The experience of drug-related client loss for healthcare professionals who support people in addiction.

INTRODUCTION: Addiction support and recovery is a multi-faceted support context in which practitioners work with clients who present with increased mortality risks. Drug-related deaths are understood to be a risk factor for complicated grief-reactions but, to date, research has neglected to explore the intricacies of drug-related client loss for practitioners who work with clients experiencing addiction. Due to wider expectations of professional endurance and the demanding nature of health care, grief-related reactions associated with the loss of a client may go unprocessed and, therefore, result in long-term health implications. METHOD: Fifteen health care professionals took part in individual semi-structured interviews, which were analyzed using reflexive thematic analysis. Participants represented various disciplines in addiction support and recovery, including homelessness, inclusion health, addiction, and emergency medicine. RESULTS: Three core themes emerged encapsulating the experience of drug-related bereavement for HCPs who support people experiencing addiction, as follows: (i) Grief Beneath the Surface, (ii) The Cost of Caring, and (iii) Finding Closure. The findings identified acute grief-related reactions in HCPs such as self-blame and shame, alongside fears of litigation and questions of clinical competency. Participants' accounts of drug-related client loss emphasized a deep professional connection with those that they work with, with grief-responses akin to the loss of peers, family members, and other close connections. The bereavement experience was complicated by unique compounding variables associated with drug-related deaths, but also by incongruity between their emotional responses to death and their professional responsibilities. CONCLUSIONS: This article highlights the complex nature of drug-related client loss, and despite their social positioning as experts in their field, HCPs' reactions to client deaths were predominantly human responses to loss. The article identified a need for targeted postvention protocols that address complicated grief while also allowing staff to resume occupational functioning in a measured manner.

Porocarcinoma of the Left Foot: A Case Review.

Eccrine porocarcinoma is a rare malignant tumor of the eccrine sweat gland. This malignancy occurs most commonly in the lower extremities. It tends to occur in patients aged 60 to 80 years, affecting men and women equally. We present the case of a 62-year-old man with a lesion on the left foot. The diagnosis of the initial biopsy was squamous cell carcinoma. Six months later, the lesion reoccurred, and a second biopsy confirmed it to be eccrine porocarcinoma.

Posttraumatic growth following a drug-related death: A family perspective.

This paper explores the experience of posttraumatic growth in families who have lost a family member to a drug-related death. Seven family units (17 participants) were interviewed, and interviews were analyzed using reflexive thematic analysis. Analyses revealed themes that reflected positive adaptation and growth, including (a) reframing the loss, (b) open dialogue and social support, and (c) reclamation of purpose. Themes are presented in this paper for their pertinence in understanding how best to negotiate adaptation through complicated grief. The paper concludes that posttraumatic growth can occur once families begin a process of acceptance and receive support through the journey.

The impact of COVID-19 on health care professionals who are exposed to drug-related deaths while supporting clients experiencing addiction.

INTRODUCTION: This paper explores the impact of the COVID-19 pandemic on health care professionals who support clients experiencing addiction. During the pandemic, addiction support became more challenging, as existing health care models had changed or been completely abolished. Clients continued to engage with social, justice, and health services in limited capacities, connecting with general practitioners, key workers, homelessness support workers, and other service providers. This marginalized population was among the most high-risk groups for adverse health outcomes during the pandemic and understanding the associated implications for practitioner well-being is crucial. METHODS: Fifteen health care professionals who work with active addiction in homelessness, public health, addiction, emergency medicine, and other areas participated in individual semi-structured interviews. Data analyses utilized reflexive thematic analysis. RESULTS: Four core themes emerged from the analysis: (i) Shift in Priority, (ii) Being Left Behind, (iii) Managing a Death, and (iv) Anxious Environment. Within each core theme, associated subthemes provide further context. The COVID-19 pandemic had a significant impact on the well-being of clinicians who work with people who use drugs, fostering a more anxious environment and compounding what can already be a high-stress occupation. Participants exhibited high levels of concern for the well-being of clients, and uncertainty permeated throughout conversations. Furthermore, staff expressed concern for their own well-being in the long term due to the inability to process adverse events, such as a service user's death, due to the chaotic nature of the pandemic. CONCLUSIONS: This paper highlights some areas of concern to address for future service delivery and presents opportunities to future-proof services as the world moves toward hybrid models of working. The inflexibility of service provision during the pandemic and the digital divide due to public health measures pushed marginalized groups further into the margins, with significant implications for practitioner occupational well-being due to feelings of anxiety, powerlessness, and concern for mortality of clients. This study collects a broad scope of experiences across disciplines in health care and demonstrates how professionals navigated unprecedented circumstances.

'Special death': Living with bereavement by drug-related death in Ireland.

This paper explores the impact of complicated grief on the family system following the drug-related death of a family member. Drug-related deaths are rife with moral stigmas, and those left behind often carry an emotional burden laden with shame and guilt. 17 bereaved family members were interviewed using semi-structured interviews and transcripts were analyzed using reflexive thematic analysis. Three core themes were generated: Renegotiation of Relationships; Experiencing Complex Emotions; and Adjusting to a New Reality. The findings demonstrate that this population experience great difficulty in processing their grief as they struggle with family breakdown, navigating supports and stigma.

Multi-parametric analysis of 57 SYNGAP1 variants reveal impacts on GTPase signaling, localization, and protein stability.

SYNGAP1 is a neuronal Ras and Rap GTPase-activating protein with important roles in regulating excitatory synaptic plasticity. While many SYNGAP1 missense and nonsense mutations have been associated with intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder (ASD), whether and how they contribute to individual disease phenotypes is often unknown. Here, we characterize 57 variants in seven assays that examine multiple aspects of SYNGAP1 function. Specifically, we used multiplex phospho-flow cytometry to measure variant impact on protein stability, pERK, pGSK3ß, pp38, pCREB, and high-content imaging to examine subcellular localization. We find variants ranging from complete loss-of-function (LoF) to wild-type (WT)-like in their regulation of pERK and pGSK3ß, while all variants retain at least partial ability to dephosphorylate pCREB. Interestingly, our assays reveal that a larger proportion of variants located within the disordered domain of unknown function (DUF) comprising the C-terminal half of SYNGAP1 exhibited higher LoF, compared to variants within the better studied catalytic domain. Moreover, we find protein instability to be a major contributor to dysfunction for only two missense variants, both located within the catalytic domain. Using high-content imaging, we find variants located within the C2 domain known to mediate membrane lipid interactions exhibit significantly larger cytoplasmic speckles than WT SYNGAP1. Moreover, this subcellular phenotype shows both correlation with altered catalytic activity and unique deviation from signaling assay results, highlighting multiple independent molecular mechanisms underlying variant dysfunction. Our multidimensional dataset allows clustering of variants based on functional phenotypes and provides high-confidence, multi-functional measures for making pathogenicity predictions.

Cellular localisation of structurally diverse diphenylacetylene fluorophores.

Fluorescent probes are increasingly used as reporter molecules in a wide variety of biophysical experiments, but when designing new compounds it can often be difficult to anticipate the effect that changing chemical structure can have on cellular localisation and fluorescence behaviour. To provide further chemical rationale for probe design, a series of donor-acceptor diphenylacetylene fluorophores with varying lipophilicities and structures were synthesised and analysed in human epidermal cells using a range of cellular imaging techniques. These experiments showed that, within this family, the greatest determinants of cellular localisation were overall lipophilicity and the presence of ionisable groups. Indeed, compounds with high log D values (>5) were found to localise in lipid droplets, but conversion of their ester acceptor groups to the corresponding carboxylic acids caused a pronounced shift to localisation in the endoplasmic reticulum. Mildly lipophilic compounds (log D = 2-3) with strongly basic amine groups were shown to be confined to lysosomes i.e. an acidic cellular compartment, but sequestering this positively charged motif as an amide resulted in a significant change to cytoplasmic and membrane localisation. Finally, specific organelles including the mitochondria could be targeted by incorporating groups such as a triphenylphosphonium moiety. Taken together, this account illustrates a range of guiding principles that can inform the design of other fluorescent molecules but, moreover, has demonstrated that many of these diphenylacetylenes have significant utility as probes in a range of cellular imaging studies.

Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction.

Functional variomics provides the foundation for personalized medicine by linking genetic variation to disease expression, outcome and treatment, yet its utility is dependent on appropriate assays to evaluate mutation impact on protein function. To fully assess the effects of 106 missense and nonsense variants of PTEN associated with autism spectrum disorder, somatic cancer and PTEN hamartoma syndrome (PHTS), we take a deep phenotypic profiling approach using 18 assays in 5 model systems spanning diverse cellular environments ranging from molecular function to neuronal morphogenesis and behavior. Variants inducing instability occur across the protein, resulting in partial-to-complete loss-of-function (LoF), which is well correlated across models. However, assays are selectively sensitive to variants located in substrate binding and catalytic domains, which exhibit complete LoF or dominant negativity independent of effects on stability. Our results indicate that full characterization of variant impact requires assays sensitive to instability and a range of protein functions.

The Unhappy Cosmetic Patient: Lessons From Unfavorable Online Reviews of Minimally and Noninvasive Cosmetic Procedures.

BACKGROUND: The number of patients receiving minimally and noninvasive cosmetic procedures is increasing. Often, patients turn to online review forums to gain and share advice regarding cosmetic procedures. Understanding and discussing patient-reported outcome data can help align physician and patient expectations and ultimately help improve the patient experience. OBJECTIVE: To determine the most common reasons patients are dissatisfied with a selection of minimally and noninvasive cosmetic procedures. MATERIALS AND METHODS: Negative patient reviews from the RealSelf.com website were analyzed, and the reason for patient discontent was recorded for the following treatments: tissue stabilized-guided subscision, cryolipolysis, electromagnetic therapy, deoxycholic acid injections, energy-induced thermolysis, radio thermoplasty, threadlifts, and ultrasound therapy. RESULTS: One thousand two hundred four reviews were included in analysis. For all treatments analyzed, the most common reason for patient dissatisfaction was ineffectiveness (n = 782, 65.0%), followed by complications (n = 301, 25.0%). The most common complications were as follows: lumps for tissue stabilized-guided subscision (n = 6, 50.0%), treated area enlargement for cryolipolysis (n = 23, 22.1%), swelling for deoxycholic acid injections (n = 9, 47.4%), numbness for energy-induced thermolysis (n = 6, 35.3%), fat loss for radio thermoplasty (n = 26, 53.1%) and ultrasound therapy (n = 32, 48.5%), and indentations for threadlifts (n = 10, 30.3%). CONCLUSION: Ineffectiveness and complications were the most common reasons for dissatisfaction among all treatments analyzed. Patient-reported outcome data may offer insight into how physicians can improve their patient's satisfaction with cosmetic procedures.

Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort.

Autism spectrum disorder (ASD) is a highly heterogeneous genetic disorder with strong evidence of ASD-association currently available only for a small number of genes. This makes it challenging to identify the underlying genetic cause in many cases of ASD, and there is a continuing need for further discovery efforts. We sequenced whole genomes of 119 deeply phenotyped ASD probands in order to identify likely pathogenic variants. We prioritized variants found in each subject by predicted damage, population frequency, literature evidence, and phenotype concordance. We used Sanger sequencing to determine the inheritance status of high-priority variants where possible. We report five novel de novo damaging variants as well as several likely damaging variants of unknown inheritance; these include two novel de novo variants in the well-established ASD gene SCN2A. The availability of rich phenotypic information and its concordance with the literature allowed us to increase our confidence in pathogenicity of discovered variants, especially in probands without parental DNA. Our results contribute to the documentation of potential pathogenic variants and their associated phenotypes in individuals with ASD.

Sound levels and safety in cosmetic laser surgery.

OBJECTIVES: Measure the sound levels produced by various lasers commonly used during routine outpatient cosmetic surgery to determine whether or not their use exceeds exposure levels set forth by the US National Institute for Occupational Safety and Health (NIOSH) and the US Occupational Safety and Health Administration (OSHA). MATERIALS AND METHODS: Using two different meters, the sound levels of lasers commonly used in cosmetic surgery were recorded during various procedures for several indications: tattoo removal, treatment of lentigines and pigmented lesions, facial erythema and vascular lesions, hair removal and resurfacing of acne scars, and photoaging. RESULTS: All but five lasers had a maximum sound level below 85 dBA, the limit proposed by NIOSH. The loudest laser examined was a fully ablative 2,940 nm Er:YAG during facial resurfacing, with an average maximum sound level of 101.5 decibels (dBA). Two other lasers used for resurfacing exceeded 85 dBA including a fractional ablative 1064 Nd:YAG with an average maximum of 97.8 and a different fully ablative 2,940 nm Er:YAG which had an average maximum of 96.3 nm. The two other lasers that exceeded 85 dBA were picosecond lasers used to treat black tattoos, including a 1,064 nm Nd:YAG with an average maximum of 93.7 dBA and a 755 nm alexandrite with an average maximum of 93.6 dBA. CONCLUSION: Although some lasers in cosmetic surgery may be perceived as being quite loud, they remain safe. Even the loudest laser studied would have to be used for nearly 2 hours before exceeding the OSHA recommended exposure limit. Even physicians who spend a large amount of time using lasers in clinical practice should be reassured that these devices are not likely to produce noise-induced hearing loss (NIHL) hearing loss. Lasers Surg. Med. 51:491-494, 2019. © 2019 Wiley Periodicals, Inc.

Use of Google Trends to Examine Interest in Mohs Micrographic Surgery: 2004 to 2016.

BACKGROUND: Mohs micrographic surgery (MMS) is the gold standard for treatment of high-risk skin cancers. There has been an upward trend in the use of this procedure as demonstrated by data from Medicare and the National Ambulatory Medical Care Survey. OBJECTIVE: To assess interest in MMS among members of the general public as measured by number of online searches, and how that interest has changed over time. MATERIALS AND METHODS: Google Trends was used to plot interest in search terms including "Mohs surgery," "basal cell carcinoma," "squamous cell carcinoma," "melanoma," and "skin cancer" from January 1, 2004, to November 30, 2016. RESULTS: Search interest for the term "Mohs surgery" has steadily increased since 2004 and correlates closely with increased interest for "basal cell carcinoma" (r = 0.82) and "squamous cell carcinoma" (r = 0.85). Search interest in MMS did not correlate well with searches for melanoma (r = -0.15) or skin cancer (r = -0.29). CONCLUSION: Public interest in MMS has continued to steadily increase in the United States, which may be a reflection of the increasing volume of MMS that is performed.

Cellulite: a review of pathogenesis-directed therapy.

Cellulite is a condition that affects the majority of postpubertal women and can negatively impact quality of life. This review discusses several proposed pathophysiologies of cellulite, and examines treatment options that have been utilized, focusing on the etiologic factor targeted by the therapies. This approach aims to help clarify the pathogenesis of cellulite and provide a road map for developing effective treatment paradigms for patients.

Vascular Calcification and Stone Disease: A New Look towards the Mechanism.

Calcium phosphate (CaP) crystals are formed in pathological calcification as well as during stone formation. Although there are several theories as to how these crystals can develop through the combined interactions of biochemical and biophysical factors, the exact mechanism of such mineralization is largely unknown. Based on the published scientific literature, we found that common factors can link the initial stages of stone formation and calcification in anatomically distal tissues and organs. For example, changes to the spatiotemporal conditions of the fluid flow in tubular structures may provide initial condition(s) for CaP crystal generation needed for stone formation. Additionally, recent evidence has provided a meaningful association between the active participation of proteins and transcription factors found in the bone forming (ossification) mechanism that are also involved in the early stages of kidney stone formation and arterial calcification. Our review will focus on three topics of discussion (physiological influences-calcium and phosphate concentration-and similarities to ossification, or bone formation) that may elucidate some commonality in the mechanisms of stone formation and calcification, and pave the way towards opening new avenues for further research.