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Ground Water Jun 2024Understanding fate and transport processes for per- and poly-fluoroalkyl substances (PFAS) is critical for managing impacted sites. "PFAS Salting Out" in groundwater,...
Understanding fate and transport processes for per- and poly-fluoroalkyl substances (PFAS) is critical for managing impacted sites. "PFAS Salting Out" in groundwater, defined herein, is an understudied process where PFAS in fresh groundwater mixes with saline groundwater near marine shorelines, which increases sorption of PFAS to aquifer solids. While sorption reduces PFAS mass discharge to marine surface water, the fraction that sorbs to beach sediments may be mobilized under future salinity changes. The objective of this study was to conceptually explore the potential for PFAS Salting Out in sandy beach environments and to perform a preliminary broad-scale characterization of sandy shoreline areas in the continental U.S. While no site-specific PFAS data were collected, our conceptual approach involved developing a multivariate regression model that assessed how tidal amplitude and freshwater submarine groundwater discharge affect the mixing of fresh and saline groundwater in sandy coastal aquifers. We then applied this model to 143 U.S. shoreline areas with sandy beaches (21% of total beaches in the USA), indirectly mapping potential salinity increases in shallow freshwater PFAS plumes as low (<10 ppt), medium (10-20 ppt), or high (>20 ppt) along groundwater flow paths before reaching the ocean. Higher potential salinity increases were observed in West Coast bays and the North Atlantic coastline, due to the combination of moderate to large tides and large fresh groundwater discharge rates, while lower increases occurred along the Gulf of Mexico and the southern Florida Atlantic coast. The salinity increases were used to estimate potential perfluorooctane sulfonic acid (PFOS) sorption in groundwater due to salting out processes. Low-category shorelines may see a 1- to 2.5-fold increase in sorption of PFOS, medium-category a 2.0- to 6.4-fold increase, and high-category a 3.8- to 25-fold increase in PFOS sorption. The analysis presented provides a first critical step in developing a large-scale approach to classify the PFAS Salting Out potential along shorelines and the limitations of the approach adopted highlights important areas for further research.
PubMed: 38940354
DOI: 10.1111/gwat.13428 -
American Journal of Medical Genetics.... Jun 2024Big data generated from exome sequencing (ES) and genome sequencing (GS) analyses can be used to detect actionable and high-penetrance variants that are not directly...
Big data generated from exome sequencing (ES) and genome sequencing (GS) analyses can be used to detect actionable and high-penetrance variants that are not directly associated with the primary diagnosis of patients but can guide their clinical follow-up and treatment. Variants that are classified as pathogenic/likely pathogenic and are clinically significant but not directly associated with the primary diagnosis of patients are defined as secondary findings (SF). The aim of this study was to examine the frequency and variant spectrum of cancer-related SF in 2020 Turkish ES data and to discuss the importance of the presence of cancer-related SF in at-risk family members in terms of genetic counseling and follow-up. A total of 2020 patients from 2020 different families were evaluated by ES. SF were detected in 28 unrelated cases (1.38%), and variants in BRCA2 (11 patients) and MLH1 (4 patients) genes were observed most frequently. A total of 21 different variants were identified, with 4 of them (c.9919_9932del and c.3653del in the BRCA2 gene, c.2002A>G in the MSH2 gene, c.26_29del in the TMEM127 gene) being novel variations. In three different families, c.1189C>T (p.Gln397*) variation in BRCA2 gene was detected, suggesting that this may be a common variant in the Turkish population. This study represents the largest cohort conducted in the Turkish population, examining the frequency and variant spectrum of cancer-related SF. With the identification of frequent variations and the detection of novel variations, the findings of this study have contributed to the variant spectrum. Genetic testing conducted in family members is presented as real-life data, showcasing the implications in terms of counseling, monitoring, and treatment through case examples.
PubMed: 38940262
DOI: 10.1002/ajmg.a.63806 -
Journal of Extracellular Biology Feb 2024Extracellular vesicles (EVs) in biofluids are highly heterogeneous entities in terms of their origins and physicochemical properties. Considering the application of EVs...
Extracellular vesicles (EVs) in biofluids are highly heterogeneous entities in terms of their origins and physicochemical properties. Considering the application of EVs in diagnostic and therapeutic fields, it is of extreme importance to establish differentiating methods by which focused EV subclasses are operationally defined. Several differentiation protocols have been proposed; however, they have mainly focused on smaller types of EVs, and the heterogeneous nature of large EVs has not yet been fully explored. In this report, to classify large EVs into subgroups based on their physicochemical properties, we have developed a protocol, named EV differentiation by sedimentation patterns (ESP), in which entities in the crude large EV fraction are first moved through a density gradient of iodixanol with small centrifugation forces, and then the migration patterns of molecules through the gradients are analysed using a non-hierarchical data clustering algorithm. Based on this method, proteins in the large EV fractions of oral fluids clustered into three groups: proteins shared with small EV cargos and enriched in immuno-related proteins (Group 1), proteins involved in energy metabolism and protein synthesis (Group 2), and proteins required for vesicle trafficking (Group 3). These observations indicate that the physiochemical properties of EVs, which are defined through low-speed gradient centrifugation, are well associated with their functions within cells. This protocol enables the detailed subclassification of EV populations that are difficult to differentiate using conventional separation methods.
PubMed: 38939901
DOI: 10.1002/jex2.143 -
JACC. Advances Jan 2024Multilevel obstruction in left ventricular inflow and outflow predisposes to arrhythmias in Shone's complex (SC).
BACKGROUND
Multilevel obstruction in left ventricular inflow and outflow predisposes to arrhythmias in Shone's complex (SC).
OBJECTIVES
The purpose of this study was to study the prevalence and outcomes (heart failure [HF] hospitalization, cardiac transplant, death) of cardiac arrhythmias in adults with SC.
METHODS
Adults with SC (defined as ≥2 lesions out of supramitral ring, parachute mitral valve, subvalvular/valvular aortic stenosis (AS), and aortic coarctation) seen at Mayo Clinic between January 1999 and March 2020 were identified and evaluated for the presence of sustained atrial fibrillation, atrial flutter, and ventricular arrhythmias (VA). Kaplan-Meier survival analysis was used to calculate the occurrence of these arrhythmias.
RESULTS
Seventy-three patients with SC (mean age at first visit 33 ± 13 years) were identified. Most common anomalies were valvular AS (88%), coarctation (85%), parachute mitral valve (44%), subvalvular AS (44%), and supramitral ring (25%). Atrial arrhythmias were diagnosed in 24 patients (33%) at a mean age of 34.6 ± 12.7 years. Patients with atrial fibrillation and atrial flutter had higher number of surgeries, left atrial size, right ventricular systolic pressure, and HF hospitalizations. A rhythm control approach was used in majority of patients (75% on antiarrhythmic drugs and 50% underwent catheter ablation). Sustained VA occurred in 6 of 73 patients of whom 4 had an ejection fraction <40%. Death and cardiac transplantation occurred in 11 and 3 patients, respectively, during a median follow-up of 7.3 ± 6.0 years.
CONCLUSIONS
In adults with SC, atrial arrhythmias occurred in one-third of patients, were associated with more HF hospitalizations, and frequently required rhythm control. Prevalence of sustained VA was 8% and implantable cardioverter-defibrillator implantation should be considered in those with reduced ejection fraction.
PubMed: 38939811
DOI: 10.1016/j.jacadv.2023.100715 -
Journal of Arrhythmia Jun 2024A notched P-wave is associated with the occurrence of atrial fibrillation (AF). However, the association between a notched P-wave and AF recurrence in patients who have...
BACKGROUND
A notched P-wave is associated with the occurrence of atrial fibrillation (AF). However, the association between a notched P-wave and AF recurrence in patients who have undergone a catheter ablation for AF is unclear.
METHODS
We enrolled 100 subjects who underwent catheter ablation for AF (paroxysmal AF: 60 cases; persistent AF: 40 cases). Twelve-lead electrocardiography (ECG) was conducted, and the peak-to-peak distance in the M shape was calculated automatically using a 12-lead ECG analysis system. A notched P-wave was defined as a P-wave with an M-shape and a peak-to-peak distance of ≥20 ms in lead II. We compared the recurrence of AF in the patients with notched P-wave and the others.
RESULTS
The mean follow-up period was 12 ± 8 months, and a recurrence of AF was observed in 28 patients. The recurrence of AF in the notched P-wave group was significantly higher than that in the controls (log rank 5.14, = .023). A notched P-wave was a significant predictor of the recurrence of AF after adjustment for age, gender, history of heart failure, history of catheter ablation, persistent AF, use of antiarrhythmic drugs, and the left atrial volume index (hazard ratio 2.470, 95% confidence interval 1.065-5.728, = .035).
CONCLUSIONS
Automatically identified notched P-waves with peak-to-peak distance ≥20 ms were associated with AF recurrence in patients who had undergone catheter ablation.
PubMed: 38939783
DOI: 10.1002/joa3.13050 -
Acta Medica Philippina 2024Based on the 2017-2020 annual report of the Department of Health-Antimicrobial Resistance Surveillance Program, significant resistance patterns have been observed for...
BACKGROUND
Based on the 2017-2020 annual report of the Department of Health-Antimicrobial Resistance Surveillance Program, significant resistance patterns have been observed for common disease-causing pathogens. In the hospital setting, antimicrobial stewardship programs have been implemented to optimize the use of antimicrobials. Drug utilization review studies provide essential feedback to improve prescribing and use of medications.
OBJECTIVES
This study aimed to review drug utilization of monitored parenteral antimicrobials among patients admitted from January to December 2019.
METHODS
The study employed a retrospective, cross-sectional, descriptive research design. A retrospective chart review of drugs administered to patients was conducted.
RESULTS
A total of 821 patients charts met the inclusion criteria. The patients' ages ranged from 18 to 98 years old and 52% were females. General Internal Medicine practitioners (28%) were the top prescribers of monitored parenteral antimicrobials primarily for the management of moderate-risk community-acquired pneumonia (39%). They were mostly indicated for empirical treatment of infections (94%) and were given for an average of 5.73 days.Only 58% of the total cases had orders for culture and sensitivity testing. Of which, principally 47% had colony cultures. Blood (29%) and sputum (27%) were the most common specimens taken for culture and sensitivity testing. The microorganisms often isolated were (19%), (18%), and (9%). In addition, extended-spectrum beta lactamase-producing gram-negative pathogens (4%) and methicillin-resistant (1%) were also isolated. All the microorganisms isolated showed most resistance to ampicillin (81%) and most susceptibility to colistin (100%). There were drug therapy-related problems encountered. There was one case of an adverse drug reaction (0.1%) and two cases of contraindications (0.2%). Therapeutic duplication was also observed in 5% of the cases. Moreover, 39% had instances of drug-drug interactions.Piperacillin-tazobactam had the highest consumption (79.50 defined daily doses/1,000-patient days) among the monitored parenteral antimicrobials.Some prescriptions were deemed inappropriate upon evaluation. 12% of cases were inappropriate based on the justification indicator. As for the critical indicators, duration of therapy (78%) was the main reason. Only four components of the DUE criteria indicators have met or exceeded the established threshold level.The cost analysis indicated that the total actual cost of therapy with the monitored parenteral antimicrobials amounted to ₱17,645,601.73. Considering Department of Health National Antibiotic Guidelines recommendations, ideal total cost of treatment was ₱14,917,214.29. Potential cumulative cost savings of ₱2,728,387.44 could have been achieved for patients admitted last 2019.
CONCLUSION
Consumption of piperacillin-tazobactam was relatively high as compared to the other monitored parenteral antimicrobials covered in this study. Physicians at the study site seldom prescribe monitored parenteral antimicrobials as recommended by the National Antibiotic Guidelines. This is evidenced in the incidence of inappropriate therapy regimens, with inapt duration of therapy as the leading explanation.From the patient's perspective, the main economic implication was on the direct medical costs, particularly the increased cost of the actual antimicrobial therapy prescribed to manage various infections. Adherence of physicians to the established guidelines and selection of the most cost-effective therapy could have resulted in considerable cost savings.
PubMed: 38939423
DOI: 10.47895/amp.vi0.7249 -
JACC. Advances Feb 2024Increased particulate matter <2.5 μm (PM) air pollution is associated with adverse cardiovascular outcomes. However, its impact on patients with prior coronary artery...
BACKGROUND
Increased particulate matter <2.5 μm (PM) air pollution is associated with adverse cardiovascular outcomes. However, its impact on patients with prior coronary artery bypass grafting (CABG) is unknown.
OBJECTIVES
The purpose of this study was to evaluate the association between major adverse cardiovascular events (MACE) (defined as myocardial infarction, stroke, or cardiovascular death) and air pollution after CABG.
METHODS
We linked 26,403 U.S. veterans who underwent CABG (2010-2019) nationally with average annual ambient PM estimates using residential address. Over a 5-year median follow-up period, we identified MACE and fit a multivariable Cox proportional hazard model to determine the risk of MACE as per PM exposure. We also estimated the absolute potential reduction in PM attributable MACE simulating a hypothetical PM lowered to the revised World Health Organization standard of 5 μg/m.
RESULTS
The observed median PM exposure was 7.9 μg/m (IQR: 7.0-8.9 μg/m; 95% of patients were exposed to PM above 5 μg/m). Increased PM exposure was associated with a higher 10-year MACE rate (first tertile 38% vs third tertile 45%; < 0.001). Adjusting for demographic, racial, and clinical characteristics, a 10 μg/m increase in PM resulted in 27% relative risk for MACE (HR: 1.27, 95% CI: 1.10-1.46; < 0.001). Currently, 10% of total MACE is attributable to PM exposure. Reducing maximum PM to 5 μg/m could result in a 7% absolute reduction in 10-year MACE rates.
CONCLUSIONS
In this large nationwide CABG cohort, ambient PM air pollution was strongly associated with adverse 10-year cardiovascular outcomes. Reducing levels to World Health Organization-recommended standards would result in a substantial risk reduction at the population level.
PubMed: 38939372
DOI: 10.1016/j.jacadv.2023.100781 -
Cureus May 2024Introduction The coronavirus disease 2019 (COVID-19) pandemic has impacted the lives of thousands of patients worldwide with many patients having residual symptoms...
Introduction The coronavirus disease 2019 (COVID-19) pandemic has impacted the lives of thousands of patients worldwide with many patients having residual symptoms months after the acute infection. The severity of lung involvement ranges from mild asymptomatic to severe acute respiratory distress syndrome (ARDS), which may lead to pulmonary fibrosis. Pulmonary fibrosis increases the long-term morbidity of post-COVID-19 patients in the form of restrictive lung disease. The six-minute walk test (6MWT), Borg scale, and spirometry are simple and low-cost tests used to evaluate a patient's exercise capacity and functional status. This study was conducted to assess the residual symptoms and functional status using spirometry and 6MWT in COVID-19 patients of moderate to severe category after three months of discharge. Methods This was an observational, prospective, and cross-sectional study conducted at a tertiary care center in North India, aiming to enroll a minimum of 50 patients who recovered from COVID-19 pneumonia. These patients were previously hospitalized with moderate to severe disease severity as defined by the Indian Council of Medical Research (ICMR) criteria, and the assessment occurred at least three months after their discharge. Individuals who were under 18 years of age or pregnant or had any respiratory or cardiac illness in the past were excluded from the study. Results A total of 50 patients were included in the study for final analysis. After a three-month follow-up, 40 (80%) patients were still symptomatic. The most commonly reported symptom was exertional dyspnea in 21 (42%), dyspnea at rest in 16 (32%), and fatigue in three (6%) patients. Of the total patients, 37 (74%) covered a distance less than expected in the six-minute walk test. The mean distance covered by patients was 426.1 ± 115.01 m, in contrast to the expected mean distance of 537.22 ± 37.61 m according to standard equations for Indian males and females. A fall in oxygen saturation by more than or equal to 3% was observed in approximately 24 (48%) patients after the six-minute walk test. The mean value of fatigue and dyspnea score was 3.2 ± 1.7 (moderate score). Among patients with moderate disease during their hospital stay, a higher proportion exhibited a normal pattern on pulmonary function tests (PFT) compared to those severely affected, 23 (69.70%) versus two (11.76%), respectively. Conclusion The persistence of symptoms and functional limitation of activities should be anticipated in patients with COVID-19. Spirometry and 6MWT can be a valuable tool in determining the prevalence of functional limitation in recovered patients of COVID-19. It can potentially help in determining and further planning the rehabilitative measures in the management of COVID-19 survivors. It can also be concluded that it is important to have a long-term follow-up in patients with moderate to severe COVID-19.
PubMed: 38939290
DOI: 10.7759/cureus.61221 -
International Journal of Cardiology.... Aug 2024A deep Y descent in the jugular venous pulse (JVP) is associated with diseases such as a decrease in right ventricular (RV) preload reserve. The present study...
BACKGROUND
A deep Y descent in the jugular venous pulse (JVP) is associated with diseases such as a decrease in right ventricular (RV) preload reserve. The present study investigated the relationship between RV-pulmonary arterial (PA) coupling and a deep Y descent, examined risk factors for a deep Y descent and clarified whether a deep Y descent was an independent risk factor for cardiac events irrespective of RV-PA coupling in patients with heart failure (HF).
METHODS
We enrolled 350 patients with HF who underwent echocardiography and JVP examination. A deep Y descent was identified by a deeper 'Y' descent than 'X' descent in the JVP waveform. We defined cardiac events of HF as follows: sudden death, death from HF, the emergent infusion of loop diuretics, or hospitalization for decompensated HF.
RESULTS AND CONCLUSIONS
A deep Y descent and cardiac events were observed in 129 and 83 patients, respectively. The prevalence of a deep Y descent increased with decreases in the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary arterial pressure (SPAP) ratio. Not only the TAPSE/SPAP ratio (odds ratio,0.756 per0.1 mm/mmHg, 95 %confidence interval [CI], 0.660-0.866, p < 0.001), but also age, atrial fibrillation, and the use of beta-blockers were independent factors for a deep Y descent in multivariate logistic model. Multivariate Cox hazard model demonstrated that a deep Y descent was for cardiac events in patients with HF (Hazard ratio,2.682, 95 %CI, 1.599-4.497, p < 0.001) irrespective of the TAPSE/SPAP ratio. The development of therapeutic strategies based on central venous waveform may be needed for patients with HF.
PubMed: 38939016
DOI: 10.1016/j.ijcha.2024.101439 -
PeerJ 2024Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in... (Observational Study)
Observational Study
Sex difference in the association between triglyceride and intracerebral bleeding risk after intravenous thrombolysis for acute ischemic stroke, a multi-center retrospective study.
BACKGROUND
Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in the association between lipid profile and the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis using recombinant tissue plasminogen activator (r-tPA).
METHODS
This multicenter retrospective observational study analyzed patients with AIS treated with intravenous r-tPA. sICH was defined as a worsening of 4 or higher points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 hours after intravenous thrombolysis in any hemorrhage subtype. We assessed the odds ratio (OR) with 95% confidence interval (CI) of lipid profile for sICH for each sex using logistic regression models adjusted for potential confounding factors.
RESULTS
Of 957 participants (median age 68 (interquartile range, 59-75), men 628 (65.6%)), 56 sICH events (36 (5.7%) in men and 20 (6.1%) in women) were observed. The risk of sICH in men decreased with increasing serum levels of triglyceride after adjustment for confounding factors ( lowest tertile, medium tertile OR 0.39, 95% CI [0.17-0.91], top tertile OR 0.33, 95% CI [0.13-0.84], overall = 0.021; per point increase, adjusted OR 0.29, 95% CI [0.13-0.63], = 0.002). Neither serum levels of total cholesterol nor low-density lipoprotein (LDL) was associated with sICH in men. In women, there was no association between any of the lipid levels and the risk of sICH.
CONCLUSIONS
This study indicated that the association between serum levels of triglyceride and sICH may vary by sex. In men, increased triglyceride levels decrease the risk of sICH; in women, this association was lost. Further studies on the biological mechanisms for sex differences in stroke risk associated with triglyceride are needed.
Topics: Humans; Male; Female; Retrospective Studies; Aged; Triglycerides; Middle Aged; Ischemic Stroke; Cerebral Hemorrhage; Tissue Plasminogen Activator; Sex Factors; Risk Factors; Thrombolytic Therapy; Fibrinolytic Agents
PubMed: 38938613
DOI: 10.7717/peerj.17558