Providing optimal care in the neonatal care units in India: How Covid-19 exacerbated existing barriers.

Nearly one quarter (600,000) of all neonatal deaths worldwide per year occur in India. To reduce neonatal mortality, the Indian Ministry of Health and Family Welfare established neonatal care units, including neonatal intensive care units and specialized neonatal care units to provide immediate care at birth, resuscitation for asphyxiation, postnatal care, follow up for high-risk newborns, immunization, and referral for additional or complex healthcare services. Despite these efforts, neonatal mortality remains high, and measures taken to reduce mortality have been severely challenged by multiple problems caused by the Covid-19 pandemic. In this qualitative study, we conducted seven focus group discussions with newborn care unit nurses and pediatric residents and 35 key informant interviews with pediatricians, residents, nurses, annual equipment maintenance contractors, equipment manufacturers, and Ministry personnel in the Vidarbha region of Maharashtra between December 2019 and November 2020. The goal of the study was to understand barriers and facilitators to providing optimal care to neonates, including the challenges imposed by the Covid-19 pandemic. Covid-19 exacerbated existing barriers to providing optimal care to neonates in these newborn care units. As a result of Covid-19, we found the units were even more short-staffed than usual, with trained pediatric nurses and essential equipment diverted from newborn care to attend to patients with Covid-19. Regular training of neonatal nursing staff was also disrupted due to Covid-19, leaving many staff without the skills to provide optimate care to neonates. Infection control was also exacerbated by Covid-19. This study highlights the barriers to providing optimal care for neonates were made even more challenging during Covid-19 because of the diversion of critically important neonatal equipment and staff trained to use that equipment to Covid-19 wards. The barriers at the individual, facility, and systems levels will remain challenging as the Covid-19 pandemic continues.

Poor power quality is a major barrier to providing optimal care in special neonatal care units (SNCU) in Central India.

Background: Approximately 25% of all neonatal deaths worldwide occur in India. The Indian Government has established Special Neonatal Care Units (SNCUs) in district and sub-district level hospitals to reduce neonatal mortality, but mortality rates have stagnated. Reasons include lack of personnel and training and sub-optimal quality of care. The role of medical equipment is critical for the care of babies, but its role in improving neonatal outcomes has not been well studied.  Methods: In a qualitative study, we conducted seven focus group discussions with SNCU nurses and pediatric residents and thirty-five key informant interviews and with pediatricians, residents, nurses, annual equipment maintenance contractors, equipment manufacturers, and Ministry of Health personnel in Maharashtra between December 2019 and November 2020. The goal of the study was to understand challenges to SNCU care. In this paper, we focus on current gaps and future needs for SNCU equipment, quality of the power supply, and use of SNCU equipment. Results: Respondents described a range of issues but highlighted poor power quality as an important cause of equipment malfunction. Other concerns were lack of timely repair that resulted in needed equipment being unavailable for neonatal care. Participants recommended procuring uninterrupted power supply (UPS) to protect equipment, improving quality/durability of equipment to withstand constant use, ensuring regular proactive maintenance for SNCU equipment, and conducting local power audits to discern and address the causes of power fluctuations. Conclusions: Poor power quality and its negative impact on equipment function are major unaddressed concerns of those responsible for the care and safety of babies in SNCUs in Central India. Further research on the power supply and protection of neonatal equipment is needed to determine a cost-effective way to improve access to supportive care in SNCUs and desired improvements in neonatal mortality rates.

Metabolic response of lung cancer cells to radiation in a paper-based 3D cell culture system.

This work demonstrates the application of a 3D culture system-Cells-in-Gels-in-Paper (CiGiP)-in evaluating the metabolic response of lung cancer cells to ionizing radiation. The 3D tissue-like construct-prepared by stacking multiple sheets of paper containing cell-embedded hydrogels-generates a gradient of oxygen and nutrients that decreases monotonically in the stack. Separating the layers of the stack after exposure enabled analysis of the cellular response to radiation as a function of oxygen and nutrient availability; this availability is dictated by the distance between the cells and the source of oxygenated medium. As the distance between the cells and source of oxygenated media increased, cells show increased levels of hypoxia-inducible factor 1-alpha, decreased proliferation, and reduced sensitivity to ionizing radiation. Each of these cellular responses are characteristic of cancer cells observed in solid tumors. With this setup we were able to differentiate three isogenic variants of A549 cells based on their metabolic radiosensitivity; these three variants have known differences in their metastatic behavior in vivo. This system can, therefore, capture some aspects of radiosensitivity of populations of cancer cells related to mass-transport phenomenon, carry out systematic studies of radiation response in vitro that decouple effects from migration and proliferation of cells, and regulate the exposure of oxygen to subpopulations of cells in a tissue-like construct either before or after irradiation.

Disulfide-Based Diblock Copolymer Worm Gels: A Wholly-Synthetic Thermoreversible 3D Matrix for Sheet-Based Cultures.

It is well-known that 3D in vitro cell cultures provide a much better model than 2D cell cultures for understanding the in vivo microenvironment of cells. However, significant technical challenges in handling and analyzing 3D cell cultures remain, which currently limits their widespread application. Herein, we demonstrate the application of wholly synthetic thermoresponsive block copolymer worms in sheet-based 3D cell culture. These worms form a soft, free-standing gel reversibly at 20-37 °C, which can be rapidly converted into a free-flowing dispersion of spheres on cooling to 5 °C. Functionalization of the worms with disulfide groups was found to be essential for ensuring sufficient mechanical stability of these hydrogels to enable long-term cell culture. These disulfide groups are conveniently introduced via statistical copolymerization of a disulfide-based dimethacrylate under conditions that favor intramolecular cyclization and subsequent thiol/disulfide exchange leads to the formation of reversible covalent bonds between adjacent worms within the gel. This new approach enables cells to be embedded within micrometer-thick slabs of gel with good viability, permits cell culture for at least 12 days, and facilitates recovery of viable cells from the gel simply by incubating the culture in buffer at 4 °C (thus, avoiding the enzymatic degradation required for cell harvesting when using commercial protein-based gels, such as Matrigel).