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

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

One stage treatment of chronic osteomyelitis using antibiotic impregnated bone graft substitute: a preliminary report

Aim: Chronic Osteomyelitis is a difficult to treat condition whose success is dependent on the eradication of foci of infection and effective dead space management, usually utilizing a multi-staged approach. Effective management is costly especially because repeated procedures requiring hospitalization are needed. We sought to determine if a single staged procedure would effectively address the logistic problems in our environment.Methods: this was a prospective study involving 15 patients with established chronic osteomyelitis (13 type A and 2 type B). Each patient had radical debridement and dead-space management using adequate quantities of Herafill® G beads.Results: Using this technique, we achieved control of infection in 66.7% of all cases seen. Four patients developed recurrence during the follow up period and one patient needed a below knee amputation for vascular complications arising from surgery.Conclusion: one stage treatment using absorbable antibiotic impregnated bone graft substitutes is a reasonable treatment option in managing chronic osteomyelitis.Keywords: Chronic Osteomyelitis, antibiotic bead