Investigation of hydrochemical characteristic, water quality and associated health risks of metals and metalloids in water resources in the vicinity of Akamkpa quarry district, southeastern, Nigeria.

Quarrying of rock aggregates generates produced water that, if not handled properly will be a source of pollution for nearby water bodies, thus affecting the chemistry of the water. This study examined the chemistry, impact of quarrying activities on water resources and the health consequences/risks posed by ingestion of the water by humans in the Akamkpa quarry region in southeastern Nigeria. Thirty (30) water samples consisting of pond water, stream water, hand dug wells, and borehole samples were collected and analyzed for their physicochemical parameters using standard methods. The results obtained from the analyses indicated that the water was moderately acidic, fresh, and not salty, with many parameters below the recommended standards with Ca2+, and HCO3- being the dominant ions present in the water resources. Rock weathering processes including silicate weathering as illustrated by hydrochemical facies, cross plots, and Gibbs diagrams are the dominant mechanisms influencing the quality and major ions chemistry of the water resources with minor contributions from dissolution, anthropogenic activities, and ion exchange. Ca-Mg-SO4-Cl and Na-K-HCO3- are the most important water types. Although the water quality index shows that the water is suitable for human use and irrigation, the mean values of As, Cd, Pb, and Se are above the acceptable limits. Additionally, the calculated contamination factor revealed the water resources are moderate to highly contaminated by As, Cd, Cr, Mo, Pb, Sb, and Se, and are therefore unsuitable for consumption with regards to these parameters. However, the residual sodium carbonate and water hazard index (WHI) values showed that 38% to 90% of sites in the quarry area were unsuitable for cultivation, 10-30% were in the low to medium impact category, and 60% were classified as risky and are from high to very high impact category. A non-cancer study of inhabitants living in the vicinity of the quarry area indicated that 6.7% of the sites have values greater than one, indicating that it may endanger the health of the people. Therefore, constant monitoring of the water quality is recommended as long-term use of contaminated water can harm humans, plants, and soils.

Associations between Post-Intensive Care Syndrome Domains in Cardiac Arrest Survivors and Their Families One Month Post-Event.

Background: Post-intensive care syndrome (PICS) affects many critical care survivors and family members. Nevertheless, the relationship between PICS-relevant domains in cardiac arrest (CA) survivors and psychological distress in their family members (henceforth, PICS-F) remains underexplored. Methods: We enrolled consecutive CA patients admitted between 16 August 2021 and 28 June 2023 to an academic medical center, along with their close family members, in prospective studies. Survivors' PICS domains were: physical dependence (Physical Self-Maintenance Scale, PSMS), cognitive impairments (Modified Telephone Interview for Cognitive Status, TICS-M), and post-traumatic stress disorder (PTSS) symptoms (PTSD Checklist-PCL 5), as well as PICS-F (PCL-5 Total Score). Hierarchical multivariate linear regressions examined associations between PICS-F and survivors' PICS domains. Results: Of 74 dyads (n = 148), survivors had a mean (SD) age of 56 ± 16 years, with 61% being male and with a median hospital stay of 28 days. Family members (43% spouses) were slightly younger (52 ± 14 years), predominantly female (72%), and of minority race/ethnicity (62%). A high prevalence of PICS assessed 28.5 days (interquartile range 10-63) post-CA was observed in survivors (78% physical dependence, 54% cognitive impairment, 30% PTSS) and in family members (30% PTSS). Survivor PTSS was significantly associated with family member distress (ß = 0.3, p = 0.02), independent of physical dependence (ß = 0.0, p = 0.9), cognitive impairment (ß = -0.1, p = 0.5), family member characteristics, and duration of hospitalization. Conclusions: Both CA survivors and their family members showed substantial evidence of likely PICS. Survivor PTSS is notably associated with family member distress, highlighting the need for dyadic interventions to enhance psychosocial outcomes.

Tumor lysate particle only vaccine (TLPO) vs. Tumor lysate particle-loaded, dendritic cell vaccine (TLPLDC) to prevent recurrence in resected stage III/IV melanoma patients: Results of a phase I/IIa trial.

BACKGROUND: The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from dendritic cells (DC) loaded ex vivo with autologous tumor lysate (TL). TLPLDC has been shown to decrease recurrence in resected Stage III/IV melanoma patients in a Phase IIb trial. The TL particle only (TLPO) vaccine is produced by loading of yeast cell wall particles with autologous TL and direct injection allowing for in vivo DC loading. We have compared the TLPO and TLPLDC vaccines in an embedded Phase I/IIa trial of a larger Phase IIb trial of the TLPLDC vaccine. METHODS: Patients rendered clinically disease-free after surgery were randomized 2:1 to receive the TLPO or TLPLDC vaccine and followed for recurrence and death. Patients had scheduled intradermal inoculations at 0, 1, 2, 6, 12, and 18 months after enrollment. Kaplan-Meier and log-rank analysis were used to compare disease-free survival (DFS) and overall survival (OS) in an intention-to-treat (ITT) analysis. RESULTS: Sixty-three patients were randomized, 43 TLPO and 20 TLPLDC. Patients randomized to the TLPO arm were more likely to be female (37.2% vs. 10.0 %, p = 0.026), but otherwise no significant clinicopathological differences were identified. No differences in related adverse events (AE) were found between treatment arms. At a median follow-up of 20.5 months, the DFS (60.8% vs. 58.7 %, p = 0.714) and OS (94.6% vs. 93.8 %, p = 0.966) were equivalent between the TLPO and TLPLDC groups, respectively. No statistical differences were found in subgroup analyses between vaccine types, which accounted for receipt of immunotherapy and the use of G-CSF pre-blood draw. CONCLUSIONS: In a randomized, double-blind Phase I/IIa trial, there were no differences in DFS or OS in resected Stage III/IV melanoma patients receiving adjuvant TLPO versus TLPLDC vaccines. Given manufacturing advantages, further efficacy testing of TLPO is warranted in a Phase III trial.

On the Nature of the Last Common Ancestor: A Story from its Translation Machinery.

The Last Common Ancestor (LCA) is understood as a hypothetical population of organisms from which all extant living creatures are thought to have descended. Its biology and environment have been and continue to be the subject of discussions within the scientific community. Since the first bacterial genomes were obtained, multiple attempts to reconstruct the genetic content of the LCA have been made. In this review, we compare 10 of the most extensive reconstructions of the gene content possessed by the LCA as they relate to aspects of the translation machinery. Although each reconstruction has its own methodological biases and many disagree in the metabolic nature of the LCA all, to some extent, indicate that several components of the translation machinery are among the most conserved genetic elements. The datasets from each reconstruction clearly show that the LCA already had a largely complete translational system with a genetic code already in place and therefore was not a progenote. Among these features several ribosomal proteins, transcription factors like IF2, EF-G, and EF-Tu and both class I and class II aminoacyl tRNA synthetases were found in essentially all reconstructions. Due to the limitations of the various methodologies, some features such as the occurrence of rRNA posttranscriptional modified bases are not fully addressed. However, conserved as it is, non-universal ribosomal features found in various reconstructions indicate that LCA's translation machinery was still evolving, thereby acquiring the domain specific features in the process. Although progenotes from the pre-LCA likely no longer exist recent results obtained by unraveling the early history of the ribosome and other genetic processes can provide insight to the nature of the pre-LCA world.

Divergent sensory pathways of sneezing and coughing.

Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3-) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST+]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.

USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.

Mammalian DNA replication relies on various DNA helicase and nuclease activities to ensure accurate genetic duplication, but how different helicase and nuclease activities are properly directed remains unclear. Here, we identify the ubiquitin-specific protease, USP50, as a chromatin-associated protein required to promote ongoing replication, fork restart, telomere maintenance, cellular survival following hydroxyurea or pyridostatin treatment, and suppression of DNA breaks near GC-rich sequences. We find that USP50 supports proper WRN-FEN1 localisation at or near stalled replication forks. Nascent DNA in cells lacking USP50 shows increased association of the DNA2 nuclease and RECQL4 and RECQL5 helicases and replication defects in cells lacking USP50, or FEN1 are driven by these proteins. Consequently, suppression of DNA2 or RECQL4/5 improves USP50-depleted cell resistance to agents inducing replicative stress and restores telomere stability. These data define an unexpected regulatory protein that promotes the balance of helicase and nuclease use at ongoing and stalled replication forks.

The electronic artificial urinary sphincter: ongoing innovation of a classic device-a narrative review.

Background and Objective: While the modern artificial urinary sphincter (AUS) has benefited from incremental innovation, which has improved both device efficacy and complication rates, the foundational technology in use in Boston Scientific's AMS800 can be traced back to the fundamental hydraulic tenets of the AS721. Research and development in adaptive technology and electronic integration stand to further improve AUS outcomes. Methods: The Medline online retrieval system was queried using the MeSH terms "artificial urinary sphincter", "electronic", "complications", "history", and "development" in various combinations. Publications were reviewed if applicable, and their reference lists were used to collect additional articles as needed. Final article inclusion was based on senior author discretion. Key Content and Findings: The AMS800 AUS is the gold standard for male stress incontinence implants. A 2015 consensus conference set out the goals for sphincter device development in the coming decades. A future ideal sphincter would adjust cuff pressure dynamically as well as function with minimal manipulation, or even via electronic control. Multiple new devices are in various states of development. During the next decade, artificial urinary sphincter technology is likely to include multiple Food and Drug Administration (FDA)-approved devices with varying features aimed at satisfying the 2015 consensus conference goal for an "ideal" AUS. Conclusions: The future of stress incontinence therapy lies in both continued innovation for the AUS, as well as advances in regenerative medicine. Electronic and adaptive developments in AUS technology will increase device safety, efficacy, and longevity while improving the user and caregiver experience. For some, regenerative medicine may even make AUS technology obsolete.

Assessing the reporting quality of pediatric neuro-oncology protocols, abstracts, and trials: Adherence to the SPIRIT and CONSORT statements.

Background: It is of vital importance to comprehensively and transparently report clinical trial activity. The SPIRIT 2013 and CONSORT 2010 statements exist to define items to be reported in clinical trial protocols and randomized controlled trials, respectively. The aim of this methodological review was to assess the reporting quality of pediatric neuro-oncology trial protocols and trial result articles. Methods: Published trial protocols and phase II/III trial result articles relating to pediatric brain tumors (published after the introduction of the SPIRIT 2013 statement), were identified through searches of 4 electronic bibliographic databases. The reporting quality of included trial protocols and result articles was assessed against the aforementioned statements. In addition, the CONSORT-A checklist was used to assess the abstracts of trial result articles. Percentage adherence was calculated for each article. Results: Nine trial protocols, 68 phase II trials, and 8 phase III trial result articles were included. Mean adherence of trial protocols to the SPIRIT statement was 76.8% (SD: 0.09). Mean adherence of trial abstracts to CONSORT-A was 67.4% (SD: 0.13) for phase II abstracts and 47.5% (SD: 0.09) for phase III abstracts. Adherence of trial result articles to CONSORT was 71.3% (SD: 0.10) for phase II trials and 70.3% (SD: 0.13) for phase III trials. Conclusions: The reporting quality of pediatric neuro-oncology trial protocols and trial result articles requires improvement, particularly in the areas of randomization and blinding. This is consistent with our previously published findings following similar assessment of reporting quality for adult neuro-oncology trial protocols and result articles.

A randomized, placebo-controlled trial of purified anthocyanins on cognitive function in individuals at elevated risk for dementia: Analysis of inflammatory biomarkers toward personalized interventions.

BACKGROUND: Dementia poses a significant global health challenge. Anthocyanins neutralize free radicals, modulate signaling pathways, inhibit pro-inflammatory genes, and suppress cytokine production and may thus have positive cognitive effects in people at increased risk of dementia. We aim to investigate the effects of purified anthocyanins on cognitive function in people at increased risk of dementia according to their inflammation status based on blood-based inflammatory biomarkers. METHODS: This is a secondary analysis of a 24-week randomized, double-blind, placebo-controlled trial. Cluster analysis was performed to categorize two groups based on their individual inflammatory biomarker profile using multiplex sandwich ELISA for the quantitative measurement of cytokines. Descriptive statistics and longitudinal models assessed cognitive outcomes. The primary comparison was the group difference at week 24 based on a modified intention-to-treat analysis. RESULTS: Cluster analysis revealed two distinct inflammatory biomarker profiles. In Cluster 1 (high levels of inflammation biomarkers), anthocyanin treatment showed a statistically significant improvement on cognitive function compared to placebo at 24 weeks. No significant differences were observed in Cluster 2 (low levels of inflammation biomarkers). The demographic characteristics, cognitive scores, and biomarker distributions were similar between treatment groups at baseline. However, cluster 1 exhibited higher BMI, diabetes prevalence, medication usage, and lower HDL cholesterol levels. CONCLUSION: Individuals with elevated levels of inflammation markers benefited from anthocyanin treatment to enhance cognitive performance, whereas those with lower levels did not. The anti-inflammatory and antioxidant properties of anthocyanins make them a promising intervention, and future prospective trials in people with increased inflammation are warranted.

Surgical outcomes and risk factors for overall mortality in brain arteriovenous malformations patients: a retrospective analysis.

Background: Brain arteriovenous malformations (AVMs) are challenging vascular lesions. Extensive follow-up studies are necessary to refine the therapeutic algorithm, and to improve long-term survival in these patients. The aim of the study was to assess surgical outcomes, and to evaluate overall long-term mortality in patients treated for brain AVMs. Methods: This retrospective single-center study included 191 patients with brain AVMs, admitted between 2012 and 2022. Clinical and angiographical particularities have been analyzed, to identify factors that might influence early outcome and overall long-term mortality. Results: Out of 79 patients undergoing surgery, 51 had ruptured AVMs with total resection achieved in 68 cases (86.1%). Deep venous drainage was associated with incomplete resection. Female sex, admission modified Rankin Scale (mRS) > 2, and eloquent location were independent predictors of poor outcomes. Multiple venous drainage was associated with a higher risk of worsened early outcome. Eloquent brain region involvement, conservative treatment, increasing age, admission mRS > 2, and comorbidities significantly decrease survival in brain AVM patients. Patients treated with interventional treatments had significantly better survival than the conservatively managed ones, when adjusting for age and admission mRS. Conclusion: The study identified female sex, poor neurologic status on admission and eloquence as independent prognostic factors for a negative outcome after surgery. Patients who received interventional treatment had significantly better survival than patients managed conservatively. We recommend employing tailored, proactive management strategies as they significantly enhance long-term survival in brain AVM patients.

Dissecting the oncogenic mechanisms of POT1 cancer mutations through deep scanning mutagenesis.

Mutations in the shelterin protein POT1 are associated with diverse cancers, but their role in cancer progression remains unclear. To resolve this, we performed deep scanning mutagenesis in POT1 locally haploid human stem cells to assess the impact of POT1 variants on cellular viability and cancer-associated telomeric phenotypes. Though POT1 is essential, frame-shift mutants are rescued by chemical ATR inhibition, indicating that POT1 is not required for telomere replication or lagging strand synthesis. In contrast, a substantial fraction of clinically-validated pathogenic mutations support normal cellular proliferation, but still drive ATR-dependent telomeric DNA damage signaling and ATR-independent telomere elongation. Moreover, this class of cancer-associated POT1 variants elongates telomeres more rapidly than POT1 frame-shifts, indicating they actively drive oncogenesis and are not simple loss-of-function mutations.

Biological control for One Health.

Biological control has been effectively exploited by mankind since 300 CE. By promoting the natural regulation of pests, weeds, and diseases, it produces societal benefits at the food-environment-health nexus. Here we scrutinize biological control endeavours and their social-ecological outcomes through a holistic 'One-Health' lens, recognizing that the health of humans, animals, plants, and the wider environment are linked and interdependent. Evidence shows that biological control generates desirable outcomes within all One Health dimensions, mitigating global change issues such as chemical pollution, biocide resistance, biodiversity loss, and habitat destruction. Yet, its cross-disciplinary achievements remain underappreciated. To remedy this, we advocate a systems-level, integrated approach to biological control research, policy, and practice. Framing biological control in a One Health context helps to unite medical and veterinary personnel, ecologists, conservationists and agricultural professionals in a joint quest for solutions to some of the most pressing issues in planetary health.

Implementation and Interim Analysis of a Standardized Renal Trauma Imaging and Urinary Extravasation Management Protocol.

INTRODUCTION: The AUA recommends delayed-phase imaging (DPI) in renal injuries to evaluate the collecting system. A renal trauma imaging protocol for early conservative management of urinary extravasation (UE) was implemented to improve guideline adherence. We aimed to determine if increased adherence led to changes in outcomes. METHODS: Patients with American Association for the Surgery of Trauma III to V renal injury presenting from January 2018 to September 2022 were identified from an institutional trauma registry. Patients were included if a contrasted CT scan of the abdomen was obtained on admission. Frequency of DPI and patient outcomes were compared before and after protocol implementation. RESULTS: Of 223 included patients, 131 (58.7%) were pre protocol and 92 (41.3%) were post protocol. Following protocol implementation, the rate of DPI on admission nearly doubled from 32.8% to 58.7% (P < .001). The rate of follow-up cross-sectional imaging increased from 18.3% to 58.7% (P < .001). Although there were no significant differences in rates of immediate or delayed interventions following protocol implementation, the postprotocol immediate intervention rate did decrease to 0%. Readmissions due to symptomatic UE were unchanged after protocol implementation (0.0% vs 0.0%). CONCLUSIONS: Implementation of a multidisciplinary renal trauma early imaging and management protocol improved AUA guideline adherence. With protocol adherence, there was also an elimination of immediate interventions for UE. Despite decreases in early intervention, there was no significant increase in interval interventions or UE-related readmissions. More research is needed to determine the role for routine follow-up imaging in conservative management of high-grade renal trauma.

Outcomes of Neonatal Cardiac Surgery: A European Congenital Heart Surgeons Association Study.

BACKGROUND: We evaluated outcomes of neonatal cardiac surgery at hospitals affiliated with the European Congenital Heart Surgeons Association (ECHSA). METHODS: All patients ≤30 days of life undergoing a cardiac surgical procedure during a 10-year period between January 2013 and December 2022 were selected from the ECHSA Congenital Database. Reoperations during the same hospitalization, percutaneous procedures, and noncardiac surgical procedures were excluded. We identified 12 benchmark operations. Primary outcomes were 30-day mortality and in-hospital mortality. Multivariable logistic regression analysis was performed to determine independent factors associated with higher mortality. Mortality between the first 5 years and second 5 years was also compared. RESULTS: The overall number of neonatal operations from 2013 to 2022 was 30,931, and 22,763 patients met the inclusion criteria of the study. The 4 most common procedures were arterial switch operation (3520 of 22,763 [15.5%]), aortic coarctation repair (3204 of 22,763 [14.1%]), shunt procedure (2351 of 22,763 [10.3%]), and Norwood operation (2115 of 22,763 [9.23%]). The 30-day mortality rate was as follows: overall population, 5.9% (1342 of 22,763); arterial switch, 3.13% (110 of 3520); Norwood operation, 16.0% (339 of 2115); and hybrid operation, 15.4% (94 of 609). In-hospital mortality rate was as follows: overall population, 9.1% (2074 of 22,763); arterial switch, 4.12% (145 of 3520); Norwood operation, 24.7% (523 of 2115); and hybrid operation, 30.5% (186 of 609). Multivariable analysis revealed that major factors impacting mortality were high-risk procedures (adjusted odds ratio, 2.74; 95% CI, 2.33-3.23; P < .001), and the need for extracorporeal membrane oxygenation (11.8; 95% CI, 9.9-14; P < .001). CONCLUSIONS: Neonatal cardiac surgery continues to pose a significant challenge, with notable mortality, particularly for neonates with functionally univentricular physiology. These data can serve as important benchmarks across Europe and offer insights regarding opportunities for improvement.

Potential misinformation in large language model descriptions of upper extremity diseases.

When a large language model was prompted to discuss upper extremity conditions and correct instances of misinformation in responses, there was notable persistent misinformation, reinforcement of unhelpful thinking and reduction of independent management of one's health (agency).

Review of Outpatient Pediatric Ethics Consults at an Academic Medical Center.

Limited data exist in the specific content of pediatric outpatient ethics consults as compared to inpatient ethics consults. Given the fundamental differences in outpatient and inpatient clinical care, we aimed to describe the distinctive nature of ethics consultation in the ambulatory setting. This is a retrospective review at a large, quaternary academic center of all outpatient ethics consults in a 6-year period. Encounter-level demographic data was recorded, and primary ethical issue and contextual features were identified using qualitative conceptual content analysis. A total of 48 consults were identified representing 44 unique patients. The most common primary ethical issue was beneficence and best interest concern comprising 20 (42%) consults, followed by refusal of recommended treatment comprising 11 (23%) consults and patient preference/assent comprising 5 (10%) consults. The most common contextual features were staff-family communication dispute/conflict comprising 28 (58%) consults, followed by legal involvement comprising 25 (52%) consults and quality of life comprising 19 (40%) consults. The most common consulting specialty was hematology/oncology. Ethical issues encountered in the provision of outpatient pediatric care are distinct and differ from those in inpatient consults. Further research is necessary to identify strategies and educational gaps in outpatient ethics consultation to increase its effectiveness and utilization.

Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer.

This Phase I/IIa open-label, single-arm clinical trial addressing advanced, refractory, metastatic breast cancer was conducted at six medical centers in the United States. We repeated inoculations with irradiated SV-BR-1-GM, a breast cancer cell line with antigen-presenting activity engineered to release granulocyte-macrophage colony-stimulating factor (GM-CSF), with pre-dose low-dose cyclophosphamide and post-dose local interferon alpha. Twenty-six patients were enrolled; 23 (88.5%) were inoculated, receiving a total of 79 inoculations. There were six Grade 4 and one Grade 5 adverse events noted (judged unrelated to SV-BR-1-GM). Disease control (stable disease [SD]) occurred in 8 of 16 evaluable patients; 4 showed objective regression of metastases, including 1 patient with near-complete regressions in 20 of 20 pulmonary lesions. All patients with regressions had human leukocyte antigen (HLA) matches with SV-BR-1-GM; non-responders were equally divided between matching and nonmatching (p = .01, Chi-squared), and having ≥2 HLA matches with SV-BR-1-GM (n = 6) correlated with clinical benefit. Delayed-type hypersensitivity (DTH) testing to candida antigen and SV-BR-1-GM generated positive responses (≥5 mm) in 11 (42.3%) and 13 (50%) patients, respectively. Quantifying peripheral circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAMLs) showed that a drop in CAMLs was significantly correlated with an improvement in progression-free survival (PFS; 4.1 months vs. 1.8 months, p = .0058). Eight of 10 patients significantly upregulated programmed cell death ligand 1 (PD-L1) on CTCs/CAMLs with treatment (p = .0012). These observations support the safety of the Bria-IMT regimen, demonstrate clinical regressions, imply a role for HLA matching, and identify a possible value for monitoring CAMLs in peripheral blood.