TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation.

Collapse of membrane lipid asymmetry is a hallmark of blood coagulation. TMEM16F of the TMEM16 family that includes TMEM16A/B Ca(2+)-activated Cl(-) channels (CaCCs) is linked to Scott syndrome with deficient Ca(2+)-dependent lipid scrambling. We generated TMEM16F knockout mice that exhibit bleeding defects and protection in an arterial thrombosis model associated with platelet deficiency in Ca(2+)-dependent phosphatidylserine exposure and procoagulant activity and lack a Ca(2+)-activated cation current in the platelet precursor megakaryocytes. Heterologous expression of TMEM16F generates a small-conductance Ca(2+)-activated nonselective cation (SCAN) current with subpicosiemens single-channel conductance rather than a CaCC. TMEM16F-SCAN channels permeate both monovalent and divalent cations, including Ca(2+), and exhibit synergistic gating by Ca(2+) and voltage. We further pinpointed a residue in the putative pore region important for the cation versus anion selectivity of TMEM16F-SCAN and TMEM16A-CaCC channels. This study thus identifies a Ca(2+)-activated channel permeable to Ca(2+) and critical for Ca(2+)-dependent scramblase activity during blood coagulation. PAPERFLICK:

Phototransformation of achiral metasurfaces into handedness-selectable transient chiral media.

Chirality is a geometric property describing the lack of mirror symmetry. This unique feature enables photonic spin-selectivity in light-matter interaction, which is of great significance in stereochemistry, drug development, quantum optics, and optical polarization control. The versatile control of optical geometry renders optical metamaterials as an effective platform for engineered chiral properties at prescribed spectral regimes. Unfortunately, geometry-imposed restrictions only allow one circular polarization state of photons to effectively interact with chiral meta-structures. This limitation motivates the idea of discovering alternative techniques for dynamically reconfiguring the chiroptical responses of metamaterials in a fast and facile manner. Here, we demonstrate an approach that enables optical, sub-picosecond conversion of achiral meta-structures to transient chiral media in the visible regime with desired handedness upon the inhomogeneous generation of plasmonic hot electrons. As a proof of concept, we utilize linearly polarized laser pulse to demonstrate near-complete conversion of spin sensitivity in an achiral meta-platform-a functionality yet achieved in a non-mechanical fashion. Owing to the generation, diffusion, and relaxation dynamics of hot electrons, the demonstrated technique for all-optical creation of chirality is inherently fast, opening new avenues for ultrafast spectro-temporal construction of chiral platforms with on-demand spin-selectivity.

KMT2D acetylation by CREBBP reveals a cooperative functional interaction at enhancers in normal and malignant germinal center B cells.

Heterozygous inactivating mutations of the KMT2D methyltransferase and the CREBBP acetyltransferase are among the most common genetic alterations in B cell lymphoma and co-occur in 40 to 60% of follicular lymphoma (FL) and 30% of EZB/C3 diffuse large B cell lymphoma (DLBCL) cases, suggesting they may be coselected. Here, we show that combined germinal center (GC)-specific haploinsufficiency of Crebbp and Kmt2d synergizes in vivo to promote the expansion of abnormally polarized GCs, a common preneoplastic event. These enzymes form a biochemical complex on select enhancers/superenhancers that are critical for the delivery of immune signals in the GC light zone and are only corrupted upon dual Crebbp/Kmt2d loss, both in mouse GC B cells and in human DLBCL. Moreover, CREBBP directly acetylates KMT2D in GC-derived B cells, and, consistently, its inactivation by FL/DLBCL-associated mutations abrogates its ability to catalyze KMT2D acetylation. Genetic and pharmacologic loss of CREBBP and the consequent decrease in KMT2D acetylation lead to reduced levels of H3K4me1, supporting a role for this posttranslational modification in modulating KMT2D activity. Our data identify a direct biochemical and functional interaction between CREBBP and KMT2D in the GC, with implications for their role as tumor suppressors in FL/DLBCL and for the development of precision medicine approaches targeting enhancer defects induced by their combined loss.

Altered Smooth Muscle Cell Histone Acetylome by the SPHK2/S1P Axis Promotes Pulmonary Hypertension.

BACKGROUND: Epigenetic regulation of vascular remodeling in pulmonary hypertension (PH) is poorly understood. Transcription regulating, histone acetylation code alters chromatin accessibility to promote transcriptional activation. Our goal was to identify upstream mechanisms that disrupt epigenetic equilibrium in PH. METHODS: Human pulmonary artery smooth muscle cells (PASMCs), human idiopathic pulmonary arterial hypertension (iPAH):human PASMCs, iPAH lung tissue, failed donor lung tissue, human pulmonary microvascular endothelial cells, iPAH:PASMC and non-iPAH:PASMC RNA-seq databases, NanoString nCounter, and cleavage under targets and release using nuclease were utilized to investigate histone acetylation, hyperacetylation targets, protein and gene expression, sphingolipid activation, cell proliferation, and gene target identification. SPHK2 (sphingosine kinase 2) knockout was compared with control C57BL/6NJ mice after 3 weeks of hypoxia and assessed for indices of PH. RESULTS: We identified that Human PASMCs are vulnerable to the transcription-promoting epigenetic mediator histone acetylation resulting in alterations in transcription machinery and confirmed its pathological existence in PH:PASMC cells. We report that SPHK2 is elevated as much as 20-fold in iPAH lung tissue and is elevated in iPAH:PASMC cells. During PH pathogenesis, nuclear SPHK2 activates nuclear bioactive lipid S1P (sphingosine 1-phosphate) catalyzing enzyme and mediates transcription regulating histone H3K9 acetylation (acetyl histone H3 lysine 9 [Ac-H3K9]) through EMAP (endothelial monocyte activating polypeptide) II. In iPAH lungs, we identified a 4-fold elevation of the reversible epigenetic transcription modulator Ac-H3K9:H3 ratio. Loss of SPHK2 inhibited hypoxic-induced PH and Ac-H3K9 in mice. We discovered that pulmonary vascular endothelial cells are a priming factor of the EMAP II/SPHK2/S1P axis that alters the acetylome with a specificity for PASMC, through hyperacetylation of histone H3K9. Using cleavage under targets and release using nuclease, we further show that EMAP II-mediated SPHK2 has the potential to modify the local transcription machinery of pluripotency factor KLF4 (Krüppel-like factor 4) by hyperacetylating KLF4 Cis-regulatory elements while deletion and targeted inhibition of SPHK2 rescues transcription altering Ac-H3K9. CONCLUSIONS: SPHK2 expression and its activation of the reversible histone H3K9 acetylation in human pulmonary artery smooth muscle cell represent new therapeutic targets that could mitigate PH vascular remodeling.

Inhibition of Mast Cell Degranulation by Novel Small Molecule MRGPRX2 Antagonists.

BACKGROUND: Mas-related G-protein coupled receptor X2 (MRGPRX2) is a promiscuous receptor on mast cells that mediates IgE-independent degranulation and has been implicated in multiple mast cell-mediated disorders, including chronic urticaria, atopic dermatitis, and pain disorders. Although it is a promising therapeutic target, few potent, selective, small molecule antagonists have been identified, and functional effects of human MRGPRX2 inhibition have not been evaluated in vivo. OBJECTIVE: We identified and characterized novel, potent, and selective orally active small molecule MRGPRX2 antagonists for potential treatment of mast cell-mediated disease. METHODS: Antagonists were identified using multiple functional assays in cell lines overexpressing human MRGPRX2, LAD2 mast cells, human peripheral stem cell-derived mast cells, and isolated skin mast cells. Skin mast cell degranulation was evaluated in Mrgprb2em(-/-) knockout (KO) and Mrgprb2em(MRGPRX2) transgenic human MRGPRX2 knock-in (KI) mice by assessment of agonist-induced skin vascular permeability. Ex vivo skin mast cell degranulation and associated histamine release was evaluated by microdialysis of human skin tissue samples. RESULTS: MRGPRX2 antagonists potently inhibited agonist-induced MRGPRX2 activation and mast cell degranulation in all mast cell types tested, in an IgE-independent manner. Orally administered MRGPRX2 antagonists also inhibited agonist-induced degranulation and resulting vascular permeability in MRGPRX2 KI mice. In addition, antagonist treatment dose dependently inhibited agonist-induced degranulation in ex vivo human skin. CONCLUSION: MRGPRX2 small molecule antagonists potently inhibited agonist-induced mast cell degranulation in vitro and in vivo as well as ex vivo in human skin, supporting potential therapeutic utility as a novel treatment for multiple human diseases involving clinically relevant mast cell activation.

Spatial and Temporal Resolution of Cyanobacterial Bloom Chemistry Reveals an Open-Ocean Trichodesmium thiebautii as a Talented Producer of Specialized Metabolites.

While the ecological role that Trichodesmium sp. play in nitrogen fixation has been widely studied, little information is available on potential specialized metabolites that are associated with blooms and standing stock Trichodesmium colonies. While a collection of biological material from a T. thiebautii bloom event from North Padre Island, Texas, in 2014 indicated that this species was a prolific producer of chlorinated specialized metabolites, additional spatial and temporal resolution was needed. We have completed these metabolite comparison studies, detailed in the current report, utilizing LC-MS/MS-based molecular networking to visualize and annotate the specialized metabolite composition of these Trichodesmium blooms and colonies in the Gulf of Mexico (GoM) and other waters. Our results showed that T. thiebautii blooms and colonies found in the GoM have a remarkably consistent specialized metabolome. Additionally, we isolated and characterized one new macrocyclic compound from T. thiebautii, trichothilone A (1), which was also detected in three independent cultures of T. erythraeum. Genome mining identified genes predicted to synthesize certain functional groups in the T. thiebautii metabolites. These results provoke intriguing questions of how these specialized metabolites affect Trichodesmium ecophysiology, symbioses with marine invertebrates, and niche development in the global oligotrophic ocean.

Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus.

The cellular and molecular mechanisms mediating histamine-independent itch in primary sensory neurons are largely unknown. Itch induced by chloroquine (CQ) is a common side effect of this widely used antimalarial drug. Here, we show that Mrgprs, a family of G protein-coupled receptors expressed exclusively in peripheral sensory neurons, function as itch receptors. Mice lacking a cluster of Mrgpr genes display significant deficits in itch induced by CQ but not histamine. CQ directly excites sensory neurons in an Mrgpr-dependent manner. CQ specifically activates mouse MrgprA3 and human MrgprX1. Loss- and gain-of-function studies demonstrate that MrgprA3 is required for CQ responsiveness in mice. Furthermore, MrgprA3-expressing neurons respond to histamine and coexpress gastrin-releasing peptide, a peptide involved in itch sensation, and MrgprC11. Activation of these neurons with the MrgprC11-specific agonist BAM8-22 induces itch in wild-type but not mutant mice. Therefore, Mrgprs may provide molecular access to itch-selective neurons and constitute novel targets for itch therapeutics.

Psychosocial stress, adult suicidal ideation, and the mediating effect of poor sleep quality during the COVID-19 pandemic in South Africa.

OBJECTIVES: South Africa instituted one of the world's strictest lockdowns during the COVID-19 pandemic, which generated heightened conditions of psychosocial stress and posed widespread mental health risks. Despite the elevated burdens of suicidal behaviors and risk of psychiatric disease in the country, few studies have examined the impacts of psychosocial stress from the pandemic on suicidal ideation in South Africa. This study examined the association between psychosocial stress experienced under the COVID-19 pandemic and adult suicidal ideation, as well as degree to which sleep quality and duration mediated this relationship. METHODS: An online survey assessed experiences of COVID-19 psychosocial stress, sleep quality and duration, and suicidal ideation in a sample of 189 South African adults during the second and third waves of the COVID-19 pandemic. A causal inference framework for mediation analysis was used to assess the degree to which sleep quality and duration explained the association between COVID-19 psychosocial stress and suicidal ideation. RESULTS: Suicidal ideation was reported in 21% of adults. Adults described having moderate sleep quality and an average of 6.9 hours of sleep per night. COVID-19 psychosocial stress significantly predicted adult suicidal ideation in fully adjusted models. Sleep quality, but not sleep duration, significantly mediated the association between COVID-19 psychosocial stress and suicidal ideation, accounting for 25.9% of the total effect. CONCLUSIONS: Poor sleep quality may play an important role in exacerbating the alarming stress-induced mental health effects of the COVID-19 pandemic. Further research is necessary to understand the underlying sleep dynamics and associated psychological and neurobiological processes that perpetuate adult suicidal ideation.

Training and Evaluation of Residents to Ensure Competent Physician Metrics to Recognize Struggling Residents.

Assessing competency across domains of knowledge, skills, and behavior is critical to ensure that graduating orthopaedic residents possess the requisite skills and attributes to enter independent orthopaedic practice. Of the domains, knowledge is most easily assessed. In addition to the AAOS Orthopaedic In-Training Examination®, which provides a yearly gauge of residents' orthopaedic knowledge relative to their peers, there are several online platforms such as Orthobullets, the American Academy of Orthopaedic Surgeons ResStudy program, and the Journal of Bone and Joint Surgery Clinical Classroom that offer online learning resources and question banks. Clinical skills are best assessed through a combination of observation tools, including live or video assessments, 360° evaluations, and objective structured clinical examinations. Surgical skills can be evaluated in two domains: live surgical cases or simulations. The American Board of Orthopaedic Surgery is attempting to standardize live surgical evaluations through the use of the O-P tool. Although most available models feature only arthroscopic procedures, surgical simulators provide for opportunity to objectively evaluate resident performance. Behavior and professionalism has traditionally been the most challenging domain to assess. The American Board of Orthopaedic Surgery's Behavior Assessment Tool has demonstrated success in pilot testing and is being introduced as the standard for measuring behavior and professionalism in orthopaedic training. Although no single assessment tool can accurately gauge a resident's overall performance, a combination of readily available tools should be used to assess competence across domains.

How to Recognize, Correct, and Avoid Intraoperative Complications During Anterior Cruciate Ligament Reconstructions.

Technical complications are a leading cause of graft failure following anterior cruciate ligament reconstructions. Complications can occur during any phase of the procedure, from graft harvesting to tunnel preparation to graft fixation. Predicting potential causes of technical difficulty and developing strategies to avoid potential pitfalls can limit the number of intraoperative complications. If adverse events do occur intraoperatively, prompt recognition and treatment can lead to favorable outcomes. It is important to discuss strategies to understand potential complications and develop tactics to avoid and correct adverse events that can occur during anterior cruciate ligament reconstruction.

Psychological legacies of intergenerational trauma under South African apartheid: Prenatal stress predicts greater vulnerability to the psychological impacts of future stress exposure during late adolescence and early adulthood in Soweto, South Africa.

BACKGROUND: South Africa's rates of psychiatric morbidity are among the highest in sub-Saharan Africa and are foregrounded by the country's long history of political violence during apartheid. Growing evidence suggests that in utero stress exposure is a potent developmental risk factor for future mental illness risk, yet the extent to which the psychiatric effects of prenatal stress impact the next generation are unknown. We evaluate the intergenerational effects of prenatal stress experienced during apartheid on psychiatric morbidity among children at ages 17-18 and also assess the moderating effects of maternal age, social support, and past household adversity. METHODS: Participants come from Birth-to-Twenty, a longitudinal birth cohort study in Soweto-Johannesburg, South Africa's largest peri-urban township which was the epicentre of violent repression and resistance during the final years of the apartheid regime. Pregnant women were prospectively enrolled in 1990 and completed questionnaires assessing social experiences, and their children's psychiatric morbidity were assessed at ages 17-18. RESULTS: Full data were available from 304 mother-child pairs in 2007-8. Maternal prenatal stress in 1990 was not directly associated greater psychiatric morbidity during at ages 17-18. Maternal age and past household adversity moderated the intergenerational mental health effects of prenatal stress such that children born to younger mothers and late adolescent/young adult children experiencing greater household adversity exhibited worse psychiatric morbidity at ages 17-18. Social support did not buffer against the long-term psychiatric impacts of prenatal stress. CONCLUSIONS: Greater prenatal stress from apartheid predicted adverse psychiatric outcomes among children born to younger mothers and adolescents/young adults who experienced greater concurrent stress. Our findings suggest that prenatal stress may affect adolescent mental health, have stress-sensitising effects, and represent possible intergenerational effects of trauma experienced under apartheid in this sample.

Proteomics analysis of an individual formalin-fixed paraffin-embedded tissue section using isobaric-tag amplification.

RATIONALE: The comprehensive analysis of formalin-fixed paraffin-embedded (FFPE) tissues is essential for retrospective clinical studies. However, detecting low-abundance proteins and obtaining proteome-scale data from FFPE samples pose analytical challenges in mass spectrometry-based proteomics. To overcome this challenge, our study focuses on implementing an isobaric labeling approach to improve the detection of low-abundance target proteins in FFPE tissues, thereby enhancing the qualitative and quantitative analysis. METHODS: We employed an isobaric labeling approach utilizing synthetic peptides or proteins to enable the qualitative and quantitative measurement of target proteins in FFPE tissue samples. To achieve this, we incorporated tandem mass tag (TMT)-labeled recombinant proteins or synthetic peptides into TMT-labeled metastatic breast cancer FFPE tissues. Through this strategy, we successfully detect coexisting CD276 (B7-H3) and CD147 proteins while identifying over 6000 proteins using targeted analysis of individual FFPE tissue sections. RESULTS: Our findings provide compelling evidence that the incorporation of isobaric labeling, along with the inclusion of TMT-labeled peptides or proteins, greatly enhances the detection of target proteins in FFPE tissue samples. By employing this approach, we were able to obtain robust qualitative measurements of CD276 and CD147 proteins, showcasing its effectiveness in identifying more than 6000 proteins in FFPE samples. CONCLUSIONS: The integration of an isobaric labeling approach, in conjunction with synthetic peptides or proteins, presents a valuable strategy for enhancing the detection and validation of target proteins in FFPE tissue analysis. This technique holds immense potential in retrospective clinical studies, as it enables comprehensive analysis of low-abundance proteins and facilitating proteome-scale investigations in FFPE samples. By leveraging this methodology, researchers can unlock new insights into disease mechanisms and advance our understanding of complex biological processes.

Anaerobic Wastewater Treatment and Potable Reuse: Energy and Life Cycle Considerations.

Anaerobic secondary treatment has the potential to facilitate energy-positive operations at wastewater treatment plants, but post-treatment of the anaerobic effluent is needed to recover dissolved methane and nutrients and remove sulfide. In this study, a life cycle assessment was conducted to compare hypothetical full-scale wastewater treatment trains and direct potable reuse trains that combine the staged anaerobic fluidized membrane bioreactor (SAF-MBR) with appropriate post-treatment. We found that anaerobic wastewater treatment trains typically consumed less energy than conventional aerobic treatment, but overall global warming potentials were not significantly different. Generally, recovery of dissolved methane for energy production resulted in lower life cycle impacts than microbial transformation of methane, and microbial oxidation of sulfide resulted in lower environmental impacts than chemical precipitation. Use of reverse osmosis to produce potable water was also found to be a sustainable method for nutrient removal because direct potable reuse trains with the SAF-MBR consumed less energy and had lower life cycle impacts than activated sludge. Moving forward, dissolved methane recovery, reduced chemical usage, and investments that enable direct potable reuse have been flagged as key research areas for further investigation of anaerobic secondary treatment options.

Pirt, a phosphoinositide-binding protein, functions as a regulatory subunit of TRPV1.

Transient receptor potential vanilloid 1 (TRPV1) is a molecular sensor of noxious heat and capsaicin. Its channel activity can be modulated by several mechanisms. Here we identify a membrane protein, Pirt, as a regulator of TRPV1. Pirt is expressed in most nociceptive neurons in the dorsal root ganglia (DRG) including TRPV1-positive cells. Pirt null mice show impaired responsiveness to noxious heat and capsaicin. Noxious heat- and capsaicin-sensitive currents in Pirt-deficient DRG neurons are significantly attenuated. Heterologous expression of Pirt strongly enhances TRPV1-mediated currents. Furthermore, the C terminus of Pirt binds to TRPV1 and several phosphoinositides, including phosphatidylinositol-4,5-bisphosphate (PIP2), and can potentiate TRPV1. The PIP2 binding is dependent on the cluster of basic residues in the Pirt C terminus and is crucial for Pirt regulation of TRPV1. Importantly, the enhancement of TRPV1 by PIP2 requires Pirt. Therefore, Pirt is a key component of the TRPV1 complex and positively regulates TRPV1 activity.

Adverse childhood experiences, traumatic events, and mental health among adults at two outpatient psychiatric facilities in Johannesburg, South Africa: a cross-sectional analysis.

BACKGROUND: Adverse childhood experiences and adult trauma, including sexual abuse, physical abuse, neglect, and interpersonal violence, are highly prevalent in low-resource settings and associated with adverse psychological outcomes. However, there is limited focus on the impact of ACEs and trauma on mental health in sub-Saharan Africa. Therefore, this study examines the impact of traumatic events and ACEs on depression, anxiety, and stress scores among outpatients receiving psychiatric care at two public mental health treatment facilities in Johannesburg, South Africa. METHODS: A sample of 309 participants were recruited between January and June 2022 at Helen Joseph Hospital and Alexandra 18th Avenue Clinic. Participants completed screening measures for mental health outcomes, including the 9-item Patient Health Questionnaire (PHQ-9), the 7-item General Anxiety Disorder scale (GAD-7) and the 10-item Perceived Stress Scale. We fitted modified Poisson and linear regression models to estimate the impact of ACEs and adult experiences of trauma on depression, anxiety, and stress scale scores. RESULTS: 47.57% (n = 147) of participants screened positive for anxiety, 44.66% (n = 138) for depression, and 17% (n = 54) for severe stress. More females screened positive for anxiety (65.31%), depression (65.94%), and stress (77.78%). Each ACE was associated with a 12% increased risk of depression, a 10% increased risk of anxiety, and a 17% increased risk of stress. In separately estimated models, each additional traumatic event during adulthood was associated with a 16% increased risk for depression, an 8% increased risk of anxiety, and a 26% increased risk of stress. Across all models, being male and self-reported physical health were consistently associated with a reduced risk for depression, anxiety, and stress. CONCLUSIONS: ACEs and experiences of traumatic events as adults were associated with significantly increased risks of anxiety, depression, and severe stress. Given high exposure to ACEs and trauma and the associated impact on the mental health of individuals, families, and communities, there is a need to strengthen and scale innovative combination interventions that address multiple stressors impacting people in low-resource settings.

Coping mechanisms during the COVID-19 pandemic and lockdown in metropolitan Johannesburg, South Africa: A qualitative study.

BACKGROUND: The COVID-19 pandemic has caused prolonged stress on numerous fronts. While the acute health impacts of psychosocial stress due to the pandemic are well-documented, less is known about the resources and mechanisms utilized to cope in response to stresses during the pandemic and lockdown. OBJECTIVE: The aim of this study was to identify and describe the coping mechanisms adults utilized in response to the stressors of the COVID-19 pandemic during the 2020 South African lockdown. METHODS: This study included adults (n = 47: 32 female; 14 male; 1 non-binary) from the greater Johannesburg region in South Africa. Interviews with both closed and open-ended questions were administered to query topics regarding the COVID-19 pandemic. Data were coded and thematically analyzed to identify coping mechanisms and experiences. RESULTS: Adults engaged in a variety of strategies to cope with the pandemic and the ensued lockdown. The ability to access or engage in multiple coping mechanisms were either enhanced or constrained by financial and familial situations. Participants engaged in seven major coping mechanisms: interactions with family and friends, prayer and religion, staying active, financial resources, mindset reframing, natural remedies, and following COVID-19 prevention protocols. CONCLUSIONS: Despite the multiple stressors faced during the pandemic and lockdown, participants relied on multiple coping strategies which helped preserve their well-being and overcome pandemic-related adversity. The strategies participants engaged in were impacted by access to financial resources and family support. Further research is needed to examine the potential impacts these strategies may have on people's health.

Collective health behavior and face mask utilization during the COVID-19 pandemic in Oklahoma, USA.

BACKGROUND: Face mask use offers an important public health tool for reducing the spread of coronavirus disease 2019 (COVID-19), yet the politicization of COVID-19 has resulted in uneven adherence. This study assesses the effects of setting characteristics and the sociodemographic composition of crowds on group-level masking rates. METHODS: We conducted 123 site observations of masking behavior at public locations across Oklahoma (USA) between June and September 2020. We used analyses of variance and t-tests to examine variation in masking and ordinary least squares regression to model the effect of setting and sociodemographic characteristics on site-level masking rates. RESULTS: The masking rate across all sites averaged 34% but varied widely. Site-level masking rates were higher at metropolitan sites and sites with a store or municipal masking mandate. The masking rate at sites where women or older adults (60+) were the predominant group did not differ significantly from other sites. Ethnically diverse sites exhibited significantly higher masking rates compared with predominantly white sites. Findings indicate that setting characteristics explained a greater amount of variation in collective masking rates than sociodemographic differences. CONCLUSIONS: This study underscores the importance of place and policy for mask adherence. In the absence of state-level mandates, masking policies at a more local level may be effective.

Perceptions and experiences of prostate cancer patients in a public tertiary hospital in urban South Africa.

ABSTRACTProstate cancer is among the most prevalent forms of cancer worldwide and is reported to have the highest incidence, mortality, and 5-year prevalence rate of all cancers among men living in Africa. Despite this widespread burden in the African continent, little is known about the perspectives and experience of prostate cancer among African men. To further understand experiences among patients living in urban South Africa, we conducted in-depth, semi-structured qualitative interviews to examine the perceptions and experiences of 28 Black African prostate cancer patients receiving treatment at a major tertiary hospital in Johannesburg, South Africa. Our data explored four major areas of patients' experiences with prostate cancer: detection, diagnosis, treatment, and follow-up care. Our results showed that the experience of living with prostate cancer among low-income, Black South African men is a stressful and emotionally painful experience due in part to men feeling that they had insufficient knowledge about their own condition and feeling disempowered or ill-equipped to manage their cancer. These feelings were strongly associated with distrust or dissatisfaction with physicians and the health care system. Resilience factors include social support from family, friends, and religious communities, acceptance of their diagnosis, religion, and positive appraisals of their medical care.

Use of intraoperative technology in total knee arthroplasty is not associated with reductions in postoperative pain.

PURPOSE: Our systematic review and meta-analysis sought to assess how technology-assistance impacts (1) post-operative pain and (2) opioid use in patients undergoing primary total knee arthroplasty (TKA). METHODS: Four online databases were queried for studies published up to October 2021 that reported on pain and opioid usage between technology-assisted and manual TKA (mTKA) patients. Mantel-Haenszel (M-H) models were utilized to calculate pooled mean difference (MDs) and 95% confidence interval (CIs). Subgroup analyses were conducted to isolate robotic-arm assisted (RAA) and computed-assisted navigation (CAN) cohorts. Risk of bias was assessed for all included non-randomized studies with the Methodological Index for Non-Randomized Studies (MINORS) tool. For the randomized control trials included in our study, the Detsky scale was applied. RESULTS: Our analysis included 31 studies, reporting on a total of 761,300 TKAs (mTKA: n = 753,554; Computer-Assisted Navigation (CAN): n = 1,309; Robotic-Arm Assisted (RAA): n = 6437). No differences were demonstrated when evaluating WOMAC (MD: 0.00, 95% CI - 0.69 to 0.69; p = 1.00), KSS (MD: 0.01, 95% CI - 1.46 to 1.49; p = 0.99), KOOS (MD - 2.91, 95% CI - 6.17 to 0.34; p = 0.08), and VAS (MD - 0.54, 95% CI - 1.01 to - 0.007; p = 0.02) pain scores between cohorts. There was mixed evidence regarding how opioid consumption differed between TKA techniques. CONCLUSION: The present analysis demonstrated no difference in terms of pain across a variety of utilized patient-reported pain measurements. However, there were mixed results regarding how opioid consumption varied between manual and technology-assisted cohorts, particularly in the immediate post-operative period. LEVEL OF EVIDENCE: III.

Mark-Up Trends in Contemporary Medicare Primary and Revision Total Joint Arthroplasty.

BACKGROUND: Understanding mark-up ratios (MRs), the ratio between a healthcare institution's submitted charge and the Medicare payment received, for high-volume orthopaedic procedures is imperative to inform policy about price transparency and reducing surprise billing. This analysis examined the MRs for primary and revision total hip and knee arthroplasty (THA and TKA) services to Medicare beneficiaries between 2013 and 2019 across healthcare settings and geographic regions. METHODS: A large dataset was queried for all THA and TKA procedures performed by orthopaedic surgeons between 2013 and 2019, using Healthcare Common Procedure Coding System (HCPCS) codes for the most frequently used services. Yearly MRs, service counts, average submitted charges, average allowed payments, and average Medicare payments were analyzed. Trends in MRs were assessed. We evaluated 9 THA HCPCS codes, averaging 159,297 procedures a year provided by a mean of 5,330 surgeons. We evaluated 6 TKA HCPCS codes, averaging 290,244 procedures a year provided by a mean of 7,308 surgeons. RESULTS: For knee arthroplasty procedures, a decrease was noted for HCPCS code 27438 (patellar arthroplasty with prosthesis) over the study period (8.30 to 6.62; P = .016) and HCPCS code 27447 (TKA) had the highest median (interquartile range [IQR]) MR (4.73 [3.64 to 6.30]). For revision knee procedures, the highest median (IQR) MR was for HCPCS code 27488 (removal of knee prosthesis; 6.12 [3.83-8.22]). While no trends were noted for both primary and revision hip arthroplasty, median (IQR) MRs in 2019 for primary hip procedures ranged from 3.83 (hemiarthroplasty) to 5.06 (conversion of previous hip surgery to THA) and HCPCS code 27130 (total hip arthroplasty) had a median (IQR) MR of 4.66 (3.58-6.44). For revision hip procedures, MRs ranged from 3.79 (open treatment of femoral fracture or prosthetic arthroplasty) to 6.10 (revision of THA femoral component). Wisconsin had the highest median MR by state (>9) for primary knee, revision knee, and primary hip procedures. CONCLUSION: The MRs for primary and revision THA and TKA procedures were strikingly high, as compared to nonorthopaedic procedures. These findings represent high levels of excess charges billed, which may pose serious financial burdens to patients and must be taken into consideration in future policy discussions to avoid price inflation.