Using PET imaging to track STING-induced interferon signaling

In the 19th century, Ilya Metchnikoff defined and broadened our initial understanding of phagocytosis and, in 1908, went on to show that a cellular component (i.e., DNA) stimulates immune responses (1). About a century later, Janeway conceptualized pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs) (2). Since then, we know that PAMP recognition by innate immune cells via PRRs activates the production of several cytokines, including interferons (IFNs), with the eventual recruitment of lymphocytes. Subsequent research discovered that innate immune recognition of double-stranded DNA (dsDNA) triggers autoimmune diseases (3). However, before the discovery of dsDNA sensors, an endoplasmic reticulum (ER) protein encoded by the TMEM173 gene, known as a stimulator of IFN genes (STING), was identified as a significant factor involving DNA recognition in innate immunity (4). Subsequently, scientists discovered that the direct cytosolic DNA sensor (cGAS) activates the expression of type 1 IFNs (5). Today, it is well known that activation of cGAS-cGAMP-STING signaling is triggered by cytosolic DNA and is necessary for antimicrobial and antitumor immune responses. In PNAS, Liang et al. (6) describe an innovative process for monitoring STING-induced IFN signaling. Induction of IFN signaling by STING occurs on detection of cytoplasmic DNA, whichmay be tumor- or microbial-derived. STING is activated when cGAS catalyzes the synthesis of cyclic dinucleotides (CDNs) including 2′3′-cGAMP (7). STING is translocated from the ER to the perinucleus, phosphorylated by TANK-binding kinase 1 (TBK1) and recruits IFN regulatory factor 3 (IRF3), which in turn is phosphorylated by TBK1, forms a dimer, and enters the nucleus. Phosphorylated IRF3 activates transcription of type 1 IFNs and other relevant cytokines (8) which bind to the heterodimeric IFN receptors (IFNAR1 and IFNAR2) and recruits Janus family kinase 1(Jak1) and tyrosine kinase 2 (Tyk2), which in turn phosphorylates and activates IFNAR1 and IFNAR2. Activated IFNAR1 and 2 phosphorylate signal transducers and activators of transcription (STAT) proteins (STAT1 and STAT2), which are transferred to the nucleus along with IFN regulatory factor 9 (IRF9), to enhance transcription of IFN target genes (9) and subsequently activate the innate and adaptive immune responses

Prevalence of Pin Tract Infection: The Role of Combined Silver Sulphadiazine and Chlorhexidine Dressing

Infection at the pin tract is a common complication of external fixation. This study was done to compare the rate of pin site infection following combined 1 % silver sulphadiazine and 5 % chlorhexidine dressing with 5%chlorhexidine dressing alone. This was a prospective controlled study which compared the results of pin site dressing using a combination of chlorhexidine and silver sulphadiazine cream(Study group)with dressing using chlorhexidine alone. Eligible patients had external fixation in the treatment of open fractures or orthopaedic conditions. Pintract infectionwas deemed to be present if erythema, cellulitis or purulent discharge occurred around a pin site. We did not distinguish between deep and superficial infection. The study group had one hundred and seventy pin sites while the control group had one hundred and sixty-four pin sites. Thirty-eight patients, in whom thirty-seven uniplanar external fixators and one Ilizarov ring fixator were used, made up both groups. Three patients (7.9%) had pin tract infection in the study group while nine patients (23.7%) had pin tract infection in the control group. Therewas a significantly lower prevalence of pin-tract infection amongst patientswhose external fixation pins were dressed with 1 % silver sulphadiazine and 5 % chlorhexidine than in those dressed with chlorhexidine alone (P=0.03). Therefore, we advocate the use of a combination of silver sulphadiazine and chlorhexidine for pin site dressing.Keywords: External fixation, Prevalence, Pin-tract Infection,Dressings

Open Inter Locked Nailing Without Targeting Device or X-Ray Guide in Revision Surgery for Non-Union of the Femur: A Case Report

We present a patient with non-union of the femur and fracture of the nail after Kuntscher nailing who went on to have union after interlocked nailing with a modified Kuntscher nail (K-nail). The interlocked intramedullary nailing was done without X-ray guide or targeting device. The essence of this report is to highlight the possibilities inherent in modification of devices and established procedures. The early result calls for a closer look at this cheap, safe and effective means of handling femoral non-union in third world societies where instrumentation and implants for interlocked nailing may not be readily available. Key Words: Interlocked-Intramedullary nail, Femur, Cortical window

The role of thermography in assessment of wounds. A scoping review

?With this scoping review, we aim to map and summarize what has been reported on thermography used to assess signs of inflammation in humans and animals with surgical or traumatic wounds.?A pattern seen from mapping the available evidence is that a healing wound will, over time, normalize in temperature and if infection occurs in a wound during healing, the temperature will rise above the "inflammation level." In other words, sudden temperature elevation in a wound should raise concerns of infection. This trend aligns with the general understanding of when to suspect infection clinically, but from the available literature, it is still not possible to set a specific temperature threshold value to differentiate between inflammation and infection.?Across diverse and explorative sources, we found a trend that wounds are warmer than non-injured skin and that this temperature rise is detectable with different modern thermographic cameras under pragmatic conditions (equal to bedside examination). This finding aligns with previously published literature where thermography has been used to assess burn wounds, diabetic foot complications and other inflammatory conditions without wounds.?By this review the available literature was mapped and grouped, and trends was revealed but since the reporting is inconsistent and the literature is diverse, firm evidence for introduction thermography for infection surveillance of surgical wounds is missing.?This scoping review revealed that modern thermographic cameras might be a promising tool for the clinician to quickly quantify the temperature pattern of surgical wounds to distinguish between inflammation and infection.Assessment of wounds based on visual appearance has poor inter- and intra-rater reliability and it is difficult to differentiate between inflammation and infection. Thermography is a user-friendly quantitative image technique that collects the skin surface temperature pattern of the wound area and immediately visualizes the temperatures as a rainbow coloured diagram. The aim of this scoping review is to map and summarize the existing evidence on how thermography has been used to assess signs of inflammation in humans and animals with surgical or traumatic wounds. The method follows the Joanna Briggs Institute methodology. The databases searched were PubMed, Embase, CINAHL and Cochrane Library. 3798 sources were identified, 2666 were screened on title and abstract, 99 on full text and 19 studies were included for review. We found that the literature is diverse and originates from a variety of scientific fields. Thermography has been used to detect and predict inflammation and infection in surgical wounds. Grading systems based on the visual appearance correlate to temperature patterns detected with thermography. The general tendency is that thermography detects the temperature in a wound with inflammation to be warmer than a reference area or the same skin area before surgery. In a surgical wound the temperature is elevated 1–2 weeks after surgery due to natural physiological inflammation that induces healing, after 2 weeks the temperature of the wound area slowly and steady decreases to baseline over 1–3 months. If a secondary temperature peak happens during the healing phase of a surgical wound, it is likely that infection has occurred. Modern handheld thermographic cameras might be a promising tool for the clinician to quickly quantify the temperature pattern of surgical wounds to distinguish between inflammation and infection. However, firm evidence supporting infection thermography surveillance of surgical wounds as a technique is missing

Adaptation of the rubber bandage for safe use as tourniquet

The safety of the pneumatic tourniquet lies in the fact that the pressure generated beneath it can be determined and is reproducible unlike the rubber bandage tourniquet with subjective and irreproducible tissue pressure. Application of the rubber bandage over the cuff of an aneroid sphygmomanometer enabled direct determination of tourniquet pressure in sixty-four patients with associated low rate of tourniquet related complications. Seventy-eight limbs, in sixty-four patients, were operated using this composite tourniquet and evaluation after surgery as well as out-patients' clinic follow-up for tourniquet complications revealed complications in six out of eight patients in whom the tourniquet time exceeded 120minutes. In conclusion, the inclusion of an aneroid sphygmomanometer to record tourniquet pressure enhanced the safety of the rubber bandage tourniquet in our study and offers an alternative to the pneumatic type in the attainment of bloodless field where the latter is unavailable

Aberrant CD8+T cells drive reproductive dysfunction in female mice with elevated IFN-γ levels

IntroductionInterferon-gamma (IFN-γ) is pivotal in orchestrating immune responses during healthy pregnancy. However, its dysregulation, often due to autoimmunity, infections, or chronic inflammatory conditions, is implicated in adverse reproductive outcomes such as pregnancy failure or infertility. Additionally, the underlying immunological mechanisms remain elusive.MethodsHere, we explore the impact of systemic IFN-γ elevation on cytotoxic T cell responses in female reproduction utilizing a systemic lupus-prone mouse model with impaired IFN-γ degradation.ResultsOur findings reveal that heightened IFN-γ levels triggered the infiltration of CD8+T cells in the pituitary gland and female reproductive tract (FRT), resulting in prolactin deficiency and subsequent infertility. Furthermore, we demonstrate that chronic IFN-γ elevation increases effector memory CD8+T cells in the murine ovary and uterus.DiscussionThese insights broaden our understanding of the role of elevated IFN-γ in female reproductive dysfunction and suggest CD8+T cells as potential immunotherapeutic targets in female reproductive disorders associated with chronic systemic IFN-γ elevation