Swami Rama Himalayan University

Osteoarthritis (OA) is a common joint condition correlated with aging, characterized by the gradual degradation of cartilage, alterations in the subchondral bone, and ongoing low-level inflammation. There is growing evidence that the senescence-associated secretory phenotype (SASP) of chondrocytes, which includes the continuous release of IL1β, IL6, TNFα, MMP3, and MMP13, offers a crucial function in driving the pathology of OA. In this review, we consolidate the existing knowledge on the molecular processes that lead to chondrocyte aging, such as NFκB/MAPK signaling, oxidative stress, mitochondrial dysfunction, and epigenetic changes. We also critically assess senotherapeutic strategies, including senolytics (dasatinib + quercetin, ABT263), senomorphics (rapamycin, metformin, pterostilbene), anti-oxidant nanomaterials, and therapies based on extracellular vesicles that specifically reduce SASP while maintaining cartilage health. This study looks at SASP biomarkers in different joint tissues. It also examines how nanotechnology and EV strategies can help renew aging chondrocytes. This review examines the impact of cartilage changes on the aging process. It offers guidance on delaying osteoarthritis, identifies early indicators, and proposes innovative treatments to maintain joint health as grow older.

Pulmonary invasive fungal infections (IFIs), particularly among immunocompromised individuals, are associated with substantial morbidity and mortality. This study aimed to evaluate the clinical profile, underlying risk factors, and diagnostic performance of the galactomannan (GM) antigen assay in the diagnosis of Invasive Pulmonary Aspergillosis (IPA).

A cross-sectional observational study was conducted over 12 months at the Himalayan Institute of Medical Sciences, Dehradun, India. A total of 224 patients with suspected pulmonary IFIs were enrolled. Cases were classified as Proven, Probable, Possible, or No IFI based on the EORTC/MSG, Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU) criteria. Respiratory and serum samples were analysed using direct potassium hydroxide (KOH) microscopy, fungal culture, and GM antigen detection via lateral flow assay. Diagnostic accuracy was determined using standard statistical analyses.

Of the 224 patients, 46.4 % were classified as Proven or Probable IFI, 34.8 % as Possible, and 18.8 % as No IFI. dyspnoea (p = 0.002) was the most strongly associated symptom. Significant risk factors included asthma/COPD (52.9 %, p = 0.001), diabetes mellitus (36.5 %, p = 0.028), immunosuppression (37.5 %, p < 0.001). Fungal culture was positive in 30.3 % of cases, with Aspergillus flavus and A. fumigatus as the predominant isolates. A bronchoalveolar lavage fluid (BALF) GM optical density index (ODI) cut-off of ≥1.0 achieved balanced sensitivity (55.56 %) and specificity (75.86 %).

The GM assay in BALF at an ODI threshold of ≥1.0 showsmodest discriminative ability for the early detection of invasive pulmonary aspergillosis (IPA). Incorporating GM testing alongside conventional diagnostics enhances early identification and facilitates prompt antifungal therapy.