Anticancer and Antibacterial Activeness of Fused Pyrimidines: Newfangled Updates.

Pyrimidine-based heterocyclic compounds are garnering substantial interest due to their essential role as a class of natural and synthetic molecules. These compounds show a diverse array of biologically relevant activities, making them highly prospective candidates for clinical translation as therapeutic agents in combating various diseases. Pyrimidine derivatives and their fused analogues, such as thienopyrimidines, pyrazolopyrimidines, pyridopyrimidines, and pyrimidopyrimidines, hold immense possibility in both anticancer and antibacterial research. These compounds exhibit notable efficacy by targeting protein kinases, which are crucial enzymes regulating fundamental cellular processes like metabolism, migration, division, and growth. Through enzyme inhibition, these derivatives disrupt key cellular signaling pathways, thereby affecting critical cellular functions and viability. The advantage lies in the ubiquity of the pyrimidine structure across various natural compounds, enabling interactions with enzymes, genetic material, and cellular components pivotal for chemical and biological processes. This interaction plays a central role in modulating vital biological activities, making pyrimidine-containing compounds indispensable in drug discovery. In the realm of anticancer therapy, these compounds strategically target key proteins like EGFR, important for aberrant cell growth. Fused pyrimidine motifs, exemplified by various drugs, are designed to inhibit EGFR, thereby impeding tumor progression. Moreover, these compounds influence potent antibacterial activity, interfering with microbial growth through mechanisms ranging from DNA replication inhibition to other vital cellular functions. This dual activity, targeting both cancer cells and microbial pathogens, underscores the versatility and potential of pyrimidine derivatives in medical applications. This review provides insights into the structural characteristics, synthesis methods, and significant medicinal applications of fused pyrimidine derivatives, highlighting their double role in combating cancer and bacterial infections.

Promoting Family Integrated Early Childhood Development During the First 1000 Days in Urban Slums of Delhi: Feasibility and Early Implementation Experience.

The first 1000 days are critical for human development. Children residing in urban slums are at higher risk of suboptimal development. This article reports the feasibility and early implementation experiences of child stimulation directed counselling integrated with nutrition and health services by community functionaries in Delhi slums. This implementation research with cohort study design has two groups. The intervention group includes: pregnant women; infants and children in second year. The comparison group (without intervention) includes: recently delivered women, children aged 13-25 months. The feedback from the community functionaries and parents of children were also obtained. 44 videos with Hindi voiceover, demonstration of tools/toys/props, and 9 calendars depicting age-appropriate child stimulation activities were prepared and packaged with health and nutrition services for delivery by the frontline functionaries. These functionaries are coaching the families on child stimulation using these audio-visual messages using Tablets and demonstration tools/toys/props twice every three months. Monitoring and feedback data on service delivery are being collected. The data from the intervention cohort shall be compared with that from the comparison group to document the impact. From 63 anganwadi centres, 130 pregnant women, 142 infants and 136 children have been recruited for the intervention. 82.9% of the families received the intervention within 2 weeks and average time taken was 15 minutes. The initial feedback from the community functionaries and parents are very encouraging. The integrated child development package is acceptable and feasible for implementation through community functionaries and possible integration into the existing programs at scale.

Improving quality of care for pregnancy, perinatal and newborn care at district and sub-district public health facilities in three districts of Haryana, India: An Implementation study.

INTRODUCTION: Improving quality of care (QoC) for childbirth and sick newborns is critical for maternal and neonatal mortality reduction. Information on the process and impact of quality improvement at district and sub-district hospitals in India is limited. This implementation research was prioritized by the Haryana State (India) to improve the QoC for maternal and newborn care at the busy hospitals in districts. METHODS: This study at nine district and sub-district referral hospitals in three districts (Faridabad, Rewari and Jhajjar) during April 2017-March 2019 adopted pre-post, quasi-experimental study design and plan-do-study-act quality improvement method. During the six quarterly plan-do-study-act cycles, the facility and district quality improvement teams led the gap identification, solution planning and implementation with external facilitation. The external facilitators monitored and collected data on indicators related to maternal and newborn service availability, patient satisfaction, case record quality, provider's knowledge and skills during the cycles. These indicators were compared between baseline (pre-intervention) and endline (post-intervention) cycles for documenting impact. RESULTS: The interventions closed 50% of gaps identified, increased the number of deliveries (1562 to 1631 monthly), improved care of pregnant women in labour with hypertension (1.2% to 3.9%, p<0.01) and essential newborn care services at birth (achieved ≥90% at most facilities). Antenatal identification of high-risk pregnancies increased from 4.1% to 8.8% (p<0.01). Hand hygiene practices improved from 35.7% to 58.7% (p<0.01). The case record completeness improved from 66% to 87% (p<0.01). The time spent in antenatal clinics declined by 19-42 minutes (p<0.01). The pooled patient satisfaction scores improved from 82.5% to 95.5% (p<0.01). Key challenges included manpower shortage, staff transfers, leadership change and limited orientation for QoC. CONCLUSION: This multipronged quality improvement strategy improved the maternal and newborn services, case documentation and patient satisfaction at district and sub-district hospitals. The processes and lessons learned shall be useful for replicating and scaling up.

Promoting family integrated early child development (during first 1000 days) in urban slums of India (fine child 3-3-1000): Study protocol.

AIMS: This project tests a novel, targeted home visitation programme for child development targeted behaviour change during the first 1,000 days for families in Delhi urban slums. BACKGROUND: The first 1,000 days have highest brain development potential and is dependent on the available nutrition, health, social and cognitive stimulus. Over 1.3 million children are born annually in the slums of India and are at risk of limited development potential. The children in urban slums at multiplicity of adversities at family, society and environmental levels. No tools are available for the community health functionaries to support the families to promote child development. DESIGN: This cohort study targets provision of behaviour change interventions targeted at three groups (pregnant women, infants and children in year 2) to document the impact on child development. METHODS: This implementation project delivers nutrition, health and child stimulation integrated services for the families through existing government community health workers and nurses. These workers shall train the families using audio-visual messages in tablets and demonstration kits for practice through quarterly home visits. Data on health, nutrition and child development shall be collected at baseline, midterm and after one year. The data from these participants shall be compared with data from recently delivered women, children aged 13 months and 25 months without intervention to document the impact. DISCUSSION: The successful implementation of the project has potential for future integration of the child development components into the existing programme at scale. The learning from this project shall be useful for India and other developing countries. IMPACT: The first 1,000 days are critical period in human brain development and cognitive function acquisition potential, which is dependent on the available nutrition, health, social and cognitive stimulus. The development potential in children born and living in the slums, who are exposed to various adversities, can be mitigated through appropriate family-level practices with support from the community health workers and Nurses. This study is documenting the feasibility and impact of home visit linked coaching of families for improving child development status during the first 1,000 days in three sums of Delhi, India.