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Tarlatamab, a DLL3-targeting bispecific T-cell engager, has rapidly assumed the role of a new standard of care in the later-line treatment of extensive-stage SCLC. Little is known about the efficacy of tarlatamab in other histologies such as DLL3-expressing metastatic pulmonary carcinoid tumor, a clinical entity without many approved management options. Here, we report the case of a patient with metastatic atypical carcinoid tumor which had progressed on multiple previous therapies. Her tumor strongly expressed DLL3 protein and had clinical response to tarlatamab therapy. This case indicates that this novel therapy may be an efficacious option in other pulmonary neuroendocrine cancers.

Abstract Immunotherapy is an expanding area of cancer treatment with significant promise. Despite their efficacy, checkpoint inhibitors are associated with a number of immune‐related adverse events; here, we described thrombocytopenia secondary todurvalumab.

The growing demand for phycobiliproteins from microalgae generates a significant volume of by-products, such as extraction cakes. These cakes are enriched with products of interest for the cosmetics market, namely free fatty acids, particularly polyunsaturated (PUFA). In this work, two cakes, one of spirulina and one of Porphyridium cruentum, were valorized using innovative natural hydrophobic deep eutectic solvents (NaDES) based on alkanediols. The most promising NaDES, as determined by physicochemical properties and screening, are mixtures of alkanediols and fatty acids. These include the mixtures of 1,3-propanediol and octanoic acid (1:5, mol/mol) and 1,3-propanediol and octanoic and decanoic acid (1:3:1, mol/mol). Two extractive processes were implemented: ultrasound-assisted extraction and an innovative mechanical process involving dual asymmetric centrifugation. The second process resulted in the production of extracts significantly enriched in PUFA, ranging from 65 to 220 mg/g dry matter with the two cakes. The extracts and NaDES demonstrated good safety with respect to epidermal keratinocyte viability (>80% at 200 µg/mL). The study of their impact on commensal and pathogenic cutaneous bacteria demonstrated significant effects on the viability of Staphylococcus aureus and Staphylococcus epidermidis (>50% decrease at 200 µg/mL) while preserving Corynebacterium xerosis and Cutibacterium acnes. These results highlight the potential of valorizing these co-products using alkanediol-based NaDES, in a strategy combining an active vector (NaDES) and a growth regulator extract, for the management of cutaneous dysbiosis involving staphylococci.

Abstract Background Mindful of social norms shaping health among women pressured to prove early fertility in Nepal, a bi-national research team developed and piloted a 4-month intervention engaging household triads (newly married women, their husbands, and mothers-in-law) toward advancing gender equity, personal agency, and reproductive health. This study evaluates the impact on family planning and fertility decision-making. Methods In 2021, Sumadhur was piloted in six villages with 30 household triads (90 participants). Pre/post surveys of all participants were analyzed using paired sample nonparametric tests and in-depth interviews with a subset of 45 participants were transcribed and analyzed thematically. Results Sumadhur significantly impacted (p

Abstract Background In Nepal and across the globe, the COVID-19 pandemic has primed an environment for increased rates of violence against women (VAW). This paper explores pandemic-driven economic insecurity and increased alcohol use as instigators of VAW and Intimate Partner Violence (IPV) within newly married households in the rural, Nawalparasi region of Nepal. Methods This study is a secondary analysis of data obtained from the Sumadhur Intervention pilot study that has been previously described and demonstrates successful implementation of group-based, household-level intervention for women’s empowerment and sexual and reproductive health education (1). Our three sets of data were collected before and during the COVID-19 pandemic. The first set is from a Longitudinal Cohort of 200 newly married women who were surveyed twice a year from February 2017 through July 2020. The second data set is a subset cohort of newly married women, their husbands, and their mothers-in-law (31 women, 31 husbands and 31 mothers-in-law) who participated in Sumadhur in January 2021. The third data set was obtained through in-depth interviews in July 2021 from 15 households following Sumadhur. The interviews were thematically coded, and subthemes were identified. A t-test of the January 2021 survey data set was run to look at correlations between income loss, alcohol consumption and experience of IPV among newly married women. All other survey data was analyzed for change over time. Results At three months after the onset of the pandemic (July 2020), the Longitudinal Cohort survey data from newly married women reported increased rates of husbands’ alcohol use as well as personal experiences of IPV as compared to pre-pandemic averages. There was a statistically significant difference (p

Deep mutational scanning can be used to investigate protein function and stability. Here, Dewachter et al. use deep mutational scanning on three essential bacterial proteins to study the mutations’ effects in their original genomic context, providing insight into the proteins’ function and their potential as targets for new antibiotic development.

A trend towards charging for access to research findings, tools and databases is becoming more prominent globally. But charging for the use of research tools and databases that are vital to research supporting national and international policy development might be unjustified. Financial barriers to accessing these tools and databases disproportionately affect low- and middle-income countries, who may have greater need for information that fuels research in their areas of concern. However, changing this trend is potentially possible. One example is the experience with the EuroQol-five-dimensional questionnaire (EQ-5D), a generic measure of health status used in economic evaluations for resource allocation decisions. Increasingly, governments and health-care providers are using the EQ-5D tool in patient-reported outcome measures to monitor quality of health-care provision, diagnose and track disease progression, and involve patients in their health care. The EuroQol Group, which owns the intellectual property rights to the EQ-5D, recently terminated their policy of charging for noncommercial, nonresearch uses of the tool. We share a brief history of this development and examine these charging policies in the context of the EQ-5D's use in national health-care research and policies, reflecting the trends and developments in the use of survey instruments on population health. [ABSTRACT FROM AUTHOR]

Abstract Public health emergencies (PHEs), such as the COVID-19 crisis, are threats to global health and public order. We recommend that countries bolster their PHE responses by investing in health technology assessment (HTA), defined as a systematic process of gathering pertinent information on and evaluating health technologies from a medical, economic, social and ethical standpoint. We present examples of how HTA organizations in low- and middle-income countries have adapted to supporting PHE-related decisions during COVID-19 and describe the ways HTA can help the response to a PHE. In turn, we advocate for HTA capacity to be further developed globally and for increased institutional acceptance of these methods as a building block for preparedness and response to future PHEs. Finally, the long-term potential of HTA in strengthening health systems and embedding confidence and transparency into scientific policy should be recognized.

Methotrexate is a dihydrofolate reductase inhibitor that interferes with DNA synthesis, DNA repair, and cellular replication. We present the first adult case of a patient who received intravenous contrast prior to administration of high-dose methotrexate, who subsequently experienced delayed methotrexate clearance and renal impairment necessitating the use of glucarpidase. This case displays a possible correlation between intravenous radiographic contrast administration and resulting toxicity due to delayed methotrexate clearance. [ABSTRACT FROM AUTHOR]

Background Moyamoya disease (MMD) is a rare cerebrovascular condition, often presenting as a headache or stroke in adults. Anesthetic management of this illness may challenge providers because it can affect the long-term neurologic outcome and hospital length of stay (LOS) in patients with MMD. Materials and Methods A literature search was conducted to assess etiology and epidemiology, as well as existing reports of intraoperative management of MMD. Due to sparse findings, the search was expanded to include studies of the use of intraoperative anesthetic agents during other neurosurgical procedures. We also retrospectively reviewed all MMD cases from January 1, 2009, to December 31, 2015, at Memorial Hermann Hospital-Texas Medical Center, where intraoperative management involved craniotomy and surgical revascularization. Data were collected primarily on the use of several anesthetic agents. The LOS and any adverse events were also recorded for each case. The data were divided into two equivalent case cohorts: (1) January 1, 2009, to February 18, 2013, and (2) February 19, 2013, to December 31, 2015. Results Remifentanil use notably increased between the first and second time periods while fentanyl use decreased. Desflurane usage also demonstrated an observed increase when our two cohorts were compared. Additionally, there was a decrease in the mean LOS between the first and second periods of 3.9 and 3.3 days, respectively. Conclusion Increasing use of remifentanil in MMD cases could be attributed to its ability to provide more stable hemodynamics during induction, maintenance, and emergence of anesthesia when compared with fentanyl. Lower systolic pressures, diastolic pressures, and heart rates were reported in patients receiving remifentanil over fentanyl. [ABSTRACT FROM AUTHOR]

Abstract Background In a setting such as Nepal with malnutrition and persistent poor maternal and infant health outcomes, developing interventions to improve the nutrition of preconception and pregnant women is essential. Objective The objectives of this paper are to describe the full design process of an intervention for newly married women, their husbands, and mothers-in-law to improve maternal nutrition and gender norms, and findings from the feasibility and acceptability pilot. Methods In this paper we describe the three phases of the design of an intervention in rural Nepal. We first conducted a mixed methods formative phase which included in depth interviews with newly married women, their husbands and mothers-in-law (N=60) and a longitudinal study for 18 months with 200 newly married women. We then designed of a household level, group, intervention, in close partnership with community members. Finally, we conducted a pilot intervention with 90 participants and collected both pre/post survey data and in-depth qualitative interviews with a subset (N= 30). All participants from all phases of the study lived in Nawalparasi district of Nepal. Qualitative data was analyzed using a thematic analysis, with inductive and deductive themes and quantitative data was analyzed using descriptive statistics. Results Our formative work highlighted lack of awareness about nutrition, and how women eating last, limited mobility, household and community inequitable gender norms and poor household-level communication contributed to low quality diets. Thus we designed Sumadhur, an intervention that brought groups of households (newly married wife, husband, and mother-in-law) together weekly for four months to strengthen relationships and gain knowledge through interactive content. We found Sumadhur to be highly feasible and acceptable by all respondents, with most (83%) attending 80% of sessions or more and 99% reporting that they would like it to continue. Pre/post surveys showed a decrease in the proportion of women eating last and increase in knowledge about nutrition in preconception and pregnancy. Qualitative interviews suggested that respondents felt it made large impacts on their lives, in terms of strengthening relationships and trust, understanding each other, and changing behaviors. Conclusions We show how a designing an intervention in close partnership with the target recipients and local stakeholders can lead to an intervention that is able to target complicated and culturally held practices and beliefs, positively benefit health and wellbeing, and that is very well received. Trial registration ClinicalTrials.gov NCT04383847 , registered 05/12/2020

BackgroundThere is some initial evidence suggesting that mindsets about the adequacy and health consequences of one’s physical activity (activity adequacy mindsets [AAMs]) can shape physical activity behavior, health, and well-being. However, it is unknown how to leverage these mindsets using wearable technology and other interventions. ObjectiveThis research examined how wearable fitness trackers and meta-mindset interventions influence AAMs, affect, behavior, and health. MethodsA total of 162 community-dwelling adults were recruited via flyers and web-based platforms (ie, Craigslist and Nextdoor; final sample size after attrition or exclusion of 45 participants). Participants received an Apple Watch (Apple Inc) to wear for 5 weeks, which was equipped with an app that recorded step count and could display a (potentially manipulated) step count on the watch face. After a baseline week of receiving no feedback about step count, participants were randomly assigned to 1 of 4 experimental groups: they received either accurate step count (reference group; 41/162, 25.3%), 40% deflated step count (40/162, 24.7%), 40% inflated step count (40/162, 24.7%), or accurate step count+a web-based meta-mindset intervention teaching participants the value of adopting more positive AAMs (41/162, 25.3%). Participants were blinded to the condition. Outcome measures were taken in the laboratory by an experimenter at the beginning and end of participation and via web-based surveys in between. Longitudinal analysis examined changes within the accurate step count condition from baseline to treatment and compared them with changes in the deflated step count, inflated step count, and meta-mindset conditions. ResultsParticipants receiving accurate step counts perceived their activity as more adequate and healthier, adopted a healthier diet, and experienced improved mental health (Patient-Reported Outcomes Measurement Information System [PROMIS]-29) and aerobic capacity but also reduced functional health (PROMIS-29; compared with their no-step-count baseline). Participants exposed to deflated step counts perceived their activity as more inadequate; ate more unhealthily; and experienced more negative affect, reduced self-esteem and mental health, and increased blood pressure and heart rate (compared with participants receiving accurate step counts). Inflated step counts did not change AAM or most other outcomes (compared with accurate step counts). Participants receiving the meta-mindset intervention experienced improved AAM, affect, functional health, and self-reported physical activity (compared with participants receiving accurate step counts only). Actual step count did not change in either condition. ConclusionsAAMs––induced by trackers or adopted deliberately––can influence affect, behavior, and health independently of actual physical activity. Trial RegistrationClinicalTrials.gov NCT03939572; https://www.clinicaltrials.gov/ct2/show/NCT03939572