes. It is known that the activation of NK3R affects the release of many neurotransmitters. The aim of this project was to investigate the effects of NK3R agonist senktide administration on neurobehavioral mechanisms in the experimental AD-like rat model. 50 male Wistar albino rats were divided into Control (C), AD, Control + NK3R agonist (CS), AD + NK3R agonist (ADS), AD + NK3Ragonist + antagonist groups (ADSO). We designed AD-like model by intrahippocampal administration of Aβ1-42. After NK3R agonist + antagonist injections, open field (OF), Morris water maze (MWM) tests were applied. Cholinergic mechanism analysis from hippocampus-cortex tissues was performed by ELISA and catecholamine analysis from brain stem tissue were performed by HPLC method. The transitions from edge to center, rearing, grooming parameters were found to be reduced in final values of OF. While the group-time interaction was significant in the OF test findings, there was no significant difference between the groups. In MWM test, ADS group showed a learning level close to control group and animals in AD and ADSO groups could not learn target quadrant in MWM test. The brain stem NA and DA concentrations were not statistically significant. Hippocampal AChE-ChAT levels were supported by positive effects of senktide on learning via the cholinergic mechanisms. As a result, NK3R agonists were found to be effective in improving cognitive functions in rats with AD pathology. In the experimental AD model, positive effects of NK3R on learning memory may be mediated by cholinergic mechanisms.

PMID:36745246 | DOI:10.1007/s00726-023-03241-0

J Ultrasound Med. 2023 Feb 6. doi: 10.1002/jum.16191. Online ahead of print.

ABSTRACT

OBJECTIVES: Recognition of intestinal lesions with substantial fibrosis is strategic for optimal management of patients with Crohn’s disease (CD). We aimed to assess the relationships between intestinal ultrasound parameters and histopathologic findings in a prospective cohort of patients with CD undergoing surgery.

METHODS: Seventeen consecutive adult CD patients with involvement of the terminal ileum or the sigmoid colon who underwent bowel resective surgeries were enrolled and performed intestinal ultrasound (IUS) within 30 days prior to surgery. Uni- and multivariable analyses were used to assess the relationships between IUS parameters and histopathological elements of lesions.

RESULTS: Sensitivity, specificity, accuracy, PPV and NPV (95% CI) of IUS in detecting stricturing and penetrating complications (surgical specimen as reference standard) were 93% (68-100), 86% (42-100), 91% (71-99), 93% (68-100) and 86% (42-100), and 78% (40-97), 92% (64-100), 86% (65-97), 88% (47-100) and 86% (57-98), respectively. Only the presence of hyperechogenic spiculates was statistically significantly associated with collagen content (b = 7.29, 95% CI = 1.88/12.69, P = .012), while only the presence of vascular signals at color Doppler (Limberg score 3 or 4) was significantly associated with active inflammation (OR = 10.0, 95% CI = 0.9/108.6, P = .037). There was a strong correlation between IUS and histological measurements of the wall thickness (r = 0.67, P = .01).

CONCLUSIONS: The presence of hyperechogenic spiculates was associated with the presence of fibrosis, while the presence of marked vascular signals was associated with the presence of inflammation. Wall thickness measured by IUS was reliable and reproducible in comparison with histological measurement.

PMID:36744584 | DOI:10.1002/jum.16191

J Magn Reson Imaging. 2023 Feb 6. doi: 10.1002/jmri.28629. Online ahead of print.

ABSTRACT

BACKGROUND: Focal nodular hyperplasia (FNH) and hepatic adenoma (HA) are two common benign liver lesions with different management options. In particular, resection is considered for large HA lesions to avoid possible bleeding complications or rarely malignant degeneration.

PURPOSE: To determine whether early enhancement of a draining hepatic vein (EDHV) and absence of perilesional enhancement (PLE) on arterial phase MR images are useful for distinguishing FNH from HA.

STUDY TYPE: Retrospective.

POPULATION: A total of 34 patients: 16 with FNH and 18 with HA lesions.

FIELD STRENGTH/SEQUENCE: A1.5 T, axial T1 fat-suppressed arterial postcontrast.

ASSESMENT: Four abdominal radiologists blinded to pathologic diagnosis assessed for the presence or absence of EDHV in association with the lesion, definitively characterized by pathology. This was considered present if contrast could be identified in a hepatic vein contiguous with the lesion in question. Secondarily, PLE was evaluated.

STATISTICAL TESTS: Fleiss’s multirater kappa statistic, Chi-squared statistic, Phi-coefficient. Significance level P < 0.05.

RESULTS: Considering all observations obtained from the four readers, an EDHV was identified with FNH 48.5% of the time. EDHV was seen with HA in 8.8% of cases. PLE was seen with significantly greater frequency in HA. The presence of an EDHV was associated with the absence of PLE.

DATA CONCLUSION: In a lesion that may be either an FNH or HA, confident identification on arterial phase images of an EDHV should lead the reader to favor FNH, while the presence PLE should dissuade the reader from FNH.

EVIDENCE LEVEL: 4.

TECHNICAL EFFICACY: Stage 2.

PMID:36744579 | DOI:10.1002/jmri.28629

Philos Trans R Soc Lond B Biol Sci. 2023 Mar 27;378(1873):20220006. doi: 10.1098/rstb.2022.0006. Epub 2023 Feb 6.

ABSTRACT

Theoretical models of the evolution of parasites and their hosts have shaped our understanding of infectious disease dynamics for over 40 years. Many theoretical models assume that the underlying ecological dynamics are at equilibrium or constant, yet we know that in a great many systems there are fluctuations in the ecological dynamics owing to a variety of intrinsic or extrinsic factors. Here, we discuss the challenges presented when modelling evolution in systems with fluctuating ecological dynamics and summarize the main approaches that have been developed to study host-parasite evolution in such systems. We provide an in-depth guide to one of the methods by applying it to two worked examples of host evolution that have not previously been studied in the literature: when cycles occur owing to seasonal forcing in competition, and when the presence of a free-living parasite causes cycles, with accompanying interactive Python code provided. We review the findings of studies that have explored host-parasite evolution when ecological dynamics fluctuate, and point to areas of future research. Throughout we stress the importance of feedbacks between the ecological and evolutionary dynamics in driving the outcomes of infectious disease systems. This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.

PMID:36744565 | DOI:10.1098/rstb.2022.0006

J Biomol Struct Dyn. 2023 Feb 6:1-16. doi: 10.1080/07391102.2023.2175257. Online ahead of print.

ABSTRACT

The co-evolution of Mycobacterium tuberculosis H37Rv along with its host systems enables the pathogenic bacterium to emerge as a multi-drug resistant form. This creates challenges for a more efficacious treatment strategy that can mitigate the infection. Working towards the same, our study followed a mathematical and statistical approach proposing that mycobacterial transcription factors regulating virulence and adaptation, host cell cytoplasmic component metabolism, oxidoreductase activity and respiratory ETC would be targets for antibiotics against Mycobacterium tuberculosis. Simultaneously, extending the statistical study on Mycobacterium-infected human cord blood CD34+ cells revealed that the human CD34+ genes, S100A8 and FGR (tyrosine-protein kinase, Src2), might be affected in the infection pathogenesis by Mycobacterium. Further, the deduced Mycobacterium-human gene interaction network proposed that mycobacterial coregulators Rv0452 (MarR family regulator) and Rv3862c (WhiB6) triggered genes controlling bacterial metabolism, which influences human immunological pathways involving TLR2 and CXCL8/MAPK8.Communicated by Ramaswamy H. Sarma.

PMID:36744528 | DOI:10.1080/07391102.2023.2175257