Integrative Bioinformatics-Gene Network Approach Reveals Linkage between Estrogenic Endocrine Disruptors and Vascular Remodeling in Peripheral Arterial Disease.

Vascular diseases, including peripheral arterial disease (PAD), pulmonary arterial hypertension, and atherosclerosis, significantly impact global health due to their intricate relationship with vascular remodeling. This process, characterized by structural alterations in resistance vessels, is a hallmark of heightened vascular resistance seen in these disorders. The influence of environmental estrogenic endocrine disruptors (EEDs) on the vasculature suggests a potential exacerbation of these alterations. Our study employs an integrative approach, combining data mining with bioinformatics, to unravel the interactions between EEDs and vascular remodeling genes in the context of PAD. We explore the molecular dynamics by which EED exposure may alter vascular function in PAD patients. The investigation highlights the profound effect of EEDs on pivotal genes such as ID3, LY6E, FOS, PTP4A1, NAMPT, GADD45A, PDGF-BB, and NFKB, all of which play significant roles in PAD pathophysiology. The insights gained from our study enhance the understanding of genomic alterations induced by EEDs in vascular remodeling processes. Such knowledge is invaluable for developing strategies to prevent and manage vascular diseases, potentially mitigating the impact of harmful environmental pollutants like EEDs on conditions such as PAD.

Homocysteine, Vitamins B6, B12, and Folate and the Risk of Ischemic and Hemorrhagic Stroke: A Case-control Study from Northeast India.

Background: Stroke is a major leading global health complication. Identification and management of risk factors associated with stroke can help in prior detection, prevention, and improvement in patient care. Purpose: To investigate the prevalence of hyperhomocysteinemia (HHcy) and Vitamins B6, B12, and folate deficiency in stroke patients and also to assess other risk factors associated with ischemic and hemorrhagic stroke. Methods: Detail history of all the subjects in the study including history of hypertension, anemia, fasting glucose, carotid artery thickness, smoking, alcohol, and dietary intake was recorded. Standard assays for homocysteine (Hcy), Vitamins B6, B12, and folate estimation were done. Lipid and renal profile tests were also performed. The prevalence and odds of having HHcy, Vitamins B6, B12, and folate deficiency, and other risk factors in ischemic and hemorrhagic stroke patients were evaluated. Student's t-tests and chi-square tests were done for statistical validation of the data. Results: Prevalence of HHcy and Vitamins B6, B12, and folate deficiency was not observed in ischemic cases. HHcy and folate deficiency was found to be prevalent in hemorrhagic stroke patients. The odds that a person with HHcy and folate deficiency has hemorrhagic stroke was found to be significantly high. Conclusion: In our study, high Hcy and low folate levels emerged as risk factors for hemorrhagic stroke.

Pool vs single sample determination of serum prolactin to explore venipuncture associated stress induced variation.

Stress is identified as a cause of transient hyperprolactinemia, whereas venipuncture is considered a source of stress for patient. The aim of this study was to investigate the association of venipuncture-induced stress with elevation of serum prolactin. This was a cross-sectional observational study conducted on a group of 150 outdoor patients visiting a tertiary care hospital. Serial sampling was performed by drawing venous blood at different time intervals (0, 30 and 60 min) by single venipuncture to measure serum prolactin to diagnose stress-induced hyperprolactinemia. The study was conducted in two phases, namely, Phase 1 and Phase 2, at different times. The Phase 1 results were divided into two groups: Group 1 (0 min) and Group 5 (pool prepared from samples collected at 0 + 30 + 60 min). Likewise, the results of Phase 2 were segregated into five groups; Group 1 (0 min), Group 2 (30 min), Group 3 (60 min), Group 4 (average of three groups), and Group 5 (pool from samples collected at 0 + 30 + 60 min). In both Phase 1 and Phase 2 of the study, there was a statistically significant (p = 0.0003 in Phase 1 and p = 0.02 in Phase 2) decrease in the mean prolactin (17.99 ± 24.76 ng/mL in Phase 1 and 19.61 ± 23.42 ng/mL in Phase 2) in the pooled samples (Group 5) in comparison to the mean prolactin (19.67 ± 27.69 ng/mL in Phase 1 and 21.06 ± 25.06 ng/mL in Phase 2) of the serum collected at 0 h (Group 1). There was no significant difference in the mean prolactin measured from the pooled samples and average prolactin calculated after individual testing from each sample collected at 0 h, 30 min and 60 min. Venipuncture-triggered fear and apprehension may result in transient hyperprolactinemia. In comparison to performing multiple testing on the samples collected at different time intervals and determining the mean, measurement of the analyte from the pooled serum is the better alternative as it can conserve both time and resources.

New observations of the endangered giant freshwater whipray, Urogymnus polylepis, provide further evidence for its distribution and breeding in the north-east coast of India.

The present study reports observations of 13 giant freshwater whipray (Urogymnus polylepis) from commercial fish landings along the north-east coast of India and updates existing records based on field observations and local social media reports. The disc width of the landed specimens ranged from 120 to 223 cm and they weighed 95-300 kg. All 13 specimens observed were mature (nine females and four males) and three females were pregnant, with embryo numbers ranging between 4 and 15. Globally, U. polylepis is listed as 'Endangered', and greater protection measures are needed in India to assist in reversing current population declines.

Inside-Out of Complement in Cancer.

The role of complement in cancer has received increasing attention over the last decade. Recent studies provide compelling evidence that complement accelerates cancer progression. Despite the pivotal role of complement in fighting microbes, complement seems to suppress antitumor immunity via regulation of host cell in the tumor microenvironment. Although most studies link complement in cancer to complement activation in the extracellular space, the discovery of intracellular activation of complement, raises the question: what is the relevance of this process for malignancy? Intracellular activation is pivotal for the survival of immune cells. Therefore, complement can be important for tumor cell survival and growth regardless of the role in immunosuppression. On the other hand, because intracellular complement (the complosome) is indispensable for activation of T cells, these functions will be essential for priming antitumor T cell responses. Here, we review functions of complement in cancer with the consideration of extra and intracellular pathways of complement activation and spatial distribution of complement proteins in tumors and periphery and provide our take on potential significance of complement as biomarker and target for cancer therapy.

Effectiveness of common macrophytes for phytoremediation of hexavalent Cr prevalent in chromite mining areas.

Hexavalent chromium Cr(VI) is carcinogenic. To reduce Cr(VI) toxicity, a study was undertaken to assess the effectiveness of common macrophytes in the range of Cr concentration prevalent in chromite mining areas at Sukinda, Odisha, India. The metal varied from 0.09 to 2.14 mg/L during 2016 - 2019 and indicated that ≅70% waterbodies are contaminated with Cr(VI). Phytoremediation experimentation using five common macrophytes resulted in Pistia stratiotes, Salvinia minima and Ipomoea aquatica as suitable species by remediating 57 to 100% Cr(VI) from 0.2 to 1.0 mg/L within 54 days. S. minima had then found to remove 1 to 1.8 and 1.6 to 2.8 times more Cr (total) than P. stratiotes and I. aquatica respectively from a level of 0.5 to 2.5 mg/L Cr(VI) within 49 days. Irrespective of plant-duration, P. stratiotes excelled over S. minima by 59 to 68% and I. aquatica by 55 to 89% in BCF value. S. minima thus proved best by removing maximum Cr per unit time while the combination of S. minima and P. stratiotes would have promise in respect of generating low volume of remediated biomass in phytoremediation of Cr(VI).Novelty statementMacrophytes differ in their response to remove metal, screening against a given metal concentration suggests the suitable species and testing signifies their effectiveness of remediating metal from contaminated sources.

The pathogenesis of mesothelioma is driven by a dysregulated translatome.

Malignant mesothelioma (MpM) is an aggressive, invariably fatal tumour that is causally linked with asbestos exposure. The disease primarily results from loss of tumour suppressor gene function and there are no 'druggable' driver oncogenes associated with MpM. To identify opportunities for management of this disease we have carried out polysome profiling to define the MpM translatome. We show that in MpM there is a selective increase in the translation of mRNAs encoding proteins required for ribosome assembly and mitochondrial biogenesis. This results in an enhanced rate of mRNA translation, abnormal mitochondrial morphology and oxygen consumption, and a reprogramming of metabolic outputs. These alterations delimit the cellular capacity for protein biosynthesis, accelerate growth and drive disease progression. Importantly, we show that inhibition of mRNA translation, particularly through combined pharmacological targeting of mTORC1 and 2, reverses these changes and inhibits malignant cell growth in vitro and in ex-vivo tumour tissue from patients with end-stage disease. Critically, we show that these pharmacological interventions prolong survival in animal models of asbestos-induced mesothelioma, providing the basis for a targeted, viable therapeutic option for patients with this incurable disease.

Performance and efficiency services for the removal of hexavalent chromium from water by common macrophytes.

Water contamination by hexavalent chromium(Cr) is an emerging issue. The removal of Cr(VI) using phytoremediation via different macrophytes was investigated in this study. To reduce Cr(VI) to the permissible level in irrigation water, the ability of four common macrophytes, viz. Pistia stratiotes (PS), Salvinia minima (SM), Ipomoea aquatica (IA) and Eichhornia crassipes (EC), to remove from 0.5 to 2.0 mg Cr(VI)/L was analyzed. The overall growth of PS was enhanced by 11 to 24%, SM by 36 to 53%, EC by 65 to 101% and IA by 4 to 13% by reducing Cr from 48 to 87% within 29 days of the experiment. In successive experiments, chromium uptake by SM surpassed ∼11.86-, ∼17.17- and ∼94-fold that of PS, EC and IA, respectively, after 15 days of growth in 0.35 to 1.75 mg Cr(VI)/L. The bioconcentration factor of SM surpassed that of PS, IA and EC by 0.64 to 1.73, 1.09 to 4.07 and 0.71 to 1.85 times, while PS exceeded IA and EC by1.71 to 2.35 and 1.07 to 1.11 times, respectively. SM was thus shown to offer efficient removal of Cr(VI), from a level ≅2.0 mg/L, while a suitable combination of SM and PS was efficient at ≤1.0 mg/L. Novelty It unravels the appropriate macrophytes in terms of biomass production and Cr- uptake pattern under natural condition for phytoremediation of aqueous Cr(VI) and in turn offer services to clean the environment.

Inclusion of multiple high-risk histopathological criteria improves the prediction of adjuvant chemotherapy efficacy in lung adenocarcinoma.

AIMS: The decision to consider adjuvant chemotherapy (AC) for non-small cell lung cancer is currently governed by clinical stage. This study aims to assess other routinely collected pathological variables related to metastasis and survival for their ability to predict the efficacy of AC in lung adenocarcinoma. METHODS AND RESULTS: A retrospective single-centre series of 620 resected lung non-mucinous adenocarcinoma cases from 2005 to 2015 was used. Digital images of all slides were subjected to central review, and data on tumour histopathology, AC treatment and patient survival were compiled. A statistical case matching approach was used to counter selection bias. Several high-risk pathological criteria predict both pathological nodal involvement and early death: positive vascular invasion status (VI+) (HR = 2.10, P < 0.001), positive visceral pleural invasion status (VPI+) (HR = 2.16, P < 0.001), and solid/micropapillary-predominant WHO tumour type (SPA/MPPA) (HR = 3.29, P < 0.001). Crucially, these criteria also identify patient groups benefiting from AC (VI + HR = 0.69, P = 0.167, VPI + HR = 0.44, P = 0.004, SPA/MPPA HR = 0.36, P = 0.006). Cases showing VI+/VPI+/SPA/MPPA histology in the absence of AC stage criteria were common (170 of 620 total), and 8 had actually received AC. This group showed much better outcomes than equivalent untreated cases in matched analysis (3-year OS 100.0% versus 31.3%). Inclusion of patients with VI+/VPI+/SPA/MPPA histology would increase AC-eligible patients from 51.0% to 84.0% of non-mucinous tumours in our cohort. CONCLUSIONS: Our data provide preliminary evidence that the consideration of AC in patients with additional high-risk pathological indicators may significantly improve outcomes in operable lung adenocarcinoma, and that AC may be currently underused.

A cross-sectional study of association of serostatus and extra-articular manifestations in patients with rheumatoid arthritis in a teaching hospital.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease, which mistakenly attacks the joints and induces the inflammatory changes that thicken the joints (the synovium) resulting in swelling and pain in and around the joints. It causes pain, joint deformity, and also affects the quality of life. The joint is affected symmetrically. It also can affect body systems, such as the cardiovascular, respiratory systems, or other systems, which manifest as extra-articular manifestations. Extra-articular manifestations of RA are documented less in India hence this study was undertaken to correlate RA with extra-articular manifestations as well as its relationship with serostatus in patients with extra-articular manifestations. MATERIALS AND METHODS: Sixty patients (age between 18-60 years) attending Medicine/Rheumatology outpatient department were included in the study (12 months) who fulfilled the 2010 RA classification criteria laid down by American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) for RA. All the subjects underwent a thorough history, clinical examination, and laboratory investigations. The relevant data were analyzed with appropriate statistical methods after 12 months' duration. RESULTS: Nearly 68.33% of the subjects were found to have extra-articular manifestations mostly in the age group of 31-40 years with prevalence higher in the female. In the seropositive patients, early morning stiffness (EMS) constitutes 63.82% of the total extra-articular manifestations in the patients followed by anemia (38.29%) and peripheral neuropathy (34.04%). On the other hand, in the seronegative cases, EMS (61.53%) followed by anemia (23.07), peripheral neuropathy (15.38%), and keratoconjunctivitis sicca (15.38%). Extra-articular manifestations in seropositive patients have a statistically significant relationship with the increase in the duration of the disease. CONCLUSION: Extra-articular manifestations need to be looked carefully as it is associated with more severe disease. Seropositivity and extra-articular manifestations both usually indicate that the RA is more severe and may affect the quality of life.

Reduced Protumorigenic Tumor-Associated Macrophages With Statin Use in Premalignant Human Lung Adenocarcinoma.

BACKGROUND: Statins have anticancer properties by acting as competitive inhibitors of the mevalonate pathway. They also have anti-inflammatory activity, but their role in suppressing inflammation in a cancer context has not been investigated to date. METHODS: We have analyzed the relationship between statin use and tumor-associated macrophages (TAMs) in a cohort of 262 surgically resected primary human lung adenocarcinomas. TAMs were evaluated by multiplex immunostaining for the CD68 pan-TAM marker and the CD163 protumorigenic TAM marker followed by digital slide scanning and partially automated quantitation. Links between statin use and tumor stage, virulence, and cancer-specific survival were also investigated in a wider cohort of 958 lung adenocarcinoma cases. All statistical tests were two-sided. RESULTS: We found a statin dose-dependent reduction in protumorigenic TAMs (CD68+CD163+) in both stromal (P = .021) and parenchymal (P = .003) compartments within regions of in situ tumor growth, but this association was lost in invasive regions. No statistically significant relationship between statin use and tumor stage was observed, but there was a statin dose-dependent shift towards lower histological grade as assessed by growth pattern (P = .028). However, statin use was a predictor of slightly worse cancer-specific survival (P = .032), even after accounting for prognostic variables in a multivariable Cox proportional hazards survival model (hazard ratio = 1.38, 95% confidence interval = 1.04 to 1.84). CONCLUSIONS: Statin use is associated with reduced numbers of protumorigenic TAMs within preinvasive lung adenocarcinoma and is related to reduced tumor invasiveness, suggesting a chemo-preventive effect in early tumor development. However, invasive disease is resistant to these effects, and no beneficial relationship between statin use and patient outcome is observed.

Integration of a Nonsteroidal Anti-Inflammatory Drug with Luminescent Copper for in Vivo Cancer Therapy in a Mouse Model.

A facile, process of fabrication of a luminescent bovine serum albumin-copper nanocluster (BSA-CuNC) customized ibuprofen nanodrug (BSA-CuNC-Ibf), encapsulating the ibuprofen was developed. Ibuprofen, which is commonly used to treat inflammation, was utilized here as a model drug. The formation of BSA-CuNC initiated by encapsulation of the Cu ions within the protein moiety followed by gradual reduction of the Cu ions by certain amino acid residues like tyrosine and tryptophan at alkaline pH resulted in the formation of BSA-CuNC within the protein template. Heat treatment and lowering the pH fitted the ibuprofen in the center by hydrogen bonding, hydrophobic and electrostatic interactions, and resulted in the formation of nanoparticles. The nanodrug (BSA-CuNC-Ibf) thus formed was characterized by transmission electron microscopy (TEM), dynamic and static light scattering (DLS), and zeta potential. The spherical shaped nanodrug has a hydrodynamic diameter of about 100.4 ± 28.9 nm. The encapsulation efficiency was found to be 94% which corresponds to 1880 µg/mL of ibuprofen in the BSA-CuNC-Ibf nanodrug. The as synthesized BSA-CuNC-Ibf exhibited cytotoxicity on both human cervical cancer cells (HeLa) and human lung cancer cells (A549). The present nanodrug when explored for its tumor preventive role on Daltons lymphoma ascites (DLA) bearing Swiss albino mice, exemplified sizable inhibition of tumor growth by reactive oxygen species mediated apoptosis and by modulating prostaglandin (PGE2) levels. It also inhibited metastasis of the cancer cells, thus enhancing the life expectancy of the mice.

A phase I delayed-start, randomized and pharmacodynamic study of metformin and chemotherapy in patients with solid tumors.

PURPOSE: Metformin activates AMP-related pathways leading to inactivation of mammalian target of rapamycin (mTOR) and suppression of its downstream effectors, crucial for cancer growth. Epidemiologic studies showed a reduced incidence and improved survival in cancer patients. We conducted a prospective phase I study to assess the safety of metformin in combination with chemotherapy in patients with solid tumors. METHODS: We conducted a delayed-start randomized trial of non-diabetic patients in two stages. In Stage 1, we randomized patients to two arms: concurrent arm (metformin with chemo) vs. delayed arm (chemo alone). In Stage 2, patients in delayed arm were crossed over to receive metformin. Patients received metformin 500 mg twice daily with chemotherapy to define dose-limiting toxicities (DLTs) in both stages. Secondary endpoints assessed adverse events (AEs) and response rates. Translational correlates included effects of metformin on expression and phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) by western blot in PBMCs. RESULTS: A total of 100 patients were enrolled (51 in delayed arm vs. 49 concurrent arm). Rate of DLTs in patients receiving metformin with chemotherapy was 6.1% vs. 7.8% in patients receiving chemotherapy alone. DLTs seen with addition of metformin included those associated with established chemo adverse events. No lactic acidosis or hypoglycemia occurred. Restaging showed stable disease in 46% at cessation of metformin. 28% of patients with measurable tumor markers showed improvement. AMPK phosphorylation showed a four- to sixfold increase in AMPK phosphorylation after metformin. CONCLUSIONS: This is the largest phase I study of metformin combined with chemotherapy, which suggests that metformin can be given safely with chemotherapy, and offers a platform for future studies. Post-metformin increase in AMPK phosphorylation may potentially explain lack of disease progression in nearly half of our patients. FUNDING: UL1 TR001064. CLINICAL TRIAL INFORMATION: NCT01442870.

In situ growth in early lung adenocarcinoma may represent precursor growth or invasive clone outgrowth-a clinically relevant distinction.

The switch from in situ to invasive tumor growth represents a crucial stage in the evolution of lung adenocarcinoma. However, the biological understanding of this shift is limited, and 'Noguchi Type C' tumors, being early lung adenocarcinomas with mixed in situ and invasive growth, represent those that are highly valuable in advancing our understanding of this process. All Noguchi Type C adenocarcinomas (n = 110) from the LATTICE-A cohort were reviewed and two patterns of in situ tumor growth were identified: those deemed likely to represent a true shift from precursor in situ to invasive disease ('Noguchi C1') and those in which the lepidic component appeared to represent outgrowth of the invasive tumor along existing airspaces ('Noguchi C2'). Overall Ki67 fraction was greater in C2 tumors and only C1 tumors showed significant increasing Ki67 from in situ to invasive disease. P53 positivity was acquired from in situ to invasive disease in C1 tumors but both components were positive in C2 tumors. Likewise, vimentin expression was increased from in situ to invasive tumor in C1 tumors only. Targeted next generation sequencing of 18 C1 tumors identified four mutations private to the invasive regions, including two in TP53, while 6 C2 tumors showed no private mutations. In the full LATTICe-A cohort, Ki67 fraction classified as either less than or greater than 10% within the in situ component of lung adenocarcinoma was identified as a strong predictor of patient outcome. This supports the proposition that tumors of all stages that have 'high grade' in situ components represent those with aggressive lepidic growth of the invasive clone. Overall these data support that the combined growth of Noguchi C tumors can represent two differing biological states and that 'Noguchi C1' tumors represent the genuine biological shift from in situ to invasive disease.

Iron-Copper Bimetallic Nanocomposite Reinforced Dressing Materials for Infection Control and Healing of Diabetic Wound.

A multifunctional nanomaterial based wound healing matrix was fabricated by modified co-precipitation and chemical reduction method. The matrix was comprised of either a bimetallic Fe-Cu nanocomposite powder or a wound bed made up of absorbent cotton swab impregnated with bimetallic Fe-Cu nanocomposite. The detailed analytical studies of both dressing materials (powder and cotton bed) were carried out with transmission electron microscopy, X-ray diffraction, field emission scanning electron microscopy, energy-dispersive X-ray, and bright field microscopy. Both the nanocomposite powder and the nanocomposite impregnated cotton swab exhibited antimicrobial activity against Gram positive and Gram negative bacteria, including multidrug-resistant bacteria (such as methicillin-resistant Staphylococcus aureus) as well as against fungus isolated from different human biological samples (pus/tissue culture/urine). For real time applications, the in vivo wound healing ability of both dressing materials was also carried out in Wistar albino rats with infected diabetic wounds. These biocompatible and biodegradable dressing materials with broad-spectrum antimicrobial properties have exhibited more than 20 mm in diameter zone of microbial growth inhibition against several types of microbes. Remarkably, they have also been found to assist in healing of infected diabetic wounds and show a prospect in the management of other infectious wounds.

Protection versus rights: age of marriage versus age of sexual consent.

As many governments worldwide have raised the legal age of marriage to 18 years, some are also considering raising the age of sexual consent. Without close-in-age exemptions, arguments to align the legal age of sexual consent with that of marriage would restrict the ability of adolescents to legally have sex. In contrast to international agreements that affirm 18 years as the minimum age for consent to marriage, international human-rights standards do not recommend specific age limits for sexual consent but urge recognition of adolescents as rights holders, including rights in relation to sexuality. The majority of the world's young people are having sex before the age of 18 years. Laws that increase the age of sexual consent can be harmful and are often used to curb adolescents' agency, including denial of adolescents' rights to make decisions about whether, when, and with whom to have sex. Such laws can also result in stigmatisation or criminalisation (or both) of individuals who have sex before marriage, and increase barriers to accessing sexual and reproductive health. By contrast, providing adolescents with appropriate information and services supports healthy development, agency, and empowerment around their rights, including the right to be informed about their bodies and the right to consent (or not) to sex. Raising the legal age of sexual consent risks restricting adolescents from accessing the health care they need to protect themselves, and there is no evidence that it prevents consensual sex or sexual coercion. Because the consideration to marry and to have sex are very different, the minimum ages need not be aligned.

BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma.

Patients diagnosed with lung squamous cell carcinoma (LUSC) have limited targeted therapies. We report here the identification and characterisation of BCL11A, as a LUSC oncogene. Analysis of cancer genomics datasets revealed BCL11A to be upregulated in LUSC but not in lung adenocarcinoma (LUAD). Experimentally we demonstrate that non-physiological levels of BCL11A in vitro and in vivo promote squamous-like phenotypes, while its knockdown abolishes xenograft tumour formation. At the molecular level we found that BCL11A is transcriptionally regulated by SOX2 and is required for its oncogenic functions. Furthermore, we show that BCL11A and SOX2 regulate the expression of several transcription factors, including SETD8. We demonstrate that shRNA-mediated or pharmacological inhibition of SETD8 selectively inhibits LUSC growth. Collectively, our study indicates that BCL11A is integral to LUSC pathology and highlights the disruption of the BCL11A-SOX2 transcriptional programme as a novel candidate for drug development.

Contesting restrictive mobility norms among female mentors implementing a sport based programme for young girls in a Mumbai slum.

BACKGROUND: Harmful gender norms are known structural barriers to many public health and development interventions involving adolescent girls. In India, restrictions on girls' liberty to move freely in public spaces contribute to school dropout and early marriage, and negatively affect girls' health and wellbeing, from adolescence into adulthood. We report on mechanisms of change among female mentors 18 to 24 years old who contested discriminatory norms while implementing a sports-based programme for adolescent girls in a Mumbai slum. METHODS: We adopted a prospective qualitative research design. Our analysis is based on case studies derived from two rounds of face to face, in -depth interviews with 10 young women recruited to serve as mentors for the project's young female athletes. We combined both thematic and narrative analysis. RESULTS: The programme created opportunities for collective action, increasing mentors' ability to think and relate in a collectivized manner, and challenged the traditional female identity constructed for young women, which centres on domestic duties. The mentors themselves negotiated freedoms both in and outside their homes, which required careful and strategic bargaining. They changed the nature of key day-to-day social interactions with parents and brothers, as well as with neighbours, parents of their groups of athletes and men on the streets. They formed a new reference group for each other in terms of what was possible and acceptable. Demonstrating greater negotiation skills within the family helped win parents' trust in the mentor's ability to be safe in public spaces. Parents became active supporters by not giving into social sanctions of neighbours and relatives thus co-producing a new identity for their daughters as respectable young women doing 'good work'. They effectively side stepped reputational risk with their presence in public spaces becoming de-sexualised. CONCLUSIONS: Mentors contested mobility restrictions by taking risks as a group first, with collective agency an important step towards greater individual agency. This research provides important insights into addressing embedded social norms that perpetuate gender discriminatory practices and the social patterning of health inequalities.