A long-acting C-natriuretic peptide for achondroplasia.

The C-natriuretic peptide (CNP) analog vosoritide has recently been approved for treatment of achondroplasia in children. However, the regimen requires daily subcutaneous injections in pediatric patients over multiple years. The present work sought to develop a long-acting CNP that would provide efficacy equal to or greater than that of vosoritide but require less frequent injections. We used a technology for half-life extension, whereby a drug is attached to tetra-polyethylene glycol hydrogels (tetra-PEG) by ß-eliminative linkers that cleave at predetermined rates. These hydrogels-fabricated as uniform ∼60-µm microspheres-are injected subcutaneously, where they serve as a stationary depot to slowly release the drug into the systemic circulation. We prepared a highly active, stable CNP analog-[Gln6,14]CNP-38-composed of the 38 C-terminal amino acids of human CNP-53 containing Asn to Gln substitutions to preclude degradative deamidation. Two microsphere [Gln6,14]CNP-38 conjugates were prepared, with release rates designed to allow once-weekly and once-monthly administration. After subcutaneous injection of the conjugates in mice, [Gln6,14]CNP-38 was slowly released into the systemic circulation and showed biphasic elimination pharmacokinetics with terminal half-lives of ∼200 and ∼600 h. Both preparations increased growth of mice comparable to or exceeding that produced by daily vosoritide. Simulations of the pharmacokinetics in humans indicated that plasma [Gln6,14]CNP-38 levels should be maintained within a therapeutic window over weekly, biweekly, and likely, monthly dosing intervals. Compared with vosoritide, which requires ∼30 injections per month, microsphere [Gln6,14]CNP-38 conjugates-especially the biweekly and monthly dosing-could provide an alternative that would be well accepted by physicians, patients, and patient caregivers.

Incidence of Pathologic Nodal Disease in Clinically Node-Negative, Microinvasive or T1a Breast Cancers.

BACKGROUND: Axillary staging in early-stage breast cancer can impact adjuvant treatment options but also has associated morbidity. The incidence of pathologic nodal positivity (pN+) in patients with microinvasive or T1a disease is poorly characterized and the value of sentinel node biopsy remains controversial. METHODS: Women with cN0 and pathologic microinvasive or T1a cancer who underwent upfront surgery were identified from the National Cancer Database. Pathologic nodal stage at the time of surgery was the primary outcome. Multivariable logistic modeling was used to assess predictors of pN+. RESULTS: Overall, 141,840 women were included; 139,206 had pathologic node-negative (pN0) disease and 2634 had pN+ disease. Rates of pN+ disease differed by receptor status, with the highest rates in hormone receptor-negative/human epidermal growth factor receptor 2-positive (HR-/HER2+) disease compared with triple-negative breast cancer (TNBC), HR-positive/HER2-negative (HR+/HER2-), and triple positive breast cancer. Rates of pN+ were also higher with lobular histology compared with ductal histology. Multivariable analysis demonstrated that compared with White women, Black women had higher odds of pN+ disease, and compared with women <50 years of age, women >70 years of age had higher odds of pN+ disease. Compared with women with HR+/HER2- disease, women with TNBC, triple-positive breast cancer, and HR-/HER2+ all had lower odds, and women with invasive lobular disease had higher odds compared with women with invasive ductal disease. Women with significant comorbidities also had higher odds of node positivity. CONCLUSION: Over 90% of patients with clinically node-negative, microinvasive and T1a breast cancer remain pathologically node-negative following axillary staging. However, higher rates of nodal disease were found among Black patients, older patients, and patients with lobular cancer and significant comorbidities.

National Patterns of Hospital Admission Versus Home Recovery Following Mastectomy for Breast Cancer.

BACKGROUND: We examined national patterns of care and perioperative outcomes for women after mastectomy, comparing home recovery (HR) with hospital admission. PATIENTS AND METHODS: Using Martketscan data (2017-2019), women ≥ 18 years old who underwent mastectomy ± reconstruction were identified and classified as either home recovery (same calendar day discharge) or hospital admission (stays > 1 calendar day). Comorbidities and receipt of chemo/immunotherapy 6 months prior to surgery and post-surgical 30-day complications were measured. Logistic regression calculated the odds of any complication by encounter type, adjusting for age, accompanying lymph node (LN) procedure, reconstruction, neoadjuvant chemo- and/or immunotherapy, and select comorbidities. RESULTS: Of 11,789 mastectomy encounters (N = 11,659 women), 4751 (40%) cases utilized HR while 7038 (60%) had hospital admission. HR patients were older (53.6 years old vs. 51.8 years old) with lower rates of reconstruction (60.2 vs. 74.5%, p < 0.001). Rates of neoadjuvant chemotherapy (19.6 vs. 20.9%, p = 0.099) and immunotherapy (3.6 vs. 3.9%, p = 0.445) were similar between groups. Complication rates were lower among HR patients with fewer postoperative hematomas (0.6 vs. 1.3%, p < 0.001) and decreased wound complications (8.5 vs. 9.8%, p = 0.019). In a multivariable analysis, the odds of any complication were approximately 20% lower for HR patients compared with admission patients (aOR 0.81, 95% CI 0.72-0.91, p < 0.001). Unplanned emergency room visits were similar between groups (6.7 vs. 7.2%, p = 0.374); yet fewer hospital re-admissions (2.5 vs. 3.5%, p = 0.003) occurred in women recovering at home. CONCLUSION: HR is a safe option compared with in-hospital admission for clinically appropriate women after mastectomy as they are less likely to experience postoperative complications, emergency department (ED) visits, or hospitalization.

A Cross-Sectional Analysis of Pediatric Necrotizing Soft Tissue Infection Cases and Racial Disparities From the 2016 to 2020 National Inpatient Sample.

INTRODUCTION: The incidence, treatment, and outcomes of necrotizing soft tissue infections (NSTIs) and associated racial disparities have been described in adults, but research in the pediatric population is limited. The purpose of this study is to provide a nationally representative characterization of pediatric NSTI and determine the presence of any racial disparities. METHODS: The National Inpatient Sample was analyzed from 2016 through 2020. Patients aged less than 20 y with a diagnosis of necrotizing fasciitis, Fournier's gangrene, or gas gangrene (based on International Classification of Diseases, Tenth Revision, Clinical Modification codes) were included for analysis. RESULTS: A total of 355 patients were identified. Black and Hispanic patients accounted for the most admissions in 2016 and 2018, respectively (P = 0.024). Compared to White patients, more Black patients were insured by Medicaid (P = 0.037) and were in the first zip code-based income quartile (P = 0.005). The leading infection overall was necrotizing fasciitis and most patients (81.7%) underwent a surgical procedure by the first calendar day after admission. Although the proportion of Black patients undergoing subcutaneous tissue and fascia excisions was more than that of White patients (P = 0.005), there were no significant differences by race in the time to first procedure, the total number of procedures, or number of postoperative complications. Our amputation and mortality rates were low and unreportable, but there were no differences by race. CONCLUSIONS: NSTI is rare in the pediatric population and mortality is low. Black patients are disproportionately diagnosed, but these disparities do not extend to disease treatment or outcomes.

Accumulation of Per- and Polyfluoroalkyl Substances (PFAS) in Coastal Sharks from Contrasting Marine Environments: The New York Bight and The Bahamas.

Per- and polyfluoroalkyl substances (PFAS) enter the marine food web, accumulate in organisms, and potentially have adverse effects on predators and consumers of seafood. However, evaluations of PFAS in meso-to-apex predators, like sharks, are scarce. This study investigated PFAS occurrence in five shark species from two marine ecosystems with contrasting relative human population densities, the New York Bight (NYB) and the coastal waters of The Bahamas archipelago. The total detected PFAS (∑PFAS) concentrations in muscle tissue ranged from 1.10 to 58.5 ng g-1 wet weight, and perfluorocarboxylic acids (PFCAs) were dominant. Fewer PFAS were detected in Caribbean reef sharks (Carcharhinus perezi) from The Bahamas, and concentrations of those detected were, on average, ∼79% lower than in the NYB sharks. In the NYB, ∑PFAS concentrations followed: common thresher (Alopias vulpinus) > shortfin mako (Isurus oxyrinchus) > sandbar (Carcharhinus plumbeus) > smooth dogfish (Mustelus canis). PFAS precursors/intermediates, such as 2H,2H,3H,3H-perfluorodecanoic acid and perfluorooctanesulfonamide, were only detected in the NYB sharks, suggesting higher ambient concentrations and diversity of PFAS sources in this region. Ultralong-chain PFAS (C ≥ 10) were positively correlated with nitrogen isotope values (δ15N) and total mercury in some species. Our results provide some of the first baseline information on PFAS concentrations in shark species from the northwest Atlantic Ocean, and correlations between PFAS, stable isotopes, and mercury further contextualize the drivers of PFAS occurrence.

On the dual behaviour of water in octanol-rich aqueous n-octanol mixtures: an X-ray scattering and computer simulation study.

Aqueous n-octanol (n = 1, 2, 3, and 4) mixtures from the octanol rich side are studied by X-ray scattering and computer simulation, with a focus on structural changes, particularly in what concerns the hydration of the hydroxyl-group aggregated chain-like structures, under the influence of various branching of the alkyl tails. Previous studies have indicated that hydroxyl-group chain-cluster formation is hindered in proportion to the branching number. Here, water mole fractions up to x = 0.2 are examined, i.e. up to the miscibility limit. It is found that water molecules within the hydroxyl-chain domains participate in the chain formations in a different manner for 1-octanol and the branched octanols. The hydration of the octanol hydroxyl chains is confirmed by the shifting of the scattering pre-peak position kPP to smaller values, both from measured and simulated X-ray scattering intensities, which corresponds to an increased size of the clusters. Experimental pre-peak amplitudes are seen to increase with increasing water content for 1-octanol, while this trend is reversed in all branched octanols, with the amplitudes decreasing with the increase of the branching number. Conjecturing that the amplitudes of pre-peaks are related to the density of the corresponding aggregates, these results are interpreted as water breaking large OH hydroxyl chains in 1-octanol, hence increasing the density of aggregates, while enhancing hydroxyl aggregates in branched alcohols by inserting itself into the OH chains. The analysis of the cluster distributions from computer simulations provide more details on the role of water. For cluster sizes smaller than dc = 2π/kPP, water is found to always play the role of a structure enforcer for all n-octanols, while for clusters of size dc water is always a destructor. For cluster sizes larger than dc, the role of water differs from 1-octanol and the branched ones: it acts as a structure maker or breaker in inverse proportion to the hindering of OH hydroxyl chain structures arising from the topology of the alkyl tails (branched or not).

The chemical composition of secondary organic aerosols regulates transcriptomic and metabolomic signaling in an epithelial-endothelial in vitro coculture.

BACKGROUND: The formation of secondary organic aerosols (SOA) by atmospheric oxidation reactions substantially contributes to the burden of fine particulate matter (PM2.5), which has been associated with adverse health effects (e.g., cardiovascular diseases). However, the molecular and cellular effects of atmospheric aging on aerosol toxicity have not been fully elucidated, especially in model systems that enable cell-to-cell signaling. METHODS: In this study, we aimed to elucidate the complexity of atmospheric aerosol toxicology by exposing a coculture model system consisting of an alveolar (A549) and an endothelial (EA.hy926) cell line seeded in a 3D orientation at the air‒liquid interface for 4 h to model aerosols. Simulation of atmospheric aging was performed on volatile biogenic (ß-pinene) or anthropogenic (naphthalene) precursors of SOA condensing on soot particles. The similar physical properties for both SOA, but distinct differences in chemical composition (e.g., aromatic compounds, oxidation state, unsaturated carbonyls) enabled to determine specifically induced toxic effects of SOA. RESULTS: In A549 cells, exposure to naphthalene-derived SOA induced stress-related airway remodeling and an early type I immune response to a greater extent. Transcriptomic analysis of EA.hy926 cells not directly exposed to aerosol and integration with metabolome data indicated generalized systemic effects resulting from the activation of early response genes and the involvement of cardiovascular disease (CVD) -related pathways, such as the intracellular signal transduction pathway (PI3K/AKT) and pathways associated with endothelial dysfunction (iNOS; PDGF). Greater induction following anthropogenic SOA exposure might be causative for the observed secondary genotoxicity. CONCLUSION: Our findings revealed that the specific effects of SOA on directly exposed epithelial cells are highly dependent on the chemical identity, whereas non directly exposed endothelial cells exhibit more generalized systemic effects with the activation of early stress response genes and the involvement of CVD-related pathways. However, a greater correlation was made between the exposure to the anthropogenic SOA compared to the biogenic SOA. In summary, our study highlights the importance of chemical aerosol composition and the use of cell systems with cell-to-cell interplay on toxicological outcomes.

The Degree of Inferior Vena Cava Filter Tilt Associated with Challenging Retrieval.

BACKGROUND: Inferior vena cava (IVC) filter tilt is associated with technical difficulties at the time of retrieval. However, the degree of tilt that predisposes patients to undergo complex or failed retrieval has not been defined. METHODS: The electronic charts of patients undergoing IVC filter removal between 2010 and 2019 at a single tertiary center were reviewed. Patient and procedural characteristics were recorded. Venograms of placement and retrieval procedures were reviewed, and IVC filter tilt was determined based on its deviation from the IVC axis. IVC diameter and the distance from the lowest renal vein were measured using corresponding filter's length for calibration. All measurements were performed by 3 reviewers and confirmed by 2 reviewers. Patients were divided into 2 groups: those who underwent successful removal procedures requiring standard retrieval methods ("simple retrieval group") and those who required advanced endovascular techniques or had failed completely IVC filter retrievals ("challenging retrieval group"). A regression analysis was performed to determine factors associated with challenging retrieval. RESULTS: There were 365 patients who underwent IVC filter retrieval (n = 294 (80.6%) and n = 71 (19.4%) in the simple and challenging groups, respectively) with no difference in age, sex, comorbidities, or indication between the 2 groups. Failed retrieval occurred in 21 patients (5.8%) and was more common among patients requiring advanced endovascular techniques compared to standard techniques (18.0% vs. 3.2%, P < 0.001). In the overall cohort, the mean filter tilt at the time of retrieval was 4.9° ± 4.4° [0c27°], and 145 patients (39.7%) had a filter tilt ≥5.0°. Compared to the simple retrieval group, patients in the challenging group had significantly longer dwell time, greater tilt of IVC filter during placement and retrieval, as well as higher tilt change between the 2 venograms. There was no correlation between the access site during placement and challenging retrieval. However, patients undergoing filter placement via right jugular vein had lower filter tilt as compared to femoral access. Patients with filter tilt ≥5.0° were more likely to have a challenging filter retrieval compared to patients with ˂5.0° tilt (29.7% vs. 12.7%, P < 0.001). Regression analysis showed that tilt ≥5.0° (odds ratio [OR] = 1.18 [1.11-1.25]), dwell time (OR = 1.04 [1.01-1.07]), and age (OR = 0.97 [0.95-0.99]) were independently associated with challenging retrieval. CONCLUSIONS: IVC filter tilt ≥5.0°, dwell time and age are associated with challenging retrieval. Right jugular vein access, multiple imaging projections, and careful filter manipulation during deployment should be considered to maintain tilt at ˂ 5.0° and decrease the likelihood of challenging retrieval.

Did smallpox cause stillbirths? Maternal smallpox infection, vaccination, and stillbirths in Sweden, 1780-1839.

While there is strong evidence that maternal smallpox infection can cause foetal loss, it is not clear whether smallpox infections were a demographically important cause of stillbirths historically. In this paper, we use parish-level data from the Swedish Tabellverket data set for 1780-1839 to test the effect of smallpox on stillbirths quantitatively, analysing periods before and after the introduction of vaccination in 1802. We find that smallpox infection was not a major cause of stillbirths before 1820, because most women contracted smallpox as children and were therefore not susceptible during pregnancy. We do find a small, statistically significant effect of smallpox on stillbirths from 1820 to 1839, when waning immunity from vaccination put a greater share of pregnant women at risk of contracting smallpox. However, the reduced prevalence of smallpox in this period limited its impact on stillbirths. Thus, smallpox was not an important driver of historical stillbirth trends.

Expanding records of occurrence of the whale shark (Rhincodon typus) in The Bahamas and a call for sustainable tourism practices.

This report updates our understanding of whale shark occurrences in The Bahamas by drawing upon a variety of data sources. Our findings reveal previously unreported sighting locations, often associated with tourism activities, underscoring the pivotal role played by nontraditional data sources in addressing knowledge gaps. These revelations emphasize the ongoing necessity for monitoring efforts. Additionally, we have found cases that raise concerns related to unregulated human-shark interactions in the region, highlighting the pressing need for sustainable tourism practices within Bahamian waters.

Colonization, diversity, and seasonality of fishes at pelagic fish aggregating devices.

The pelagic zone of the ocean can be a challenging environment in which to conduct research and as a result we lack the robust baseline abundance and diversity data, compared to what is available in more accessible coastal habitats, to be able to track changes or stressors to the biota in this environment. Many large-scale fisheries target pelagic fish, and much of the information available on these species is based on fisheries-dependent data that may be biased towards hotspots and commercially valuable fishes. Here, a long-term video and visual fish survey was conducted on two subsurface moored fish aggregating devices (FADs) in the pelagic waters of the central Bahamas to determine the feasibility of using moored pelagic FADs as tools for collecting fish abundance and diversity data. A wide range of species was documented, including large migratory fish that are the focus of commercial and recreational fisheries, and smaller often overlooked species on which little abundance or seasonality information exists. We found that FADs colonize quickly and reach a peak stable (albeit seasonally cyclical) abundance and diversity within the first several months after deployment. Species richness was higher in video surveys, but abundance was higher in visual surveys, except for sharks. Our results highlight the need to tailor survey methods to fit the context and study objective, and provide further evidence for the importance of fisheries-independent data in monitoring pelagic species.

Host genetic identity determines parasite community structure across time and space in oyster restoration.

Intraspecific variation in host susceptibility to individual parasite species is common, yet how these effects scale to mediate the structure of diverse parasite communities in nature is less well understood. To address this knowledge gap, we tested how host genetic identity affects parasite communities on restored reefs seeded with juvenile oysters from different sources-a regional commercial hatchery or one of two wild progenitor lines. We assessed prevalence and intensity of three micro- and two macroparasite species for 4 years following restoration. Despite the spatial proximity of restored reefs, oyster source identity strongly predicted parasite community prevalence across all years, with sources varying in their relative susceptibility to different parasites. Oyster seed source also predicted reef-level parasite intensities across space and through time. Our results highlight that host intraspecific variation can shape parasite community structure in natural systems, and reinforce the importance of considering source identity and diversity in restoration design.

Energetic connectivity of diverse elasmobranch populations - implications for ecological resilience.

Understanding the factors shaping patterns of ecological resilience is critical for mitigating the loss of global biodiversity. Throughout aquatic environments, highly mobile predators are thought to serve as important vectors of energy between ecosystems thereby promoting stability and resilience. However, the role these predators play in connecting food webs and promoting energy flow remains poorly understood in most contexts. Using carbon and nitrogen isotopes, we quantified the use of several prey resource pools (small oceanic forage, large oceanics, coral reef, and seagrass) by 17 species of elasmobranch fishes (n = 351 individuals) in The Bahamas to determine their functional diversity and roles as ecosystem links. We observed remarkable functional diversity across species and identified four major groups responsible for connecting discrete regions of the seascape. Elasmobranchs were responsible for promoting energetic connectivity between neritic, oceanic and deep-sea ecosystems. Our findings illustrate how mobile predators promote ecosystem connectivity, underscoring their functional significance and role in supporting ecological resilience. More broadly, strong predator conservation efforts in developing island nations, such as The Bahamas, are likely to yield ecological benefits that enhance the resilience of marine ecosystems to combat imminent threats such as habitat degradation and climate change.

Popular to a Point: The Enduring Political Challenges of the Public Option.

Policy Points A decade after failing to make it into the Affordable Care Act, the public option reemerged as a health reform goal at both the national and state levels, with polls reporting strong, bipartisan support. A 2020 poll that probed both support for one public option approach (Medicare "buy-in") and attitudes toward government suggests that differences in these attitudes could plague reform advocates' efforts. Although the COVID-19 pandemic viscerally highlighted the need for a more coherent health care system-including universal coverage-other recent evolutions in the broader US political context could undermine reform.

Association of Postoperative Delirium and Parkinson Disease After Common United States Surgical Procedures.

INTRODUCTION: To determine the association of Parkinson disease (PD) and postoperative delirium following common surgical procedures. METHODS: We performed a retrospective database analysis of the National Inpatient Sample. We used a matched sample of patients with and without PD who underwent any of ten common surgical procedures in the US, 2005-2014. Primary outcome measure was postoperative delirium for patients with and without PD. Secondary measures included disposition, length of stay, and hospital costs. RESULTS: There were 3,235,866 patients receiving any of the ten most common operative procedures, 2005-2014. There were 35,743 patients with and without PD matched based on age, sex, elective admission status, Charlson Comorbidity index, and presence of dementia. Median age was 77 y (interquartile range 72-82), median Charlson Comorbidity index was 1 (standard deviation 0-2), 46.6% were female, and 46.8% were admitted electively. The three most common operative procedures were hip arthroplasty (28.5%), knee arthroplasty (16.1%), and percutaneous coronary angioplasty (14.9%). Postoperative delirium was present in 1519 patients with PD compared to 828 matched patients without PD (4.2% versus 2.3%; P < 0.001). The adjusted odds ratio of postoperative delirium for PD compared to the matched cohort without PD was 1.88 (95% confidence interval 1.73-2.05). Those undergoing spinal fusion (adjusted odds ratio 2.99, 95% confidence interval 2.06-4.38) had the greatest odds of delirium. For patients with PD, adjusted length of stay, adjusted hospital costs, and adjusted odds of postacute care facility discharge were greater compared to the matched cohort without PD. CONCLUSIONS: Patients with PD are more likely to develop postoperative delirium and have a more complicated postoperative course with longer length of stay and greater hospitalization costs.

Diverticulitis in Older Adults: Is Cognitive Impairment Associated With Outcomes?

INTRODUCTION: Older age is associated with increased prevalence of both diverticulitis and cognitive impairment. The association between cognitive impairment and outcomes among older adults presenting to the emergency department (ED) for diverticulitis is unknown. METHODS: Adults aged ≥65 y presenting to an ED with a primary diagnosis of colonic diverticulitis were identified using the Nationwide Emergency Department Sample (2016-2019) and stratified by cognitive impairment status in this retrospective cohort study. Multivariable Poisson regression models adjusted for patient age, sex, Elixhauser Comorbidity Index, primary payer status, and presence of complicated diverticulitis quantified relative risk of a) inpatient admission, b) operative intervention, and c) in-hospital mortality comparing patients with or without a diagnosis code suggestive of cognitive impairment. RESULTS: Among 683,444 older adults with an ED encounter for diverticulitis from 2016 to 2019, there were 468,226 patients with isolated colonic diverticulitis and 26,388 (5.6%) with comorbid cognitive impairment. After adjustment, the risk of inpatient admission for those with cognitive impairment was 18% higher than for those without cognitive impairment (adjusted relative risks [aRR]: 1.18, 95% confidence interval [CI]: 1.17-1.20). Those with cognitive impairment were 34% more likely to undergo colectomy than those without cognitive impairment (aRR: 1.34, 95% CI: 1.24-1.44). Older adults with cognitive impairment had a 32% greater mortality than those without cognitive impairment (aRR: 1.32, 95% CI: 1.05-1.67). CONCLUSIONS: Among older adults presenting for ED care with a primary diagnosis of colonic diverticulitis, individuals with cognitive impairment had higher rates of hospitalization, operative intervention, and in-hospital mortality than those without cognitive impairment.

An Evaluation of Sex-Based Differences in Surrogate Consent for Older Adults Undergoing Surgical Intervention.

INTRODUCTION: Differences between female and male patients have been identified in many facets of medicine. We sought to understand whether differences in frequency of surrogate consent for operation exist between older female and male patients. MATERIALS AND METHODS: A descriptive study was designed using data from the hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program. Patients age 65 y and older who underwent operation between 2014 and 2018 were included. RESULTS: Of 51,618 patients identified, 3405 (6.6%) had surrogate consent for surgery. Overall, 7.7% of females had surrogate consent compared to 5.3% of males (P < 0.001). Stratified analysis based on age categories showed no difference in surrogate consent between female and male patients aged 65-74 yy (2.3% versus 2.6%, P = 0.16), but higher rates of surrogate consent in females than males among patients aged 75-84 y old (7.3% versus 5.6%, P < 0.001) and age ≥85 y (29.7% versus 20.8%, P < 0.001). A similar relationship was seen between sex and preoperative cognitive status. There was no difference in preoperative cognitive impairment in female and male patients age 65-74 y (4.4% versus 4.6%, P = 0.58), but higher rates of preoperative cognitive impairment were seen in females than males for those age 75-84 (9.5% versus 7.4%, P < 0.001) and aged ≥85 y (29.4% versus 21.3%, P < 0.001). Matching for age and cognitive impairment, there was no significant difference between rate of surrogate consent in males and females. CONCLUSIONS: Female patients are more likely than males to undergo surgery with surrogate consent. This difference is not based on patient sex alone - females undergoing operation are older than their male counterparts and more likely to be cognitively impaired.

Indoor Versus Outdoor: Does Occupational Sunlight Exposure Increase Melanoma Risk? A Systematic Review.

INTRODUCTION: Melanoma is the fifth most common cancer diagnosed in the United States, representing 5.6% of all new cancer cases. There are conflicting reports correlating a relationship between primarily outdoor occupations, associated with increased exposure to direct sunlight, and the incidence of cutaneous melanoma. Our objective was to outline and critically evaluate the relevant literature related to chronic occupational exposure to sunlight and risk of developing cutaneous melanoma. METHODS: The study protocol for this systematic review was submitted to the International Prospective Register of Systematic Reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. For each relevant study included, the following information was extracted: author names, publication year, study name, study design, age, exposure assessment, outcome, comparison, number of cases, case ascertainment, and descriptive and adjusted statistics. Study quality and evidence certainty was assessed using the Grading of Recommendations, Assessment, Development and Evaluations model. RESULTS: The initial database search yielded 1629 articles for review and following full-text screening, a total of 14 articles were included for final analysis. Of the studies included, seven articles were retrospective case control and seven were cohort studies. The studies did not report any differences in the likelihood of cutaneous melanoma development based upon membership in the outdoor versus indoor occupation groups included in each study. CONCLUSIONS: Overall, the articles included in this systematic review did not report an increased risk of developing cutaneous melanoma among individuals with outdoor occupations. Further investigation is required to determine if other occupational or life-style-related risk factors exist, to help support the development of individualized skin screening recommendations and improve the early detection of melanoma in all populations.

Humic-like Substances (HULIS) in Ship Engine Emissions: Molecular Composition Effected by Fuel Type, Engine Mode, and Wet Scrubber Usage.

Humic-like substances (HULIS), known for their substantial impact on the atmosphere, are identified in marine diesel engine emissions obtained from five different fuels at two engine loads simulating real world scenarios as well as the application of wet sulfur scrubbers. The HULIS chemical composition is characterized by electrospray ionization (ESI) ultrahigh resolution mass spectrometry and shown to contain partially oxidized alkylated polycyclic aromatic compounds as well as partially oxidized aliphatic compounds, both including abundant nitrogen- and sulfur-containing species, and clearly different to HULIS emitted from biomass burning. Fuel properties such as sulfur content and aromaticity as well as the fuel combustion efficiency and engine mode are reflected in the observed HULIS composition. When the marine diesel engine is operated below the optimum engine settings, e.g., during maneuvering in harbors, HULIS-C emission factors are increased (262-893 mg kg-1), and a higher number of HULIS with a shift toward lower degree of oxidation and higher aromaticity is detected. Additionally, more aromatic and aliphatic CHOS compounds in HULIS were detected, especially for high-sulfur fuel combustion. The application of wet sulfur scrubbers decreased the HULIS-C emission factors by 4-49% but also led to the formation of new HULIS compounds. Overall, our results suggest the consideration of marine diesel engines as a relevant regional source of HULIS emissions.

Arterial Diameter and Percentage of Monocytes are Sex-Dependent Predictors of Early Arteriovenous Fistula Maturation.

BACKGROUND: Arteriovenous fistulae mature less frequently in women than in men, leading to inferior patency and decreased fistula utilization in women. We hypothesized that both anatomic and physiologic sex differences explain reduced maturation. METHODS: The electronic medical records of patients who had a primary arteriovenous fistula created from 2016 to 2021 at a single center were reviewed; sample size was determined using a power calculation. Postoperative ultrasound and laboratory tests were obtained at least 4 weeks after fistula creation. Primary unassisted fistula maturation was determined up to 4 years postprocedure. RESULTS: A total of 28 women and 28 men with a brachial-cephalic fistula were analyzed. The inflow brachial artery diameter was smaller in women than in men, both preoperatively (4.2 ± 0.9 vs. 4.9 ± 1.0 mm, P = 0.008) and postoperatively (4.8 ± 0.8 vs. 5.3 ± 0.9 mm, P = 0.039). Despite similar preoperative brachial artery peak systolic velocity, women had significantly lower postoperative arterial velocity (P = 0.027). Fistula flow was reduced in women, particularly in the midhumerus (747.0 ± 570.4 vs. 1,117.1 ± 471.3 cc/min, P = 0.003). Percentages of neutrophils and lymphocytes were similar among women and men 6 weeks after fistula creation. However, women had reduced monocytes (8.5 ± 2.0 vs. 10.0 ± 2.6%, P = 0.0168). Among 28 men, 24 of 28 (85.7%) achieved unassisted maturation, whereas only 15 of 28 (53.6%) women had fistulae that matured without intervention. Secondary analysis using logistic regression suggested that postoperative arterial diameter was associated with maturation in men, while postoperative monocyte percentage was associated with maturation in women. CONCLUSIONS: Sex differences during arteriovenous fistula maturation are present in arterial diameter and velocity, suggesting that both anatomic and physiologic differences in arterial inflow contribute to sex differences in fistula maturation. In men, postoperative arterial diameter is correlated with maturation, whereas in women, the significantly lower proportion of circulating monocytes suggests a role for the immune response in fistula maturation.