A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma.

Multiple Myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We established a harmonized consortium to generate an Immune Atlas of MM aimed at informing disease etiology, risk stratification, and potential therapeutic strategies. We generated a transcriptome profile of 1,149,344 single cells from the bone marrow of 263 newly diagnosed patients enrolled in the CoMMpass study and characterized immune and hematopoietic cell populations. Associating cell abundances and gene expression with disease progression revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing patients. Furthermore, signaling analyses suggested active intercellular communication involving APRIL-BCMA, potentially promoting tumor growth and survival. Finally, we demonstrate that integrating immune cell levels with genetic information can significantly improve patient stratification.

An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis.

Myeloid cells are known to suppress antitumour immunity1. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitors to transcriptionally programme the development of immunosuppressive tumour-promoting myeloid cells. Consequentially, depletion of basophils profoundly reduced tumour burden and normalized myelopoiesis. We subsequently initiated a clinical trial of the IL-4Rα blocking antibody dupilumab2-5 given in conjunction with PD-1/PD-L1 checkpoint blockade in patients with relapsed or refractory NSCLC who had progressed on PD-1/PD-L1 blockade alone (ClinicalTrials.gov identifier NCT05013450 ). Dupilumab supplementation reduced circulating monocytes, expanded tumour-infiltrating CD8 T cells, and in one out of six patients, drove a near-complete clinical response two months after treatment. Our study defines a central role for IL-4 in controlling immunosuppressive myelopoiesis in cancer, identifies a novel combination therapy for immune checkpoint blockade in humans, and highlights cancer as a systemic malady that requires therapeutic strategies beyond the primary disease site.

Treatment and Prevention of Umbilical Sagging with Laser-assisted Liposuction: The New Happy Protocol.

Sagging of the periumbilical skin, also known as the "sad umbilicus," is one of the most common postoperative complications in liposuction. It is characterized by an increase in the width and decrease in the height of the umbilicus. Technological advances in power-assisted liposuction resulting in skin tightening have been central to improvements in the treatment of sagging skin. Laser-assisted liposuction is a procedure in which a laser fiber induces lipolysis and skin tightening. Laser treatment delivered using a 980-nm diode laser may result in up to 30% skin surface area contraction. The aim of this study was to describe a new technique called the "happy protocol" for the treatment and prevention of the sad umbilicus. The periumbilical region is treated using a 980-nm diode laser set to an output power of 20 W, with a total delivered energy of 5000 J. The developed technique may be applied to correct shape distortions or to create a natural-looking and aesthetically pleasant umbilicus during liposuction. A decrease in the width of the umbilicus followed by an increase in height are observed in the first postoperative days. Patients who were followed up for 7 months postoperatively showed positive aesthetic results. The final outcome was an oval-shaped umbilicus, with increased height and reduced sagging in the periumbilical region.

Qualidade de vida de indivíduos praticantes de Qigong na comunidade / Quality of life of Qigong's practitioners at community

A qualidade de vida (QV) reflete a satisfação dos indivíduos e sua avaliação é importante para o estabelecimento de atividades de saúde. Os exercícios de Qigong constituem uma prática da Medicina Tradicional Chinesa (MTC) que visa promover saúde e QV. Este estudo tem por objetivo caracterizar a qualidade de vida e o perfil de queixas de um grupo de Práticas Corpo-Mente desenvolvido pelo projeto Grupo de Atenção Integral e Pesquisa em Acupuntura e Medicina Tradicional Chinesa (GAIPA) na atenção básica de Fortaleza. Estudo descritivo transversal, realizado com 10 indivíduos assíduos nas atividades realizadas no período de novembro a dezembro de 2015, com dados coletados nas fichas de avaliação e instrumento WHOQOL-abreviado. A maioria dos indivíduos era mulheres com idade média de 59 anos, apresentavam QV caracterizada de regular a boa, sendo o domínio físico o de pior pontuação, possivelmente devido alta prevalência de queixas como lombalgia e ansiedade. Com base nos dados, se faz necessário o desenvolvimento de ações que integrem saúde física e mental na atenção básica.(AU)

The Quality of Life (QL) reflects individual's satisfaction. The proper assessment is important to the establishment of Healthy activities. The Qigong exercises are consisted by practices from the Traditional Chinese Medicine, which may promote Health and QL. The aim of this study was to characterize QL and most complains from a body-mind exercises' Qigong's group developed by GAIPA project at Fortaleza's Primary Attention. It was an Transversal Descriptive Study, composed with a sample of assiduous 10 participants at activities at 09/2015-12/2015 period. Data were collected from evaluation records papers and WHOQOL-bref. The majority were composed by Women at fifty nine years old. The QL from those subjects was evaluated as regular/good, with Physic Domain being the worst score, probably because of high prevalence of complains such as Low back pain and anxiety. Acoording data, it makes necessary the development of strategies that integrate body and mental health in Primary Attention.(AU)