Does dexamethasone therapy affect intimal hyperplasia after injury in rat abdominal aorta models?

BACKGROUND: Intimal hyperplasia is a normal adaptive feature of arteries in response to injuries, which include invasive vascular interventions. Its development limits the long-term success of bypass grafts. Various pharmacological agents have been successfully employed in experimental models to reduce the degree of intimal hyperplasia. In our study, we investigated the efficacy of dexamethasone in reducing intimal hyperplasia in rat abdominal aortas after partial transection and primary repair. METHODS: In this study, 20 Wistar Albino rats were randomly selected and divided into four groups to compare the effects of low- and high-dose dexamethasone on intima and media thickness compared to the control. Group A (n=5) was the control group, where only skin incision and laparotomy were performed. For Group B (n=5), a median laparotomy was performed, the abdominal aorta was partially transected, and repaired with an 8.0 prolene suture. Doses of 0.1 mg/kg and 0.2 mg/kg dexamethasone were administered in Group C (n=5) and Group D (n=5), respectively. After two weeks, all rats were euthanized, and the repaired abdominal aortas were excised and examined histopathologically. Intima and media thicknesses were measured using the 'Olympus AnalySIS 5' program (Olympus Corporation, Japan) after digital photos were taken. RESULTS: Based on the measurements, we demonstrated that after transection and repair of the abdominal aorta, the intima/media ratio was not significantly different between the low-dose dexamethasone and non-dexamethasone groups. The intima/media ratio was significantly lower in the high-dose dexamethasone group than in the non-dexamethasone and low-dose dexamethasone groups. CONCLUSION: After vascular interventions, dexamethasone treatment may reduce intimal hyperplasia and increase patency by providing vascular remodeling.

Major and Trace Elements of Baobab Leaves in Different Habitats and Regions in Sudan: Implication for Human Dietary Needs and Overall Health.

The metabolic needs of the human body and preventing infections require a diet with sufficient amounts of essential nutrients. This study aimed to investigate the importance of Baobab (Adansonia digitata L.) dried leaves as a healthy food source by determining the content of macro and trace elements in different habitats and regions. This study was conducted in Sudan and covered three different habitats, wetland (W), plainland (P), and mountain (M), in two regions (Blue Nile and Kordofan). The dry matter (DM) of Baobab leaves was considered for analyzed menials, and the results showed that the mean values were significantly affected by habitats where Baobab trees grew. The highest contents of potassium K (1653 ± 34 mg/100 g) and sodium (Na) 7.67 ± 1.18 mg/100 g were found in the W zone, whereas the highest contents of calcium (Ca) 2903 ± 187 mg/100 g and magnesium (Mg) 529 ± 101 mg/100 g were detected in the M and P zones, respectively. In addition, the two regions showed significant differences in trace and macro elements, i.e., higher levels of iron (Fe) 17.17 ± 2.76 mg/100 g and magnesium (556 ± 55 mg/100 g) were found in the Kordofan region while higher levels of zinc (Zn) 2.548 ± 0.55 mg/100 g and calcium (2689 ± 305 mg/100) were in the Blue Nile region. These varying amounts of elements can be used in our daily diets because of their potentially healthy effects, especially in areas where access to nutrient-rich foods is limited.

Generation of Mammalian Astrocyte Functional Heterogeneity.

Mammalian astrocytes have regional roles within the brain parenchyma. Indeed, the notion that astrocytes are molecularly heterogeneous could help explain how the central nervous system (CNS) retains embryonic positional information through development into specialized regions into adulthood. A growing body of evidence supports the concept of morphological and molecular differences between astrocytes in different brain regions, which might relate to their derivation from regionally patterned radial glia and/or local neuron inductive cues. Here, we review evidence for regionally encoded functions of astrocytes to provide an integrated concept on lineage origins and heterogeneity to understand regional brain organization, as well as emerging technologies to identify and further investigate novel roles for astrocytes.

Computer vision syndrome among Sudanese medical students: a growing medical issue in the digital world.

Computer vision syndrome (CVS) refers to a set of eye-related symptoms that arise from prolonged computer usage. A survey was conducted to investigate the demographic characteristics, factors contributing to, and preventive measures against CVS. Out of 159 participants, 31.0% experienced seven or more symptoms, indicating a notable prevalence. The study found no significant correlation between age or academic years and CVS occurrence (P values of 0.481 and 0.392, respectively). However, gender exhibited a statistically significant relationship, with females students showing a higher prevalence than males (P=0.018; τ=0.105*). Notably, the distance from the screen had a highly significant inverse correlation with CVS occurrence (P=0.000; τ=-0.207**), indicating that greater distance reduced the risk. Additionally, using a screen filter (P=0.000; τ=0.184**) and adjusting screen brightness (P=0.017; τ=0.101*) were associated with CVS occurrence. Among preventive measures, only the use of an anti-glare screen showed a significant association with reducing CVS risk (P=0.018; τ=-0.099*). Given these findings, raising awareness about CVS among medical students is recommended, especially as curricula in medical colleges evolve.

Human skeletal muscle aging atlas.

Skeletal muscle aging is a key contributor to age-related frailty and sarcopenia with substantial implications for global health. Here we profiled 90,902 single cells and 92,259 single nuclei from 17 donors to map the aging process in the adult human intercostal muscle, identifying cellular changes in each muscle compartment. We found that distinct subsets of muscle stem cells exhibit decreased ribosome biogenesis genes and increased CCL2 expression, causing different aging phenotypes. Our atlas also highlights an expansion of nuclei associated with the neuromuscular junction, which may reflect re-innervation, and outlines how the loss of fast-twitch myofibers is mitigated through regeneration and upregulation of fast-type markers in slow-twitch myofibers with age. Furthermore, we document the function of aging muscle microenvironment in immune cell attraction. Overall, we present a comprehensive human skeletal muscle aging resource ( https://www.muscleageingcellatlas.org/ ) together with an in-house mouse muscle atlas to study common features of muscle aging across species.

Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19.

BACKGROUND: Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. METHODS: Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. FINDINGS: Forty patients (32M:8F, age: 22-98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. INTERPRETATION: The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established. FUNDING: UK Research and Innovation/Medical Research Council through the UK Coronavirus Immunology Consortium, Barbour Foundation, General Sir John Monash Foundation, Newcastle University, JGW Patterson Foundation, Wellcome Trust.

A human embryonic limb cell atlas resolved in space and time.

Human limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed limbs over the subsequent months1. This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common2. Decades of work with model organisms have defined the fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization of this process in humans has yet to be performed. Here we detail human embryonic limb development across space and time using single-cell and spatial transcriptomics. We demonstrate extensive diversification of cells from a few multipotent progenitors to myriad differentiated cell states, including several novel cell populations. We uncover two waves of human muscle development, each characterized by different cell states regulated by separate gene expression programmes, and identify musculin (MSC) as a key transcriptional repressor maintaining muscle stem cell identity. Through assembly of multiple anatomically continuous spatial transcriptomic samples using VisiumStitcher, we map cells across a sagittal section of a whole fetal hindlimb. We reveal a clear anatomical segregation between genes linked to brachydactyly and polysyndactyly, and uncover transcriptionally and spatially distinct populations of the mesenchyme in the autopod. Finally, we perform single-cell RNA sequencing on mouse embryonic limbs to facilitate cross-species developmental comparison, finding substantial homology between the two species.

Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients.

Diffuse alveolar damage (DAD) is the histological expression of acute respiratory distress syndrome and characterises lung pathology due to infection with SARS-CoV-2, and other respiratory pathogens of clinical significance. DAD reflects a time-dependent immunopathological process, progressing from an early/exudative stage through to an organising/fibrotic stage, yet within an individual these different stages of DAD may coexist. Understanding the progression of DAD is central to the development of new therapeutics to limit progressive lung damage. Here, we applied highly multiplexed spatial protein profiling to autopsy lung tissues derived from 27 patients who died from COVID-19 and identified a protein signature (ARG1, CD127, GZMB, IDO1, Ki67, phospho-PRAS40 (T246) and VISTA) that distinguishes early DAD from late DAD with good predictive accuracy. These proteins warrant further investigation as potential regulators of DAD progression.

Spatial multiomics map of trophoblast development in early pregnancy.

The relationship between the human placenta-the extraembryonic organ made by the fetus, and the decidua-the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels1. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia2. Here we have generated a spatially resolved multiomics single-cell atlas of the entire human maternal-fetal interface including the myometrium, which enables us to resolve the full trajectory of trophoblast differentiation. We have used this cellular map to infer the possible transcription factors mediating EVT invasion and show that they are preserved in in vitro models of EVT differentiation from primary trophoblast organoids3,4 and trophoblast stem cells5. We define the transcriptomes of the final cell states of trophoblast invasion: placental bed giant cells (fused multinucleated EVTs) and endovascular EVTs (which form plugs inside the maternal arteries). We predict the cell-cell communication events contributing to trophoblast invasion and placental bed giant cell formation, and model the dual role of interstitial EVTs and endovascular EVTs in mediating arterial transformation during early pregnancy. Together, our data provide a comprehensive analysis of postimplantation trophoblast differentiation that can be used to inform the design of experimental models of the human placenta in early pregnancy.

A spatially resolved atlas of the human lung characterizes a gland-associated immune niche.

Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org ). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new 'gland-associated immune niche' has implications for respiratory health.

A surgical method to be reminded for the treatment of symptomatic ipsilateral central venous occlusions in patients with hemodialysis access: Axillo-axillary venous bypass case report and review of the literature.

BACKGROUND: In this case report, we present two chronic hemodialysis patients with upper extremity swelling due to central venous occlusions together with their clinical presentation, surgical management and brief review of the literature. METHODS: The first patient who was a 63-year-old female patient with a history of multiple bilateral arteriovenous fistulas (AVFs) was referred to our clinic. Physical examination demonstrated a functioning right brachio-cephalic AVF, with severe edema of the right arm, dilated venous collaterals, facial edema, and unilateral breast enlargement. In her history, multiple ipsilateral subclavian venous catheterizations were present for sustaining temporary hemodialysis access. The second patient was a 47-year-old male with a history of failed renal transplant, CABG surgery, multiple AV fistula procedures from both extremities, leg amputation caused by peripheral arterial disease, and decreased myocardial functions. He was receiving 3/7 hemodialysis and admitted to our clinic with right arm edema, accompanied by pain, stiffness, and skin hyperpigmentation symptoms ipsilateral to a functioning brachio-basilic AVF. He was not able to flex his arms, elbow, or wrist due to severe edema. RESULTS: Venography revealed right subclavian vein stenosis with patent contralateral central veins in the first patient. She underwent percutaneous transluminal angioplasty (PTA) twice with subsequent re-occlusions. After failed attempts of PTA, the patient was scheduled for axillo-axillary venous bypass in order to preserve the AV access function. In second patient, venography revealed right subclavian vein occlusion caused secondary to the subclavian venous catheters. Previous attempts for percutaneously crossing the chronic subclavian lesion failed multiple times by different centers. Hence, the patient was scheduled for axillo-axillary venous bypass surgery. CONCLUSION: In case of chronic venous occlusions, endovascular procedures may be ineffective. Since preserving the vascular access function is crucial in this particular patient population, venous bypass procedures should be kept in mind as an alternative for central venous reconstruction, before deciding on ligation and relocation of the AVF.

Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients.

Diffuse alveolar damage (DAD) is a histopathological finding associated with severe viral infections, including SARS-CoV-2. However, the mechanisms mediating progression of DAD are poorly understood. Applying protein digital spatial profiling to lung tissue obtained from a cohort of 27 COVID-19 autopsy cases from the UK, we identified a protein signature (ARG1, CD127, GZMB, IDO1, Ki67, phospho-PRAS40 (T246), and VISTA that distinguishes early / exudative DAD from late / organising DAD with good predictive accuracy. These proteins warrant further investigation as potential immunotherapeutic targets to modulate DAD progression and improve patient outcome.

Follow-up Results of Endovascular Aneurysm Repair Following Abdominal Visceral Debranching

ABSTRACT Introduction: The aim of this study is to present a series of six cases with thoracoabdominal aneurysm treated with hybrid technique in our center. Methods: Between May 2015 and December 2018, the data of six patients with thoracoabdominal aneurysms and various comorbidities who underwent visceral debranching followed by endovascular aortic aneurysm repair were reviewed retrospectively. Results: Patients' mean age was 65.3±19.6 years. All of them were male. Comorbidities were old age, congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, previous surgical interventions, and/or esophageal hemangioma. Except for one patient who underwent coronary artery bypass grafting (inflow was taken from ascending aorta), debranching was performed from the right iliac artery. Debranching of four visceral arteries (superior mesenteric artery, celiac trunk, and bilateral renal right arteries) was performed in three patients, of three visceral arteries (superior mesenteric artery, celiac trunk, right renal artery) was performed in one, and of two visceral arteries (superior mesenteric artery, celiac trunk) was performed in two patients. Great saphenous vein and 6-mm polytetrafluoroethylene grafts were used in one and five patients, respectively, for debranching. Endovascular aneurysm repair was performed following debranching procedures as soon as the patients were stabilized. In total, three patients died at the early, mid, and long-term follow-up due to multiorgan failure, pneumonia, and unknown reasons. Conclusion: Hybrid repair of thoracoabdominal aneurysms may be an alternative to fenestrated or branched endovascular stent grafts in patients with increased risk factors for open surgical thoracoabdominal aneurysm repair; however, the procedure requires experience and care.

Spatial genomics maps the structure, nature and evolution of cancer clones.

Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour1-3. Although these are believed to arise according to the principles of somatic evolution, the exact spatial growth patterns and underlying mechanisms remain elusive4,5. Here, to address this need, we developed a workflow that generates detailed quantitative maps of genetic subclone composition across whole-tumour sections. These provide the basis for studying clonal growth patterns, and the histological characteristics, microanatomy and microenvironmental composition of each clone. The approach rests on whole-genome sequencing, followed by highly multiplexed base-specific in situ sequencing, single-cell resolved transcriptomics and dedicated algorithms to link these layers. Applying the base-specific in situ sequencing workflow to eight tissue sections from two multifocal primary breast cancers revealed intricate subclonal growth patterns that were validated by microdissection. In a case of ductal carcinoma in situ, polyclonal neoplastic expansions occurred at the macroscopic scale but segregated within microanatomical structures. Across the stages of ductal carcinoma in situ, invasive cancer and lymph node metastasis, subclone territories are shown to exhibit distinct transcriptional and histological features and cellular microenvironments. These results provide examples of the benefits afforded by spatial genomics for deciphering the mechanisms underlying cancer evolution and microenvironmental ecology.

The role of phylogenetic relatedness on alien plant success depends on the stage of invasion.

Darwin's naturalization hypothesis predicts successful alien invaders to be distantly related to native species, whereas his pre-adaptation hypothesis predicts the opposite. It has been suggested that depending on the invasion stage (that is, introduction, naturalization and invasiveness), both hypotheses, now known as Darwin's naturalization conundrum, could hold true. We tested this by analysing whether the likelihood of introduction for cultivation, as well as the subsequent stages of naturalization and spread (that is, becoming invasive) of species alien to Southern Africa are correlated with their phylogenetic distance to the native flora of this region. Although species are more likely to be introduced for cultivation if they are distantly related to the native flora, the probability of subsequent naturalization was higher for species closely related to the native flora. Furthermore, the probability of becoming invasive was higher for naturalized species distantly related to the native flora. These results were consistent across three different metrics of phylogenetic distance. Our study reveals that the relationship between phylogenetic distance to the native flora and the success of an alien species changes from one invasion stage to the other.

Single-cell roadmap of human gonadal development.

Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries1. Historically, limited tissue accessibility, a lack of reliable in vitro models and critical differences between humans and mice have hampered our knowledge of human gonadogenesis, despite its importance in gonadal conditions and infertility. Here, we generated a comprehensive map of first- and second-trimester human gonads using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy. We extracted human-specific regulatory programmes that control the development of germline and somatic cell lineages by profiling equivalent developmental stages in mice. In both species, we define the somatic cell states present at the time of sex specification, including the bipotent early supporting population that, in males, upregulates the testis-determining factor SRY and sPAX8s, a gonadal lineage located at the gonadal-mesonephric interface. In females, we resolve the cellular and molecular events that give rise to the first and second waves of granulosa cells that compartmentalize the developing ovary to modulate germ cell differentiation. In males, we identify human SIGLEC15+ and TREM2+ fetal testicular macrophages, which signal to somatic cells outside and inside the developing testis cords, respectively. This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, which can guide in vitro gonadogenesis.

Detection of Cytomegalovirus Infection in Infants with Biliary Atresia: A Meta-analysis.

Objectives Biliary atresia (BA) is the most common indication of liver transplantation in children. Several reports attributed BA to both prenatal and perinatal etiologies, including a viral infection-induced autoimmune response that targets the bile ducts. Cytomegalovirus (CMV) remains the most common virus being linked to BA. This meta-analysis aimed to estimate to what extent CMV infection is detected in patients with BA. Methods This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE, Embase, Scopus, WHO-Virtual Health Library (VHL), ScienceDirect, and Google Scholar were used for the systematic search. The risk of bias was assessed using the Newcastle-Ottawa scale. Random effects model was used to estimate the pooled prevalence estimate with the corresponding 95% confidence interval (CI) using Comprehensive Meta-Analysis Software version 3.3. Results A total of 19 studies that fulfilled the eligibility criteria were included in the meta-analysis. The total number of infants with BA was 630 patients, and the pooled overall prevalence of CMV infection among them was 25.4% (95% CI: 15.9%-38.0%). There was high heterogeneity among studies (I 2 = 85.1%, p < .001), and subgroup analyses showed significant regional differences (X 2 = 48.9, p <.001). Data on the prognosis of CMV-associated BA were scarce and obtainable from few studies that suggested an association between detection of CMV infection and poor prognosis of BA. Conclusions The limited available data demonstrates that the rate of detection of CMV infection is high in infants with BA. There is still a need for large studies with appropriate controls for obtaining more reliable results about the various aspects of the association between CMV infection and BA.