Establishing Core Symptoms of Acute Serotonin Reuptake Inhibitor Withdrawal: Results from an International Survey of Online Peer-Support Communities.

BACKGROUND: Serotonin reuptake inhibitor (SRI) antidepressants are commonly associated with withdrawal reactions. The Discontinuation Emergent Signs and Symptoms (DESS) checklist has been considered the gold standard research and screening tool for SRI withdrawal but has several limitations, including its length, lack of specificity, and omission of baseline symptom and symptom severity scores, making it impractical for use in clinical or research settings. We investigated the prevalence and severity of common SRI withdrawal symptoms to determine whether a very small subset of symptoms can capture most occurrences of SRI withdrawal. METHODS: We surveyed 344 members of online peer-support communities aged 18-65, reporting withdrawal symptoms after chronic SRI treatment. The severity of nine common withdrawal symptoms was evaluated at baseline and during the withdrawal period. RESULTS: Dizziness, brain zaps, irritability/agitation, and anxiety/nervousness demonstrated the largest increase in severity during withdrawal relative to baseline. Nearly all (97.7%) of the 344 subjects and all (100%) 153 subjects with relatively low baseline symptom scores (total<5) reported a worsening of one of these four symptoms. The presence of a baseline anxiety disorder did not affect rates of withdrawal-emergent anxiety/nervousness. CONCLUSION: Nearly all surveyed subjects reported worsening either of dizziness, brain zaps, irritability/agitation, or anxiety/nervousness in acute withdrawal. A screening test incorporating these four core symptoms may be sufficiently sensitive to rule out SRI withdrawal and may be valuable in clinical and research settings. Incorporating withdrawal symptom severity may further enhance specificity.

Oxygen uptake rates have contrasting responses to temperature in the root meristem and elongation zone.

Growing at either 15 or 25°C, roots of Arabidopsis thaliana, Columbia accession, produce cells at the same rate and have growth zones of the same length. To determine whether this constancy is related to energetics, we measured oxygen uptake by means of a vibrating oxygen-selective electrode. Concomitantly, the spatial distribution of elongation was measured kinematically, delineating meristem and elongation zone. All seedlings were germinated, grown, and measured at a given temperature (15 or 25°C). Columbia was compared to lines where cell production rate roughly doubles between 15 and 25°C: Landsberg and two Columbia mutants, er-105 and ahk3-3. For all genotypes and temperatures, oxygen uptake rate at any position was highest at the root cap, where mitochondrial density was maximal, based on the fluorescence of a reporter. Uptake rate declined through the meristem to plateau within the elongation zone. For oxygen uptake rate integrated over a zone, the meristem had steady-state Q10 values ranging from 0.7 to 2.1; by contrast, the elongation zone had values ranging from 2.6 to 3.3, implying that this zone exerts a greater respiratory demand. These results highlight a substantial energy consumption by the root cap, perhaps helpful for maintaining hypoxia in stem cells, and suggest that rapid elongation is metabolically more costly than is cell division.

Contextual dimensions of moral injury: An interdisciplinary review.

The concept of moral injury, referring to the psychological impact of having one's moral expectations and beliefs violated, is gaining a firm place in research on military trauma. Yet, although moral injury has the recognized potential to extend the understanding of trauma beyond the individualizing and pathologizing focus of the clinical realm, most studies nevertheless focus on clinical assessment, diagnosis and treatment. This review aims to contribute to a better understanding of contextual dimensions of moral injury. To this end, it complements current theory on moral injury with a systematic review of literature relevant to contextual factors in moral injury. It draws together insights from psychology, philosophy, theology and social sciences into spiritual/existential, organizational, political and societal dimensions of moral injury. Thus an interdisciplinary theoretical foundation is created for context-sensitive research and interventions.

Accidentally Asymmetric Dark Matter.

We study the effect of a first-order phase transition in a confining SU(N) dark sector with heavy dark quarks. The baryons of this sector are the dark matter candidates. During the confinement phase transition the heavy quarks are trapped inside isolated, contracting pockets of the deconfined phase, giving rise to a second stage of annihilation that dramatically suppresses the dark quark abundance. The surviving abundance is determined by the local accidental asymmetry in each pocket. The correct dark matter abundance is obtained for O(1-100) PeV dark quarks, above the usual unitarity bound.

Heavy Thermal Dark Matter from a New Collision Mechanism.

We propose a new thermal freeze-out mechanism that results in dark matter masses exceeding the unitarity bound by many orders of magnitude, without violating perturbative unitarity or modifying the standard cosmology. The process determining the relic abundance is χζ^{†}→ζζ, where χ is the dark matter candidate. For m_{ζ}

Development of an online map of safe gun storage sites in Maryland for suicide prevention.

Reducing access to lethal means of self-harm is a cornerstone of suicide prevention, and temporary, voluntary gun storage outside the home is one recommended approach. With the goal of facilitating access to gun storage outside the home in Maryland, we developed an online map of gun shops and law enforcement agencies willing to offer temporary, voluntary gun storage on a case-by-case basis. This project was modelled off of prior work by the Colorado Firearm Safety Coalition. As of July 2020, 32 gun shops and 3 law enforcement agencies agreed to be listed on our map. Others were hesitant to participate due to perceived legal and logistical barriers to temporary firearm storage. We demonstrate the feasibility of creating an online map that lists organisations offering temporary gun storage in Maryland. This brief report details our process, barriers encountered, and future considerations to improve access to offsite gun storage options.

Energy-Based Tissue Fusion for Sutureless Closure: Applications, Mechanisms, and Potential for Functional Recovery.

As minimally invasive surgical techniques progress, the demand for efficient, reliable methods for vascular ligation and tissue closure becomes pronounced. The surgical advantages of energy-based vessel sealing exceed those of traditional, compression-based ligatures in procedures sensitive to duration, foreign bodies, and recovery time alike. Although the use of energy-based devices to seal or transect vasculature and connective tissue bundles is widespread, the breadth of heating strategies and energy dosimetry used across devices underscores an uncertainty as to the molecular nature of the sealing mechanism and induced tissue effect. Furthermore, energy-based techniques exhibit promise for the closure and functional repair of soft and connective tissues in the nervous, enteral, and dermal tissue domains. A constitutive theory of molecular bonding forces that arise in response to supraphysiological temperatures is required in order to optimize and progress the use of energy-based tissue fusion. While rapid tissue bonding has been suggested to arise from dehydration, dipole interactions, molecular cross-links, or the coagulation of cellular proteins, long-term functional tissue repair across fusion boundaries requires that the reaction to thermal damage be tailored to catalyze the onset of biological healing and remodeling. In this review, we compile and contrast findings from published thermal fusion research in an effort to encourage a molecular approach to characterization of the prevalent and promising energy-based tissue bond.

Systems analysis of auxin transport in the Arabidopsis root apex.

Auxin is a key regulator of plant growth and development. Within the root tip, auxin distribution plays a crucial role specifying developmental zones and coordinating tropic responses. Determining how the organ-scale auxin pattern is regulated at the cellular scale is essential to understanding how these processes are controlled. In this study, we developed an auxin transport model based on actual root cell geometries and carrier subcellular localizations. We tested model predictions using the DII-VENUS auxin sensor in conjunction with state-of-the-art segmentation tools. Our study revealed that auxin efflux carriers alone cannot create the pattern of auxin distribution at the root tip and that AUX1/LAX influx carriers are also required. We observed that AUX1 in lateral root cap (LRC) and elongating epidermal cells greatly enhance auxin's shootward flux, with this flux being predominantly through the LRC, entering the epidermal cells only as they enter the elongation zone. We conclude that the nonpolar AUX1/LAX influx carriers control which tissues have high auxin levels, whereas the polar PIN carriers control the direction of auxin transport within these tissues.

"It's Not Like You Need to Live 10 or 20 Years": Challenges to Patient-Centered Care in Gynecologic Oncologist-Patient Interactions.

The literature suggests that the patient-perspective approach (i.e., eliciting and responding to patients' perspectives, including beliefs, preferences, values, and attitudes) to patient-centered care (PCC) is not a reliable predictor of positive outcomes; however, little is known about why the patient-perspective approach does not necessarily lead to positive outcomes. By using discourse analysis to examine 44 segments of oncologist-patient interactions, we found that providers' use of patient-perspective contextualization can affect the quality of care through (a) constructing the meanings of patient conditions, (b) controlling interpreting frames for patient conditions, and (c) manipulating patient preferences through strategic information sharing. We concluded that providers' use of patient-perspective contextualization is an insufficient indicator of PCC because these discursive strategies can be used to control and manipulate patient preferences and perspectives. At times, providers' patient-perspective contextualization can silence patients' voice and appear discriminatory.

Conflicting Notions on Violence and PTSD in the Military: Institutional and Personal Narratives of Combat-Related Illness.

Research indicates that soldiers struggling with PTSD under-utilize mental health care. Quantitative studies of barriers to care point to the importance of soldiers' beliefs about mental health and mental health interventions in their care-seeking behavior, yet these studies still struggle to understand the particular beliefs involved and the ways they impact care-seeking behavior. This preliminary study makes a start in examining these questions through qualitative literature analysis. It maps out dominant messages surrounding PTSD in military mental health interventions, and explores how they can both shape and conflict with soldiers' personal notions. It does so by analyzing these messages and notions as institutional and personal (illness) narratives. Institutional military PTSD-narratives, which draw on mainstream scientific and clinical models, appear to communicate contradictory notions on the meanings of violence and its psychological consequences, often without acknowledging these contradictions. As such, these narratives seem to shape struggles of soldiers, both within themselves and with the military institution. The identified conflicts indicate, contrary to the individualizing and decontextualizing focus of dominant PTSD-understandings, that soldiers' struggles also have social and moral dimensions. This has important implications for both research into PTSD-interventions and understandings of PTSD as such.

Tissue storage ex vivo significantly increases vascular fusion bursting pressure.

INTRODUCTION: Harvested biological tissue is a common medium for surgical device assessment in a laboratory setting; this study aims to differentiate between surgical device performance in the clinical and laboratory environments prior to and following tissue storage. Vascular tissue fusion devices are sensitive to tissue-device temperature gradients, tissue pre-stretch in vivo and tissue water content, each of which can vary during tissue storage. In this study, we compare the results of tissue fusion prior to and following storage using a standardized bursting pressure protocol. METHODS: Epigastric veins from seven porcine models were subject to identical bursting pressure protocols after fusion. One half of each vein was fused in vivo, harvested and immediately analyzed for burst pressure; the remainder was stored (0.9% Phosphate Buffered Saline, 24h, 4 °C) and then analyzed ex vivo. Histological slides were prepared for qualitative analysis of in versus ex vivo fusions. RESULTS: Bursting pressures of vessels fused ex vivo (514.7 ± 187.0 mmHg) were significantly greater than those of vessels fused in vivo (310 ± 127.7 mmHg, p = 2.06 E-10). Histological imaging of venous axial cross-sections indicated the lamination of adventitia and media layers ex vivo, whereas in vivo samples consisted only of adventitia. CONCLUSION: These findings suggest that the fusion of porcine venous tissue ex vivo may overestimate the clinical performance of fusion devices. Prior work has indicated that increased tissue hydration and the lamination of tissue layers both positively affect arterial fusion bursting pressures. The bursting pressure increase observed herein may therefore be due to storage-induced alterations in tissue composition and mechanics of the fusion interface. While harvested tissue provides an accessible medium for comparative study, the fusion of vascular tissue in vivo may avoid storage-induced biomechanical alterations and is likely a better indicator of fusion device performance in a clinical setting.

Bond Strength of Thermally Fused Vascular Tissue Varies With Apposition Force.

Surgical tissue fusion devices ligate blood vessels using thermal energy and coaptation pressure, while the molecular mechanisms underlying tissue fusion remain unclear. This study characterizes the influence of apposition force during fusion on bond strength, tissue temperature, and seal morphology. Porcine splenic arteries were thermally fused at varying apposition forces (10-500 N). Maximum bond strengths were attained at 40 N of apposition force. Bonds formed between 10 and 50 N contained laminated medial layers; those formed above 50 N contained only adventitia. These findings suggest that commercial fusion devices operate at greater than optimal apposition forces, and that constituents of the tunica media may alter the adhesive mechanics of the fusion mechanism.

Sequential induction of auxin efflux and influx carriers regulates lateral root emergence.

In Arabidopsis, lateral roots originate from pericycle cells deep within the primary root. New lateral root primordia (LRP) have to emerge through several overlaying tissues. Here, we report that auxin produced in new LRP is transported towards the outer tissues where it triggers cell separation by inducing both the auxin influx carrier LAX3 and cell-wall enzymes. LAX3 is expressed in just two cell files overlaying new LRP. To understand how this striking pattern of LAX3 expression is regulated, we developed a mathematical model that captures the network regulating its expression and auxin transport within realistic three-dimensional cell and tissue geometries. Our model revealed that, for the LAX3 spatial expression to be robust to natural variations in root tissue geometry, an efflux carrier is required--later identified to be PIN3. To prevent LAX3 from being transiently expressed in multiple cell files, PIN3 and LAX3 must be induced consecutively, which we later demonstrated to be the case. Our study exemplifies how mathematical models can be used to direct experiments to elucidate complex developmental processes.

The carrier AUXIN RESISTANT (AUX1) dominates auxin flux into Arabidopsis protoplasts.

The ability of the plant hormone auxin to enter a cell is critical to auxin transport and signaling. Auxin can cross the cell membrane by diffusion or via auxin-specific influx carriers. There is little knowledge of the magnitudes of these fluxes in plants. Radiolabeled auxin uptake was measured in protoplasts isolated from roots of Arabidopsis thaliana. This was done for the wild-type, under treatments with additional unlabeled auxin to saturate the influx carriers, and for the influx carrier mutant auxin resistant 1 (aux1). We also used flow cytometry to quantify the relative abundance of cells expressing AUX1-YFP in the assayed population. At pH 5.7, the majority of auxin influx into protoplasts - 75% - was mediated by the influx carrier AUX1. An additional 20% was mediated by other saturable carriers. The diffusive influx of auxin was essentially negligible at pH 5.7. The influx of auxin mediated by AUX1, expressed as a membrane permeability, was 1.5 ± 0.3 µm s(-1) . This value is comparable in magnitude to estimates of efflux permeability. Thus, auxin-transporting tissues can sustain relatively high auxin efflux and yet not become depleted of auxin.

Karyotype depends on sperm head morphology in some amniote groups.

The karyotype of an organism is the set of gross features that characterize the way the genome is packaged into separate chromosomes. It has been known for decades that different taxonomic groups often have distinct karyotypic features, but whether selective forces act to maintain these differences over evolutionary timescales is an open question. In this paper we analyze a database of karyotype features and sperm head morphology in 103 mammal species with spatulate sperm heads and 90 sauropsid species (birds and non-avian reptiles) with vermiform heads. We find that mammal species with a larger head area have more chromosomes, while sauropsid species with longer heads have a wider range of chromosome lengths. These results remain significant after controlling for genome size, so sperm head morphology is the relevant variable. This suggest that post-copulatory sexual selection, by acting on sperm head shape, can influence genome architecture.

Regulation of solute flux through plasmodesmata in the root meristem.

Plasmodesmata permit solutes to move between cells nonspecifically and without having to cross a membrane. This symplastic connectivity, while straightforward to observe using fluorescent tracers, has proven difficult to quantify. We use fluorescence recovery after photobleaching, combined with a mathematical model of symplastic diffusion, to assay plasmodesmata-mediated permeability in the Arabidopsis (Arabidopsis thaliana) root meristem in wild-type and transgenic lines, and under selected chemical treatments. The permeability measured for the wild type is nearly 10-times greater than previously reported. Plamodesmal permeability remains constant in seedlings treated with auxin (30 mM indoleacetic acid for 2 and 24 h; 100 nm indoleacetic acid for 2 h); however, permeability is diminished in two lines previously reported to have impaired plasmodesmal function as well as in wild-type seedlings treated for 24 h with 0.6 mM tryptophan. Moreover, plasmodesmal permeability is strongly altered by applied hydrogen peroxide within 2 h of treatment, being approximately doubled at a low concentration (0.6 mM) and nearly eliminated at a higher one (6 mM). These results reveal that the plasmodesmata in the root meristem carry a substantial flux of small molecules and that this flux is subject to rapid regulation.

Root gravitropism requires lateral root cap and epidermal cells for transport and response to a mobile auxin signal.

Re-orientation of Arabidopsis seedlings induces a rapid, asymmetric release of the growth regulator auxin from gravity-sensing columella cells at the root apex. The resulting lateral auxin gradient is hypothesized to drive differential cell expansion in elongation-zone tissues. We mapped those root tissues that function to transport or respond to auxin during a gravitropic response. Targeted expression of the auxin influx facilitator AUX1 demonstrated that root gravitropism requires auxin to be transported via the lateral root cap to all elongating epidermal cells. A three-dimensional model of the root elongation zone predicted that AUX1 causes the majority of auxin to accumulate in the epidermis. Selectively disrupting the auxin responsiveness of expanding epidermal cells by expressing a mutant form of the AUX/IAA17 protein, axr3-1, abolished root gravitropism. We conclude that gravitropic curvature in Arabidopsis roots is primarily driven by the differential expansion of epidermal cells in response to an influx-carrier-dependent auxin gradient.