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JPMA. the Journal of the Pakistan... Jun 2024Congenital eyelid imbrication syndrome (CEIS) is a rare condition presenting at birth and is characterised by overriding of the upper lid on the lower lid. It is due to...
Congenital eyelid imbrication syndrome (CEIS) is a rare condition presenting at birth and is characterised by overriding of the upper lid on the lower lid. It is due to longer upper lid, than the lower lid. Overriding leads to spontaneous eversion of the upper lids. In our patient, examination revealed canthal tendon laxity and hyperaemia of the tarsal conjunctiva. All the rest of the structures in the eyeball and adnexa were normal. Spontaneous eversion occurred in two weeks as the upper lid grew with time. No treatment was required.
Topics: Humans; Pakistan; Eyelids; Female; Male; Eyelid Diseases; Infant, Newborn
PubMed: 38948995
DOI: 10.47391/JPMA.9457 -
Frontiers in Neuroscience 2024Previous neuroimaging studies have revealed structural and functional brain abnormalities in patients with cervical spondylosis (CS). However, the results are divergent...
BACKGROUND
Previous neuroimaging studies have revealed structural and functional brain abnormalities in patients with cervical spondylosis (CS). However, the results are divergent and inconsistent. Therefore, the present study conducted a multi-modal meta-analysis to investigate the consistent structural and functional brain alterations in CS patients.
METHODS
A comprehensive literature search was conducted in five databases to retrieve relevant resting-state functional magnetic resonance imaging (rs-fMRI), structural MRI and diffusion tensor imaging (DTI) studies that measured brain functional and structural differences between CS patients and healthy controls (HCs). Separate and multimodal meta-analyses were implemented, respectively, by employing Anisotropic Effect-size Signed Differential Mapping software.
RESULTS
13 rs-fMRI studies that used regional homogeneity, amplitude of low-frequency fluctuations (ALFF) and fractional ALFF, seven voxel-based morphometry (VBM) studies and one DTI study were finally included in the present research. However, no studies on surface-based morphometry (SBM) analysis were included in this research. Due to the insufficient number of SBM and DTI studies, only rs-fMRI and VBM meta-analyses were conducted. The results of rs-fMRI meta-analysis showed that compared to HCs, CS patients demonstrated decreased regional spontaneous brain activities in the right lingual gyrus, right middle temporal gyrus (MTG), left inferior parietal gyrus and right postcentral gyrus (PoCG), while increased activities in the right medial superior frontal gyrus, bilateral middle frontal gyrus and right precuneus. VBM meta-analysis detected increased GMV in the right superior temporal gyrus (STG) and right paracentral lobule (PCL), while decreased GMV in the left supplementary motor area and left MTG in CS patients. The multi-modal meta-analysis revealed increased GMV together with decreased regional spontaneous brain activity in the left PoCG, right STG and PCL among CS patients.
CONCLUSION
This meta-analysis revealed that compared to HCs, CS patients had significant alterations in GMV and regional spontaneous brain activity. The altered brain regions mainly included the primary visual cortex, the default mode network and the sensorimotor area, which may be associated with CS patients' symptoms of sensory deficits, blurred vision, cognitive impairment and motor dysfunction. The findings may contribute to understanding the underlying pathophysiology of brain dysfunction and provide references for early diagnosis and treatment of CS.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, CRD42022370967.
PubMed: 38948928
DOI: 10.3389/fnins.2024.1415411 -
Advances in Radiation Oncology Jul 2024For lung stereotactic body radiation therapy, 4-dimensional computed tomography is often used to delineate target volumes, whereas organs at risk (OARs) are typically...
PURPOSE
For lung stereotactic body radiation therapy, 4-dimensional computed tomography is often used to delineate target volumes, whereas organs at risk (OARs) are typically outlined on either average intensity projection (AIP) or midventilation (MidV = 30% phase) images. AIP has been widely adopted as it represents a true average, but image blurring often precludes accurate contouring of critical structures such as central airways. Here, we compare AIP versus MidV planning for centrally located tumors via respiratory motion-inclusive (RMI) plans to better evaluate dose delivered throughout the breathing cycle.
METHODS AND MATERIALS
Independently contoured and optimized AIP and MidV plans were created for 16 treatments and rigidly copied to each of the 10 breathing phase-specific computed tomography image sets. Resulting dose distributions were deformably registered back to the MidV image set (used as reference because of clearer depiction of anatomy compared with motion-blurred AIP) and averaged to create RMI plans. Doses to central OARs were compared between plans.
RESULTS
Mean absolute dose differences were low for all comparisons (range, 0.01-2.87 Gy); however, individual plans exhibited differences >20 Gy. Dose differences >5 Gy were observed most often for plan comparisons involving AIP-based plans (MidV vs AIP 23, AIP RMI vs AIP 12, MidV RMI vs AIP RMI 7, and MidV RMI vs MidV 8 times). Inclusion of respiratory motion reduced large dose differences. Standard OAR thresholds were exceeded up to 5 times for each plan comparison scenario and always involved proximal bronchial tree D4 cc tolerance dose. AIP-based contours were larger by, on average, 3% to 15%.
CONCLUSIONS
Large dose differences were observed when plans with AIP-based contours were compared with MidV-based contours, indicating that observed dose differences were likely due to contoured volume differences rather than the effect of motion. Because of blurring with AIP images, MidV RMI-based planning may offer a more accurate method to determine dose to critical OARs in the presence of respiratory motion.
PubMed: 38948918
DOI: 10.1016/j.adro.2024.101525 -
Radiology Case Reports Aug 2024Caudal regression syndrome (CRS) is a rare genetic disorder affecting less than 0.1%-0.5% of newborns that manifests as the total or partial absence of lower vertebral...
Caudal regression syndrome (CRS) is a rare genetic disorder affecting less than 0.1%-0.5% of newborns that manifests as the total or partial absence of lower vertebral structures including the sacral spine. The etiology of CRS remains elusive, but there is compelling evidence supporting a genetic predisposition and a correlation with maternal diabetes. This study presents the case of a 7-year-old girl exhibiting symptoms consistent with CRS including lower limb deficits, abnormal gait, urinary incontinence, and scoliosis. The findings from an MRI scan revealed notable anomalies such as hemivertebra in the dorsal spine, renal deformities, and the absence of secondary neurulation elements in the spine. We chose to delay the hemivertebra surgery because the scoliosis was not highly pronounced. Rather, we directed the child to the urology department for the management of her kidney deformities. This case contributes to the understanding of CRS and underscores the importance of comprehensive diagnostic approaches in elucidating its complex manifestations.
PubMed: 38948903
DOI: 10.1016/j.radcr.2024.05.002 -
BioRxiv : the Preprint Server For... Jun 2024Cellular mechanical properties influence cellular functions across pathological and physiological systems. The observation of these mechanical properties is limited in...
Cellular mechanical properties influence cellular functions across pathological and physiological systems. The observation of these mechanical properties is limited in part by methods with a low throughput of acquisition or with low accessibility. To overcome these limitations, we have designed, developed, validated, and optimized a microfluidic cellular deformation system (MCDS) capable of mechanotyping suspended cells on a population level at a high throughput rate of ∼300 cells pers second. The MCDS provides researchers with a viable method for efficiently quantifying cellular mechanical properties towards defining prognostic implications of mechanical changes in pathology or screening drugs to modulate cytoskeletal integrity.
PubMed: 38948841
DOI: 10.1101/2024.06.17.599307 -
BioRxiv : the Preprint Server For... Jun 2024Kidney tubular cells are submitted to two distinct mechanical forces generated by the urine flow: shear stress and hydrostatic pressure. In addition, the mechanical...
Kidney tubular cells are submitted to two distinct mechanical forces generated by the urine flow: shear stress and hydrostatic pressure. In addition, the mechanical properties of the surrounding extracellular matrix modulate tubule deformation under constraints. These mechanical factors likely play a role in the pathophysiology of kidney diseases as exemplified by autosomal dominant polycystic kidney disease, in which pressure, flow and matrix stiffness have been proposed to modulate the cystic dilation of tubules with mutations. The lack of systems recapitulating the mechanical environment of kidney tubules impedes our ability to dissect the role of these mechanical factors. Here we describe a perfused kidney-on-chip with tunable extracellular matrix mechanical properties and hydrodynamic constraints, that allows a decoupling of shear stress and flow. We used this system to dissect how these mechanical cues affect tubule dilation. Our results show two distinct mechanisms leading to tubular dilation. For PCT cells (proximal tubule), overproliferation mechanically leads to tubular dilation, regardless of the mechanical context. For mIMCD-3 cells (collecting duct), tube dilation is associated with a squamous cell morphology but not with overproliferation and is highly sensitive to extracellular matrix properties and hydrodynamic constraints. Surprisingly, flow alone suppressed mIMCD-3 tubule dilation observed in static conditions, while the addition of luminal pressure restored it. Our model emulating nephron geometrical and mechanical organization sheds light on the roles of mechanical constraints in ADPKD and demonstrates the importance of controlling intraluminal pressure in kidney tubule models.
PubMed: 38948811
DOI: 10.1101/2024.06.18.599137 -
BioRxiv : the Preprint Server For... Jun 2024Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is the most common liver disease worldwide. The progression...
Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is the most common liver disease worldwide. The progression to fibrosis, occurring against a backdrop of hepatic steatosis and inflammation, critically determines liver-related morbidity and mortality. Inflammatory processes contribute to various stages of MAFLD and thought to instigate hepatic fibrosis. For this reason, targeting inflammation has been heavily nominated as a strategy to mitigate liver fibrosis. Lipopolysaccharide binding protein (LBP) is a secreted protein that plays an established role in innate immune responses. Here, using adoptive transfer studies and tissue-specific deletion models we show that hepatocytes are the dominant contributors to circulating LBP. In a murine model of MAFLD, hepatocyte-specific deletion of LBP restrained hepatic inflammation and improved liver function abnormalities, but not measures of fibrosis. Human studies, including genetic evidence, corroborate an important role for LBP in hepatic inflammation with minimal impact on fibrosis. Collectively, our data argues against the idea that targeting hepatic inflammation is a viable approach to reducing fibrosis.
PubMed: 38948798
DOI: 10.1101/2024.06.17.599212 -
BioRxiv : the Preprint Server For... Jun 2024Nuclear homeostasis requires a balance of forces between the cytoskeleton and nucleus. Variants in disrupt this balance by weakening the nuclear lamina, resulting in...
Nuclear homeostasis requires a balance of forces between the cytoskeleton and nucleus. Variants in disrupt this balance by weakening the nuclear lamina, resulting in nuclear damage in contractile tissues and ultimately muscle disease. Intriguingly, disrupting the LINC complex that connects the cytoskeleton to the nucleus has emerged as a promising strategy to ameliorate cardiomyopathy. Yet how LINC disruption protects the cardiomyocyte nucleus remains unclear. To address this, we developed an assay to quantify the coupling of cardiomyocyte contraction to nuclear deformation and interrogated its dependence on the lamina and LINC complex. We found that the LINC complex was surprisingly dispensable for transferring the majority of contractile strain into the nucleus, and that increased nuclear strain in deficient myocytes was not rescued by LINC disruption. However, LINC disruption eliminated the cage of microtubules encircling the nucleus, and disrupting microtubules was sufficient to prevent nuclear damage induced by deficiency. Through computational modeling we simulated the mechanical stress fields surrounding cardiomyocyte nuclei and show how microtubule compression exploits local vulnerabilities to damage -deficient nuclei. Our work pinpoints localized, microtubule-dependent force transmission through the LINC complex as a pathological driver and therapeutic target for cardiomyopathy.
PubMed: 38948795
DOI: 10.1101/2024.02.10.579774 -
BioRxiv : the Preprint Server For... Jun 2024We take a unique approach to understanding the causes of podocyte injury in collagen IV nephropathies, a crucial step in developing targeted therapies for conditions...
RATIONALE
We take a unique approach to understanding the causes of podocyte injury in collagen IV nephropathies, a crucial step in developing targeted therapies for conditions like Alport Syndrome.
OBJECTIVES
We characterize the structural, functional, and biophysical properties of glomerular capillaries and podocytes in mice and analyze kidney cortex transcriptional profiles at various disease stages. We investigate the effects of the ER stress mitigator TUDCA on these parameters. Furthermore, we used human FSGS associated podocyte enriched genes to identify molecular pathways rescued by TUDCA thereby offering potential therapeutic targets for Alport Syndrome.
FINDINGS
We find a clear disease progression timeline in mice. Podocyte injury develops by 3 months, with glomeruli reaching maximum deformability at 4 months, associated with a 40% loss of podocytes. This is followed by progressive stiffening of glomerular capillaries, increasing proteinuria, reduced renal function, inflammatory infiltrates, and fibrosis from months 4 to 8. Bulk RNA sequencing at 2, 4, and 7 months reveals a progressive increase in expression of genes related to cytokine and chemokine signaling, matrix and cell injury, and activation of the TNF pathway, similar to observations in a NEPTUNE FSGS cohort. Podocyte-enriched genes from FSGS patients mapped to mice found that TUDCA, which mitigated glomerular and renal injury suppressed molecular pathways associated with extracellular matrix and basement membrane synthesis, podocyte stress and hypertrophy.
CONCLUSIONS
We uncover two distinct phases of nephropathy progression. The first is characterized by podocytopathy, increased glomerular capillary deformability and accelerated podocyte loss, and the second by increased capillary wall stiffening and renal inflammatory and profibrotic pathway activation. The response of podocytes to TUDCA treatment provides novel insights into downstream signaling pathways, offering potential therapeutic targets for treating Alport and related nephropathies.
PubMed: 38948788
DOI: 10.1101/2024.02.26.582201 -
BioRxiv : the Preprint Server For... Jun 2024Severe invagination of the nuclear envelope is a hallmark of cancers, aging, neurodegeneration, and infections. However, the outcomes of nuclear invagination remain...
UNLABELLED
Severe invagination of the nuclear envelope is a hallmark of cancers, aging, neurodegeneration, and infections. However, the outcomes of nuclear invagination remain unclear. This work identified a new function of nuclear invagination: regulating ribosome biogenesis. With expansion microscopy, we observed frequent physical contact between nuclear invaginations and nucleoli. Surprisingly, the higher the invagination curvature, the more ribosomal RNA and pre-ribosomes are made in the contacted nucleolus. By growing cells on nanopillars that generate nuclear invaginations with desired curvatures, we can increase and decrease ribosome biogenesis. Based on this causation, we repressed the ribosome levels in breast cancer and progeria cells by growing cells on low-curvature nanopillars, indicating that overactivated ribosome biogenesis can be rescued by reshaping nuclei. Mechanistically, high-curvature nuclear invaginations reduce heterochromatin and enrich nuclear pore complexes, which promote ribosome biogenesis. We anticipate that our findings will serve as a foundation for further studies on nuclear deformation.
HIGHLIGHTS
Nuclear invaginations regulate ribosome biogenesis by physically contacting nucleoli.High-curvature nuclear tunnels increase ribosome biogenesis.Nanopillars reduce ribosome biogenesis by transforming high-curvature nuclear invaginations to low-curvature ones.
PubMed: 38948754
DOI: 10.1101/2024.06.21.597078