bluuebunny/crossref_metadata_2025 huggingface dataset:
Toll-like receptor 2, hyaluronan, and neutrophils play a key role in plaque erosion: the OPTICO–ACS study
Authors: Meteva Denitsa , Vinci Ramona , Seppelt Claudio , Abdelwahed Youssef S , Pedicino Daniela , Nelles Gregor , Skurk Carsten , Haghikia Arash , Rauch-Kröhnert Ursula , Gerhardt Teresa , Straessler Elisabeth , Zhao Yingjie , Golla Felix , Joner Michael , Rai Himanshu , Kratzer Adelheid , Arnal Hector Giral , Liuzzo Giovanna , Klotsche Jens , Crea Filippo , Landmesser Ulf , Leistner David M , Kränkel Nicolle
Published: June 2023

Background and aims

In one-third of patients with acute coronary syndrome (ACS), thrombosis occurs despite an intact fibrous cap (IFC) (IFC–ACS, ‘plaque erosion’). Recent studies emphasize neutrophils as the immediate inflammatory response in this pathology, but their exact molecular activation patterns are still poorly understood and may represent future therapeutic targets.

Methods and results

Thirty-two patients with IFC–ACS and matched patients with ACS with ruptured fibrous cap (RFC) (RFC–ACS) from the OPTICO–ACS study were included, and blood samples were collected from the local site of the culprit lesion and the systemic circulation. Neutrophil surface marker expression was quantified by flow cytometry. Neutrophil cytotoxicity towards endothelial cells was examined in an ex vivo co-culture assay. Secretion of active matrix metalloproteinase 9 (MMP9) by neutrophils was evaluated using zymography in supernatants and in plasma samples. Optical coherence tomography (OCT)–embedded thrombi were used for immunofluorescence analysis. Toll-like receptor 2 (TLR2) expression was higher on neutrophils from IFC–ACS than RFC–ACS patients. TLR2 stimulation increased the release of active MMP9 from local IFC–ACS–derived neutrophils, which also aggravated endothelial cell death independently of TLR2. Thrombi of IFC–ACS patients exhibited more hyaluronidase 2 with concomitant increase in local plasma levels of the TLR2 ligand: hyaluronic acid.

Conclusion

The current study provides first in-human evidence for distinct TLR2-mediated neutrophil activation in IFC–ACS, presumably triggered by elevated soluble hyaluronic acid. Together with disturbed flow conditions, neutrophil-released MMP9 might be promoting endothelial cell loss–triggered thrombosis and therefore providing a potential future target for a phenotype-specific secondary therapeutic approach in IFC–ACS.
‘Curiouser and curiouser’: Childhood Figures to Live By, in Writings in French by Lydia Flem and Philippe Forest
Authors: Bainbrigge Susan
Published: June 2023

This article analyses selected writings in French by Lydia Flem and Philippe Forest, with a focus on the intertextual presence of literary figures from well-known sources, identifications with figures from imaginary worlds and their relationship to the writing project. These authors’ curiosity about the place of storytelling in understanding selves and lives extends to the question of how literature connects with experiences that otherwise remain inaccessible or elude conscious awareness. The formal and thematic functions of Lewis Carroll’s Alice and J. M. Barrie’s Peter Pan are examined in Flem’s Comment je me suis séparée de ma fille et de mon quasi-fils and Forest’s L’Enfant éternel. The article argues that via the perspectives of the (parental) narrators in both texts, these literary figures mobilize the creative expression of experiences of change and loss. The (re)turn to literature takes place not because it saves, or consoles, these writers insist; rather, they describe the compelling and paradoxically sustaining functions of reading and writing even as they precisely fail to offer up any certain resolution. Literature’s capacity to enliven curiosity about human experience means that writing is life; literary figures live with and in them. In a similar spirit to Deborah Levy’s description of ‘living autobiography’, the article argues that Flem and Forest attest to the need and desire to write in an ‘engaged’ way, characteristic of a writing practice that encompasses concrete and imaginary worlds, reality and fantasy. From explorations of transition and loss, Flem’s ‘bébé de papier’ and Forest’s ‘être de papier’ emerge.
Rapid Evolution of Glycan Recognition Receptors Reveals an Axis of Host–Microbe Arms Races beyond Canonical Protein–Protein Interfaces
Authors: Hilbert Zoë A , Haffener Paige E , Young Hannah J , Schwiesow Mara J W , Leffler Ellen M , Elde Nels C
Published: June 2023

Detection of microbial pathogens is a primary function of many mammalian immune proteins. This is accomplished through the recognition of diverse microbial-produced macromolecules including proteins, nucleic acids, and carbohydrates. Pathogens subvert host defenses by rapidly changing these structures to avoid detection, placing strong selective pressures on host immune proteins that repeatedly adapt to remain effective. Signatures of rapid evolution have been identified in numerous immunity proteins involved in the detection of pathogenic protein substrates, but whether similar signals can be observed in host proteins engaged in interactions with other types of pathogen-derived molecules has received less attention. This focus on protein–protein interfaces has largely obscured the study of fungi as contributors to host–pathogen conflicts, despite their importance as a formidable class of vertebrate pathogens. Here, we provide evidence that mammalian immune receptors involved in the detection of microbial glycans have been subject to recurrent positive selection. We find that rapidly evolving sites in these genes cluster in key functional domains involved in carbohydrate recognition. Further, we identify convergent patterns of substitution and evidence for balancing selection in one particular gene, MelLec, which plays a critical role in controlling invasive fungal disease. Our results also highlight the power of evolutionary analyses to reveal uncharacterized interfaces of host–pathogen conflict by identifying genes, like CLEC12A, with strong signals of positive selection across mammalian lineages. These results suggest that the realm of interfaces shaped by host–microbe conflicts extends beyond the world of host–viral protein–protein interactions and into the world of microbial glycans and fungi.
Gravitational inversion for arbitrary surface mass distribution—application to earth's time-variable gravity with topography
Authors: Chao Benjamin F
Published: June 2023

The aim of this paper is gravitational inversion, that is, the determination of the mass density distribution of a central body when given the observed external gravitational field that is produced by the mass itself. This inversion for a 3-D mass distribution is known to be grossly non-unique; whereas that for a 2-D mass distribution on a spherical surface is known to be unique. The latter justifies the surface ‘mascon’, or equivalent-water-thickness, solutions when not considering any interior mass transports for the Earth's time-variable gravity as observed by the GRACE satellite. In this paper, using the gravitational multipole formalism cast in the framework of linear Hilbert space with the notion of inner product, we do two things further: (i) we prove mathematically that the 2-D gravitational inversion on an arbitrary surface is unique; and (ii) we derive the algorithm that leads to the unique exact 2-D mass distribution solution, up to a truncated finite spherical harmonic degree. This pertains directly to reaching refined GRACE mascon solutions that account for the actual Earth surface shape including the ellipsoidal figure and the topography. In the process, we also (re)formulate the exact equations, for spherical or arbitrary shape, unifying the formulae that have appeared in the GRACE-relevant literature.
Mitochondrial dysfunction and mitophagy defects in LRRK2-R1441C Parkinson’s disease models
Authors: Williamson Matthew G , Madureira Marta , McGuinness William , Heon-Roberts Rachel , Mock Elliot D , Naidoo Kalina , Cramb Kaitlyn M L , Caiazza Maria-Claudia , Malpartida Ana B , Lavelle Martha , Savory Katrina , Humble Stewart W , Patterson Ryan , Davis John B , Connor-Robson Natalie , Ryan Brent J , Wade-Martins Richard
Published: June 2023

Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene have been identified as one of the most common genetic causes of Parkinson’s disease (PD). The LRRK2 PD-associated mutations LRRK2G2019S and LRRK2R1441C, located in the kinase domain and in the ROC-COR domain, respectively, have been demonstrated to impair mitochondrial function. Here, we sought to further our understanding of mitochondrial health and mitophagy by integrating data from LRRK2R1441C rat primary cortical and human induced pluripotent stem cell-derived dopamine (iPSC-DA) neuronal cultures as models of PD. We found that LRRK2R1441C neurons exhibit decreased mitochondrial membrane potential, impaired mitochondrial function and decreased basal mitophagy levels. Mitochondrial morphology was altered in LRRK2R1441C iPSC-DA but not in cortical neuronal cultures or aged striatal tissue, indicating a cell-type-specific phenotype. Additionally, LRRK2R1441C but not LRRK2G2019S neurons demonstrated decreased levels of the mitophagy marker pS65Ub in response to mitochondrial damage, which could disrupt degradation of damaged mitochondria. This impaired mitophagy activation and mitochondrial function were not corrected by the LRRK2 inhibitor MLi-2 in LRRK2R1441C iPSC-DA neuronal cultures. Furthermore, we demonstrate LRRK2 interaction with MIRO1, a protein necessary to stabilize and to anchor mitochondria for transport, occurs at mitochondria, in a genotype-independent manner. Despite this, we found that degradation of MIRO1 was impaired in LRRK2R1441C cultures upon induced mitochondrial damage, suggesting a divergent mechanism from the LRRK2G2019S mutation.
Cell-type specific defects inPTEN-mutant cortical organoids converge on abnormal circuit activity
Authors: Pigoni Martina , Uzquiano Ana , Paulsen Bruna , Kedaigle Amanda J , Yang Sung Min , Symvoulidis Panagiotis , Adiconis Xian , Velasco Silvia , Sartore Rafaela , Kim Kwanho , Tucewicz Ashley , Tropp Sarah Yoshimi , Tsafou Kalliopi , Jin Xin , Barrett Lindy , Chen Fei , Boyden Edward S , Regev Aviv , Levin Joshua Z , Arlotta Paola
Published: June 2023

De novo heterozygous loss-of-function mutations in phosphatase and tensin homolog (PTEN) are strongly associated with autism spectrum disorders; however, it is unclear how heterozygous mutations in this gene affect different cell types during human brain development and how these effects vary across individuals. Here, we used human cortical organoids from different donors to identify cell-type specific developmental events that are affected by heterozygous mutations in PTEN. We profiled individual organoids by single-cell RNA-seq, proteomics and spatial transcriptomics and revealed abnormalities in developmental timing in human outer radial glia progenitors and deep-layer cortical projection neurons, which varied with the donor genetic background. Calcium imaging in intact organoids showed that both accelerated and delayed neuronal development phenotypes resulted in similar abnormal activity of local circuits, irrespective of genetic background. The work reveals donor-dependent, cell-type specific developmental phenotypes of PTEN heterozygosity that later converge on disrupted neuronal activity.
Prenylation is essential for the enrichment of cone phosphodiesterase-6 (PDE6) in outer segments and efficient cone phototransduction
Authors: Moakedi Faezeh , Aljammal Rawaa , Poria Deepak , Saravanan Thamaraiselvi , Rhodes Scott B , Reid Chyanne , Guan Tongju , Kefalov Vladimir J , Ramamurthy Visvanathan
Published: June 2023

Phosphodiesterase-6 (PDE6) is the key phototransduction effector enzyme residing in the outer segment (OS) of photoreceptors. Cone PDE6 is a tetrameric protein consisting of two inhibitory subunits (γ′) and two catalytic subunits (α′). The catalytic subunit of cone PDE6 contains a C-terminus prenylation motif. Deletion of PDE6α′ C-terminal prenylation motif is linked to achromatopsia (ACHM), a type of color blindness in humans. However, mechanisms behind the disease and roles for lipidation of cone PDE6 in vision are unknown. In this study, we generated two knock-in mouse models expressing mutant variants of cone PDE6α′ lacking the prenylation motif (PDE6α′∆C). We find that the C-terminal prenylation motif is the primary determinant for the association of cone PDE6 protein with membranes. Cones from PDE6α′∆C homozygous mice are less sensitive to light, and their response to light is delayed, whereas cone function in heterozygous PDE6α′∆C/+ mice is unaffected. Surprisingly, the expression level and assembly of cone PDE6 protein were unaltered in the absence of prenylation. Unprenylated assembled cone PDE6 in PDE6α′∆C homozygous animals is mislocalized and enriched in the cone inner segment and synaptic terminal. Interestingly, the disk density and the overall length of cone OS in PDE6α′∆C homozygous mutants are altered, highlighting a novel structural role for PDE6 in maintaining cone OS length and morphology. The survival of cones in the ACHM model generated in this study bodes well for gene therapy as a treatment option for restoring vision in patients with similar mutations in the PDE6C gene.
Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome
Authors: Bruel Ange-Line , Ganga Anil Kumar , Nosková Lenka , Valenzuela Irene , Martinovic Jelena , Duffourd Yannis , Zikánová Marie , Majer Filip , Kmoch Stanislav , Mohler Markéta , Sun Jingbo , Sweeney Lauren K , Martínez-Gil Núria , Thauvin-Robinet Christel , Breslow David K
Published: June 2023

Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogeneous disorders characterized by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in over 20 genes encoding ciliary proteins have been found to cause OFDS through deleterious structural or functional impacts on primary cilia. We identified by exome sequencing bi-allelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families. Affected individuals presented a novel form of OFDS (OFDS-RAB34) accompanied by cardiac, cerebral, skeletal and anorectal defects. RAB34 encodes a member of the Rab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Unlike many genes required for cilium assembly, RAB34 acts selectively in cell types that use the intracellular ciliogenesis pathway, in which nascent cilia begin to form in the cytoplasm. We find that the protein products of these pathogenic variants, which are clustered near the RAB34 C-terminus, exhibit a strong loss of function. Although some variants retain the ability to be recruited to the mother centriole, cells expressing mutant RAB34 exhibit a significant defect in cilium assembly. While many Rab proteins have been previously linked to ciliogenesis, our studies establish RAB34 as the first small GTPase involved in OFDS and reveal the distinct clinical manifestations caused by impairment of intracellular ciliogenesis.
A unified paradigm for defining elasmobranch aggregations
Authors: McInturf A G , Bowman J , Schulte J M , Newton K C , Vigil B , Honig M , Pelletier S , Cox N , Lester O , Cantor M , Chapple T K
Published: June 2023

Elasmobranchs are highly diverse in movement, sensory capacity, and behavioural responses to the environment, leading to differences in the function and nature of associations and interactions between individuals, populations, and species. The term “aggregation” has been widely and variably used to describe co-occurrence across elasmobranch species, but its defining criteria remain vague and indeterminate. The lack of standardized terminology hinders comparisons across studies, species, and systems. It can cause misinterpretation about the drivers of aggregation formation or grouping behaviour and limits the impact of elasmobranch behavioural research. Here, we propose generalizable definitions of aggregation and supporting terms, adapted from more mature socioecological theory in other systems, which can be applied across elasmobranchs. We discuss the drivers and types of elasmobranch aggregations, detail the criteria required to identify an aggregation based on our definition, and offer direction on future methods and reporting to advance the field. These proposed definitions and reporting protocols standardize the study of elasmobranch socioecology, will generate greater understanding of the mechanisms underlying behaviour and distribution across species, and support more cross-system comparisons. Finally, this information can offer greater predictive power into when and how aggregations may form, leading to more proactive management strategies to mitigate anthropogenic threats.
Discrete Quantum Subgroups of Complex Semisimple Quantum Groups
Authors: Kitamura Kan
Published: June 2023

We classify discrete quantum subgroups in the quantum double of the $q$-deformation of a compact semisimple Lie group, regarded as the complexification. We also record their classifications in some variants of quantum groups. Along the way, we show that quantum doubles of non-Kac-type compact quantum groups do not admit the quantum analog of lattices considered by Brannan–Chirvasitu–Viselter.
Spectral Torical Band Inequalities and Generalizations of the Schoen–Yau Black Hole Existence Theorem
Authors: Hirsch Sven , Kazaras Demetre , Khuri Marcus , Zhang Yiyue
Published: June 2023

Generalized torical band inequalities give precise upper bounds for the width of compact manifolds with boundary in terms of positive pointwise lower bounds for scalar curvature, assuming certain topological conditions. We extend several incarnations of these results in which pointwise scalar curvature bounds are replaced with spectral scalar curvature bounds. More precisely, we prove upper bounds for the width in terms of the principal eigenvalue of the operator $-\Delta +cR$, where $R$ denotes scalar curvature and $c>0$ is a constant. Three separate strategies are employed to obtain distinct results holding in different dimensions and under varying hypotheses, namely we utilize spacetime harmonic functions, $\mu $-bubbles, and spinorial Callias operators. In dimension 3, where the strongest result is produced, we are also able to treat open and incomplete manifolds, and establish the appropriate rigidity statements. Additionally, a version of such spectral torus band inequalities is given where tori are replaced with cubes. Finally, as a corollary, we generalize the classical work of Schoen and Yau, on the existence of black holes due to concentration of matter, to higher dimensions and with alternate measurements of size.
Application of 3D Transparent Facemasks in Long-Term Outpatient Rehabilitation of Facial Scars After Burns: A Retrospective Cohort Study of Improved Appearance of Target Scars With Different Healing Time
Authors: Zheng Weiting , Xu Wanting , Zhou Xianliang , Li Hua , Li Pengtao , Xu Qinglian
Published: June 2023

Severe facial burns may cause scarring problems and affect living quality of patients. With the advent of 3D facemasks, it is being used to treat facial scars; however, its efficacy must be confirmed by adequate studies. A retrospective analysis of 26 patients who visited rehabilitation outpatient clinic from 2017 to 2022. Patients were separated into two groups based on the time to healing (TTH) following burn injury: early healing group (TTH ≤ 21 days) and late healing group (TTH > 21 days). To compare treatment outcomes and differences between the two groups, 3D facemask application was assessed using the Vancouver Scar Scale (VSS), patient satisfaction, and complications. In both groups, there were significant improvements in the total VSS scores (P < .01) and each VSS subscore (P < .01). These scar characteristics improved over time as the treatment progressed. Compared with the late healing group, the early healing group had more obvious effects on improving scar pigmentation (P < .05) and vascularity (P < .05) at similar assessment time points after burns. At the last assessment, there was a significant difference in total VSS scores between groups (P = .009). For the early and late healing groups, respectively, the mean gradient value (SE) of the total VSS scores was 1.550 (0.373) and 1.283 (0.224) over the course of the treatment periods. 3D facemasks are effective in the rehabilitation of facial scars caused by burns, which should be used for prevention and treatment in the initial stages of scar development.
Community health workers and the communicative transformation of work-life interrelationships during the COVID-19 pandemic
Authors: Golden Annis G , Jorgenson Jane , Williams Amy
Published: June 2023

This study focuses on work-life interrelationships for community health workers (CHWs) during the COVID-19 pandemic. CHWs serve as liaisons between marginalized communities and health and human service organizations to facilitate access to services. Required physical distancing transformed their work from embodied, face-to-face interaction to almost wholly mediated by communication technologies. Interviews were conducted with 52 participants to identify CHWs’ adaptive strategies for communication, consequences of their adaptations for their experience of work and work-life interrelationships, and their communicative management of negative unintended consequences. Communicative practices that were emergent from participant accounts are examined through the lenses of four mutually informing research frameworks: the impact of technologically mediated remote work on work-life interrelationships, technological capital and differentiated digital inequalities, the text work/body work continuum, and gendered emotional work. Implications for the future of community-based care workers and for other workers with respect to communication, technology, and managing work-life boundaries are examined.
Transparency, openness and privacy among software professionals: discourses and practices surrounding use of the digital calendar
Authors: Ciccone Vanessa
Published: June 2023

Research on the groupware calendar system (GCS) has sought to understand its situated use in workplace contexts, revealing insights around design, culture, and self-understanding. A critical look at how knowledge workers use the GCS, and conceptualize of this use, reveals often overlooked sociotechnical values that figure prominently in workers’ lives. At a time when the public–private entanglement has become top-of-mind, this article adds to research on the GCS and professional subjectivity. It shows how organizational values circulate through use of the GCS and explores how hierarchy is negotiated on it, in part through design. It finds that senior-level workers are afforded opportunities to make their calendars private, while nonsenior workers are met with frustration when doing so. The article draws from a multi-sited ethnography, focusing on interviews with software workers in Canada. Findings suggest that the logistical functions of the GCS shape the affective dimensions related to its use.
Signaling and meaning in organizational analytics: coping with Goodhart’s Law in an era of digitization and datafication
Authors: Treem Jeffrey W , Barley William C , Weber Matthew S , Barbour Joshua B
Published: June 2023

The future of work will be measured. The increasing and widespread adoption of analytics, the use of digital inputs and outputs to inform organizational decision making, makes the communication of data central to organizing. This article applies and extends signaling theory to provide a framework for the study of analytics as communication. We report three cases that offer examples of dubious, selective, and ambiguous signaling in the activities of workers seeking to shape the meaning of data within the practice of analytics. The analysis casts the future of work as a game of strategic moves between organizations, seeking to measure behaviors and quantify the performance of work, and workers, altering their behavioral signaling to meet situated goals. The framework developed offers a guide for future examinations of the asymmetric relationship between management and workers as organizations adopt metrics to monitor and evaluate work.
Pre-framing an emerging technology before it is deployed at work: the case of artificial intelligence and radiology
Authors: Rezazade Mehrizi Mohammad Hosein
Published: June 2023

Various occupations are increasingly confronted with promises that new technologies will transform their work long before these technologies are deployed in their workplace. Although we know how new technologies are framed when they are introduced to work, we have limited understanding of how practitioners frame an emerging technology before it is deployed. Building on frame literature and examining the case of artificial intelligence (AI) in diagnostic radiology, I show how radiologists go beyond technological promises by engaging in constructing multiple frames ex ante (pre-frames). These pre-frames are neither technology-centric nor work-centric, but rather are dialectic technology–work frames, through which their accounts of both technology and work are simultaneously (re)constructed. They not only help radiologists settle around certain ways of relating AI to their work, but also unsettle their accounts by unearthing unresolved debates, raising new questions, and impelling them to consider divergent reaction strategies.
A multicenter randomized controlled trial of esophagectomy with or without prophylactic supraclavicular node dissection: a phase 3 trial (JCOG2013, MODERN3)
Authors: Tsunoda Shigeru , Tsubosa Yasuhiro , Sasaki Keita , Machida Ryunosuke , Kita Ryosuke , Fukuda Haruhiko , Koyanagi Kazuo , Takeuchi Hiroya , Kamei Takashi , Mine Shinji , Noma Kazuhiro , Kato Ken , Kitagawa Yuko ,   the Japan Esophageal Oncology Group of Japan Clinical Oncology Group
Published: June 2023

The need for prophylactic supraclavicular lymph node dissection during esophagectomy with radical lymphadenectomy remains controversial. A randomized phase III trial was launched in August 2022 to confirm the non-inferiority of esophagectomy with D2 lymphadenectomy except for supraclavicular lymph node dissection to standard D2 lymphadenectomy in terms of overall survival for patients with resectable upper or middle thoracic esophageal cancer. This study will enroll 480 patients from 54 Japanese institutions over 5 years. The primary endpoint includes overall survival, and the secondary endpoints include relapse-free survival, perioperative and late complication incidences, supraclavicular lymph node recurrence, salvage cervical treatment incidence, synchronous cervical and abdominal procedure proportion, operation time and the number of operating surgeons. This trial has been registered at the Japan Registry of Clinical Trials under study number jRCT1030220248.
A novel method of transapical ProtekDuo rapid deployment cannula as temporary left ventricular assist device
Authors: Ravipati Harish , Nooli Nishank P , Hoopes Charles W , Gongora Enrique , McILwain Britt , Tyndal Charles M , Orozco-Hernandez Erik J
Published: June 2023

Peripheral extracorporeal membrane oxygenation (ECMO) is one of the most common strategies for cardiogenic shock. ECMO cannulation is associated with an increased risk of complications. We describe a minimally invasive, off-pump technique to provide adequate hemodynamic support and left ventricular unloading. A 54-year-old male with nonischemic cardiomyopathy and severe peripheral vascular disease with cardiogenic shock was initially supported with inotropes and an intra-aortic balloon pump. Despite continued support, he continued to deteriorate, and we escalated to a temporary left ventricular support with a CentriMag, using a transapical ProtekDuo Rapid Deployment cannula via mini left-thoracotomy. This approach provides adequate hemodynamic support, left ventricular unloading and early ambulation. After 9 days, the patient’s functional status was improved and was medically optimized. The patient received a left ventricular assist device as destination therapy. He was discharged home, resumed his normal activities and has been doing well for more than 27 months.
(006) Methamphetamine-Induced Vaginal Lubrication
Authors: Mott M , Goeders N
Published: June 2023

Introduction

Vaginal dryness is a frequent complaint, especially in post-menopausal women. The physiology underlying the production of vaginal lubrication in response to arousing stimuli is established; however, no current pharmacological agents successfully target mechanisms within this physiology. Previous research from our lab has demonstrated that female methamphetamine (meth) users experience the immediate production of excessive vaginal lubrication, accompanied by a warmth or flushing sensation spreading from the chest areas to the pelvic region, when using the drug intravenously (IV). The physiological source of this previously undescribed effect of meth could present a potential mechanism to enhance a woman’s natural production of vaginal lubrication, providing a potentially life-changing option to patients experiencing vaginal dryness.

Objectives

The purpose of the current study was to determine if vaginal lubrication induced by IV meth use reported in a previous study from our lab occurs in rats, and if this effect is dose-dependent. This study also sought to begin to uncover the mechanism behind this phenomenon.

Methods

Adult female Wistar rats (n=8) were implanted with chronic indwelling jugular catheters and allowed at least one week to recover from surgery. Rats anesthetized with isoflurane gas were intravenously infused with one of seven doses of meth ranging from 0.015-0.96 mg/kg meth or saline IV via the implanted catheter. Pre-weighed cotton-tipped swabs inserted into the vaginal canal collected fluid secreted following drug administration. The change in weight of the swab was taken as the weight of fluid produced. Consequent studies examined several signaling molecules in plasma known to have an influence on vaginal lubrication, including the steroid hormones estradiol, progesterone and testosterone, as well as the gaseous vasodilator nitric oxide. These molecules were measured at time points up to 60 minutes after meth administration.

Results

As hypothesized, meth increased vaginal lubrication in a dose-dependent manner. Doses of 0.06 and 0.24 mg/kg of meth induced significant increases in vaginal lubrication compared to saline. Further, compared to pre-meth levels, significant increases in estradiol were seen at two and 15 minutes after meth administration. Significant increases in progesterone, testosterone and nitric oxide were seen ten minutes after meth administration.

Conclusions

This study has far-reaching implications since the majority of women will experience vaginal dryness at least once, if not recurrently. The underlying mechanism of meth-induced vaginal lubrication, when elucidated, may provide a pharmacological target in treating not only meth use disorder, but also the millions of women suffering from vaginal dryness.

Disclosure

No.
(035) EndoCouples: Working with Couples Struggling with Painful Sex Due to Endometriosis
Authors: Brown K
Published: June 2023

Introduction

Endometriosis (endo) is a chronic gynecological illness that affects millions of women. Endo has three main symptoms that are often the trigger for diagnosis though diagnosis can only be confirmed through laparoscopy. Laparoscopy is a surgical procedure that allows a surgeon to view the organs in the abdomen and the presence of endometriosis. The third most common symptom of endometriosis after infertility and dysmenorrhea (painful periods) is dyspareunia or pain with intercourse. Presentations with dyspareunia are typically first thought to be psychological and related to instances of childhood sexual abuse, frigidity, relationship issues, or sexual inexperience without consideration of a biological impact. The majority of the medical literature on endometriosis addresses the physical impact of endometriosis and quality of life as well as infertility, but the emotional impact on the couple relationship is often overlooked and under researched.

Objectives

The goal of this study was to explore the specific impact of dyspareunia due to endometriosis on the intimate relationship from the lived experience of couples.

Methods

With this goal in mind, it was best to use a qualitative phenomenological methodology. By choosing to use a qualitative approach and a smaller sample, this study explored in-depth all the variables that each couple brings to their experiences of the same symptoms of the same chronic illness – dyspareunia due to endometriosis.

Results

All ten couples talked about how the dyspareunia had affected the intimate and sexual parts of their relationships in varying degrees ranging from occasional pain with penetration to the complete inability to have intercourse. The couples talked about how the pain has changed the way they have intercourse and the learning curve they have experienced in continuing to try to have a fulfilling sexual relationship.

Conclusions

Couples with dyspareunia due to endometriosis are not all destined to a relationship without sex or intimacy. Relationship talk, creativity, alternatives to intercourse, and communication about boundaries during sex have provided these couples with opportunities to intimately connect. These couples demonstrate examples of resilience and exhibit skills to be incorporated in developing a therapeutic treatment model for couples with endo.

Disclosure

No.
Improved functional properties of the potential probiotic Lacticaseibacillus paracasei ItalPN16 growing in cheese whey
Authors: Barreto Pinilla Cristian Mauricio , Brandelli Adriano , Galland Fabiana , Spadoti Leila Maria , Torres Silva e Alves Adriana
Published: June 2023

The production of probiotic bacteria requires specific and expensive culture media for maintain their viability and metabolic response during gastro-intestinal transit and cell adhesion process. The aim of this study was to compare the ability of the potential probiotic Laticaseibacillus paracasei ItalPN16 to grow in plain sweet whey (SW) and acid whey (AW), evaluating changes in some probiotic properties related to the culture media. Pasteurized SW and AW were suitable media for L. paracasei growth, since counts above 9 Log CFU/ml were achieved using <50% of the total sugars in both whey samples after 48 h at 37°C. The L. paracasei cells obtained from AW or SW cultures showed increased resistance to pH 2.5 and 3.5, higher autoaggregation, and lower cell hydrophobicity, as compared with the control of MRS. SW also improved the biofilm formation ability and cell adhesion capability to Caco-2 cells. Our results indicate that the L. paracasei adaptation to the SW conditions, inducing metabolic changes that improved its stability to acid stress, biofilm formation, autoaggregation, and cell adhesion properties, which are important functional probiotic properties. Overall, the SW could be considered as low-cost culture medium for sustainable biomass production of L. paracasei ItalPN16.
The Healing Power of Social Connection
Authors: Rauch Sheila A.M. , Rothbaum Barbara Olasov
Published: June 2023

In this chapter, you learn about the importance of social connections and specific ways to plan for and increase social connections. Our connections to other people often define how we view ourselves and our roles and expectations in life. We care about people, and we care what other people think about us. When we have a difficult experience, a normal response is to consider how those around us might think about what happened to us. Reaching out for social support is one of the best ways to manage difficult experiences. Unfortunately, when we are stressed we often avoid other people. Avoiding people is even more common if we feel guilty or worried that others may blame us for part or all of what happened. The Making Meaning of Difficult Experiences: Self-Guided Program provides the framework to use or increase your social connections to help in your recovery from difficult experiences.
SCS Screening Trial
Authors: Kreis Paul G. , Hills Ammon A. , Prasad Ravi , Fishman Scott M.
Published: June 2023

This chapter covers the process of spinal cord stimulation (SCS) screening trial. The FDA has provided approval for SCS as a tool for managing chronic and intractable pain. As the SCS is considered an invasive procedure, written informed consent of the patient is required. Patients are also required to undergo an evaluation of their detailed history and physical examination before committing to the SCS treatment. People who failed to respond with initial medication and treatment should be subjected to SCS, as further medication could lead to greater disability and side effects. Additionally, the pain diagnosis of a patient determines the success rate of the SCS treatment.
Radiation Safety
Authors: Seibert J. Anthony , Fishman Scott M. , Kreis Paul G.
Published: June 2023

This chapter explores the safe use of radiation amidst spinal cord stimulation (SCS) procedures. As ciné (real-time) fluoroscopy is needed to guide needle insertions and facilitate directing stimulator leads, a better understanding of fluoroscopy is essential, including the principles of safe and effective use of radiation. The chapter expounds on the process and repercussions of x-ray examinations. The biological effects of radiation from fluoroscopy largely depend on the dose, duration, and distance of the procedure. While normal repair mechanisms can render the impact of radiation on human tissues inconsequential, greater radiation exposure still implicates a greater potential risk for harm.
Sterile Technique
Authors: Kreis Paul G. , Hills Ammon A. , Galante Joseph M.
Published: June 2023

This chapter highlights the importance of cleanliness in all invasive procedures, primarily focusing on spinal cord stimulation (SCS) implantation. The most important factors for preventing postoperative infections range from the sound judgment and technique of medical professionals and the patient’s general health and disease state. Moreover, the development of sterile techniques goes hand in hand with the discoveries in microbiology and germ theory. As preventive measures are essential, surgical site infection (SSI) is regarded as the most common non-equipment-related complication of SCS implantation. Thus, improved surgical technique, technology, and understanding of patient risk factors have resulted in a decline in SCS infection rates.
Electricity and Spinal Cord Stimulation
Authors: Pritzlaff Scott G. , Hills Ammon A. , Kreis Paul G.
Published: June 2023

This chapter focuses on the effects of current, voltage, and impedance, in line with the basic theory of spinal cord stimulation (SCS). Various modalities of stimulation are deemed to involve the activation or suppression of neurons. Paresthesia sensations are not required to be felt by patients to ensure that the new modalities of stimulations are effective. The chapter notes the usage of percutaneous leads and surgical leads in utilizing electric currents for SCS treatment. It also looks into the concept of perception threshold, which covers the measure of the minimum stimulation pulse amplitude needed to generate a perceptible paresthesia sensation.
Trial of Spinal Cord Stimulation
Authors: Pritzlaff Scott G. , Kreis Paul G. , Fishman Scott M.
Published: June 2023

This chapter cites the importance of the location and stimulation settings needed for maximum effectivity and minimum infection risk for patients undergoing and being comfortable with spinal cord stimulation (SCS) treatment. Before the permanent SCS implantation, a patient could undergo a percutaneous trial or a tunneled trial that involves placement of a disposable trial lead with varying permanence. Successful implantation depends on the technical aspects of the trial’s optimal performance. To maximize the trial period, split trials are conducted to test numerous devices and waveforms with a single set of leads. Recent evidence found that trial outcomes may have a similar success rate with paresthesia-based mapping.
Permanent Spinal Cord Stimulator Placement
Authors: Pritzlaff Scott G. , Kreis Paul G. , Fishman Scott M.
Published: June 2023

This chapter discusses the issues and considerations for permanent implantation after a successful spinal cord stimulation (SCS). The implantation of a permanent system should be scheduled and performed in an operating room (OR) with full equipment, a fluoroscopy table, and C-arm. However, the preparation for a permanent system depends on whether the patient underwent a percutaneous trial or a tunneled trial. The required length of the lead and its extension should be determined prior to the permanent procedure while also considering the possible site for the implantable pulse generator (IPG). Additionally, patients are required to be alert and communicative during lead placement and intraoperative stimulation testing.
Wound Healing, Postoperative Wound Management, and Discharge Education
Authors: Singh Naileshni S. , Kreis Paul G. , Fishman Scott M.
Published: June 2023

This chapter focuses on the significance of wound healing in an effort to prevent dying from hemorrhage and infection. Wound repair is the process where the tissue attempts to restore its barriers to fluid loss and infection while also increasing blood flow and structural integrity of the wounded region. Tremendous advances have been recorded in the science of wound care and restoration since the discovery of epidermal growth factors. Thus, the implanter of spinal cord stimulation (SCS) should have a basic understanding of wound healing and infection risks to optimize outcomes and recognize failing wound healing when it happens. The chapter also notes the phases of wound healing.
Peripheral Nerve Stimulation
Authors: Pritzlaff Scott G. , Hills Ammon A. , Jung Michael J. , DeMesa Charles J.
Published: June 2023

This chapter discusses the stimulation of the peripheral nervous system (PNS), which was initially performed to treat refractory neuropathic pain. The PNS includes neural structures such as cranial nerves, spinal nerves, and peripheral nerves that could function for sensory, motor, or a mix of both. The gate control theory suggests a gating mechanism for how the PNS system would modulate pain. To treat chronic pain linked to the PNS, invasive surgical dissection is often performed to implant the PNS close to the involved nerve. Peripheral nerve trauma and hemiplegic shoulder pain (HSP) are only some of the indications for needing PNS therapy.
Social Psychiatry
Authors: Malhotra Savita , Chauhan Nidhi
Published: June 2023

Children, about one-fourth of the world’s population, are society’s most valuable natural resource, and it is imperative to care for them and provide them with the most fulfilling and enriching ingredients, enabling them to become physically and mentally healthy. Children’s cognitive, motor, speech and language, and socio-emotional developmental domains have a bearing on future learning, academic achievement, social relationships, employment, and community participation. Development in each specific domain is affected by a multitude of biological, psychological, and social factors acting in unison and altering/modifying the outcome. Social factors that include maternal health, early feeding practices, family environment, and living conditions play an important role starting from conception, pregnancy, and the postnatal period in shaping childhood, adolescence, and adulthood. Cultural beliefs, attitudes, social policies, socioeconomic status, and safe and adequate living conditions are all factors in children’s development. Social psychiatrists and all socially conscious individuals should take an active role in promoting these essential elements to the world’s children.
Culture
Authors: Pumariega Andres J. , Ruiz Pedro
Published: June 2023

Culture is central to the understanding and interpretation of human psychological and psychosocial development. It contributes to the diversity of human development and human thought, and it is the basis on which societies are ultimately based. It is also central to mental health, with all understanding and interventions around mental health needing to be ultimately based on culture. This chapter outlines the role of culture in human behavior and development, culturally related stressors, the inter-relationship between culture and psychopathology, and key elements of culturally informed mental health services. We discuss guidelines that promote cultural competence in clinical assessment and the delivery of mental health services, and also briefly review evidence related to culturally informed treatment approaches.
The Impacts of Music, Concerts, and Dance on Mental Health
Authors: Bostic Jeff Q. , Goins Kristine , Bostic Basie
Published: June 2023

Music and dance are important social instruments to enhance communication, social cohesion, and to enhance emotional expression that intensifies connections to others. In addition, music enhances human effort, resilience, and emotional regulation. Music bonds people together, facilitates human expression through movement and dance, and intensifies social experiences such as through concerts. This chapter reviews the neurobiological, psychological, interpersonal, and social aspects of music and dance, their evolution for human expression and wellness, their clinical application in enhancing mental health, and their contribution to community and societal cohesion. These important contributions of music and dance to mental health and the research behind them should be considered at policy levels as well as in more integrated approaches to population mental health.
Marginalized People
Authors: Kastrup Marianne
Published: June 2023

The chapter describes an overview of the concept of marginalized people, and the delineation of the population. The WHO Alma Ata and the UN Sustainable Developmental Goals are discussed in light of marginalization. The rights to health and the access to mental healthcare and the factors preventing such groups from enjoying this right are outlined. Among marginalized populations dealt with in the chapter are ethnic and racial groups, women, LGBTQ, indigenous populations, children and adolescents, and homeless and prison populations. Barriers to achieving full access to healthcare comprise, for example, lack of economic resources, discrimination, restrictive policies, or cultural unacceptability. Many approaches may be taken to overcome the current situation and reduce the marginalization.
Poverty, Hunger, Homelessness
Authors: Pumariega Andres J. , Gogineni Rama Rao
Published: June 2023

Poverty, hunger, and homelessness have been shown to be perhaps the greatest adverse biological and social risk factors for mental health problems and disorders worldwide. This chapter is a summary of the effects of poverty, homelessness, and hunger, including sections on their scope and impact on children and adults worldwide, and their impact on psychology and mental health. It also includes recommendations to governmental entities, advocates, and care providers on mitigating their adverse effects.
Social Psychiatry
Authors: Venkatraman Lakshmi , Mohan Greeshma , Raghavan Vijaya , Padmavati R. , Thara R.
Published: June 2023

Psychotic disorders are caused by a complex interplay of biological, psychological, social, and environmental factors. With increasing awareness and emphasis on the social determinants of mental health disorders, the authors of this chapter examine the social and environmental risk factors associated with psychotic disorders and summarize them broadly under perinatal and postnatal risk factors. They also elucidate the impact of the psychotic disorders on important social dimensions such as employment, marriage, quality of life, and stigma. Also, social interventions in the management of psychotic disorders are described briefly. Though studies have identified a wide range of variables, the relative influence of these domains has yet to be unequivocally established. Many of these will have to be tested with rigor in many low- and middle-income countries.