Perforation, Migration, and Omentum Embedding of a Levonorgestrel Intrauterine Device: A Case Report.

The intrauterine device (IUD) is currently one of the most widely used methods due to its great effectiveness. Uterine perforation and migration of the device is one of its most serious complications, although rare. In most patients, it usually occurs at the time of placement and goes unnoticed; however, it can also occur late. The diagnosis is established by imaging studies, preferring abdominal ultrasound, and its treatment should be removal in all cases. We present the case of a 27-year-old woman, with a history of levonorgestrel IUD placement two years earlier, who presented with chronic pelvic pain. During a gynecological consultation, the IUD threads were not evident. An abdominal CT scan showed that the IUD was in the abdominal cavity, so open abdominal surgery was performed where the IUD was found embedded in the omentum and the segment of the omentum containing the IUD was resected. The patient evolved satisfactorily and was discharged 24 hours after surgery.

SOX6 expression and aneurysms of the thoracic and abdominal aorta.

Abdominal and thoracic aortic aneurysms (AAAs, TAAs) remain a major cause of deaths worldwide, in part due to the lack of reliable prognostic markers or early warning signs. Sox6 has been found to regulate renin controlling blood pressure. We hypothesized that Sox6 may serve as an important regulator of the mechanisms contributing to hypertension-induced aortic aneurysms. Phenotype and laboratory-wide association scans in a clinical cohort found that SOX6 gene expression is associated with aortic aneurysm in subjects of European ancestry. Sox6 and tumor necrosis factor alpha (TNF-α) expression were upregulated in aortic tissues from patients affected by either AAA or TAA. In Sox6 knockout mice with angiotensin-II-induced AAA, we found that Sox6 plays critical role in the development and progression of AAA. Our data support a regulatory role of SOX6 in the development of hypertension-induced AAA, suggesting that Sox6 may be a therapeutic target for the treatment of aortic aneurysms.

Intraoperative Oxygen Treatment, Oxidative Stress, and Organ Injury Following Cardiac Surgery: A Randomized Clinical Trial.

Importance: Liberal oxygen (hyperoxia) is commonly administered to patients during surgery, and oxygenation is known to impact mechanisms of perioperative organ injury. Objective: To evaluate the effect of intraoperative hyperoxia compared to maintaining normoxia on oxidative stress, kidney injury, and other organ dysfunctions after cardiac surgery. Design, Setting, and Participants: This was a participant- and assessor-blinded, randomized clinical trial conducted from April 2016 to October 2020 with 1 year of follow-up at a single tertiary care medical center. Adult patients (>18 years) presenting for elective open cardiac surgery without preoperative oxygen requirement, acute coronary syndrome, carotid stenosis, or dialysis were included. Of 3919 patients assessed, 2501 were considered eligible and 213 provided consent. Of these, 12 were excluded prior to randomization and 1 following randomization whose surgery was cancelled, leaving 100 participants in each group. Interventions: Participants were randomly assigned to hyperoxia (1.00 fraction of inspired oxygen [FiO2]) or normoxia (minimum FiO2 to maintain oxygen saturation 95%-97%) throughout surgery. Main Outcomes and Measures: Participants were assessed for oxidative stress by measuring F2-isoprostanes and isofurans, for acute kidney injury (AKI), and for delirium, myocardial injury, atrial fibrillation, and additional secondary outcomes. Participants were monitored for 1 year following surgery. Results: Two hundred participants were studied (median [IQR] age, 66 [59-72] years; 140 male and 60 female; 82 [41.0%] with diabetes). F2-isoprostanes and isofurans (primary mechanistic end point) increased on average throughout surgery, from a median (IQR) of 73.3 (53.1-101.1) pg/mL at baseline to a peak of 85.5 (64.0-109.8) pg/mL at admission to the intensive care unit and were 9.2 pg/mL (95% CI, 1.0-17.4; P = .03) higher during surgery in patients assigned to hyperoxia. Median (IQR) change in serum creatinine (primary clinical end point) from baseline to postoperative day 2 was 0.01 mg/dL (-0.12 to 0.19) in participants assigned hyperoxia and -0.01 mg/dL (-0.16 to 0.19) in those assigned normoxia (median difference, 0.03; 95% CI, -0.04 to 0.10; P = .45). AKI occurred in 21 participants (21%) in each group. Intraoperative oxygen treatment did not affect additional acute organ injuries, safety events, or kidney, neuropsychological, and functional outcomes at 1 year. Conclusions: Among adults receiving cardiac surgery, intraoperative hyperoxia increased intraoperative oxidative stress compared to normoxia but did not affect kidney injury or additional measurements of organ injury including delirium, myocardial injury, and atrial fibrillation. Trial Registration: ClinicalTrials.gov Identifier: NCT02361944.

Identification of CDK4/6 Inhibitors as Small Molecule NLRP3 Inflammasome Activators that Facilitate IL-1ß Secretion and T Cell Adjuvanticity.

Several FDA-approved adjuvants signal through the NLRP3 inflammasome and IL-1ß release. Identifying small molecules that induce IL-1ß release could allow targeted delivery and structure-function optimization, thereby improving safety and efficacy of next-generation adjuvants. In this work, we leverage our existing high throughput data set to identify small molecules that induce IL-1ß release. We find that ribociclib induces IL-1ß release when coadministered with a TLR4 agonist in an NLRP3- and caspase-dependent fashion. Ribociclib was formulated with a TLR4 agonist into liposomes, which were used as an adjuvant in an ovalbumin prophylactic vaccine model. The liposomes induced antigen-specific immunity in an IL-1 receptor-dependent fashion. Furthermore, the liposomes were coadministered with a tumor antigen and used in a therapeutic cancer vaccine, where they facilitated rejection of E.G7-OVA tumors. While further chemical optimization of the ribociclib scaffold is needed, this study provides proof-of-concept for its use as an IL-1 producing adjuvant in various immunotherapeutic contexts.

Molecular identification and prevalence of plerocercoid larvae (Cestoda: Diphyllobothriidae) in some commercial fish species from Peru.

Diphyllobothriosis, a fish-borne zoonosis in South America, is mainly caused by the Pacific broad tapeworm Adenocephalus pacificus Nybelin, 1931, a parasite of considerable concern in fishery resources due to its impact on public health. A new diphyllobothrid, Diphyllobothrium sprakeri Hernández-Orts et al. Parasites Vectors 14:219, 2021, was recently described from sea lions from the Pacific Coast, but marine fish acting as intermediate hosts are unknown. The objective of this study was to confirm the presence of plerocercoid larvae of Diphyllobothriidae Lühe, 1910 (Cestoda: Diphyllobothriidea) in nine fish species of commercial importance in Peru. Of a total of 6999 fish (5861 Engraulis ringens, 853 Sciaena deliciosa, 6 Sciaena callaensis, 171 Scomber japonicus, 40 Trachurus murphyi, 40 Ariopsis seemanni, 18 Merluccius peruanus, 5 Sarda chiliensis, and 5 Coryphaena hippurus), 183 were infected with plerocercoid larvae, representing a total prevalence of 2.61% and a mean intensity of 3.2. Based on mtDNA cox1 sequences of 43 plerocercoids, a phylogenetic analysis revealed that 41 belong to A. pacificus and two to D. sprakeri. These findings are first molecular data for D. sprakeri larvae, and the infections of E. ringens and T. murphyi by plerocercoid larvae represent the first records of intermediate/paratenic hosts for this species. Hence, the findings of the current study enhance our understanding of the presence of diphyllobothriid species in commercial fish from the Southeastern Pacific Ocean and their potential impact on seafood safety for local human populations.

Oral Health Literacy and Determinants among an Elderly Community in Portugal.

High average life expectancy has caused an increase in the elderly population and with it arises the need to characterize this population regarding their health and, in particular, their oral health. The purpose of this study was to assess and characterize oral health, oral rehabilitation, oral health literacy, oral health perception and quality of life in a sample of elderly participants of a physical activity program in Portugal. An observational cross-sectional study was designed with a group of 206 individuals. All the individuals were clinically assessed, DMFT, PSR and the plaque index were registered, and a questionnaire was applied in the form of a "face-to-face" interview with questions related to the quality of life related to oral health (GOHAI index and the REALD-30 scale). Of the 206 study participants, 90.3% admit brushing their teeth daily, 6.3% practice daily flossing, and 5.8% had a dental appointment in the last 12 months. Applying the REALD-30 scale, 22.7% have a low level (score 0-14), 43.7% a moderate level (score 15-22) and 33.6% a high level (score 23-29) of oral health literacy. The GOHAI scale reveals that 37.4% have a high self-perception of their oral health. A considerable proportion of the sample studied present a moderate level of oral health literacy. Therefore, educating each person about their oral health when participating in a specific health program and developing proposals for oral health promotion activities should be widely considered as a strategy towards primary prevention. Future oral health literacy sessions should be held in order to improve oral health and quality of life among the community.

Determinants and Practice Variability of Oxygen Administration during Surgery in the United States: A Retrospective Cohort Study.

BACKGROUND: The best approaches to supplemental oxygen administration during surgery remain unclear, which may contribute to variation in practice. This study aimed to assess determinants of oxygen administration and its variability during surgery. METHODS: Using multivariable linear mixed-effects regression, the study measured the associations between intraoperative fraction of inspired oxygen and patient, procedure, medical center, anesthesiologist, and in-room anesthesia provider factors in surgical cases of 120 min or longer in adult patients who received general anesthesia with tracheal intubation and were admitted to the hospital after surgery between January 2016 and January 2019 at 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry. RESULTS: The sample included 367,841 cases (median [25th, 75th] age, 59 [47, 69] yr; 51.1% women; 26.1% treated with nitrous oxide) managed by 3,836 anesthesiologists and 15,381 in-room anesthesia providers. Median (25th, 75th) fraction of inspired oxygen was 0.55 (0.48, 0.61), with 6.9% of cases less than 0.40 and 8.7% greater than 0.90. Numerous patient and procedure factors were statistically associated with increased inspired oxygen, notably advanced American Society of Anesthesiologists classification, heart disease, emergency surgery, and cardiac surgery, but most factors had little clinical significance (less than 1% inspired oxygen change). Overall, patient factors only explained 3.5% (95% CI, 3.5 to 3.5%) of the variability in oxygen administration, and procedure factors 4.4% (95% CI, 4.2 to 4.6%). Anesthesiologist explained 7.7% (95% CI, 7.2 to 8.2%) of the variability in oxygen administration, in-room anesthesia provider 8.1% (95% CI, 7.8 to 8.4%), medical center 23.3% (95% CI, 22.4 to 24.2%), and 53.0% (95% CI, 52.4 to 53.6%) was unexplained. CONCLUSIONS: Among adults undergoing surgery with anesthesia and tracheal intubation, supplemental oxygen administration was variable and appeared arbitrary. Most patient and procedure factors had statistical but minor clinical associations with oxygen administration. Medical center and anesthesia provider explained significantly more variability in oxygen administration than patient or procedure factors.

Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Mitochondrial CypD Acetylation Promotes Endothelial Dysfunction and Hypertension.

BACKGROUND: Nearly half of adults have hypertension, a major risk factor for cardiovascular disease. Mitochondrial hyperacetylation is linked to hypertension, but the role of acetylation of specific proteins is not clear. We hypothesized that acetylation of mitochondrial CypD (cyclophilin D) at K166 contributes to endothelial dysfunction and hypertension. METHODS: To test this hypothesis, we studied CypD acetylation in patients with essential hypertension, defined a pathogenic role of CypD acetylation in deacetylation mimetic CypD-K166R mutant mice and endothelial-specific GCN5L1 (general control of amino acid synthesis 5 like 1)-deficient mice using an Ang II (angiotensin II) model of hypertension. RESULTS: Arterioles from hypertensive patients had 280% higher CypD acetylation coupled with reduced Sirt3 (sirtuin 3) and increased GCN5L1 levels. GCN5L1 regulates mitochondrial protein acetylation and promotes CypD acetylation, which is counteracted by mitochondrial deacetylase Sirt3. In human aortic endothelial cells, GCN5L1 depletion prevents superoxide overproduction. Deacetylation mimetic CypD-K166R mice were protected from vascular oxidative stress, endothelial dysfunction, and Ang II-induced hypertension. Ang II-induced hypertension increased mitochondrial GCN5L1 and reduced Sirt3 levels resulting in a 250% increase in GCN5L1/Sirt3 ratio promoting CypD acetylation. Treatment with mitochondria-targeted scavenger of cytotoxic isolevuglandins (mito2HOBA) normalized GCN5L1/Sirt3 ratio, reduced CypD acetylation, and attenuated hypertension. The role of mitochondrial acetyltransferase GCN5L1 in the endothelial function was tested in endothelial-specific GCN5L1 knockout mice. Depletion of endothelial GCN5L1 prevented Ang II-induced mitochondrial oxidative stress, reduced the maladaptive switch of vascular metabolism to glycolysis, prevented inactivation of endothelial nitric oxide, preserved endothelial-dependent relaxation, and attenuated hypertension. CONCLUSIONS: These data support the pathogenic role of CypD acetylation in endothelial dysfunction and hypertension. We suggest that targeting cytotoxic mitochondrial isolevuglandins and GCN5L1 reduces CypD acetylation, which may be beneficial in cardiovascular disease.

Comparative Meta-Analysis of Minimally Invasive and Conventional Approaches for Caries Removal in Permanent Dentition.

Background and Objectives: Addressing deep carious lesions poses significant challenges in daily dental practice due to the inherent complexity of their treatment. Traditionally, complete removal of carious tissues has been the norm, potentially leading to pulp tissue exposure and subsequent pulpitis. In contemporary dentistry, there is a growing preference for minimally invasive techniques, such as selective removal, offering a more conservative approach with enhanced predictability and success rates. Materials and Methods: Our study commenced with a comprehensive systematic review. After that, we performed a meta-analysis focused exclusively on randomized controlled trials involving permanent dentition. Our investigation incorporated seven selected articles, which scrutinized success rates and the incidence of pulp exposure in minimally invasive techniques (MIT) versus conventional techniques (CT). Statistical analysis employed U Mann-Whitney and Wilcoxon tests to interpret the results. Results: Although the difference did not reach statistical significance, MIT demonstrated marginally superior success rates compared to CT. Furthermore, MIT exhibited a lower percentage of pulp exposure when contrasted with CT. However, due to the limited sample size, statistical significance for this difference could not be established. Conclusions: Minimally invasive techniques for caries removal emerge as a conservative and promising approach to safeguard pulp tissues in comparison to conventional techniques. The need for additional randomized controlled trials is emphasized to unequivocally establish the superior success rates of these procedures over their conventional counterparts.

Sipping a sustainable life: Exploring drivers and barriers in consumer attitudes toward non or low alcoholic spirits.

Alcohol consumption continues to be prevalent and is on the rise in many countries, posing a grave risk for the health and wellbeing of millions and creating a strain on health services worldwide. A hopeful trend has emerged, however, as consumers' growing preference for healthier, sustainable lifestyles has led traditional alcoholic brands to innovate, launching reduced or non-alcoholic (NoLo) options. This aligns with the SDGs and is reflected in NoLo spirits representing four of Spain's top ten disruptive innovations of 2022. This paper uses a mixed methodology in a qualitative-quantitative sequential approach to gain insight into this phenomenon. The study involved 13 in-depth interviews with HoReCa (an acronym for Hotels, Restaurants, and Caterings) professionals and four focus groups among consumers. Second, behavioral reasoning theory (BRT) was used in a quantitative study aiming to explore motivations for and against consuming NoLo spirits. Data from a survey of 620 participants was conducted and analyzed using SEM-PLS to measure the antecedents of consumer's behavioral intention towards NoLo spirits and to gauge the potential for marketing opportunities. The research reveals that the purchase intention of NoLo spirits is strongly related to health consciousness, while enjoying the effects of alcohol for fun and entertainment, and the social pressure to drink hinders its consumption. In addition, it was found that "reasons for" are more substantial than "reasons against" the consumption of those beverages, differing significantly by age group. Results offer implications for theory and practice, including recommendations for practitioners and regulators willing to improve sustainability in the industry. Further, this paper helps augment the innovation adoption literature by using BRT in the paradoxical context of consumers' increasing alcohol abuse despite their professed attempts to adopt healthier lifestyles.

Mineral and potentially toxic element profiles in the soil-feed-animal continuum: Implications for public, environmental, and livestock health in three pasture-based sheep farming systems.

Grazing livestock derive most of their mineral requirements from foraging. The presence of toxic elements in soils has become a significant concern for food safety and ecosystem services. Understanding the mineral content profiles in soil and forage is crucial for assessing animal health, predicting potential transfers of minerals or heavy metals into the food-chain, and assessing threats to the environment and human health. In this study, Na, Mg, P, K, Ca, Mn, Fe, Co, Cu, Zn, Se, As, Cd, Hg, and Pb were measured to determine the mineral status of three different pasture-based farming systems (with grazing sheep livestock) in a Spanish region of significant economic importance. A risk assessment evaluation of animal, environmental, and human health was performed on soil, forage, feed, serum, milk, and wool. Notably, traces of Pb, and As were identified in pastures in all farms. Our calculation of pollution indices revealed moderate levels of contamination by various elements, including Co, Cu, Zn, Se, As, Cd, Hg, and Pb. The two farms with more intense agrosystem practices showed a significant potential ecological risk, characterized by high soil levels of Hg and Cd. Animals from these farms also had high concentrations of these metals in wool. Although the target Hazard Quotient derived from milk consumption suggests that dairy products from this area are safe for consumption for adults, only milk from a dehesa farm (mix of woodland and pastureland) was free of potential health concerns related to Pb exposure. Our assessment of mineral profiles reveals a cohesive relationship between soil quality and derived animal products, particularly of the Merino sheep breeding and farming system. The results reveal the importance of adopting and reinforcing strategies to preserve dehesas as a sustainable and environmentally friendly agrosystem in the western Mediterranean region.

The Added Value of Face-to-Face Supervision to a Therapeutic Exercise-Based App in the Management of Patients with Chronic Low Back Pain: A Randomized Clinical Trial.

Low back pain (LBP) is a significant global health challenge due to its high prevalence, and chronicity and recurrence rates, with projections suggesting an increase in the next years due to population growth and aging. The chronic and recurrent nature of LBP, responsible for a significant percentage of years lived with disability, underscores the need for effective management strategies, including self-management strategies advocated by current guidelines, to empower patients and potentially improve healthcare efficiency and clinical outcomes. Therefore, the aim of this study was to analyze the added value of face-to-face visits in patients with chronic LBP undergoing a self-management program based on therapeutic exercises on pain intensity, disability, quality of life and treatment adherence and satisfaction. A randomized clinical trial was conducted, allocating 49 patients into a experimental group with a mobile health (mHealth) app usage and face-to-face sessions and 49 patients into an active control group without face-to-face sessions. Pain intensity, disability and quality of life were assessed at baseline, 4 weeks postintervention and 12 weeks postintervention. Patients' satisfaction and adherence were assessed at the end of the study. The multivariate general model revealed no statistically significant time × group interaction for any outcome (p > 0.0068) but mental quality of life (p = 0.006). Within-group differences revealed significant improvements for all the clinical indicators (all, p < 0.001). Patients allocated to the experimental group reported greater satisfaction and adherence (both, p < 0.001) compared to the control group. The use of mHealth apps such as Healthy Back® as part of digital health initiatives may serve as a beneficial approach to enhance the management of LBP.

[Hidradenitis suppurativa]. / Hidradenitis supurativa.

Hidradenitis suppurativa (HS) is a chronic and debilitating inflammatory disease derived from the pilosebaceous unit, that affects approximately 1% of the general population. Clinically, it is characterized by inflammatory nodules, abscesses, and tunnels in the intertriginous areas of the body, especially in the axillary, inguinal, and anogenital regions. The etiopathogenesis of HS is not completely understood, although it is considered to be multifactorial, and the result of a complex interaction between genetic, hormonal, environmental, and immunological factors. In this sense, several proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-L-1ß, and IL-17, among others, appear to play a crucial role in the pathogenesis of the disease. Currently, HS is recognized as a systemic disease associated with numerous comorbidities, including cardiovascular, immune-mediated, and endocrine-metabolic diseases. The treatment of HS must be carried out with an individualized and patient-oriented approach, considering medical and surgical treatment modalities.

Biomarker responses and lethal dietary doses of tau-fluvalinate and coumaphos in honey bees: Implications for chronic acaricide toxicity.

Evidence suggests that acaricide residues, such as tau-fluvalinate and coumaphos, are very prevalent in honey bee colonies worldwide. However, the endpoints and effects of chronic oral exposure to these compounds remain poorly understood. In this study, we calculated LC50 and LDD50 endpoints for coumaphos and tau-fluvalinate, and then evaluated in vivo and in vitro effects on honey bees using different biomarkers. The LDD50 values for coumaphos were 0.539, and for tau-fluvalinate, they were 12.742 in the spring trial and 8.844 in the autumn trial. Chronic exposure to tau-fluvalinate and coumaphos resulted in significant changes in key biomarkers, indicating potential neurotoxicity, xenobiotic biotransformation, and oxidative stress. The Integrated Biomarker Response was stronger for coumaphos than for tau-fluvalinate, supporting their relative lethality. This study highlights the chronic toxicity of these acaricides and presents the first LDD50 values for tau-fluvalinate and coumaphos in honey bees, providing insights into the risks faced by colonies.

Aerobic Exercise and Neuropathic Pain: Insights from Animal Models and Implications for Human Therapy.

This narrative review explores the complex relationship between aerobic exercise (AE) and neuropathic pain (NP), particularly focusing on peripheral neuropathies of mechanical origin. Pain, a multifaceted phenomenon, significantly impacts functionality and distress. The International Association for the Study of Pain's definition highlights pain's biopsychosocial nature, emphasizing the importance of patient articulation. Neuropathic pain, arising from various underlying processes, presents unique challenges in diagnosis and treatment. Our methodology involved a comprehensive literature search in the PubMed and SCOPUS databases, focusing on studies relating AE to NP, specifically in peripheral neuropathies caused by mechanical forces. The search yielded 28 articles and 1 book, primarily animal model studies, providing insights into the efficacy of AE in NP management. Results from animal models demonstrate that AE, particularly in forms like no-incline treadmill and swimming, effectively reduces mechanical allodynia and thermal hypersensitivity associated with NP. AE influences neurophysiological mechanisms underlying NP, modulating neurotrophins, cytokines, and glial cell activity. These findings suggest AE's potential in attenuating neurophysiological alterations in NP. However, human model studies are scarce, limiting the direct extrapolation of these findings to human neuropathic conditions. The few available studies indicate AE's potential benefits in peripheral NP, but a lack of specificity in these studies necessitates further research. In conclusion, while animal models show promising results regarding AE's role in mitigating NP symptoms and influencing underlying neurophysiological mechanisms, more human-centric research is required. This review underscores the need for targeted clinical trials to fully understand and harness AE's therapeutic potential in human neuropathic pain, especially of mechanical origin.