RESUMEN
Kyphoscoliosis is a well-known spinal deformity. The abnormal curvature in both the coronal and sagittal planes presents unique challenges during pregnancy. This case discusses the management of a 27-year-old primigravida with thoracolumbar kyphoscoliosis, who underwent an emergency cesarean section at 39.3 weeks of gestation. An interdisciplinary team consisting of an obstetrician, pulmonologist, orthopedic surgeon, anesthesiologist, and physiotherapist collaborated in her care. In such cases, successful outcomes require a tailored approach that prioritizes maternal-fetal well-being and minimizes potential complications associated with complex spinal deformity during pregnancy and childbirth.
RESUMEN
BACKGROUND: We have recently provided the evidence of interconvertible cellular states, driving non-genetic heterogeneity among stem-like oral cancer cells (oral-SLCCs). Here, NOTCH pathway-activity status is explored as one of the possible mechanisms behind this stochastic plasticity. METHODS: Oral-SLCCs were enriched in 3D-spheroids. Constitutively-active and inactive status of NOTCH pathway was achieved by genetic or pharmacological approaches. RNA sequencing and real-time PCR was performed for gene expression studies. in vitro cytotoxicity assessments were performed by AlamarBlue assay and in vivo effects were studied by xenograft growth in zebrafish embryo. RESULTS: We have observed stochastic plasticity in oral-SLCCs, spontaneously maintaining both NOTCH-active and inactive states. While cisplatin refraction was associated with post-treatment adaptation to the active-state of NOTCH pathway, oral-SLCCs with inactive NOTCH pathway status showed aggressive tumor growth and poor prognosis. RNAseq analysis clearly suggested the upregulation of JAK-STAT pathway in NOTCH pathway-inactive subset. The 3D-spheroids with lower NOTCH-activity status displayed significantly higher sensitivity to JAK-selective drugs, Ruxolitinib or Tofacitinib or siRNA mediated downregulation of tested partners STAT3/4. Oral-SLCCs were programmed to adapt the inactive status of NOTCH pathway by exposing to γ-secretase inhibitors, LY411575 or RO4929097, followed by targeting with JAK-inhibitors, Ruxolitinib or Tofacitinib. This approach resulted in a very significant inhibition in viability of 3D-spheroids as well as xenograft initiation in Zebrafish embryos. CONCLUSION: Study revealed for the first time that NOTCH pathway-inactive state exhibit activation of JAK-STAT pathways, as synthetic lethal pair. Therefore, co-inhibition of these pathway may serve as novel therapeutic strategy against aggressive oral cancer.
RESUMEN
The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has negatively impacted the global healthcare and economic systems worldwide. The COVID-19 pandemic has also created an emotional and psychological pandemic among people of all ages irrespective of economic status and physical wellbeing. As a consequence of prolonged lockdowns, one of the most severely affected age groups globally is the young adults' group, especially students. Uncertainties in the academic calendar, restricted outdoor activities, and unusual daily routines during lockdowns led to higher incidences of stress, anxiety, and depression among students worldwide. In this review, we summarise the available evidence on the effect of lockdowns on students and discuss possible positive impacts of yoga and meditation on various psychological, emotional, and immunological parameters, which can significantly influence the general wellbeing and academic performance of students. Perspectives shared in the review will also bring awareness on how yoga and meditation could boost students' performance and assist them in maintaining physical and mental wellbeing during stressful conditions such as future epidemics and pandemics with novel infections. This information could help create better educational curriculums and healthy routines for students.