Active pulmonary tuberculosis: something old, something new, something borrowed, something blue.

Tuberculosis remains a major global health issue affecting all countries and age groups. Radiology plays a crucial role in the diagnosis and management of pulmonary tuberculosis (PTB). This review aims to improve understanding and diagnostic value of imaging in PTB. We present the old, well-established findings ranging from primary TB to the common appearances of post-primary TB, including dissemination with tree-in-bud nodularity, haematogenous dissemination with miliary nodules and lymphatic dissemination. We discuss new concepts in active PTB with special focus on imaging findings in immunocompromised individuals. We illustrate PTB appearances borrowed from other diseases in which the signs were initially described: the reversed halo sign, the galaxy sign and the cluster sign. There are several radiological signs that have been shown to correlate with positive or negative sputum smears, and radiologists should be aware of these signs as they play an important role in guiding the need for isolation and empirical anti-tuberculous therapy

The Nuclear Ionized Gas in the Radio Galaxy M84 (NGC 4374)

We present optical images of the nucleus of the nearby radio galaxy M84 (NGC 4374 = 3C272.1) obtained with the Wide Field/Planetary Camera 2 (WFPC2) aboard the Hubble Space Telescope (HST). Our three images cover the H$\alpha$ + [N II] emission lines as well as the V and I continuum bands. Analysis of these images confirms that the H$\alpha$ + [N II] emission in the central 5'' (410 pc) is elongated along position angle (P.A.) \approx 72\arcdeg, which is roughly parallel to two nuclear dust lanes.Our high-resolution images reveal that the H$\alpha$ + [N II] emission has three components, namely a nuclear gas disk,an `ionization cone', and outer filaments. The nuclear disk of ionized gas has diameter $\approx 1'' = 82$ pc and major axis P.A. \approx 58\arcdeg \pm 6\arcdeg. On an angular scale of 0\farcs5, the major axis of this nuclear gas disk is consistent with that of the dust. However, the minor axis of the gas disk (P.A. \approx 148\arcdeg) is tilted with respect to that of the filamentary H$\alpha$ + [N II] emission at distances > 2'' from the nucleus; the minor axis of this larger scale gas is roughly aligned with the axis of the kpc-scale radio jets (P.A. \approx 170\arcdeg). The ionization cone (whose apex is offset by \approx 0\farcs3 south of the nucleus) extends 2'' from the nucleus along the axis of the southern radio jet. This feature is similar to the ionization cones seen in some Seyfert nuclei, which are also aligned with the radio axes.Comment: 11 pages plus 4 figure

Human meniscus cells express hypoxia inducible factor-1α and increased SOX9 in response to low oxygen tension in cell aggregate culture

In previous work we demonstrated that the matrix-forming phenotype of cultured human cells from whole meniscus was enhanced by hypoxia (5% oxygen). Because the meniscus contains an inner region that is devoid of vasculature and an outer vascular region, here we investigate, by gene expression analysis, the separate responses of cells isolated from the inner and outer meniscus to lowered oxygen, and compared it with the response of articular chondrocytes. In aggregate culture of outer meniscus cells, hypoxia (5% oxygen) increased the expression of type II collagen and SOX9 (Sry-related HMG box-9), and decreased the expression of type I collagen. In contrast, with inner meniscus cells, there was no increase in SOX9, but type II collagen and type I collagen increased. The articular chondrocytes exhibited little response to 5% oxygen in aggregate culture, with no significant differences in the expression of these matrix genes and SOX9. In both aggregate cultures of outer and inner meniscus cells, but not in chondrocytes, there was increased expression of collagen prolyl 4-hydroxylase (P4H)α(I) in response to 5% oxygen, and this hypoxia-induced expression of P4Hα(I) was blocked in monolayer cultures of meniscus cells by the hypoxia-inducible factor (HIF)-1α inhibitor (YC-1). In fresh tissue from the outer and inner meniscus, the levels of expression of the HIF-1α gene and downstream target genes (namely, those encoding P4Hα(I) and HIF prolyl 4-hydroxylase) were significantly higher in the inner meniscus than in the outer meniscus. Thus, this study revealed that inner meniscus cells were less responsive to 5% oxygen tension than were outer meniscus cells, and they were both more sensitive than articular chondrocytes from a similar joint. These results suggest that the vasculature and greater oxygen tension in the outer meniscus may help to suppress cartilage-like matrix formation

What is the impact of Apps in medical education? A study of CAPSULE, a case-based learning App

Introduction - Mobile applications (Apps) are popular in medical education; yet, the actual benefits for students are yet to be formally researched. Clinical And Professional Studies Unique Learning Environment (CAPSULE) is an App created by Brighton and Sussex Medical School. The App provides 650 cases offered to students in their final two years of the undergraduate programme. The App performed consistently well in student feedback, and therefore, a study into the educational benefits of the App was constructed. Methods - A cross-sectional study was performed following two years of use by students to investigate the relationship between App usage and decile ranking. Results - The study found that the students who completed more cases tended to score higher per case (p value=0.0037). The study also found a trend between having higher case scores and being part of a stronger decile (p value=0.019). Conclusions - Greater App usage was linked with performing better in the App itself and this was further associated with being in a stronger decile rank. From a user perspective, the data generated from the App could help with identifying students who are underperforming or help students to recognise areas on which they need to focus

Evolution of the Most Massive Galaxies to z ~ 0.6: II. The link between radio AGN activity and star formation

We analyze the optical spectra of massive (log M*/Msun > 11.4) radio-loud galaxies at z~0.2 and z~0.6. By comparing stellar population parameters of these radio-loud samples with radio-quiet control samples, we investigate how the presence of a radio-emitting jet relates to the recent star formation history of the host galaxy. We also investigate how the emission-line properties of the radio galaxies evolve with redshift by stacking their spectra. Our main results are the following. (1) Both at low and at high redshift, half as many radio-loud as radio-quiet galaxies have experienced significant star formation in the past Gyr. (2) The Balmer absorption line properties of massive galaxies that have experienced recent star formation show that star formation occurred as a burst in many of these systems. (3) Both the radio and the emission-line luminosity of radio AGN evolve significantly with redshift. However, radio galaxies with similar stellar population parameters, have similar emission-line properties both at high- and at low-redshift. These results suggest that massive galaxies experience cyclical episodes of gas accretion, star formation and black hole growth, followed by the production of a radio jet that shuts down further activity. The behaviour of galaxies with log M*/Msun > 11.4 is the same at z = 0.6 as it is at z = 0.2, except that higher redshift galaxies experience more star formation and black hole growth and produce more luminous radio jets during each accretion cycle.Comment: 14 pages, 12 figures, submitted to MNRA

Sunyaev-Zel'dovich observations of galaxy clusters out to the virial radius with the Arcminute Microkelvin Imager

We present observations using the Small Array of the Arcminute Microkelvin Imager (AMI; 14-18 GHz) of four Abell and three MACS clusters spanning 0.171-0.686 in redshift. We detect Sunyaev-Zel'dovich (SZ) signals in five of these without any attempt at source subtraction, although strong source contamination is present. With radio-source measurements from high-resolution observations, and under the assumptions of spherical $\beta$-model, isothermality and hydrostatic equilibrium, a Bayesian analysis of the data in the visibility plane detects extended SZ decrements in all seven clusters over and above receiver noise, radio sources and primary CMB imprints. Bayesian evidence ratios range from 10^{11}:1 to 10^{43}:1 for six of the clusters and 3000:1 for one with substantially less data than the others. We present posterior probability distributions for, e.g., total mass and gas fraction averaged over radii internal to which the mean overdensity is 1000, 500 and 200, r_200 being the virial radius. Reaching r_200 involves some extrapolation for the nearer clusters but not for the more-distant ones. We find that our estimates of gas fraction are low (compared with most in the literature) and decrease with increasing radius. These results appear to be consistent with the notion that gas temperature in fact falls with distance (away from near the cluster centre) out to the virial radius.Comment: 18 pages, 10 figures, submitted to MNRAS (updated authors and fixed Figure 1

Keratinocyte growth factor impairs human thymic recovery from lymphopenia

Background: The lymphocyte-depleting antibody alemtuzumab is a highly effective treatment of relapsing-remitting multiple sclerosis (RRMS); however 50% of patients develop novel autoimmunity post-treatment. Most at risk are individuals who reconstitute their T-cell pool by proliferating residual cells, rather than producing new T-cells in the thymus; raising the possibility that autoimmunity might be prevented by increasing thymopoiesis. Keratinocyte growth factor (palifermin) promotes thymopoiesis in non-human primates. Methods: Following a dose-tolerability sub-study, individuals with RRMS (duration ≤10 years; expanded disability status scale ≤5·0; with ≥2 relapses in the previous 2 years) were randomised to placebo or 180mcg/kg/day palifermin, given for 3 days immediately prior to and after each cycle of alemtuzumab, with repeat doses at M1 and M3. The interim primary endpoint was naïve CD4+ T-cell count at M6. Exploratory endpoints included: number of recent thymic-emigrants (RTEs) and signaljoint T-cell receptor excision circles (sjTRECs)/mL of blood. The trial primary endpoint was incidence of autoimmunity at M30. Findings: At M6, individuals receiving palifermin had fewer naïve CD4+T-cells (2.229x107 /L vs. 7.733x107 /L; p=0.007), RTEs (16% vs. 34%) and sjTRECs/mL (1100 vs. 3396), leading to protocoldefined termination of recruitment. No difference was observed in the rate of autoimmunity between the two groups Conclusion: In contrast to animal studies, palifermin reduced thymopoiesis in our patients. These results offer a note of caution to those using palifermin to promote thymopoiesis in other settings, particularly in the oncology/haematology setting where alemtuzumab is often used as part of the conditioning regime.Trial - MRC and Moulton Trust Funding Me (senior Author) - Wellcome Trust Funding

Exogenous IFN-alpha Administration Reduces Influenza A Virus Replication in the Lower Respiratory Tract of Rhesus Macaques

To determine the role of innate immune responses in controlling influenza A virus replication, rhesus macaques (RM) were administered pegylated IFN-alpha prior to virus challenge. Systemic and mucosal pegylated IFN-alpha administration induced expression of the interferon-stimulated genes (ISG) MxA and OAS in the airways. RM treated with IFN-alpha 24 hours prior to influenza virus challenge had significantly lower peak vRNA levels in the trachea compared to untreated animals. In addition to blunting viral replication, IFN-alpha treatment minimized the weight loss and spike in body temperature after influenza infection of RM. These results confirm the importance of IFN-alpha induced innate immune responses in the rapid control of influenza A virus replication in primates

Toward Shared Decision-Making in Degenerative Cervical Myelopathy: Protocol for a Mixed Methods Study

BACKGROUND Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this. OBJECTIVE The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes. METHODS Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders. RESULTS Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway. CONCLUSIONS This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/46809