Progerin Can Induce DNA Damage in the Absence of Global Changes in Replication or Cell Proliferation.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by features of accelerated aging, and individuals with HGPS seldom live beyond their mid-teens. The syndrome is commonly caused by a point mutation in the LMNA gene which codes for lamin A and its splice variant lamin C, components of the nuclear lamina. The mutation causing HGPS leads to production of a truncated, farnesylated form of lamin A referred to as "progerin." Progerin is also expressed at low levels in healthy individuals and appears to play a role in normal aging. HGPS is associated with an accumulation of genomic DNA double-strand breaks (DSBs) and alterations in the nature of DSB repair. The source of DSBs in HGPS is often attributed to stalling and subsequent collapse of replication forks in conjunction with faulty recruitment of repair factors to damage sites. In this work, we used a model system involving immortalized human cell lines to investigate progerin-induced genomic damage. Using an immunofluorescence approach to visualize phosphorylated histone H2AX foci which mark sites of genomic damage, we report that cells engineered to express progerin displayed a significant elevation of endogenous damage in the absence of any change in the cell cycle profile or doubling time of cells. Genomic damage was enhanced and persistent in progerin-expressing cells treated with hydroxyurea. Overexpression of wild-type lamin A did not elicit the outcomes associated with progerin expression. Our results show that DNA damage caused by progerin can occur independently from global changes in replication or cell proliferation.

IGF-1 and IGFBP-1 as Possible Predictors of Response to Lifestyle Intervention-Results from Randomized Controlled Trials.

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some individuals do not experience anticipated improvements despite weight loss. Biomarkers to identify such individuals at early stages are lacking. Insulin-like growth factor 1 (IGF- 1) and Insulin-like growth factor binding protein 1(IGFBP-1) were shown to predict T2DM onset in prediabetes. We assessed whether these markers also predict the success of lifestyle interventions, thereby possibly guiding personalized strategies. We analyzed the fasting serum levels of IGF-1, IGFBP-1, and Insulin-like growth factor binding protein 2 (IGFBP-2) in relation to changes in metabolic and anthropometric parameters, including intrahepatic lipids (IHLs) and visceral adipose tissue (VAT) volume, measured by magnetic resonance imaging (MRI), in 345 participants with a high risk for prediabetes (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), and significance was set at p < 0.05. Within the 1-year intervention, overall significant improvements were observed. Stratifying individuals by baseline IGF-1 and IGFBP-1 percentiles revealed significant differences: higher IGF-1 levels were associated with more favorable changes compared to lower levels, especially in VAT and IHL. Lower baseline IGFBP-1 levels were associated with greater improvements, especially in IHL and 2 h glucose. Higher bioactive IGF-1 levels might predict better metabolic outcomes following lifestyle interventions in prediabetes, potentially serving as biomarkers for personalized interventions.

Excessive Preoperative Testing in Otolaryngology: A Retrospective Comparison of Primary Care and Perioperative Providers.

OBJECTIVE: To assess the association between provider type (primary care provider [PCP] or perioperative provider) and excessive preoperative testing. STUDY DESIGN: Cross-sectional study. SETTING: Academic medical center. METHODS: Electronic medical records of adult patients who obtained an outpatient preoperative assessment and underwent surgery in the Department of Otolaryngology-Head and Neck Surgery during the first 2 weeks of January 2019 (n = 94) were reviewed. Patients receiving preoperative tests beyond those recommended by the guidelines were deemed to have had excessive testing. Descriptive statistics were used to characterize the study population. Simple and multivariate logistic regression were used to analyze the association between the outcome and the predictor variables. RESULTS: Overall, 44.7% of preoperative evaluations had excessive testing. Patients who had their preoperative evaluation performed by a perioperative provider had 89% lower odds of having excessive preoperative testing compared to those evaluated by a PCP (odds ratio = 0.11, 95% confidence interval: [0.03, 0.37], P < .001). Female sex, younger age, and higher risk of major adverse cardiac events were associated with greater odds of excessive testing. CONCLUSION: Excessive preoperative testing is more commonly performed by PCPs compared to perioperative providers. These results give preliminary evidence in support of a potential shift in the clinical responsibility of preoperative evaluation from PCPs to perioperative providers in order to reduce excessive testing and promote high-value health care. The next steps include validating these findings, identifying reasons for differential guideline concordance, and intervening accordingly.

Bacillus Calmette-Guérin immunotherapy induces an efficient antitumor response to control murine melanoma depending on MyD88 signaling.

Bacillus Calmette-Guérin (BCG) is the first line treatment for bladder cancer and it is also proposed for melanoma immunotherapy. BCG modulates the tumor microenvironment (TME) inducing an antitumor effective response, but the immune mechanisms involved still poorly understood. The immune profile of B16-F10 murine melanoma cells was assessed by infecting these cells with BCG or stimulating them with agonists for different innate immune pathways such as TLRs, inflammasome, cGAS-STING and type I IFN. B16-F10 did not respond to any of those stimuli, except for type I IFN agonists, contrasting with bone marrow-derived macrophages (BMDMs) that showed high production of proinflammatory cytokines. Additionally, we confirmed that BCG is able to infect B16-F10, which in turn can activate macrophages and spleen cells from mice in co-culture experiments. Furthermore, we established a subcutaneous B16-F10 melanoma model for intratumoral BCG treatment and compared wild type mice to TLR2-/-, TLR3-/-, TLR4-/-, TLR7-/-, TLR3/7/9-/-, caspase 1-/-, caspase 11-/-, IL-1R-/-, cGAS-/-, STING-/-, IFNAR-/-, MyD88-/-deficient animals. These results in vivo demonstrate that MyD88 signaling is important for BCG immunotherapy to control melanoma in mice. Also, BCG fails to induce cytokine production in the co-culture experiments using B16-F10 and BMDMs or spleen cells derived from MyD88-/- compared to wild-type (WT) animals. Immunotherapy with BCG was not able to induce the recruitment of inflammatory cells in the TME from MyD88-/- mice, impairing tumor control and IFN-γ production by T cells. In conclusion, MyD88 impacts on both innate and adaptive responses to BCG leading to an efficient antitumor response against melanoma.

Active juvenile systemic lupus erythematosus is associated with distinct NK cell transcriptional and phenotypic alterations.

While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the contribution of natural killer (NK) cells to disease pathogenesis. There is even less evidence about the role of NK cells in the more severe phenotype with juvenile-onset (J)SLE. In this study, analysis of the phenotype and function of NK cells in a large cohort of JSLE patients demonstrated that total NK cells, as well as perforin and granzyme A expressing NK cell populations, were significantly diminished in JSLE patients compared to age- and sex-matched healthy controls. The reduction in NK cell frequency was associated with increased disease activity, and transcriptomic analysis of NK populations from active and low disease activity JSLE patients versus healthy controls confirmed that disease activity was the main driver of differential NK cell gene expression. Pathway analysis of differentially expressed genes revealed an upregulation of interferon-α responses and a downregulation of exocytosis in active disease compared to healthy controls. Further gene set enrichment analysis also demonstrated an overrepresentation of the apoptosis pathway in active disease. This points to increased propensity for apoptosis as a potential factor contributing to NK cell deficiency in JSLE.

Deletion of Tissue Factor Pathway Inhibitor Isoform Beta or Gamma, but not Alpha, Improves Clotting in Hemophilia Mice.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) regulates tissue factor (TF)-triggered coagulation. Humans and mice express transcripts encoding for multi-distributed (endothelial, platelet, and plasma) 3-Kunitz domain TFPIα and endothelial membrane-anchored 2-Kunitz TFPIß. Mice express a third transcript, γ, that encodes plasma lipoprotein-associated 2-Kunitz TFPI. In humans, proteolysis of α and/or ß produces plasma lipoprotein-associated 2-Kunitz TFPI at lower levels. In clinical trials, monoclonal antibodies that target all TFPI isoforms extend coagulation and correct bleeding in hemophilia patients but with some thrombosis risks. OBJECTIVES: Determine the impact of TFPI isoform-specific deletions on promoting clotting in hemophilia mice. METHODS: Engineered TFPI isoform-specific, hemophilia (FVIII-null) mice were evaluated for clotting. RESULTS: Mice expressing any single TFPI isoform are healthy. Thrombin generation assays identified TFPIγ as the dominant anticoagulation isoform in mouse plasma. Hemostasis was assessed by serial bleeding times from a tail vein laceration. Repeatedly, after a clot forms, it is manually disrupted; the number of clots/disruptions occurring over a 15-minute period is reported. C57BL/6 and hemophilia mice clot on average 25.6 versus 5.4 times, respectively. On a hemophilia background, TFPIß or TFPIγ-specific deletion improves clotting to 14.6 and 15.2 times, respectively (p<0.0001). TFPIα-specific deletion is without impact, clotting 5.1 times. Heterozygous deletion of TFPIß is effective, clotting 11.8 times (p<0.0001). Heterozygous deletion of TFPIα or TFPIγ alone is ineffective clotting 3.0 and 6.1 times, respectively; but heterozygous TFPIαγ deletion improves clotting to 11.2 times (p<0.001). CONCLUSION: In hemophilia mice, endothelial TFPIß and plasma γ-derived 2-Kunitz TFPI individually contribute more to bleeding than total TFPIα.

Circadian regulation of macromolecular complex turnover and proteome renewal.

Although costly to maintain, protein homeostasis is indispensable for normal cellular function and long-term health. In mammalian cells and tissues, daily variation in global protein synthesis has been observed, but its utility and consequences for proteome integrity are not fully understood. Using several different pulse-labelling strategies, here we gain direct insight into the relationship between protein synthesis and abundance proteome-wide. We show that protein degradation varies in-phase with protein synthesis, facilitating rhythms in turnover rather than abundance. This results in daily consolidation of proteome renewal whilst minimising changes in composition. Coupled rhythms in synthesis and turnover are especially salient to the assembly of macromolecular protein complexes, particularly the ribosome, the most abundant species of complex in the cell. Daily turnover and proteasomal degradation rhythms render cells and mice more sensitive to proteotoxic stress at specific times of day, potentially contributing to daily rhythms in the efficacy of proteasomal inhibitors against cancer. Our findings suggest that circadian rhythms function to minimise the bioenergetic cost of protein homeostasis through temporal consolidation of protein turnover.

Management of Lithium Dosing Around Delivery: An Observational Study.

Objectives: Recommendations on lithium dosing around delivery vary, with several guidelines suggesting that lithium should be discontinued prior to delivery. We aimed to evaluate the validity of these recommendations by investigating 1) maternal lithium blood level changes following delivery, and 2) the association between neonatal lithium blood levels at delivery and neonatal outcomes. Methods: In this retrospective observational cohort study, we included women with at least one lithium blood level measurement during the final week of pregnancy and the first postpartum week. For aim 2, we included a subcohort of women with neonates for whom neonatal lithium blood levels (obtained from the umbilical cord or a neonatal vein puncture within 24 hours of delivery) were available. Results: There were a total of 233 maternal lithium blood level measurements; 55 (23.6%) in the week before delivery and 178 (76.4%) in the week after. There was no association between time and lithium blood level/dose ratio (Pearson correlation coefficient -0.03, P = .63). Additionally, we included a total of 29 neonates for whom a lithium measurement was performed within 24 hours postpartum. Maternal and neonatal lithium blood levels were strongly correlated. We observed no associations between neonatal lithium blood levels at delivery and neonatal outcomes. Conclusion: Based on our findings, we do not recommend lowering the dosage or discontinuation of lithium prior to delivery. Stable dosing can prevent subtherapeutic lithium serum levels, which is especially important in the postpartum period when relapse risks are highest.Appeared originally in Bipolar Disord 2021; 23:49-54.

Impact of upper airway obstruction management in Robin Sequence on need for myringotomy tubes.

OBJECTIVE: Investigate an association between upper airway obstruction (UAO) management in Robin Sequence (RS) and need for bilateral myringotomy and tubes (BMT). METHODS: Retrospective chart review of RS patients treated at a tertiary free-standing pediatric hospital from 1995 to 2020 was performed. Patients were grouped based on airway management: conservative, tracheostomy, tongue-lip adhesion (TLA), and mandibular distraction osteogenesis (MDO). Demographic data, cleft palate (CP) association, numbers of BMT and ear infections, and audiogram data including tympanograms were collected. One-way ANOVA and Chi-square/Fisher's exact tests were used to compare continuous and categorical data, respectively. Multivariable regression analysis was used to compare BMT rates between treatment groups. RESULTS: One hundred forty-eight patients were included, 70.3 % of which had CP. Most patients (67.6 %) had at least one BMT; 29.1 % required two or more BMT. The rate of BMT was higher in patients with CP compared to those with intact palates (p = 0.003; 95 % CI 1.30-3.57) and those treated with tracheostomy (p = 0.043; 95 % CI 1.01, 2.27). Surgically managed patients were more likely to have hearing loss (67.5 % vs. 35.3 %, p = 0.017) and ear infections (42.1 % vs. 20.0 %, p = 0.014) pre-compared to post-procedure for airway management. CONCLUSION: Most RS patients require at least 1 set of BMT. Those with CP and/or treated with tracheostomy had a higher likelihood of needing BMT. Rate of hearing loss and ear infection was higher in surgically managed RS patients. Patients with RS and overt CP require a statistically higher number of BMTs compared to those with either submucous cleft palate or intact palate.

Evidence of SARS-CoV-2 convergent evolution in immunosuppressed patients treated with antiviral therapies.

BACKGROUND: The factors contributing to the accelerated convergent evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not fully understood. Unraveling the contribution of viral replication in immunocompromised patients is important for the early detection of novel mutations and developing approaches to limit COVID-19. METHODS: We deep sequenced SARS-CoV-2 RNA from 192 patients (64% hospitalized, 39% immunosuppressed) and compared the viral genetic diversity within the patient groups of different immunity and hospitalization status. Serial sampling of 14 patients was evaluated for viral evolution in response to antiviral treatments. RESULTS: We identified hospitalized and immunosuppressed patients with significantly higher levels of viral genetic diversity and variability. Further evaluation of serial samples revealed accumulated mutations associated with escape from neutralizing antibodies in a subset of the immunosuppressed patients treated with antiviral therapies. Interestingly, the accumulated viral mutations that arose in this early Omicron wave, which were not common in the patient viral lineages, represent convergent mutations that are prevalent in the later Omicron sublineages, including the XBB, BA.2.86.1 and its descendent JN sublineages. CONCLUSIONS: Our results illustrate the importance of identifying convergent mutations generated during antiviral therapy in immunosuppressed patients, as they may contribute to the future evolutionary landscape of SARS-CoV-2. Our study also provides evidence of a correlation between SARS-CoV-2 convergent mutations and specific antiviral treatments. Evaluating high-confidence genomes from distinct waves in the pandemic with detailed patient metadata allows for discerning of convergent mutations that contribute to the ongoing evolution of SARS-CoV-2.

Incidence and management of secondary deformities after megaendoprosthetic proximal femur replacement in skeletally immature bone sarcoma patients.

INTRODUCTION: Megaendoprosthetic reconstruction of bone defects in skeletally immature patients has led to the development of unique complications and secondary deformities not observed in adult patient cohorts. With an increasing number of megaendoprosthetic replacements performed, orthopedic oncologists still gain experience in the incidence and type of secondary deformities caused. In this study, we report the incidence, probable cause and management outcome of two secondary deformities after megaendoprosthetic reconstruction of the proximal femur: hip dysplasia and genu valgum. MATERIALS AND METHODS: Retrospective analysis of 14 patients who underwent primary and/or repeat reconstruction/surgery with a megaendoprosthetic proximal femur replacement between 2018 and 2022. RESULTS: Mean patient age was 9.1 years (range 4-17 years). Stress shielding was observed in 71.4%. Hip dislocation was the most frequent complication (50%). While four dislocations occurred without an underlying deformity, secondary hip dysplasia was identified in 58.3% (n = 7/12) of intraarticular resections and reconstructions, leading to dislocation in 71.4% (n = 5/7). A genu valgum deformity was observed in 41.6% (n = 5/12). The incidence of secondary hip dysplasia and concomitant genu valgum was 42.9% (n = 3/7). Triple pelvic osteotomy led to rebound hip dysplasia in two cases (patients aged < 10 years), whereas acetabular socket replacement led to stable hip joints over the course of follow-up. Temporary hemiepiphyseodesis was applied to address secondary genu valgum. CONCLUSIONS: Patients aged < 10 years were prone to develop secondary hip dysplasia and genu valgum following proximal femur replacement in this study. Management of secondary deformities should depend on remaining skeletal growth. Stress shielding was observed in almost all skeletally immature patients.

The Potential of Fecal Volatile Organic Compound Analysis for the Early Diagnosis of Late-Onset Sepsis in Preterm Infants: A Narrative Review.

Early diagnosis and treatment of late-onset sepsis (LOS) is crucial for survival, but challenging. Intestinal microbiota and metabolome alterations precede the clinical onset of LOS, and the preterm gut is considered an important source of bacterial pathogens. Fecal volatile organic compounds (VOCs), formed by physiologic and pathophysiologic metabolic processes in the preterm gut, reflect a complex interplay between the human host, the environment, and microbiota. Disease-associated fecal VOCs can be detected with an array of devices with various potential for the development of a point-of-care test (POCT) for preclinical LOS detection. While characteristic VOCs for common LOS pathogens have been described, their VOC profiles often overlap with other pathogens due to similarities in metabolic pathways, hampering the construction of species-specific profiles. Clinical studies have, however, successfully discriminated LOS patients from healthy individuals using fecal VOC analysis with the highest predictive value for Gram-negative pathogens. This review discusses the current advancements in the development of a non-invasive fecal VOC-based POCT for early diagnosis of LOS, which may potentially provide opportunities for early intervention and targeted treatment and could improve clinical neonatal outcomes. Identification of confounding variables impacting VOC synthesis, selection of an optimal detection device, and development of standardized sampling protocols will allow for the development of a novel POCT in the near future.

The effect of forward postural lean on running economy, kinematics, and muscle activation.

BACKGROUND: Running economy, commonly defined as the metabolic energy demand for a given submaximal running speed, is strongly associated with distance running performance. It is commonly believed among running coaches and runners that running with increased forward postural lean either from the ankle or waist improves running economy. However, recent biomechanical research suggests using a large forward postural lean during running may impair running economy due to increased demand on the leg muscles. PURPOSE: This study tests the effect of altering forward postural lean and lean strategy on running economy, kinematics, and muscle activity. METHODS: 16 healthy young adult runners (23±5 years, 8M/8F) ran on a motorized treadmill at 3.58m/s using three postural lean angles [upright, moderate lean (50% of maximal lean angle), and maximal lean] and two strategies (lean from ankle and lean from waist [trunk lean]). Metabolic energy consumption, leg kinematics, and muscle activation data were recorded for all trials. RESULTS: Regardless of lean strategy, running with an increased forward postural lean (up to 8±2 degrees) increased metabolic cost (worsened economy) by 8% (p < .001), increased hip flexion (p < .001), and increased gluteus maximus (p = .016) and biceps femoris (p = .02) muscle activation during the stance phase. This relation between running economy and postural lean angle was similar between the ankle and trunk lean strategies (p = .743). CONCLUSION: Running with a large forward postural lean reduced running economy and increased reliance on less efficient extensor leg muscles. In contrast, running with a more upright or moderate forward postural lean may be more energetically optimal, and lead to improved running performance.

Fecal microbiota and volatile metabolome pattern alterations precede late-onset meningitis in preterm neonates.

OBJECTIVE: The fecal microbiota and metabolome are hypothesized to be altered before late-onset neonatal meningitis (LOM), in analogy to late-onset sepsis (LOS). The present study aimed to identify fecal microbiota composition and volatile metabolomics preceding LOM. METHODS: Cases and gestational age-matched controls were selected from a prospective, longitudinal preterm cohort study (born <30 weeks' gestation) at nine neonatal intensive care units. The microbial composition (16S rRNA sequencing) and volatile metabolome (gas chromatography-ion mobility spectrometry (GC-IMS) and GC-time-of-flight-mass spectrometry (GC-TOF-MS)), were analyzed in fecal samples 1-10 days pre-LOM. RESULTS: Of 1397 included infants, 21 were diagnosed with LOM (1.5%), and 19 with concomitant LOS (90%). Random Forest classification and MaAsLin2 analysis found similar microbiota features contribute to the discrimination of fecal pre-LOM samples versus controls. A Random Forest model based on six microbiota features accurately predicts LOM 1-3 days before diagnosis with an area under the curve (AUC) of 0.88 (n=147). Pattern recognition analysis by GC-IMS revealed an AUC of 0.70-0.76 (P<0.05) in the three days pre-LOM (n=92). No single discriminative metabolites were identified by GC-TOF-MS (n=66). CONCLUSION: Infants with LOM could be accurately discriminated from controls based on preclinical microbiota composition, while alterations in the volatile metabolome were moderately associated with preclinical LOM.

Does a participatory live music practice support nurses to deliver compassionate care to hospitalised patients? A qualitative study.

AIM: To gain more insight into how nurses experience a participatory live music practice in relation to their ability to deliver compassionate care to medically hospitalised patients. DESIGN: Qualitative interpretive design. METHODS: Sixteen nurses participating in a live music practice with patients were interviewed using in-depth interviews with open-ended questions. Audio recordings were transcribed verbatim and subsequently coded. Theory-driven inductive and deductive approaches were applied in thematic data analysis. RESULTS: We identified four themes: (1) Nurses' empathy and compassion; (2) The caring nurse-patient relationship; (3) Person-centred approaches to care and (4) Nurses' subjective wellbeing. By observing patients' reactions to the music, nurses described that they obtained a deeper insight and understanding of patients' emotional wellbeing. These observations led to increased feelings of compassion in patient contact and stimulated informal communication between nurses and patients through a sense of shared humanity. According to nurses, these aspects positively affected collaboration with patients in delivering care and stimulated them to pursue person-centred approaches to care. Participating in the live music practice also positively affected nurses' wellbeing, enhanced relaxation and created an ambiance in which compassion could be expressed. CONCLUSION: A live music practice can positively contribute to the delivery of compassionate care by providing meaningful shared moments that increase feelings of empathy and compassion and strengthen the caring relationship. IMPLICATIONS FOR THE PROFESSION: Offering a live music practice at the ward and bedside offers a unique possibility to enhance engagement in person-centred, compassionate care. IMPACT: While compassion and compassionate care are essential component of nursing, nurses often experience multiple barriers to its provision in daily practice. An innovative way to stimulate compassionate care is through the participation of nurses and patients in a live music practice, providing a meaningful moment shared between them. This stimulates feelings of shared humanity and bonding in the caring relationship. REPORTING METHOD: The COnsolidated criteria for REporting Qualitative research (COREQ). No Patient or Public Contribution.

Brain oscillatory processes related to sequence memory in healthy older adults.

Sequence memory is subject to age-related decline, but the underlying processes are not yet fully understood. We analyzed electroencephalography (EEG) in 21 healthy older (60-80 years) and 26 young participants (20-30 years) and compared time-frequency spectra and theta-gamma phase-amplitude-coupling (PAC) during encoding of the order of visually presented items. In older adults, desynchronization in theta (4-8 Hz) and synchronization in gamma (30-45 Hz) power did not distinguish between subsequently correctly and incorrectly remembered trials, while there was a subsequent memory effect for young adults. Theta-gamma PAC was modulated by item position within a sequence for older but not young adults. Specifically, position within a sequence was coded by higher gamma amplitude for successive theta phases for later correctly remembered trials. Thus, deficient differentiation in theta desynchronization and gamma oscillations during sequence encoding in older adults may reflect neurophysiological correlates of age-related memory decline. Furthermore, our results indicate that sequences are coded by theta-gamma PAC in older adults, but that this mechanism might lose precision in aging.

Heavy metal leaching from wood ash before and after hydration and carbonation.

Wood ashes can be used, e.g., as soil fertilizer or in construction materials; however, it is important to ensure that such use will not cause spreading of heavy metals and subsequent harm to the environment. Wood fly ashes (WFAs) generally have higher concentrations of heavy metals than wood bottom ashes. This paper focuses on the leaching of heavy metals from WFA, specifically identifying WFA characteristics that influence the leaching and changes in leaching caused by hydration and carbonation in ambient air. Chemometric modeling based on characteristics for eight different WFAs suggested that the leaching of Cr and Zn was associated with the concentration of K and the leaching of SO42-, indicating a connection to the soluble K2(SO4) commonly found in WFAs. During the aging, both pH and conductivity of the WFAs decreased showing the formation of new phases. The leaching of Cd, Cu, Ni, and Pb was low initially and decreased to non-measurable after the aging. So did the leaching of Zn except from one of the WFAs. Thus, the part of the heavy metals, which were leaching originally, was built into the newly formed phases. The Cr leaching also showed a general decrease during the aging, however, not to similarly low levels. This means that the leaching Cr fraction was either not influenced by the aging processes or the formed phases contained water-soluble Cr. The continued leaching of Cr needs more attention as it may be the toxic and carcinogenic Cr(IV). As the chemistry and mineralogy of WFAs, inclusive of the mobility of the heavy metals, are subject to changes, increased knowledge on the chemistry determining these changes is needed to choose environmentally sound recycling options.

The dermatopathologist-patient consultation program: A pilot study on patient perspectives and interest.

BACKGROUND: Despite the integral contribution of dermatopathologists in diagnosing skin lesions, their role often remains unclear to patients, likely due to little face-to-face interaction. More healthcare systems have begun introducing patient-pathologist consultation programs that allow patients to discuss results with a pathologist and view tissue under a microscope. To our knowledge, only one study has been published exploring patient perspectives of these programs and no studies exist regarding interest in dermatopathology. METHODS: An anonymous survey was distributed via online support groups for various dermatologic diagnoses. RESULTS: Patients demonstrated a high level of interest in the dermatopathologist-patient consultation program, with 81.3% expressing at least moderate interest in discussing their diagnosis with a dermatopathologist and 79.2% expressing at least moderate interest in examining their tissue under the microscope with a dermatopathologist. The rationale for interest included various themes: (1) knowledge/understanding, (2) empowerment, (3) emotional support, (4) general interest, and (5) improved trust. CONCLUSIONS: Patients with cancerous and non-cancerous dermatologic diagnoses demonstrate high interest in a dermatopathologist-patient consultation program. Efforts to pilot this type of program can build upon the infrastructure of current pathologist consultation programs. Future efforts should be taken by hospital leadership, clinicians, and dermatopathologists to determine physician interest and address logistical challenges to the implementation of these programs.