Stable nebulization and muco-trapping properties of Regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries around the world, can effectively trap SARS-CoV-2 virus-like-particles in fresh human airway mucus. IN-006, a reformulation of Regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.

Stakeholders facilitating hope and empowerment amidst social suffering: A qualitative documentary analysis exploring lives of homeless women with mental illness.

BACKGROUND: Globally homeless mentally ill (HMI) individuals are considered one of the most vulnerable populations. An individual-centric, psychopathology-oriented focus of the existing mental health-care system limits the understanding of the HMI individuals through the disability lens overlooking their strengths and resilience that enable them to survive extremely hostile environments. Contemporary mental health research has embraced a paradigm shift that allows researchers to look beyond the predominant medical model to give precedence to a socio-culturally contexted and experientially firm understanding of human behaviour. AIM: Through the theoretical lens of social suffering, this article attempts to understand the lived experiences of the HMI women, the perspective of their caregivers and the standpoint of service providers in the context of homelessness and mental illness. METHODOLOGY: A documentary analysis as a qualitative research methodology has been used to reflect upon the concerns mentioned above. Following Figueroa's approach to the analysis of audio-visual texts, the documentary Lapata Zindagi, directed by Radhika Lata Murthy, has woven the stories of four HMI women and their caregivers have been analysed. The two-phased analysis involved constructivist grounded theory procedures. RESULTS: The methodological steps, rigour and the resulting categories (experience of social suffering associated with homelessness among HMI women, denial of care and rights within patriarchy, helplessness associated with the burden of caregiving and roles of NGO and community in building hope and empowerment) have been discussed through the lens of social suffering and how stakeholders might facilitate hope and empowerment amidst it. CONCLUSION: The article highlights the dire and urgent need to integrate mental health into primary health care and community-based intervention and move beyond clinical recovery to nurture 'hope' to enable recovery and empowerment for such marginalised populations.

On the Social Constructionist Approach to Traumatized Selves in Post-disaster Settings: State-Induced Violence in Nandigram, India.

Through the use of concepts such as traumatization and posttraumatic stress disorder (PTSD), the distressing experiences of survivors are understood in psychology and psychiatry primarily as the behavioural symptoms resulting supposedly from an incomplete emotional and cognitive processing of traumatic events. Due to such an exclusive focus on the intra-psychic processes, besides the survivors' healing facilitated by cultural beliefs and symbols, their trauma-related distress associated with the cultural interpretation of loss is also generally ignored. This paper illustrates the utility of the social constructionist paradigm in understanding the survivors' experiences of suffering and healing within the cultural and socio-political context of violence through an ethnographic study among the poor farmers of Nandigram, India, inflicted by violence from the state government as it tried to forcibly acquire their land to build a chemical factory. How the traumatized selves experience intense distress resulting from disruptions to a sense of wholeness and how this wholeness may be reformulated through culturally valued beliefs are highlighted in the themes of suffering ('experience of PTSD symptoms', 'betrayed self', 'overwhelmed by loss', and 'biographical disruption') and healing ('moral re-affirmation', 'sense of togetherness', 'sense of security due to change in political environment') presented in the vignettes.

Missed non-small cell lung cancer: radiographic findings of potentially resectable lesions evident only in retrospect.

PURPOSE: To assess for change in the 1990s in the failure of detection at chest radiography of potentially resectable non-small cell lung cancer (NSCLC) lesions compared with experience in the previous decade. MATERIALS AND METHODS: From 1993 to 2001, an observational cohort was identified that consisted of 40 instances of NSCLC evident retrospectively at chest radiography but undetected by a radiologist at a time when the cancer was potentially resectable for cure. Sizes and locations of the tumors were assessed. Pearson chi(2) testing was performed to compare the sex distribution of lung cancer in the present series with population data for the sex distribution of lung cancer in the United States during the present study. RESULTS: Twenty-five (62%) undetected NSCLCs were in men and 15 (38%) were in women, yielding a ratio not significantly different from that for the sex distribution of NSCLC according to national data (chi(2) = 0.22, P =.64). Median patient age was 62 years (range, 37-87 years). Median diameter of the missed cancers was 1.9 cm. Missed cancers were most commonly located in the upper lobes (right, 45%; left, 28%; total, 72%), especially in the apical and posterior segments/subsegments (60% of all the missed cancers). A clavicle obscured 22% of the missed cancers. Eighty-five percent of the missed cancers were in peripheral locations. CONCLUSION: Potentially resectable NSCLC lesions missed at chest radiography were characterized by predominantly peripheral (85%) and upper lobe (72%) locations and by apical and posterior segmental/subsegmental locations in an upper lobe (60%). Distribution by sex of the missed cancers was comparable to national data for NSCLC. The missed cancers had a median diameter of 1.9 cm.