A tale of two exemplars: the maternal and newborn mortality transitions of two state clusters in India.

BACKGROUND: India's progress in reducing maternal and newborn mortality since the 1990s has been exemplary across diverse contexts. This paper examines progress in two state clusters: higher mortality states (HMS) with lower per capita income and lower mortality states (LMS) with higher per capita income. METHODS: We characterised state clusters' progress in five characteristics of a mortality transition model (mortality levels, causes, health intervention coverage/equity, fertility and socioeconomic development) and examined health policy and systems changes. We conducted quantitative trend analyses, and qualitative document review, interviews and discussions with national and state experts. RESULTS: Both clusters reduced maternal and neonatal mortality by over two-thirds and half respectively during 2000-2018. Neonatal deaths declined in HMS most on days 3-27, and in LMS on days 0-2. From 2005 to 2018, HMS improved coverage of antenatal care with contents (ANCq), institutional delivery and postnatal care (PNC) by over three-fold. In LMS, ANCq, institutional delivery and PNC rose by 1.4-fold. C-sections among the poorest increased from 1.5% to 7.1% in HMS and 5.6% to 19.4% in LMS.Fewer high-risk births (to mothers <18 or 36+ years, birth interval <2 years, birth order 3+) contributed 15% and 6% to neonatal mortality decline in HMS and LMS, respectively. Socioeconomic development improved in both clusters between 2005 and 2021; HMS saw more rapid increases than LMS in women's literacy (1.5-fold), household electricity (by 2-fold), improved sanitation (3.2-fold) and telephone access (6-fold).India's National (Rural) Health Mission's financial and administrative flexibility allowed states to tailor health system reforms. HMS expanded public health resources and financial schemes, while LMS further improved care at hospitals and among the poorest. CONCLUSION: Two state clusters in India progressed in different mortality transitions, with efforts to maximise coverage at increasingly advanced levels of healthcare, alongside socioeconomic improvements. The transition model characterises progress and guides further advances in maternal and newborn survival.

Small molecules that disrupt RAD54-BLM interaction hamper tumor proliferation in colon cancer chemoresistance models.

RAD54 and BLM helicase play pivotal roles during homologous recombination repair (HRR) to ensure genome maintenance. BLM amino acids (aa 181-212) interact with RAD54 and enhance its chromatin remodeling activity. Functionally, this interaction heightens HRR, leading to a decrease in residual DNA damage in colon cancer cells. This contributes to chemoresistance in colon cancer cells against cisplatin, camptothecin, and oxaliplatin, eventually promoting tumorigenesis in preclinical colon cancer mouse models. ChIP-Seq analysis and validation revealed increased BLM and RAD54 corecruitment on the MRP2 promoter in camptothecin-resistant colon cancer cells, leading to BLM-dependent enhancement of RAD54-mediated chromatin remodeling. We screened the Prestwick small-molecule library, with the intent to revert camptothecin- and oxaliplatin-induced chemoresistance by disrupting the RAD54-BLM interaction. Three FDA/European Medicines Agency-approved candidates were identified that could disrupt this interaction. These drugs bound to RAD54, altered its conformation, and abrogated RAD54-BLM-dependent chromatin remodeling on G5E4 and MRP2 arrays. Notably, the small molecules also reduced HRR efficiency in resistant lines, diminished anchorage-independent growth, and hampered the proliferation of tumors generated using camptothecin- and oxaliplatin-resistant colon cancer cells in both xenograft and syngeneic mouse models in BLM-dependent manner. Therefore, the 3 identified small molecules can serve as possible viable candidates for adjunct therapy in colon cancer treatment.

Comparison of Safety and Efficacy of Two Brands of Botulinum Toxin A for the Treatment of Lateral Canthal Lines (Crow's Feet): A Split-Face Study.

Aim: To compare the safety and efficacy of Stunnox with the international brand of botulinum toxin A on lateral canthal lines. Materials and Methods: This was a nonrandomized, controlled, pilot, split-face study in 47 patients who were given two brands of Botulinum toxin A for the treatment of lateral canthal lines for 12 weeks. Evaluation of lines was assessed with grades of 0 (none), 1 (mild), 2 (moderate), and 3 (severe) at a maximum smile and rest by using ANTERA 3D camera. Results: There was a statistical significance in lateral canthal lines wrinkles reduction on the Stunnox sides compared to pretreatment and at weeks 4, 8, and 12, respectively (all P < 0.05). The wrinkle reduction was similar to the effects of the control internationally available brand of botulinum toxin A. The clinical improvement of lateral canthal line wrinkles was greatest at 4 weeks after injection and the improvement lasted until 12 weeks of treatment with no adverse events observed. Conclusion: In this split-face study, Stunnox botulinum toxin A showed a moderate but significant wrinkle-soothing effect without obvious side effects on the lateral canthal.

Safe Delivery application with facilitation increases knowledge and confidence of obstetric and neonatal care among frontline health workers in India.

Background: Digital learning tools have proliferated among healthcare workers in India. Evidence of their effectiveness is however minimal. We sought to examine the impact of the Safe Delivery App (SDA) on knowledge and confidence among frontline health workers (HW) in India. We also studied whether facilitation to address technical challenges enhanced self-learning. Methods: Staff nurses and nurse-midwives from 30 facilities in two states were divided into control and intervention groups through randomization. Knowledge and confidence were assessed at baseline and after 6 months. Three rounds of facilitation addressing technical challenges in downloading and usage along with reminders about the next phase of learning were conducted in the intervention group. A user satisfaction scale along with qualitative interviews was conducted in the intervention group at the endline along with qualitative interviews on facilitation. Results: The knowledge and confidence of the healthcare workers significantly increased from the baseline to endline by 4 percentage points (P < 0.001). The participants who received facilitation had a higher mean score difference in knowledge and confidence compared to those who did not receive facilitation (P < 0.001). The participants were highly satisfied with the app and video was the most-watched feature. They reported a positive experience of the facilitation process. Conclusion: The effectiveness and acceptability of the SDA indicate the applicability of mHealth learning tools at the primary healthcare level. In a time of rapid digitalization of training, facilitation or supportive supervision needs further focus while on-ground digital training could be invested in to overcome digital illiteracy among healthcare workers.

Systems E-approach for women at risk (SEWA)-A digital health solution for detection of high-risk pregnancies.

BACKGROUND: High-risk pregnancy (HRP) puts current pregnancy at an increased risk of complications. In the absence of pre-existing HRP implementation model of the country, in collaboration with the Government of Himachal Pradesh, a new digital HRP model called the 'SEWA-A System E-approach for Women at risk' was developed. The current article demonstrates a model for the early identification and line listing of high-risk pregnant women (PW) with appropriate referrals and increased engagement with the healthcare workers using a digital tool in the form of the Android App. METHODS: SEWA was implemented as a pilot intervention in two community development blocks of the Chamba district. The key implementation steps included finalizing protocols for the identification of HRPs, defining processes and roles, mapping health facilities, setting up the communication loop, and developing of digital solutions. The digital app, used by the auxiliary nurse midwife (ANM) and program officers, tracked PW for a year from October 19 to October 20 and recorded the ANC visits, referrals, and birth outcomes. A qualitative assessment was conducted among the health workers to find out their level of acceptance. RESULTS: A total of 1,340 high-risk PW were identified. The intervention year saw a rise in the identification of HRP to 27.9% from 3.5% in the previous year. A total of 2,559 conditions were tagged to the identified 1,340 women categorized into current pregnancy (81%), previous pregnancy (16%), and any existing chronic illness (3%). A majority of the women who required urgent referrals were provided referrals. The application recorded 53% of the delivered HRP with a digital birth preparedness plan, prepared and shared with the PW and Accredited Social Health Activists (ASHA), by text message for compliance. CONCLUSION: The SEWA application is a feasible and sustainable solution to complement the competency of the care providers for early identification of the high-risk conditions and reduce the burden of preventable unprecedented deaths around the time of birth.

Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword?

DNA damage repair response is an important biological process involved in maintaining the fidelity of the genome in eukaryotes and prokaryotes. Several proteins that play a key role in this process have been identified. Alterations in these key proteins have been linked to different diseases including cancer. BLM is a 3'-5' ATP-dependent RecQ DNA helicase that is one of the most essential genome stabilizers involved in the regulation of DNA replication, recombination, and both homologous and non-homologous pathways of double-strand break repair. BLM structure and functions are known to be conserved across many species like yeast, Drosophila, mouse, and human. Genetic mutations in the BLM gene cause a rare, autosomal recessive disorder, Bloom syndrome (BS). BS is a monogenic disease characterized by genomic instability, premature aging, predisposition to cancer, immunodeficiency, and pulmonary diseases. Hence, these characteristics point toward BLM being a tumor suppressor. However, in addition to mutations, BLM gene undergoes various types of alterations including increase in the copy number, transcript, and protein levels in multiple types of cancers. These results, along with the fact that the lack of wild-type BLM in these cancers has been associated with increased sensitivity to chemotherapeutic drugs, indicate that BLM also has a pro-oncogenic function. While a plethora of studies have reported the effect of BLM gene mutations in various model organisms, there is a dearth in the studies undertaken to investigate the effect of its oncogenic alterations. We propose to rationalize and integrate the dual functions of BLM both as a tumor suppressor and maybe as a proto-oncogene, and enlist the plausible mechanisms of its deregulation in cancers.

'Good health means being mentally, socially, emotionally and physically fit': women's understanding of health and ill health during and after pregnancy in India and Pakistan: a qualitative study.

OBJECTIVE: To explore what women consider health and ill health to be, in general, and during and after pregnancy. Women's views on how to approach screening for mental ill health and social morbidities were also explored. SETTINGS: Public hospitals in New Delhi, India and Islamabad, Pakistan. PARTICIPANTS: 130 women attending for routine antenatal or postnatal care at the study healthcare facilities. INTERVENTIONS: Data collection was conducted using focus group discussions and key informant interviews. Transcribed interviews were coded by topic and grouped into categories. Thematic framework analysis identified emerging themes. RESULTS: Women are aware that maternal health is multidimensional and linked to the health of the baby. Concepts of good health included: nutritious diet, ideal weight, absence of disease and a supportive family environment. Ill health consisted of physical symptoms and medical disease, stress/tension, domestic violence and alcohol abuse in the family. Reported barriers to routine enquiry regarding mental and social ill health included a small number of women's perceptions that these issues are 'personal', that healthcare providers do not have the time and/or cannot provide further care, even if mental or social ill health is disclosed. CONCLUSIONS: Women have a good understanding of the comprehensive nature of health and ill health during and after pregnancy. Women report that enquiry regarding mental and social ill health is not part of routine maternity care, but most welcome such an assessment. Healthcare providers have a duty of care to deliver respectful care that meets the health needs of women in a comprehensive, integrated, holistic manner, including mental and social care. There is a need for further research to understand how to support healthcare providers to screen for all aspects of maternal morbidity (physical, mental and social); and for healthcare providers to be enabled to provide support and evidence-based care and/or referral for women if any ill health is disclosed.

Comparative study on immunoglobulin Y transfer from breeding hens to egg yolk and progeny chicks in different breeds of poultry.

AIM: This study was undertaken to compare the immunoglobulin Y (IgY) level and its efficacy in laying hens of four different breeds of poultry (viz., Vanraja, Gramapriya, BlackRock, and KalingaBrown) and its relative transfer in egg yolk and chick. MATERIALS AND METHODS: This study was conducted in 48 apparently healthy laying hens vaccinated with Salmonella inactivated polyvalent vaccine, eggs and progeny chicks; 12 each from four different breeds of poultry, viz., Vanraja, Gramapriya, BlackRock, and KalingaBrown. The methodology included measurement of egg and yolk weight, total protein and IgY in egg yolk, total serum protein and IgY in breeding hens, and progeny chicks and extent of IgY transfer from hens to yolk then to chicks. Further, Salmonella-specific antibodies in breeding hens, egg yolk and progeny chicks were assessed using O and H antigen by tube agglutination test. RESULTS: The egg weight differed nonsignificantly (p>0.05) among breeds, however, breed wise significant variation (p<0.01) was reported in yolk weight. The weight of egg yolk significantly affects the total protein and IgY concentration although these levels per unit of volume did not differ. Total protein was significantly higher (p<0.01) in KalingaBrown and Gramapriya as compared to Vanraja and BlackRock. Non-significant (p>0.05) difference among breed was found in total protein of egg yolk and chick. The IgY concentration in hens, egg yolk and chick was found to be in the range of 5.35±0.63-5.83±0.65, 2.3±0.1-2.6±0.2, and 1.3±0.11-1.7±0.16 mg/ml, respectively which is uniform and independent of total protein concentration at all the three levels. Significant breed variations were not observed in maternal IgY transfer from breeding hens to chicks and were 25.62±1.42-36.06±4.34% of total IgY in parent flock. Moderate to higher rate of seroprevalence with peak titers of 1:640 against Salmonella-specific antibodies was observed in only 41.6% of breeding hens. CONCLUSION: No significant difference in the rate of transfer of IgY was observed in four breeds studied (viz., Vanraja, Gramapriya, BlackRock, and KalingaBrown) and moderate seropositivity was detected for Salmonella-specific antibodies in progeny chicks.