Search

1. Changes in nasal airways resistance (NAR) following the topical application of histamine and allergen solutions were measured by passive anterior rhinomanometry. 2. The repeatability of five consecutive measurements of resting NAR prior to provocation with histamine or allergen (expressed as the coefficient of variation) was 32.8% and following instillation of saline control solution 37.2%. 3. The repeatability of five consecutive measurements of NAR during the nasal obstruction produced by histamine and allergen was similar to that recorded prior to provocation; the coefficients of variation (median values) being 39.6% and 33.1% respectively. The degree of variability was not related to the dose of agonist or the degree of nasal obstruction. 4. The reproducibility of histamine or allergen induced changes in NAR on four separate weekly occasions showed no significant intra-subject differences. 5. The effects of sodium cromoglycate (SCG), clemastine and ketotifen administered to the nasal mucosa 30 min before provocation with histamine and allergen were compared in a random order, double-blind, placebo controlled study. 6. Clemastine and SCG, but not ketotifen, significantly inhibited the nasal response to increasing concentrations of histamine. None of the drugs administered in the concentrations used in this study significantly inhibited the nasal response to allergen. [ABSTRACT FROM AUTHOR]

Objective: To ascertain the impact of prior antiplatelet and statin therapy on symptomatic embolic events in [corrected] infective endocarditis (IE).Patients and Methods: We studied a retrospective cohort of adult patients with a diagnosis of IE who presented to Mayo Clinic (Rochester, MN) from January 1, 2003, to December 31, 2006. Patients were grouped into those who received treatment before infection or controls who did not receive treatment for both antiplatelet therapy and, separately, statin therapy. Because of the retrospective study design and thus the nonrandomized treatment groups, a propensity score approach was used to account for the confounding factors that may have influenced treatment allocation. Antiplatelet therapy included aspirin, dipyridamole, clopidogrel, ticlopidine or any combination of these agents. Statin therapy included atorvastatin, simvastatin, pravastatin, lovastatin, rosuvastatin, or fluvastatin. The primary end point was a symptomatic embolic event that occurred before or during hospitalization. Multivariable logistic regression was used to assess the propensity-adjusted effects of continuous daily therapy with antiplatelet and statin agents on risk of symptomatic emboli. Likewise, Cox proportional hazards regression was used to test for an independent association with 6-month mortality for each of the treatments.Results: The study cohort comprised 283 patients with [corrected] IE. Twenty-eight patients (24.1%) who received prior continuous antiplatelet therapy developed a symptomatic embolic event compared with 66 (39.5%) who did not receive such treatment. After adjusting for propensity to treat, the effect of antiplatelet therapy on embolic risk was not statistically significant (odds ratio, 0.71; 95% confidence interval [CI], 0.37-1.36; P=.30). Only 14 patients (18.2%) who received prior continuous statin therapy developed a symptomatic embolic event compared with 80 (39.4%) of the 203 patients who did not. After adjusting for propensity to treat with statin therapy, the benefit attributable to statins was significant (odds ratio, 0.30; 95% CI, 0.14-0.62; P=.001). The 6-month mortality rate of the entire cohort was 28% (95% CI, 23%-34%). No significant difference was found in the propensity-adjusted rate of 6-month mortality between patients who had and had not undergone prior antiplatelet therapy (P=.91) or those who had and had not undergone prior statin therapy (P=.87).Conclusion: The rate of symptomatic emboli associated with IE was reduced in patients who received continuous daily statin therapy before onset of IE. Despite fewer embolic events observed in patients who received antiplatelet agents, a significant association was not found after adjusting for propensity factors. A continued evaluation of these drugs and their potential impact on subsequent embolism among IE patients is warranted. [ABSTRACT FROM AUTHOR]

The current study begins by optimizing the deucravacitinib molecule in the gas phase at the ωB97XD/cc-pVDZ level of theory using density functional theory and proceeds to study its intramolecular interactions. Further, a molecule of EtOH was introduced at different locations on the deucravacitinib molecule, and the noncovalent interactions arising from them were also investigated using several computational tools. In this way, eight deucravacitinib-EtOH systems ( 1-8 ) were identified and their electronic environment was studied after evaluating their binding energy. Using natural bond orbital analysis, the localization of charges between the donor and acceptor fragments in these interacting systems was examined. The nature of interactions was analyzed using the reduced gradient approach (NCI analysis), and few hydrogen bonding interactions (intermolecular and intramolecular) were found in each system. The strength of these hydrogen bonding interactions was further investigated by using theoretical tools such as atoms in molecules analysis and independent gradient model based on Hirshfeld partition analysis. The binding energy of deucravacitinib with EtOH was decomposed into energy components based on the domain-based local pair natural orbital coupled cluster technique using LED analysis. The results from the hydrogen bonding interaction analysis using different computational tools were found to be consistent with the calculated order of binding energy of systems 1-8 and they also pointed toward the higher stability of system 3 .

Introduction Myocardial infarction (MI) in young South Indians presents a shifting epidemiological landscape, challenging traditional perceptions of cardiovascular diseases. This study investigates the clinical and angiographic profiles of MI in this subgroup of the population in detail, emphasizing the interaction between lifestyle, environmental, and genetic factors that contribute to the incidence of MI in younger people. Methodology Utilizing a descriptive observational design, the study analyzed data from 70 young adults (aged 18-45 years) admitted to Frontier Lifeline Hospital, Chennai, with acute MI over six months. Patient demographics, clinical characteristics, and angiographic findings were collected and analyzed using standardized protocols. Statistical analysis employed chi-square tests and subgroup analyses to assess associations and differences between diabetic and non-diabetic patients. Results The study revealed a predominance of males (84.29%) among MI cases, with ST-elevation myocardial infarction (STEMI) being the most common presentation (52.86%). Anterior wall involvement was prevalent (50%), and left ventricular systolic dysfunction (LVSD) was observed in the majority (67%) of patients. Chest pain (87%) was the predominant symptom, and diabetes (47%) and hypertension (47%) were the risk variables that were most common. Angiographically, the left anterior descending artery (LAD) was often affected (51%), with single-vessel disease predominating (41.43%). Conclusion The findings underscore the significance of early detection and intervention strategies for MI in young South Indians. Gender-specific risk assessment, prompt diagnosis, and tailored treatment approaches are imperative. The high prevalence of LVSD highlights the burden of cardiac morbidity, particularly in diabetic individuals. Lifestyle modifications and weight management interventions are crucial for MI prevention. This study provides insights into the frequency and features of MI in young South Indians, emphasizing the importance of collaborative efforts for early identification and control of modifiable risk factors to mitigate the burden of coronary artery disease (CAD) in this population subset., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee (IEC), Frontier Lifeline Hospital issued approval FLL/IEC/04/2019. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Prakash et al.)

Background: Emergency medicine (EM) trainee comfort level with lumbar puncture (LP) has decreased over time due to changing practice guidelines, particularly amongst pediatric patients. We implemented a "just in time" (JIT) brief educational video based on a previously published LP Performance Scoring Checklist to improve trainee efficiency and competence in LP performance., Methods: Our pilot quasi-experimental study took place January-June 2022 within a large, academic Midwestern emergency department (ED) with an established 3-year EM residency program. All 9 interns performed a timed diagnostic LP on an infant LP model in January, scored according to the LP Performance Scoring Checklist. In June, interns repeated the timed LP procedure directly after watching a brief educational video based on major checklist steps. The study was deemed exempt by the Institutional Review Board., Results: All interns completed both assessments. At baseline, interns had logged performance of median 2 (IQR 0-5) LPs and spent 12.9 (10.3-14.4) minutes performing the procedure. Post-intervention, interns had logged an additional median 2 (0-5) LPs and completed the procedure faster with an average time of 10.3 (9.7-11.3) minutes (p = 0.004). A median of 5 (4-7) major steps were missed at baseline, compared to 1 (1-2) at time of post-intervention assessment (p = 0.015)., Conclusion: Development of a brief educational video improved efficiency and competency amongst our intern class in performing an infant LP when viewed Just-In-Time. Similar efforts may improve education and performance of other rare (or decreasing in frequency) procedures within EM training., (© 2024. The Author(s).)

Background: Exposure to social norms about fruit and vegetable intake has been shown to increase individuals' consumption of these foods. Further, exposure to socially endorsed 'healthy' food posts can increase consumption of low energy-dense (LED), relative to high energy-dense (HED) foods. The current pilot study aimed to investigate whether exposure to healthy eating (vs. control) social media accounts can shift normative perceptions about what others eat, eating intentions and self-reported food consumption., Methods: In a 2 (condition) × 2 (type of food consumed) mixed factorial design, 52 male and female students were asked to follow either healthy eating (intervention) or interior design (control) Instagram accounts over a two-week period. Baseline and post-intervention measures assessed normative perceptions of Instagram users' consumption of fruit and vegetables (LED foods), and energy dense snacks and sugar sweetened beverages (HED foods). Participants' intentions to consume, and self-reported consumption of these foods, were also measured., Results: There were no significant changes in perceptions about what others eat, or participants' own eating intentions ( p s > 0.05). However, the intervention increased participants' self-reported consumption of LED foods by 1.37 servings (per day) and decreased consumption of HED foods by 0.81 items (per day), compared to the control condition ( ps  < 0.05)., Conclusions: This novel pilot study demonstrates that a social norm-based social media intervention can successfully encourage healthier eating, with a large effect after two weeks. Certain social media platforms may therefore provide a viable tool for nudging healthy eating. Future work will aim to replicate these findings in a larger and more diverse sample., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Cycloplatination of symmetrical N , N ', N ''-triarylguanidines, (ArNH) 2 C[double bond, length as m-dash]NAr with cis -[Pt(TFA) 2 (S(O)Me 2 ) 2 ] in toluene afforded cis -[Pt(TAG)(TFA)(S(O)Me 2 )] (TAG = triarylguanidinate(1-)-κ C ,κ N ; TFA = OC(O)CF 3 ; 6-9) in 75-82% yields. The reactions of 6-9 and the previously known cis -[Pt(TAG)X(S(O)Me 2 )] (X = Cl (1) and TFA (2-5)) with acetylacetone (acacH) or 2-picolinic acid (picH) in the presence of a base afforded [Pt(TAG)(acac)] (acac = acetylacetonate-κ 2 O , O '; 10-18) and [Pt(TAG)(pic)] (pic = 2-picolinate-κ N ,κ O ; 19) in high yields. The new complexes were characterised by analytical, IR and multinuclear NMR spectroscopies. Further, molecular structures of 11, 12, 13·0.5 toluene and 14-19 were determined by single crystal X-ray diffraction. Absorption spectra of 10-19 in solution and their emission spectra in crystalline form were measured. Platinacycles 10-19 are bluish green light emitter in the crystalline form, and emit in the λ PL = 488-529 nm range (11 and 13-19) while 12 emits at λ PL = 570 nm. Unlike other platinacycles, the emission band of 12 is broad, red shifted, and this pattern is ascribed to the presence of an intermolecular N-H⋯Pt interaction involving the endocyclic amino unit of the six-membered [Pt(TAG)] ring and the Pt(ii) atom in the adjacent molecule in an asymmetric unit of the crystal lattice. Lifetime measurements were carried out for all platinacycles in crystalline form, which revealed lifetime in the order of nanoseconds. The origin of absorption and emission properties of 11, 15, 18 and 19 were studied by TD-DFT calculations., Competing Interests: There is no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Triple-negative breast cancer (TNBC) is a leading cause of cancer mortality and lacks modern therapy options. Modulated electro-hyperthermia (mEHT) is an adjuvant therapy with demonstrated clinical efficacy for the treatment of various cancer types. In this study, we report that mEHT monotherapy stimulated interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) expression, and consequently cyclooxygenase 2 (COX-2), which may favor a cancer-promoting tumor microenvironment. Thus, we combined mEHT with nonsteroid anti-inflammatory drugs (NSAIDs): a nonselective aspirin, or the selective COX-2 inhibitor SC236, in vivo. We demonstrate that NSAIDs synergistically increased the effect of mEHT in the 4T1 TNBC model. Moreover, the strongest tumor destruction ratio was observed in the combination SC236 + mEHT groups. Tumor damage was accompanied by a significant increase in cleaved caspase-3, suggesting that apoptosis played an important role. IL-1β and COX-2 expression were significantly reduced by the combination therapies. In addition, a custom-made nanostring panel demonstrated significant upregulation of genes participating in the formation of the extracellular matrix. Similarly, in the B16F10 melanoma model, mEHT and aspirin synergistically reduced the number of melanoma nodules in the lungs. In conclusion, mEHT combined with a selective COX-2 inhibitor may offer a new therapeutic option in TNBC., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background : Maximizing survival for patients with primary cutaneous melanomas (melanomas) depends on an early diagnosis and appropriate management. Several new drugs have been shown to improve survival in high-risk melanoma patients. Despite well-documented guidelines, many patients do not receive optimal management, particularly when considering patient age. Objective : to provide an update on melanoma management from the time of the decision to biopsy a suspicious skin lesion. Methods : We reviewed melanoma-management research published between 2018 and 2023 and identified where such findings impact and update the management of confirmed melanomas. Pubmed, Google Scholar, Ovid and Cochrane Library were used as search tools. Results : We identified 81 publications since 2017 that have changed melanoma management; 11 in 2018, 12 in 2019, 10 in 2020, 12 in 2021, 17 in 2022 and 18 in 2023. Discussion : Delayed or inaccurate diagnosis is more likely to occur when a partial shave or punch biopsy is used to obtain the histopathology. Wherever feasible, a local excision with a narrow margin should be the biopsy method of choice for a suspected melanoma. The Breslow thickness of the melanoma remains the single most important predictor of outcome, followed by patient age and then ulceration. The BAUSSS biomarker, (Breslow thickness, Age, Ulceration, Subtype, Sex and Site) provides a more accurate method of determining mortality risk than older currently employed approaches, including sentinel lymph node biopsy. Patients with metastatic melanomas and/or nodal disease should be considered for adjuvant drug therapy (ADT). Further, high-risk melanoma patients are increasingly considered for ADT, even without disease spread. Invasive melanomas less than 1 mm thick are usually managed with a radial excision margin of 10 mms of normal skin. If the thickness is 1 to 2 mm, select a radial margin of 10 to 20 mm. When the Breslow thickness is over 2 mm, a 20 mm clinical margin is usually undertaken. In situ melanomas are usually managed with a 5 to 10 mm margin or Mohs margin control surgery. Such wide excisions around a given melanoma is the only surgery that can be regarded as therapeutic and required. Patients who have had one melanoma are at increased risk of another melanoma. Ideal ongoing management includes regular lifelong skin checks. Total body photography should be considered if the patient has many naevi, especially when atypical/dysplastic naevi are identified. Targeted approaches to improve occupational or lifestyle exposure to ultraviolet light are important. Management also needs to include the consideration of vitamin D supplementary therapy.

Circadian rhythms differ between young adult males and females. For example, males tend to be later chronotypes, preferring later timing of sleep and activity, than females. Likewise, there are sex differences in body composition and cardiorespiratory fitness. Few studies have investigated the association between circadian rhythms, cardiorespiratory fitness, and body composition. We sought to determine whether chronotype and circadian phase were associated with cardiorespiratory fitness, body composition, and anthropometric measures in sedentary males and females. Fifty-nine adults participated in the study. Circadian phase and chronotype were measured using dim light melatonin onset (DLMO) and the Morningness-Eveningness Questionnaire (MEQ) score. We used peak oxygen uptake (VO 2peak ) results from a maximal graded exercise test to assess cardiorespiratory fitness. Body composition, BMI, and circumferences were collected as markers of adiposity. We observed a sex difference in the association between DLMO and VO 2peak . For males, a later DLMO was associated with a lower VO 2peak . VO 2peak did not vary based on DLMO in females. Later circadian phase was also associated with increased body fat percentage, fat mass index, and abdominal circumference in males, but not females. Collectively, these results suggest that males who are later chronotypes may be at risk of obesity and low cardiorespiratory fitness., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)