The First Differentiated TB Care Model From India: Delays and Predictors of Losses in the Care Cascade.

To reduce TB deaths in resource-limited settings, a differentiated care strategy can be used to triage patients with high risk of severe illness (i.e., those with very severe undernutrition, respiratory insufficiency, or inability to stand without support) at diagnosis and refer them for comprehensive assessment and inpatient care. Globally, there are few examples of implementing this type of strategy in routine program settings. Beginning in April 2022, the Indian state of Tamil Nadu implemented a differentiated care strategy called Tamil Nadu-Kasanoi Erappila Thittam (TN-KET) for all adults aged 15 years and older with drug-susceptible TB notified by public facilities. Before evaluating the impact on TB deaths, we sought to understand the retention and delays in the care cascade as well as predictors of losses. During April-June 2022, 14,961 TB patients were notified and 11,599 (78%) were triaged. Of those triaged, 1,509 (13%) were at high risk of severe illness; of these, 1,128 (75%) were comprehensively assessed at a nodal inpatient care facility. Of 993 confirmed as severely ill, 909 (92%) were admitted, with 8% unfavorable admission outcomes (4% deaths). Median admission duration was 4 days. From diagnosis, the median delay in triaging and admission of severely ill patients was 1 day each. Likelihood of triaging decreased for people with extrapulmonary TB, those diagnosed in high-notification districts or teaching hospitals, and those transferred out of district. Predictors of not being comprehensively assessed included: aged 25-34 years, able to stand without support, and diagnosis at a primary or secondary-level facility. Inability to stand without support was a predictor of unfavorable admission outcomes. To conclude, the first quarter of implementation suggests that TN-KET was feasible to implement but could be improved by addressing predictors of losses in the care cascade and increasing admission duration.

--Eleven tips for operational researchers working with health programmes: our experience based on implementing differentiated tuberculosis care in south India.

Due to the workload and lack of a critical mass of trained operational researchers within their ranks, health systems and programmes may not be able to dedicate sufficient time to conducting operational research (OR). Hence, they may need the technical support of operational researchers from research/academic organisations. Additionally, there is a knowledge gap regarding implementing differentiated tuberculosis (TB) care in programme settings. In this 'how we did it' paper, we share our experience of implementing a differentiated TB care model along with an inbuilt OR component in Tamil Nadu, a southern state in India. This was a health system initiative through a collaboration of the State TB cell with the Indian Council of Medical Research institutes and the World Health Organisation country office in India. The learnings are in the form of eleven tips: four broad principles (OR on priority areas and make it a health system initiative, implement simple and holistic ideas, embed OR within routine programme settings, aim for long-term engagement), four related to strategic planning (big team of investigators, joint leadership, decentralised decision-making, working in advance) and three about implementation planning (conducting pilots, smart use of e-tools and operational research publications at frequent intervals). These may act as a guide for other Indian states, high TB burden countries that want to implement differentiated care, and for operational researchers in providing technical assistance for strengthening implementation and conducting OR in health systems and programmes (TB or other health programmes). Following these tips may increase the chances of i) an enriching engagement, ii) policy/practice change, and iii) sustainable implementation.

Characterization of NCC-RbC-51, an RB cell line isolated from a metastatic site.

Retinoblastoma (RB) is a childhood eye tumor, caused by the RB1 gene mutation. Since RB is a rapidly proliferating tumor, the patient presents with a Group-D/E tumor at the time of diagnosis. Enucleation is preferred in most unilateral cases to prevent metastasis. Various cell lines have been established to study the tumor's growth pattern and target the cancer cells. The commonly used cell lines are WERI-Rb-1 and Y79, both isolated from the primary tumor of RB. Cell lines established from the metastatic site of RB have not been characterized before. In this study, we have characterized NCC-RbC-51, derived from RB tumor to cervical lymph node site and investigated its potential to represent a highly aggressive and metastatic tumor. We compared the proliferative and invasive properties of NCC-RbC-51 with a cell line isolated from the primary site, WERI-Rb-1. NCC-RbC-51 had higher rates of proliferation and apoptosis and had better invasive ability. Copy number variation analysis and the pathways predicted from these show that the pathways altered in NCC-RbC-51 could contribute to its metastatic nature. In all, the results suggest that NCC-RbC-51, a cell line isolated from metastatic site, could be a potential model to study aggressive/invasive RB.

Obtaining titanium dioxide nanoparticles with spherical shape and antimicrobial properties using M. citrifolia leaves extract by hydrothermal method.

In this work, we synthesized titanium dioxide (TiO2) nanoparticles using leaf extract of Morinda citrifolia (M. citrifolia) by the advanced hydrothermal method. The synthesized TiO2 nanoparticles were characterized by X-ray diffraction (XRD), Fourier transmission infrared (FT-IR), Ultraviolet-visible diffuse reflectance (UV-Vis DRS), Ultraviolet-visible spectroscopy (UV-Vis), Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM with EDX) techniques. The XRD major peak at 27.3° corresponds to the (110) lattice plane of tetragonal rutile TiO2 phase and average crystalline size of nanoparticles is 10nm. The FT-IR result confirmed that TiO2 nanoparticles and the presences of very few amount of anthraquinone and phenolic compounds of the leaf extract. The obtained nanoparticles were also characterized by UV-Vis DRS absorption spectroscopy and an intense band at 423nm clearly reveals the formation of nanoparticles. SEM images with EDX spectra clearly reveal the size of the nanoparticles, between 15 and 19nm in excellent quasi-spherical shape, by virtue of stabilization (capping) agent. The presence of elements-titanium and oxygen was verified with EDX spectrum. Furthermore, the inhibitory activity of green synthesized TiO2 nanoparticles was tested against human pathogens like Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger by the agar well-diffusion method. The TiO2 nanoparticles exhibited superior antimicrobial activity against Gram-positive bacteria, demonstrating their antimicrobial value against pathogenic diseases.