Peripheral Neutrophil to Lymphocyte Ratio (NLR), a cogent clinical adjunct for Ki-67 in breast cancer.

BACKGROUND: Clinical utility of Ki-67 immunohistochemistry (IHC) in breast cancer (BC) is mainly limited to decide for the use of chemotherapy and estimate prognosis in patients with either Ki-67 index < 5% or > 30%; however, lacunae still exists pertaining to its analytical validity. Neutrophilia is common in cancer with accompanying lymphocytopenia. Neutrophil to lymphocyte ratio (NLR) captures the intricate balance between pro-tumor neutrophilia and anti-tumor lymphocyte immunity. This study aimed to correlate cellular proliferation in breast cancer with NLR. METHODS: An observational study was carried out including 73 cases of BC; pre-treatment NLR and Ki-67 grading were performed. NLR < 3 was considered low, while ≥ 3 was high. The Ki-67 expression was graded as low ≤ 5%, intermediate 6-29%, or high ≥ 30%. Various clinico-pathological variables were studied, and the association of categorical variables was analyzed using Pearson's chi-square test, and a p-value of < 0.05 was taken as significant. RESULTS: Ki-67 correlated significantly with modified Scarff-Bloom-Richardson (SBR) grade (p < 0.01), and tumor-node-metastasis (TNM) stage (p < 0.001). Correlation of NLR was not significant with SBR grade (p > 0.05) and molecular subtype (p > 0.05); however, NLR was found to be significantly correlated with TNM stage (p < 0.001) and Ki-67 (p < 0.001). CONCLUSION: NLR is fast emerging as a personalized theranostic marker in breast cancer. Instead of determining a generalized cut-off value, individual baseline NLR and its dynamics with disease progression will help manage patients better, obviating some of the drawbacks associated with Ki-67.

Transcriptional advantage influence odorant receptor gene choice.

Odorant receptors (ORs) obey mutual exclusivity and monoallelic mode of expression. Efforts are ongoing to decipher the molecular mechanism that drives the 'one-neuron-one-receptor' rule of olfaction. Recently, single-cell profiling of olfactory sensory neurons (OSNs) revealed the expression of multiple ORs in the immature neurons, suggesting that the OR gene choice mechanism is much more complex than previously described by the silence-all-and-activate-one model. These results also led to the genesis of two possible mechanistic models i.e. winner-takes-all and stochastic selection. We developed Reverse Cell Tracking (RCT), a novel computational framework that facilitates OR-guided cellular backtracking by leveraging Uniform Manifold Approximation and Projection embeddings from RNA Velocity Workflow. RCT-based trajectory backtracking, coupled with statistical analysis, revealed the OR gene choice bias for the transcriptionally advanced (highest expressed) OR during neuronal differentiation. Interestingly, the observed selection bias was uniform for all ORs across different spatial zones or their relative expression within the olfactory organ. We validated these findings on independent datasets and further confirmed that the OR gene selection may be regulated by Upf3b. Lastly, our RNA dynamics-based tracking of the differentiation cascade revealed a transition cell state that harbors mixed molecular identities of immature and mature OSNs, and their relative abundance is regulated by Upf3b.

The care and transport of trauma victims by layperson emergency medical systems: a qualitative study in Delhi, India.

INTRODUCTION: Ambulance-based emergency medical systems (EMS) are expensive and remain rare in low- and middle-income countries, where trauma victims are usually transported to hospital by passing vehicles. Recent developments in transportation network technologies could potentially disrupt this status quo by allowing coordinated emergency response from layperson networks. We sought to understand the barriers to bystander assistance for trauma victims in Delhi, India, and implications for a layperson-EMS. METHODS: We used qualitative methods to analyse data from 50 interviews with frontline stakeholders (including taxi drivers, medical professionals, legal experts and police), one stakeholder consultation and a review of documents. RESULTS: Respondents noted that most trauma victims in Delhi are rapidly brought to hospital by bystanders, taxis and police. While ambulances are common, they are primarily used for interfacility transfers. Entrenched medico-legal practices result in substantial police presence at the hospital, which is a major source of harassment of good Samaritans and interferes with patient care. Trauma victims are often turned away by for-profit hospitals due to their inability to pay, leading to delays in treatment. Recent policy efforts to circumscribe the role of police and force for-profit hospitals to stabilise patients appear to have been unsuccessful. CONCLUSIONS: Existing healthcare and medico-legal practices in India create large systemic impediments to improving trauma outcomes. Until India's ongoing health and transport sector reforms succeed in ensuring that for-profit hospitals reliably provide care, good Samaritans and layperson-EMS providers should take victims with uncertain financial means to public facilities. To avoid difficulties with police, providers of a layperson-EMS would likely need official police sanction and carry visible symbols of their authority to provide emergency transport. Delhi already has several key components of an EMS (including dispatcher coordinated police response, large ambulance fleet) that could be integrated and expanded into a complete system of emergency care.

Structural dynamics of lytic polysaccharide monoxygenases reveals a highly flexible substrate binding region.

Lytic polysaccharide monooxygenases (LPMOs), which are found in fungi, bacteria, and viruses, are redox enzymes utilizing copper to break glycosidic bonds in recalcitrant crystalline form of polysaccharides, such as chitin and cellulose. They are classified by the Carbohydrate-Active enZYmes (CAZy) database under various families. LPMOs's structure with a flat substrate binding region has been shown to contribute to its function, however, the role that LPMOs structural dynamics play during polysaccharide degradation and its mechanism of binding towards substrate are relatively unknown. Here, we report an exhaustive implementation of coarse-grained simulations using Elastic Network Models on multiple LPMO structures to shed light on how their structural dynamics contribute to their chemical function. Using Gaussian network models and Anisotropic network models, we show that the substrate binding region is highly flexible with significant and sustained micro-scale level conformational changes. Significantly, the loops on the binding side of the substrate are most mobile, in concert with the dynamic modes influencing the motions during binding. We also observed dynamic differences between four families of LPMO, namely AA9, AA10, AA11, and AA13 that consist of more than one structure. Specifically, the patterns of motion in the loop regions among the AA9 structures are distinct from those in the AA10 structures.

An Implementation Research Approach to Evaluating Health Insurance Programs: Insights from India.

One of the distinguishing features of implementation research is the importance given to involve implementers in all aspects of research, and as users of research. We report on a recent implementation research effort in India, in which researchers worked together with program implementers from one of the longest serving government funded insurance schemes in India, the Rajiv Aarogyasri Scheme (RAS) in the state of undivided Andhra Pradesh, that covers around 70 million people. This paper aims to both inform on the process of the collaborative research, as well as, how the nature of questions that emerged out of the collaborative exercise differed in scope from those typically asked of insurance program evaluations. Starting in 2012, and over the course of a year, staff from the Aarogyasri Health Care Trust (AHCT), and researchers held a series of meetings to identify research questions that could serve as a guide for an evaluation of the RAS. The research questions were derived from the application of a Logical Framework Approach ("log frame") to the RAS. The types of questions that emerged from this collaborative effort were compared with those seen in the published literature on evaluations of insurance programs in low- and middle-income countries (LMICs). In the published literature, 60% of the questions pertained to output/outcome of the program and the remaining 40%, relate to processes and inputs. In contrast, questions generated from the RAS participatory research process between implementers and researchers had a remarkably different distribution - 81% of questions looked at program input/processes, and 19% on outputs and outcomes. An implementation research approach can lead to a substantively different emphasis of research questions. While there are several challenges in collaborative research between implementers and researchers, an implementation research approach can lead to incorporating tacit knowledge of program implementers into the research process, research questions that are more relevant to the research needs of policy-makers, and greater knowledge translation of the research findings.

Health systems research in the time of health system reform in India: a review.

BACKGROUND: Research on health systems is an important contributor to improving health system performance. Importantly, research on program and policy implementation can also create a culture of public accountability. In the last decade, significant health system reforms have been implemented in India. These include strengthening the public sector health system through the National Rural Health Mission (NRHM), and expansion of government-sponsored insurance schemes for the poor. This paper provides a situation analysis of health systems research during the reform period. METHODS: We reviewed 9,477 publications between 2005 and 2013 in two online databases, PubMed and IndMED. Articles were classified according to the WHO classification of health systems building blocks. RESULTS: Our findings indicate the number of publications on health systems progressively increased every year from 92 in 2006 to 314 in 2012. The majority of papers were on service delivery (40%), with fewer on information (16%), medical technology and vaccines (15%), human resources (11%), governance (5%), and financing (8%). Around 70% of articles were lead by an author based in India, the majority by authors located in only four states. Several states, particularly in eastern and northeastern India, did not have a single paper published by a lead author located in a local institution. Moreover, many of these states were not the subject of a single published paper. Further, a few select institutions produced the bulk of research. Of the foreign author lead papers, 77% came from five countries (USA, UK, Canada, Australia, and Switzerland). CONCLUSIONS: The growth of published research during the reform period in India is a positive development. However, bulk of this research is produced in a few states and by a few select institutions Further strengthening health systems research requires attention to neglected health systems domains like human resources, financing, and governance. Importantly, research capacity needs to be strengthened in states and institutions that have a scarcity of researchers, as well as states that have been the focus of little research. While more funding for health systems research is required, this funding needs to be targeted at deficient health systems domains, geographical areas, and institutions.

Whose problem is it anyway? Crimes against women in India.

The recent public outcry following a brutal gang rape of a young woman in India's national capital was a watershed moment in the world's largest democracy. It generated widespread public and political support for strengthening legal provisions to punish sex offenders. Although the legal response is a useful deterrent against such heinous crimes, women continue to suffer due to deeply rooted social prejudices that make them vulnerable to violence and discrimination in society. In this commentary, we aim to analyse the current developments with respect to gender violence in India within a background of the social position of women in Indian society. Using secondary data related to sex-selective abortions and crimes against women, and a critical review of the portrayal of women in Indian cinema, we reflect on the role of health workers, researchers and public health professionals in shaping a social response towards improving gender parity in our country.