Disulfiram Reduces Atherosclerosis and Enhances Efferocytosis, Autophagy, and Atheroprotective Gut Microbiota in Hyperlipidemic Mice.

BACKGROUND: Pyroptosis executor GsdmD (gasdermin D) promotes atherosclerosis in mice and humans. Disulfiram was recently shown to potently inhibit GsdmD, but the in vivo efficacy and mechanism of disulfiram's antiatherosclerotic activity is yet to be explored. METHODS AND RESULTS: We used human/mouse macrophages, endothelial cells, and smooth muscle cells and a hyperlipidemic mouse model of atherosclerosis to determine disulfiram antiatherosclerotic efficacy and mechanism. The effects of disulfiram on several atheroprotective pathways such as autophagy, efferocytosis, phagocytosis, and gut microbiota were determined. Atomic force microscopy was used to determine the effects of disulfiram on the biophysical properties of the plasma membrane of macrophages. Disulfiram-fed hyperlipidemic apolipoprotein E-/- mice showed significantly reduced interleukin-1ß release upon in vivo Nlrp3 (NLR family pyrin domain containing 3) inflammasome activation. Disulfiram-fed mice showed smaller atherosclerotic lesions (~27% and 29% reduction in males and females, respectively) and necrotic core areas (~50% and 46% reduction in males and females, respectively). Disulfiram induced autophagy in macrophages, smooth muscle cells, endothelial cells, hepatocytes/liver, and atherosclerotic plaques. Disulfiram modulated other atheroprotective pathways (eg, efferocytosis, phagocytosis) and gut microbiota. Disulfiram-treated macrophages showed enhanced phagocytosis/efferocytosis, with the mechanism being a marked increase in cell-surface expression of efferocytic receptor MerTK. Atomic force microscopy analysis revealed altered biophysical properties of disulfiram-treated macrophages, showing increased order-state of plasma membrane and increased adhesion strength. Furthermore, 16sRNA sequencing of disulfiram-fed hyperlipidemic mice showed highly significant enrichment in atheroprotective gut microbiota Akkermansia and a reduction in atherogenic Romboutsia species. CONCLUSIONS: Taken together, our data show that disulfiram can simultaneously modulate several atheroprotective pathways in a GsdmD-dependent as well as GsdmD-independent manner.

Response to: regarding the significance of anti-COVID-IgA antibody response in COVID-19 breakthrough infection.

In response to Chen et al.'s comments on our paper regarding the significance of anti-COVID-IgA antibody response in COVID-19 breakthrough infection in vaccinated patients, we have highlighted the role and the scope of this paper in this correspondence. The role of anti-COVID-19-IgA is already known. The objective of the previous study was to see its role in breakthrough-infected patients. To analyse this effect, we recruited patients with COVID-19 infection after they were fully vaccinated and compared them with the vaccinated group who did not get the infection. Both groups were equally exposed to the virus as all of them were health care workers. We also showed that the anti-COVID-19-NP-IgA was absent in the healthy cohort of our study groups, signifying the absence of natural infection in them during this period. The article also highlights the importance of vaccinating all individuals including those who are immunosuppressed, as it prevents severe COVID-19 infection in these individuals. The physicians should be aware of the fact that immunosuppressed patients are more likely to get COVID-19 breakthrough infection. However, proper vaccination with booster doses prevents severe infection in them.

Timing of mastectomy and the effect on the likelihood of outpatient surgery and cost savings in breast cancer patients.

BACKGROUND: Same-day discharge after mastectomy has potential patient- and hospital-level benefits; however, few data are available regarding factors affecting the likelihood of same-day discharge in order to address barriers. We sought to evaluate factors contributing to same-day discharge, focusing on the timing of mastectomy during the operative day. METHODS: We conducted a single-institution retrospective review of patients who underwent mastectomies for malignancy over a 3-y time frame. Clinicopathologic variables were collected along with a binary variable for mastectomy start time (morning versus afternoon). Our primary endpoint was rate of same-day discharge. A multivariable logistic regression model was constructed from significant univariate variables to determine independent predictors of same-day discharge. A secondary endpoint was a cost-utility analysis for morning versus afternoon start time, using hospital cost data. RESULTS: There were 451 patients included in the analysis. Factors associated with same-day discharge rate included the American Society of Anesthesiologists score, use of a preoperative regional anesthesia block, type of mastectomy performed, individual surgeon variation, and a morning start for the mastectomy. On multivariable analysis, morning start was a strong independent predictor of same-day discharge (odd ratio = 2.83; 95% CI, 1.75-4.60). The cost-utility analysis favored a morning start, with average cost savings of $550 per patient. CONCLUSION: Despite patient- and surgeon-specific variations, simple scheduling policies can improve same-day discharge rates after mastectomy, leading to improved hospital bed use and cost reduction.

Low-Dose Rivaroxaban as Extended Prophylaxis Reduces Postdischarge Venous Thromboembolism in Patients With Malignancy and IBD.

BACKGROUND: Despite guidelines suggesting the use of extended prophylaxis for prevention of venous thromboembolism in patients with colorectal cancer and perhaps IBD, routine use is low and scant data exist regarding oral forms of therapy. OBJECTIVE: The purpose was to compare the incidence of postdischarge venous thromboembolism in patients given extended prophylaxis with low-dose rivaroxaban. DESIGN: We used propensity matching to compare pre- and postintervention analyses from a 2-year period before instituting extended prophylaxis. SETTING: All colorectal patients at a single institution were prospectively considered for extended prophylaxis. PATIENTS: Patients with a diagnosis of IBD or colorectal cancer who underwent operative resection were included. INTERVENTIONS: Those considered for extended prophylaxis were prescribed 10 mg of rivaroxaban for 30 days postsurgery. MAIN OUTCOME MEASURES: The primary outcome was venous thromboembolism incidence 30 days postdischarge. The secondary outcome was bleeding rates, major or minor. RESULTS: Of the 498 patients considered for extended prophylaxis, 363 were discharged with rivaroxaban, 81 on baseline anticoagulation, and 54 without anticoagulation. Propensity-matched cohorts based on stoma creation, operative approach, procedure type, and BMI were made to 174 historical controls. After excluding cases of inpatient venous thromboembolism, postoperative rates were lower in the prospective cohort (4.8% vs 0.6%, p = 0.019). In the prospective group, 36 episodes of bleeding occurred, 26 (7.2%) were discharged with rivaroxaban, 8 (9.9%) discharged on other anticoagulants, and 2 (3.7%) with no postoperative anticoagulation. Cases of major bleeding were 1.1% (4/363) in the rivaroxaban group, and each required intervention. LIMITATIONS: The study was limited to a single institution and did not include a placebo arm. CONCLUSIONS: Among patients with IBD and colorectal cancer, extended prophylaxis with low-dose rivaroxaban led to a significant decrease in postdischarge thromboembolic events with a low bleeding risk profile. See Video Abstract . RIVAROXABN EN DOSIS BAJAS COMO PROFILAXIS PROLONGADA REDUCE LA TROMBOEMBOLIA VENOSA POSTERIOR AL ALTA, EN PACIENTES CON NEOPLASIAS MALIGNAS Y ENFERMEDAD INFLAMATORIA INTESTINAL: ANTECEDENTES:A pesar de las normas que sugieren el uso de profilaxis extendida para la prevención del tromboembolismo venoso en pacientes con cáncer colorrectal y tal vez enfermedad inflamatoria intestinal, el uso rutinario es bajo y existen escasos datos sobre las formas orales de terapia.OBJETIVO:Comparar la incidencia de tromboembolismo venoso posterior al alta, en pacientes que recibieron profilaxis prolongada con dosis bajas de rivaroxabán.DISEÑO:Utilizamos el emparejamiento de propensión para comparar un análisis previo y posterior a la intervención de un período de 2 años antes de instituir la profilaxis extendida.AJUSTE:Todos los pacientes colorrectales en una sola institución fueron considerados prospectivamente para profilaxis extendida.PACIENTES:Incluidos pacientes con diagnóstico de enfermedad inflamatoria intestinal o cáncer colorrectal sometidos a resección quirúrgica.INTERVENCIONES:A los considerados para profilaxis extendida se les prescribió 10 mg de rivaroxabán durante 30 días postoperatorios.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la incidencia de tromboembolismo venoso 30 días después del alta. El resultado secundario fueron las tasas de hemorragia, mayor o menor.RESULTADOS:De los 498 pacientes considerados para profilaxis extendida, 363 fueron dados de alta con rivaroxabán, 81 con anticoagulación inicial y 54 sin anticoagulación. Se realizaron cohortes emparejadas por propensión basadas en la creación de la estoma, abordaje quirúrgico, tipo de procedimiento y el índice de masa corporal en 174 controles históricos. Después de excluir los casos de tromboembolismo venoso hospitalizado, las tasas posoperatorias fueron más bajas en la cohorte prospectiva (4,8% frente a 0,6%, p = 0,019). En el grupo prospectivo ocurrieron 36 episodios de hemorragia, 26 (7,2%) fueron dados de alta con rivaroxaban, 8 (9,9%) fueron dados de alta con otros anticoagulantes y 2 (3,7%) sin anticoagulación posoperatoria. Los casos de hemorragia mayor fueron del 1,1% (4/363) en el grupo de rivaroxabán y cada uno requirió intervención.LIMITACIONES:Limitado a una sola institución y no incluyó un grupo de placebo.CONCLUSIONES:Entre los pacientes con enfermedad inflamatoria intestinal y cáncer colorrectal, la profilaxis extendida con dosis bajas de rivaroxabán condujo a una disminución significativa de los eventos tromboembólicos posteriores al alta, con un perfil de riesgo de hemorragia bajo. (Traducción-Dr. Fidel Ruiz Healy).

Health risks assessment and source admeasurement of potentially dangerous heavy metals (Cu, Fe, and Ni) in rapidly growing urban settlement.

Environmental contamination is a global challenge that impacts every aspect of ecosystem. The contaminants from anthropogenic or industrial trash continually recirculate into the environment, agricultural land, plants, livestock, and ultimately into humans by way of the food chain. After an increase in human and farmland animal deaths from illnesses due to contaminated drinking water, toxic metal water poisoning has remained a global concern. Diverse environmental and enforcement organisations have attempted to regulate the activities that serve as precursors to these heavy metals which have been proven ineffective. These unnecessary metals have severely hampered most biological processes. The presence of hazardous metals, which are harmful at extremely high levels and have a negative effect on the health of living bodies generally degrades the nutritional value of water. In order to evaluate the heavy metals (Cu, Ni, and Fe) toxicity of groundwater in pri-urban areas, the current study was conducted that have been considered as advance solution to tackle climate change which influence coastal ecosystem. Additionally, the impacts of soil and plant (spinach and brassica) contamination from groundwater were evaluated. The heavy metals were examined in the soil and groundwater samples (Pb, Fe and Ni). While Fe concentrations in water samples were found to be high as 1.978 mg/L as compared to Ni and Cu values low. According to WHO guidelines, the mean value of Fe exceeds the limit value. Similarly, Cu had a higher mean value (0.7 mg/L) in soil samples than other metals (Ni and Fe). In comparison to Ni and Cu, the Fe concentrations in spinach and brassica plants samples are greater, at 17.2 mg/L and 3.22 mg/L, respectively. The possible effects of metal poisoning of groundwater and plants on human health have been assessed using the Hazard Quotient (HQ), Evaluated Daily Intake (EDI), and Incremental Life Time Cancer Risk formulas (ILTCR). When drinking Ni-contaminated water, humans are more at risk of developing cancer (0.0031) than Fe and Cu. Metal concentrations in water and brassica showed substantially more scattered behaviour on the plot and no meaningful relationship, although PCA and masked matrix correlation showed a fair association between Ni and Cu in brassica (r2: 0.46) and Fe and Ni in spinach (r2: 0.31). According to the study's findings, it is anticipated that special management and groundwater monitoring will be needed in the examined area to reduce the health risks related to drinking water that has been contaminated with metals.

Benign-by-design plant extract-mediated preparation of copper oxide nanoparticles for environmentally related applications.

A facile, cost-competitive, scalable and novel synthetic approach is used to prepare copper oxide (CuO) nanoparticles (NPs) using Betel leaf (Piper betle) extracts as reducing, capping, and stabilizing agents. CuO-NPs were characterized using various analytical techniques, including Fourier-transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), as well as photoluminescence (PL) measurements. The activity of CuO-NPs was investigated towards Congo red dye degradation, supercapacitor energy storage and antibacterial activity. A maximum of 89% photodegradation of Congo red dye (CR) was obtained. The nanoparticle modified electrode also exhibited a specific capacitance (Csp) of 179 Fg-1. Furthermore, the antibacterial potential of CuO NPs was evaluated against Bacillus subtilis and Pseudomonas aeruginosa, both strains displaying high antibacterial performance.

Can we let our patients sleep in the hospital? A randomized controlled trial of a pragmatic sleep protocol in surgical oncology patients.

BACKGROUND: Postoperative inpatients experience increased stress due to pain and poor restorative sleep than non-surgical inpatients. OBJECTIVES AND METHODS: A total of 101 patients, undergoing major oncologic surgery, were randomized to a postoperative sleep protocol (n = 50) or standard postoperative care (n = 51), between August 2020 and November 2021. The primary endpoint of the study was postoperative sleep time after major oncologic surgery. Sleep time and steps were measured using a Fitbit Charge 4®. RESULTS: There was no statistically significant difference found in postoperative sleep time between the sleep protocol and standard group (median sleep time of 427 min vs. 402 min; p = 0.852, respectively). Major complication rates were similar in both groups (7.4% vs. 8.9%). Multivariate analysis found sex and Charlson Comorbidity Index to be significant factors affecting postoperative sleep time and step count. Postoperative delirium was only observed in the standard group, although this did not reach statistical significance. There were no in hospital mortalities. CONCLUSION: The use of a sleep protocol was found to be safe in our study population. There was no statistical difference in postoperative sleep time or major complications. Institution of a more humane sleep protocol for postoperative inpatients should be considered.

Utility and costs of surveillance imaging for low- and very low-risk gastrointestinal stromal tumors.

BACKGROUND: There is limited evidence on the optimal surveillance approach in patients with low- and very low-risk gastrointestinal stromal tumors, resulting in inconsistent and arbitrary approaches to surveillance in this population. In this study, we reviewed our institutional approach to surveillance in patients with low- and very low-risk gastrointestinal stromal tumors and the costs associated with detecting recurrence. METHODS: We retrospectively reviewed consecutive adult patients treated for low- and very low-risk gastrointestinal stromal tumors at our institution from 2010 to 2019. Data collected included patient and tumor characteristics, surgical management, and postoperative follow-up. Surveillance-related expenses were calculated using estimates of average costs obtained from our institution. A cost analysis was performed to evaluate estimated yearly costs based on the surveillance strategy used. RESULTS: There were 60 patients included. The mean age at diagnosis was 63.9 (±12.5) years. The primary tumor was typically in the stomach (73%; n = 44). Computed tomography scan of the abdomen and pelvis with intravenous contrast was the most common surveillance modality (total = 226 scans). No recurrences were identified. Median follow-up duration was 49.0 (interquartile range = 19.5-61.5) months. The mean number of surveillance images per patient was 4 (±2.6). Surveillance imaging was obtained more frequently than just annually in 83% (n = 50) of patients, with an estimated yearly cost of $2,840.77 (interquartile range = $2,273.62-$3,895.92) and no detection of recurrence. CONCLUSION: In this study population, patients with low- and very low-risk gastrointestinal stromal tumors underwent frequent imaging studies for surveillance with little yield and at substantial cost. Further multi-institutional studies on practice patterns and outcomes of surveillance are warranted to better inform standardized surveillance recommendations.

A Comprehensive Review of Modifiable Cardiovascular Risk Factors and Genetic Influences in Dementia Prevention.

Dementia poses a growing global health challenge, demanding a multifaceted approach to prevention. This comprehensive review delves into the interplay between modifiable cardiovascular risk factors and genetic influences in dementia prevention. We examine key risk factors, including hypertension, diabetes, hyperlipidemia, obesity, smoking, and physical inactivity, elucidating their impact on dementia risk and the underlying biological mechanisms. Genetic factors, notably familial Alzheimer's disease (FAD) and the apolipoprotein E (APOE) gene, are explored in detail, offering insights into their contributions to dementia susceptibility. Importantly, we highlight the complex interrelationship between genetics and modifiable risk factors, emphasizing the need for personalized prevention strategies. Integrating lifestyle modifications and genetic considerations, a holistic approach is paramount in dementia prevention. Implications for public health initiatives and clinical practices underscore the urgency of tailored interventions. Our call to action urges continued research, precision medicine implementation, and collaborative efforts to mitigate the burden of dementia and enhance cognitive well-being globally.

Specific domains of positive childhood experiences (PCEs) associated with improved adult health: A nationally representative study.

Background: Positive childhood experiences (PCEs) are supportive relationships and environments associated with improved health when aggregated into composite scores. Adverse childhood experiences (ACEs), a reciprocal measure to PCEs, are associated with worse health in aggregate scores and when disaggregated into measures of specific ACE types (hereafter domains). Understanding the associations between specific PCE domains and health, while accounting for ACEs, may direct investigations and intervention planning to foster PCE exposure. Methods: We analyzed data from the nationally representative United States longitudinal Panel Study of Income Dynamics. Five PCE domains were examined: (i) peer support and healthy school climate, (ii) neighborhood safety, (iii) neighborhood support, and nurturing relationships with (iv) maternal and (v) paternal figures. Survey weighted logistic regression models tested associations between each PCE domain measure and adult general health rating, controlling for demographic covariates and nine ACE exposures: physical, emotional, or sexual abuse/assault; emotional neglect; witnessing intimate partner violence or household substance use; having a parent with mental illness; any parental separation or divorce; and/or having a deceased or estranged parent. Secondary outcomes included adult functional status and mental and physical health diagnoses. We also tested for statistical interactions between PCE domain and ACE score measures. Results: The sample included 7105 adults. Higher scores for the "peer support and healthy school climate" and "neighborhood safety" domain measures showed the most protective relationships with the adverse health conditions tested, most notably for mental illness. The relationship between PCE domain measures and health outcomes was attenuated, but not statistically moderated by ACE exposure. Conclusion: Experiencing childhood peer support, a healthy school climate, and neighborhood safety were especially protective against multiple adult health conditions, including for ACE exposed individuals. Interventions that promote PCEs may yield population health gains.

Disulfiram reduces atherosclerosis and enhances efferocytosis, autophagy, and atheroprotective gut microbiota in hyperlipidemic mice.

Pyroptosis executor Gasdermin (GsdmD) promotes atherosclerosis in mice and humans. Disulfiram (DSF) was recently shown to potently inhibit GsdmD, but the in-vivo efficacy and mechanism of DSF's anti-atherosclerotic activity is yet to be explored. We used human/mouse macrophages and a hyperlipidemic mouse model of atherosclerosis to determine DSF anti-atherosclerotic efficacy and mechanism. DSF-fed hyperlipidemic apoE -/- mice showed significantly reduced IL-1ß release upon in-vivo Nlrp3 inflammasome assembly and showed smaller atherosclerotic lesions (∼27% and 29% reduction in males and females, respectively). The necrotic core area was also smaller (∼50% and 46% reduction in DSF-fed males and females, respectively). DSF induced autophagy in macrophages, hepatocytes/liver, and in atherosclerotic plaques. DSF modulated other atheroprotective pathways such as efferocytosis, phagocytosis, and gut microbiota. DSF-treated macrophages showed enhanced phagocytosis/efferocytosis, with a mechanism being a marked increase in cell-surface expression of efferocytic receptor MerTK. Atomic-force microscopy analysis revealed altered biophysical membrane properties of DSF treated macrophages, showing increased ordered-state of the plasma membrane and increased adhesion strength. Furthermore, the 16sRNA sequencing of DSF-fed hyperlipidemic mice showed highly significant enrichment in atheroprotective gut microbiota Akkermansia and a reduction in atherogenic Romboutsia species. Taken together, our data shows that DSF can simultaneously modulate multiple atheroprotective pathways, and thus may serve as novel adjuvant therapeutic to treat atherosclerosis.

Significance of Anti-COVID-IgA antibody response in COVID-19 breakthrough infection in vaccinated patients - a single-centered study from Pakistan.

An increasing number of breakthrough-COVID-19-vaccinated individuals are being reported across the world. Humoral immunity has a crucial role in combating infection. In this study, we aimed to assess the importance of anti-COVID-S1-IgA and anti-COVID-NP-IgA in confirmed COVID-19 after vaccination (breakthrough infection group). Blood samples were collected from the breakthrough infection group within one week of breakthrough infections (n = 34). A second sample was also collected after 4 to 8 weeks (n = 27). Blood samples of healthy individuals (n = 29) were collected 4-8 weeks after the completion of vaccination. Anti-COVID-S1-IgA and anti-COVID-NP-IgA were detected by ELISA. Statistical analysis was performed using IBM SPSS version 24. In this study, we found a higher positivity rate for anti-COVID-S1-IgA in the breakthrough infection group (70% vs. 28% in healthy individuals). Anti-COVID-NP-IgA was not found in the control group (11% in the breakthrough infection group vs. 0 in healthy individuals). In the breakthrough-infected group, the positivity rate of anti-COVID-NP-IgA decreased significantly (median titers 16.9 IU/ml decreased to 4.2 IU/ml) p = 0.001), while anti-COVID-S1-IgA increased over a period of 4-8 weeks (9.35-16.35 IU/ml). Importantly, IgA response to both COVID-19 NP and S1 antigens was not found in 13 patients at initial testing. The findings of this study show that serum IgA may have a role both in breakthrough infections and also in the prevention of severe infection. Sluggish anti-COVID-19-IgA antibody response may be responsible for the occurrence of COVID-19 infection in breakthrough infection. On the other hand, more sustained anti-COVID-19-S1-IgA over a longer period of time may have a role in preventing these patients from severe infections and hospitalization. However, a study on a larger sample size including patients with severe disease after vaccination is required to prove this hypothesis. To the best of our knowledge, this is the first study reporting the importance of serum IgA in breakthrough-infected patients from our region.

Applications of Metformin in Dentistry-A review.

Metformin is a versatile drug with numerous medical uses. It is known primarily as an anti-hyperglycemic drug that has become the main oral blood-glucose-lowering medication for managing type 2 diabetes mellitus globally. Its use has been reported in a variety of oral conditions and dentistry in general. Recent clinical trials have indicated the effectiveness of adjunct topical application of metformin in improving the periodontal parameters of patients with diabetes and periodontitis. Additionally, studies have suggested that metformin stimulates odontogenic differentiation and mineral synthesis of stem cells in the tooth pulp. Metformin also stimulates osteoblast proliferation, decreases osteoclast activity and exerts regenerative effects on periodontal bone, thus making it a viable candidate for periodontal regeneration. Metformin monotherapy significantly enhances osseointegration of endosseous implants and has been reported to have anti-cancer effects on oral squamous cell carcinoma by impeding tumor progression. Animal studies have indicated that metformin improves orthodontic tooth movement and resists orthodontic appliance corrosion. This narrative review aims to provide a current summary of research highlighting the prospective uses of metformin in dentistry.

State-of-the-art adsorption and adsorptive filtration based technologies for the removal of trace elements: A critical review.

Water and wastewater are contaminated with various types of trace elements that are released from industrial activities. Their presence, at concentrations above the permissible limit, will cause severe negative impacts on human health and the environment. Due to their cost-effectiveness, simple design, high efficiency, and selectivity, adsorption, and adsorptive filtration are techniques that have received lots of attention as compared to other water treatment techniques. Adsorption isotherms and kinetic studies help to understand the mechanisms of adsorption and adsorption rates, which can be used to develop and optimize different adsorbents. This state-of-the-art review provides and combines the advancements in different conventional and advanced adsorbents, biosorbents, and adsorptive membranes for the removal of trace elements from water streams. Herein, this review discusses the sources of different trace elements and their impact on human health. The review also covers the adsorption technique with a focus on various advanced adsorbents, their adsorption capacities, and adsorption isotherm modeling in detail. In addition, biosorption is critically discussed together with its mechanisms and biosorption isotherms. In the end, the application of various advanced adsorptive membranes is discussed and their comparison with adsorbents and biosorbents is systematically presented.

Impavido attenuates inflammation, reduces atherosclerosis, and alters gut microbiota in hyperlipidemic mice.

Impavido (Miltefosine) is an FDA-approved drug for treating leishmaniasis and primary amebic meningoencephalitis. We have shown previously that Miltefosine increased cholesterol release and dampened Nlrp3 inflammasome assembly in macrophages. Here, we show that Miltefosine reduced LPS-induced choline uptake by macrophages, and attenuated Nlrp3 inflammasome assembly in mice. Miltefosine-fed mice showed reduced plasma IL-1ß in a polymicrobial cecal slurry model of systemic inflammation. Miltefosine-fed mice showed increased reverse cholesterol transport to the plasma, liver, and feces. Hyperlipidemic apoE-/- mice fed with WTD + Miltefosine showed significantly reduced weight gain and markedly reduced atherosclerotic lesions versus mice fed with WTD. The 16S rDNA sequencing and analysis of gut microbiota showed marked alterations in the microbiota profile of Miltefosine-fed hyperlipidemic apoE-/- versus control, with the most notable changes in Romboutsia and Bacteriodes species. Taken together, these data indicate that Miltefosine causes pleiotropic effects on lipid metabolism, inflammasome activity, atherosclerosis, and the gut microbiota.

Synthesis of nanostructured novel ion-imprinted polymer for selective removal of Cu2+ and Sr2+ ions from reverse osmosis concentrated brine.

This study aims to prepare an ion-imprinted polymer (IIP) using copper sulfate as a template and potassium persulfate as an initiator to selectively adsorb copper ions (Cu2+) from aqueous solutions and in an attempt to also test its applicability for removing strontium ions (Sr2+). The prepared polymer was denoted by IIP-Cu. Various physical and chemical characterizations were performed for the prepared IIP-Cu. The scanning electron microscopy and transmission electron microscopy analyses confirmed the cavities formed after the removal of the template. It also indicated that the IIP-Cu had a rough and porous topology. The X-ray photoelectron spectroscopy confirmed the successful removal of the Cu template from IIP-Cu. The Brunauer-Emmet-Teller revealed that the surface area of IIP-Cu is as high as 152.3 m2/g while the pore radius is 8.51 nm. The effect of pH indicated that the maximum adsorption of Cu2+ was achieved at pH 8 with 98.7%. Isotherm studies revealed that the adsorption of Cu2+ was best explained using Langmuir models with a maximum adsorption capacity of 159 mg/g. The effect of temperature revealed that an increase in temperature had an adverse impact on Cu2+ removal from the aqueous solution, which was further confirmed by thermodynamic studies. The negative value of standard enthalpy change (-4.641 kJ/mol) revealed that the adsorption of Cu2+ onto IIP-Cu was exothermic. While the continuous increase in Gibbs free energy from -6776 kJ/mol to -8385 kJ/mol with the increase in temperature indicated that the adsorption process was spontaneous and feasible. Lastly, the positive value of the standard entropy change (0.023 J/mol.K) suggested that the Cu2+ adsorption onto IIP-Cu had a good affinity at the solid-liquid surface. The efficiency of the prepared IIP-Cu was also tested by studying the adsorption capacity using Sr2+ and real brine water. The results revealed that IIP-Cu was able to remove 63.57% of Sr2+ at pH 8. While the adsorption studies revealed that the experiment was best described using the Langmuir model with a maximum adsorption capacity of 76.92 mg/g. Additionally, IIP-Cu was applied in a real brine sample, which consisted of various metal ions. The highest percentage of Cu2+ removal was 90.6% and the lowest was 65.63% in 1:4 and 1:1 brine ratios, respectively. However, this study indicates the successful application of IIP-Cu in a real sample when it comes to the effective and efficient removal of Cu2+ in a solution consisting of various competing ions.

Myeloid-cell-specific role of Gasdermin D in promoting lung cancer progression in mice.

The activities of the NLRP3 and AIM2 inflammasomes and Gasdermin D (GsdmD) are implicated in lung cancer pathophysiology but it's not clear if their contributions promote or retard lung cancer progression. Using a metastatic Lewis lung carcinoma (LLC) cell model, we show that GsdmD knockout (GsdmD-/-) mice form significantly fewer cancer foci in lungs, exhibit markedly decreased lung cancer metastasis, and show a significant ∼50% increase in median survival rate. The cleaved forms of GsdmD and IL-1ß were detected in lung tumor tissue, indicating inflammasome activity in lung tumor microenvironment (TME). Increased migration and growth of LLC cells was observed upon exposure to the conditioned media derived from inflammasome-induced wild type, but not the GsdmD-/-, macrophages. Using bone marrow transplantations, we show a myeloid-specific contribution of GsdmD in lung cancer metastasis. Taken together, our data show that GsdmD plays a myeloid-specific role in lung cancer progression.

A Balancing Act: How Professionals in the Foster Care System Balance the Harm of Intimate Partner Violence as Compared to the Harm of Child Removal.

The striking prevalence of child exposure to intimate partner violence (IPV) and its associated adverse health outcomes necessitates a robust response from professionals who must grapple with the ethical dilemma of how to serve and support children in these circumstances. In 2020, 42 participants from four different professional backgrounds (attorneys, nonprofit leadership, licensed therapists, and social workers) were interviewed or participated in a focus group discussion. All groups acknowledged the shortfalls of current intervention practices, which often result in child removal. Group 1, which included social workers that work for children's legal services, minor's counsel, and Los Angeles Department of Child and Family Services social workers, were more conflicted in their recommendations for change. Some Group 1 participants recommended more training, while others thought more training would make little difference and recommended more substantial changes to prevent child removal when possible. Group 2, which included parents' counsel, and Group 3, which included social workers, attorneys, and nonprofit leadership at IPV nonprofits, were more closely aligned in their recommendations, primarily focusing on systemic changes to the child welfare system. Participants whose employment required them to advocate for parents tend to view child removal from a non-offending parent as harmful for both the child and IPV survivor. These findings illuminate how the perspectives of these diverse participants are influenced by their professional and personal experiences.

Surgeon Burnout and Usage of Personal Communication Devices: Examining the Technology "Empowerment/Enslavement Paradox".

INTRODUCTION: Access to patients' electronic medical records (EMRs) on personal communication devices (PCDs) is beneficial but can negatively impact surgeons. In a recent op-ed, Cohen et al. explored this technology "empowerment/enslavement paradox" and its potential effect on surgeon burnout. We examined if there is a relationship between accessing EMRs on PCDs and surgeon burnout. METHODS: This was a cohort study with retrospective and prospective arms. Trainees and attendings with a background in general surgery completed the Maslach Burnout Index for Medical Personnel, a validated survey scored on three areas of burnout (emotional exhaustion, depersonalization, and low personal accomplishment). Data on login frequency to EMRs on PCDs over the previous 6 mo were obtained. Pearson correlation coefficients were calculated to determine if burnout and login frequency were associated. RESULTS: There were 52 participants included. Residents were 61.5% (n = 32) of participants. The mean login frequency over 6 mo was 431.0 ± 323.9. The mean scores (out of 6) for emotional exhaustion, depersonalization, and personal accomplishment were 2.3 ± 1.1, 1.9 ± 1.2, and 4.9 ± 0.8, respectively. There was no correlation between burnout and logins. Residents had higher median depersonalization scores (2.3 versus 1.2, P = 0.03) and total logins (417.5 versus 210.0, P < 0.001) than attendings. Participants who overestimated logins had higher median emotional exhaustion and depersonalization scores than those who underestimated (2.6 versus 1.4, P = 0.03, and 2.4 versus 0.8, P = 0.003, respectively). CONCLUSIONS: Using EMRs on PCDs is common, but frequency of logins did not correlate with burnout scores in this study. However, perception of increased workload may contribute to experiencing burnout.