Lymphangioleiomyomatosis (LAM) is a rare fatal cystic lung disease due to bi-allelic inactivating mutations in tuberous sclerosis complex (TSC1/TSC2) genes coding for suppressors of the mechanistic target of rapamycin complex 1 (mTORC1). The origin of LAM cells is still unknown. Here, we profile a LAM lung compared to an age- and sex-matched healthy control lung as a hypothesis-generating approach to identify cell subtypes that are specific to LAM. Our single-cell RNA sequencing (scRNA-seq) analysis reveals novel mesenchymal and transitional alveolar epithelial states unique to LAM lung. This analysis identifies a mesenchymal cell hub coordinating the LAM disease phenotype. Mesenchymal-restricted deletion of Tsc2 in the mouse lung produces a mTORC1-driven pulmonary phenotype, with a progressive disruption of alveolar structure, a decline in pulmonary function, increase of rapamycin-sensitive expression of WNT ligands, and profound female-specific changes in mesenchymal and epithelial lung cell gene expression. Genetic inactivation of WNT signaling reverses age-dependent changes of mTORC1-driven lung phenotype, but WNT activation alone in lung mesenchyme is not sufficient for the development of mouse LAM-like phenotype. The alterations in gene expression are driven by distinctive crosstalk between mesenchymal and epithelial subsets of cells observed in mesenchymal Tsc2-deficient lungs. This study identifies sex- and age-specific gene changes in the mTORC1-activated lung mesenchyme and establishes the importance of the WNT signaling pathway in the mTORC1-driven lung phenotype.

N-methyl-d-aspartate (NMDA) receptors are widely expressed in the central nervous system. However, their presence and function at extraneuronal sites is less well characterized. In the present study, we examined the expression of NMDA receptor subunit mRNA and protein in human pulmonary artery (HPA) by quantitative polymerase chain reaction (PCR), immunohistochemistry and immunoblotting. We demonstrate that both GluN1 and GluN2 subunit mRNAs are expressed in HPA. In addition, GluN1 and GluN2 (A–D) subunit proteins are expressed by human pulmonary artery smooth muscle cells (HPASMCs) in vitro and in vivo. These subunits localize on the surface of HPASMCs and form functional ion channels as evidenced by whole-cell patch-clamp electrophysiology and reduced phenylephrine-induced contractile responsiveness of human pulmonary artery by the NMDA receptor antagonist MK801 under hypoxic condition. HPASMCs also express high levels of serine racemase and vesicular glutamate transporter 1, suggesting a potential source of endogenous agonists for NMDA receptor activation. Our findings show HPASMCs express functional NMDA receptors in line with their effect on pulmonary vasoconstriction, and thereby suggest a novel therapeutic target for pharmacological modulations in settings associated with pulmonary vascular dysfunction.

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Objective: Diaphragm paralysis is a relatively uncommon entity that can be both congenital and acquired in nature. While commonly asymptomatic, it can also cause a significant decrease in pulmonary function and reserve, particularly in patients with underlying pulmonary diseases. Our aim was to summarize the current literature regarding the minimally invasive techniques used in the surgical correction of acquired diaphragm paralysis via traditional and robotic minimally invasive approaches. Methods: We conducted a systematic review of available literature using the Cochrane methodology and reported findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Results: A total of 6,561 citations were identified through initial database and reference searches, of which 90 articles met the inclusion criteria for review. After further assessment, 33 appropriate full-text studies were selected for the review. Of the selected publications, the majority represented case reports and single-center retrospective studies with level of evidence 4. Only 1 level 2b study (individual cohort study) was identified, comparing minimally invasive and open approaches. Conclusions: Each of the minimally invasive approaches has its unique benefits and disadvantages, which are summarized and delineated in this article. Ultimately, no preferred method of diaphragm plication for diaphragm paralysis can be recommended at this time based on clinical data. The choice of procedure and surgical approach continues to be selected based on the surgeon's experience and preference.

Background: Currarino-Silverman (CS) syndrome is an extremely rare congenital deformity of the anterior chest wall. The syndrome is often combined with congenital heart defects and spinal abnormalities. As of currently, there is a lack of definite description in the literature about this type of pectus deformity.Typically, patients do not require surgical intervention for medical reasons, and the correction is usually only for cosmetic purposes. The purpose of this study was to demonstrate surgical intervention for CS syndrome at a tertiary care facility, and to summarize the available literature. Methods: Patients with CS syndrome were retrospectively reviewed from a period of June 2012 to August 2019. An extensive literature search for "Currarino-Silverman syndrome," "pouter pigeon chest," "chondromanubrial deformity," "type 2 pectus carinatum" and "pectus arcuatum" was performed. Results: Four clinical cases of CS syndrome are presented, two of which were symptomatic and corrected.The procedure of choice was the modified Ravitch-type thoracoplasty with double osteotomy and implantation of support plates. Conclusions: There is no clear definition of CS syndrome in the literature. Correct and uniform classification plays a crucial role in the surgical treatment of this pathology. Due to the extreme rarity of the disease, challenging deformity, and variable anatomy of the fused sternum, there are no clear guidelines in treatment approaches. The correction is mostly pursued only for cosmetic results, and the best surgical option for CS syndrome remains the relatively aggressive Ravitch-type procedure with multi-level wedge osteotomy.