Updating and profiling the natural product-likeness of Latin American compound libraries.

Compound databases of natural products play a crucial role in drug discovery and development projects and have implications in other areas, such as food chemical research, ecology and metabolomics. Recently, we put together the first version of the Latin American Natural Product database (LANaPDB) as a collective effort of researchers from six countries to ensemble a public and representative library of natural products in a geographical region with a large biodiversity. The present work aims to conduct a comparative and extensive profiling of the natural product-likeness of an updated version of LANaPDB and the individual ten compound databases that form part of LANaPDB. The natural product-likeness profile of the Latin American compound databases is contrasted with the profile of other major natural product databases in the public domain and a set of small-molecule drugs approved for clinical use. As part of the extensive characterization, we employed several chemoinformatics metrics of natural product likeness. The results of this study will capture the attention of the global community engaged in natural product databases, not only in Latin America but across the world.

Cognitive phenotypes in patients with drug-resistant temporal lobe epilepsy: Relationships with cortisol and affectivity.

OBJECTIVE: Drug-resistant temporal lobe epilepsy (TLE) is a neurological disorder characterized by cognitive deficits. This study examined whether patients with TLE and different cognitive phenotypes differ in cortisol levels and affectivity while controlling for demographic and clinical variables. Methods: In this cross-sectional study, 79 adults with TLE underwent neuropsychological evaluation in which memory, language, attention/processing speed, executive function, and affectivity were assessed. Six saliva samples were collected in the afternoon to examine the ability of the hypothalamic-pituitary-adrenal (HPA) axis to descend according to the circadian rhythm (C1 to C6). The cortisol area under the curve concerning ground (AUCg) was computed to examine global cortisol secretion. RESULTS: Three cognitive phenotypes were identified: memory impairment, generalized impairment, and no impairment. The memory-impairment phenotype showed higher cortisol levels at C4, C5, and C6 than the other groups (p = 0.03, η2 = 0.06), higher cortisol AUCg than the generalized-impairment phenotype (p = 0.004, η2 = 0.14), and a significant reduction in positive affectivity after the evaluation (p = 0.026, η2 = 0.11). Higher cortisol AUCg and reductions in positive affectivity were significant predictors of the memory-impairment phenotype (p < 0.001; Cox and Snell R2 = 0.47). CONCLUSIONS: Patients with memory impairment had a slower decline in cortisol levels in the afternoon, which could be interpreted as an inability of the HPA axis to inhibit itself. Thus, chronic stress may influence hippocampus-dependent cognitive function more than other cognitive functions in patients with TLE.

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference.

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference. DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill children. DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements. CONCLUSIONS: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials.

Management of Extracorporeal Membrane Oxygenation Anticoagulation in the Perioperative Period: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic review-informed, modified Delphi consensus regarding the management of children on extracorporeal membrane oxygenation (ECMO) undergoing invasive procedures or interventions developed by the Pediatric Anticoagulation on ECMO CollaborativE (PEACE) Consensus Conference. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: ECMO anticoagulation and hemostasis management in the perioperative period and during procedures. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. Seventeen references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. DATA SYNTHESIS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. Four good practice statements, 7 recommendations, and 18 consensus statements are presented. CONCLUSIONS: Although agreement among experts was strong, important future research is required in this population for evidence-informed recommendations.

Symptomatology in Unilateral Versus Bilateral Superior Canal Dehiscence Patients Undergoing Unilateral Surgery.

OBJECTIVE: To compare symptomatology in patients with unilateral versus bilateral superior semicircular canal dehiscence who underwent unilateral surgical repair. STUDY DESIGN: Retrospective cohort study. SETTING: Single surgeon series at tertiary academic medical center from 2002 to 2021. METHODS: Patients were administered a standardized questionnaire regarding the presence or absence of 16 symptoms (11 auditory and 8 vestibular) pre- and postoperatively. Symptom rates were compared between patients with unilateral and bilateral dehiscence, and paired statistical testing was used to analyze symptom improvement with surgery. RESULTS: Our final cohort included 125 patients, 93 (74%) with unilateral superior canal dehiscence syndrome (SCDS) and 32 (26%) with bilateral SCDS. Bilateral patients had an increased burden of auditory and vestibular symptoms compared to unilateral patients before surgery (7.6 vs 6.2, P = .03) and after surgery (3.1 vs 1.9, P = .02). Both groups experienced a significant reduction of symptoms following repair (P < .01 for both). CONCLUSION: Our study has 2 key findings: First, patients with bilateral dehiscence seem to be more symptomatic, reporting more auditory and vestibular symptoms both before and after surgery. Second, bilateral patients still seem to benefit from unilateral repair, demonstrating a significant reduction in the number of symptoms with surgery. Our findings may help inform the management of the sizable proportion of SCDS patients with bilateral defects.

Clostridium perfringens Empyema: Anaerobic Invasion in an Uncommon Location.

Clostridium perfringens bacteremia arises due to skin inoculation from the external environment or translocation from the gastrointestinal tract. In the event of bacteremia, it tends to colonize in anaerobic environments due to its obligatory anaerobic nature. Its inoculation in the lung, albeit rare, can occur if an anaerobic nidus is created. In the presented case, the patient developed C. perfringens bacteremia andempyema in the area of lung necrosis caused by acute pulmonary embolism. He did not have any history of chest trauma, and the source of bacteremia was deemed to be via gut translocation. The patient was noted to have multiple gastric ulcers on endoscopy and jejunal wall thickening, which likely led to the bacterial translocation into the bloodstream. He underwent video-assisted thoracoscopic surgery-assisted decortication and intravenous antibiotics, eventually leading to clinical improvement. To identify the source of Clostridium in the absence of penetrating trauma, a thorough gastrointestinal evaluation, including a colonoscopy, is warranted to identify the pathology leading to the gastrointestinal translocation.

Clinical Course and Outcomes of Autoimmune Versus Non-Autoimmune Surgically Induced Scleral Necrosis: A Multicentric Comparative Study.

BACKGROUND: To analyze the clinical course and outcomes of autoimmune vs. non-autoimmune surgically induced scleral necrosis (SISN). METHODS: Multicentric, retrospective, comparative cohort study. Eighty-two eyes of 70 patients with SISN were classified according to pathogenic mechanism into autoimmune vs. non-autoimmune. Main outcome measures included necrosis onset, type of surgery, associated systemic disease, visual acuity, and treatment were analysed in patients followed for ≥ 6 months. RESULTS: Forty-six (65.7%) patients were women, and the median age was 66 (range: 24-90) years. Most patients (82.9%) had unilateral disease. The median time between surgery and SISN onset was 58 (1-480) months. Thirty-one (37.8%) eyes were classified as autoimmune, and 51 (62.2%) as non-autoimmune SISN. Autoimmune SISN was associated with a shorter time between the surgical procedure and SISN onset than non-autoimmune cases (median of 26 vs. 60 months, p = 0.024). Also, autoimmune SISN was associated with cataract extraction (93.5% vs. 25.5%, p < 0.001), severe scleral inflammation (58.1% vs. 17.6%, p < 0.001), and higher incidence of ocular complications (67.7% vs. 33.3%, p = 0.002) than non-autoimmune cases. Remission was achieved with medical management alone in 44 (86.3%) eyes from the non-autoimmune and in 27 (87.1%) from the autoimmune group (p = 0.916). Surgical management was required in 11 (13.4%) eyes, including two requiring enucleations due to scleral perforation and phthisis bulbi. CONCLUSIONS: Eyes with autoimmune SISN had a higher rate of cataract surgery, severe scleral inflammation, and ocular complications. Early SISN diagnosis and appropriate management, based on clinical features and pathogenic mechanisms, are critical to avoid sight-threatening complications.

Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status.

ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age-related diseases. Here, we show that hepatic phospho-active ACLY correlates with overweight and Model for End-stage Liver Disease score in humans. Wild-type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB-204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy-fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. In vivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy-fed mice, and improved locomotion in mice exposed to cardiotoxin-induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration.

Balance in Transition: Unraveling the Link Between Menopause and Vertigo.

The onset of menopause, marked by hormonal fluctuations and a decline in estrogen levels, is suggested to be linked to increased susceptibility to vestibular disturbances. Estrogen, beyond its established association with reproductive physiology, plays modulatory roles in various physiological systems, including neurosensory function. The vestibular system, crucial for balance and spatial orientation, is influenced by hormonal changes during menopause, potentially contributing to the emergence of vertigo symptoms. This interplay between hormones and the vestibular system is a burgeoning area of research with clinical implications, offering insights into novel diagnostic and therapeutic approaches for managing postmenopausal women with vestibular disorders. The article reviews current scientific literature, delves into the hormonal intricacies of menopause, and investigates potential mechanisms underlying the connection between hormonal fluctuations and vertigo symptoms.

High potential extracts from cocoa byproducts through sonotrode optimal extraction and a comprehensive characterization.

Cocoa pod husk (CPH) and cocoa bean shell (CBS) are by-products obtained during pre-processing and processing of cocoa beans. Several bioactive compounds have been identified in these by-products that can be used for commercial applications as a way to promote the circular economy. Therefore, the objective of this paper was to recover bioactive compounds from CPH and CBS by sonoextraction process, to determine the type, content, and antioxidant activity in optimized extracts. To achieve our purpose, an optimization strategy using Box-Behnken Design coupled response surface methodology (MRS) was applied. The extraction conditions were optimized. The results obtained for CBS were: TPC (193 mg GAE/g), TEAC (1.02 mmol TE/g), FRAP (1.02 mmol FeSO4/g) and ORAC (2.6 mmol TE/g), while for CPH, the reported values were: TPC (48 mg GAE/g), TEAC (0.30 mmol TE/g), FRAP (0.35 mmol FeSO4/g) and ORAC (0.43 mmol TE/g) under the optimized conditions: Time (XA): 15 min, Amplitude (XB): 80 %, Ethanol (XC): 50 %. The LC-ESI-qTOF-MS analysis results allowed the identification of 79 compounds, of which 39 represent the CBS extract, while 40 compounds were identified in CPH extract. To conclude, sonotrode based extraction could be considered as an efficient and fast alternative for the recovery of bioactive substances from CBS and CPH.

The Effect of Resistance Training with Outdoor Fitness Equipment on the Body Composition, Physical Fitness, and Physical Health of Middle-Aged and Older Adults: A Randomized Controlled Trial.

This study examined the effect of outdoor-fitness-equipment-based resistance training on the health parameters of middle-aged and older adults, as well as analyzing the effect of age on the results found. A total of 149 volunteers were randomly assigned to the training (TG) and control (CG) groups. The TG performed two weekly sessions of resistance training for 8 weeks using outdoor fitness equipment, while the CG continued with their regular daily activities. Body composition was measured using DXA, and the maximal isometric voluntary contraction in knee extension, elbow flexion, and hand grip were assessed, along with the 4 m walk test, the Timed Up and Go Test, and the Short Form 36 Health Survey Questionnaire. The TG showed a significant increase in the lean mass index (p = 0.002) and maximal isometric voluntary contraction in both legs (p < 0.001) and arms (p < 0.001), as well as in physical functioning (p < 0.001) and the role physical dimension (p = 0.006) of the Short Form 36 Health Survey Questionnaire, compared to the CG, which showed a decrease in all these variables. In addition, the TG showed a greater decrease in fat mass (p < 0.001), fat mass index (p = 0.003), and the Timed Up and Go Test (p < 0.001) than the CG. Age conditioned the evolution of most of the variables analyzed (p < 0.05). In conclusion, resistance training with outdoor fitness equipment may be useful for improving the health of middle-aged and older adults, although age is a factor that could influence the adaptations found.

Bioactive Compounds and Potential Health Benefits through Cosmetic Applications of Cherry Stem Extract.

Cherry stems, prized in traditional medicine for their potent antioxidant and anti-inflammatory properties, derive their efficacy from abundant polyphenols and anthocyanins. This makes them an ideal option for addressing skin aging and diseases. This study aimed to assess the antioxidant and anti-inflammatory effects of cherry stem extract for potential skincare use. To this end, the extract was first comprehensively characterized by HPLC-ESI-qTOF-MS. The extract's total phenolic content (TPC), antioxidant capacity, radical scavenging efficiency, and its ability to inhibit enzymes related to skin aging were determined. A total of 146 compounds were annotated in the cherry stem extract. The extract effectively fought against NO· and HOCl radicals with IC50 values of 2.32 and 5.4 mg/L. Additionally, it inhibited HYALase, collagenase, and XOD enzymes with IC50 values of 7.39, 111.92, and 10 mg/L, respectively. Based on the promising results that were obtained, the extract was subsequently gently integrated into a cosmetic gel at different concentrations and subjected to further stability evaluations. The accelerated stability was assessed through temperature ramping, heating-cooling cycles, and centrifugation, while the long-term stability was evaluated by storing the formulations under light and dark conditions for three months. The gel formulation enriched with cherry stem extract exhibited good stability and compatibility for topical application. Cherry stem extract may be a valuable ingredient for creating beneficial skincare cosmeceuticals.

Targeting bacterial growth in biofilm conditions: rational design of novel inhibitors to mitigate clinical and food contamination using QSAR.

Antimicrobial resistance (AMR) is a pressing global issue exacerbated by the abuse of antibiotics and the formation of bacterial biofilms, which cause up to 80% of human bacterial infections. This study presents a computational strategy to address AMR by developing three novel quantitative structure-activity relationship (QSAR) models based on molecular topology to identify potential anti-biofilm and antibacterial agents. The models aim to determine the chemo-topological pattern of Gram (+) antibacterial, Gram (-) antibacterial, and biofilm formation inhibition activity. The models were applied to the virtual screening of a commercial chemical database, resulting in the selection of 58 compounds. Subsequent in vitro assays showed that three of these compounds exhibited the most promising antibacterial activity, with potential applications in enhancing food and medical device safety.

[Feeling analysis on allergen immunotherapy on Twitter using an unsupervised machine learning model]. / Análisis de sentimientos acerca de la inmunoterapia con alérgenos en Twitter mediante un modelo de aprendizaje automático no supervisado.

OBJECTIVE: Analyze feelings about allergen-specific immunotherapy on Twitter using the VADER model VADER (Valence Aware Dictionary and sEntiment Reasoner) model. METHODS: tweets related to specific allergen immunotherapy were obtained through the Twitter Application Programming Interface (API). The keywords "allergy shot" were used between January 1, 2012, and December 31, 2022. The data was processed by removing URLs, usernames, hashtags, multiple spaces, and duplicate tweets. Subsequently, a sentiment analysis was performed using the VADER model. RESULTS: A total of 34,711 tweets were retrieved, of which 1928 were eliminated. Of the remaining 32,783 tweets, 32.41% expressed a negative sentiment, 31.11% expressed a neutral sentiment, and 36.47% expressed a positive sentiment, with an average polarity of 0.02751 (neutral) over the 11-year period. CONCLUSIONS: The average polarity of tweets about allergen-specific immunotherapy is neutral over the 11 years analyzed. There was an annual increase in the average polarity over the years, with 2017, 2018, and 2022 having positive polarity averages. Additionally, the number of tweets decreased over time.

OBJETIVO: Analizar los sentimientos acerca de la inmunoterapia alérgeno-específica en Twitter mediante el modelo VADER (Valence Aware Dictionary and sEntiment Reasoner). MÉTODOS: Se utilizaron tweets relacionados con la inmunoterapia alérgeno-específica obtenidos a través del API (Application Programming Interface) de Twitter. Se incorporaron las palabras clave "allergy shot" en el período comprendido entre el 1 de enero de 2012 y el 31 de diciembre de 2022. Los datos obtenidos fueron procesados, eliminando las URL, nombres de usuarios, hashtags, espacios múltiples y tweets duplicados. Posteriormente, se realizó un análisis de sentimientos utilizando el modelo VADER. RESULTADOS: Se recolectaron 34,711 tweets, de los que se eliminaron 1928. De los 32,783 tweets restantes, se encontró que el 32.41% de los usuarios expresó un sentimiento negativo, el 31.11% un sentimiento neutral y el 36.47% un sentimiento positivo, con una media de polaridad de 0.02751 (neutral) a lo largo de los 11 años. CONCLUSIONES: La polaridad media de los tweets acerca de la inmunoterapia alérgeno-específica es neutral a lo largo de los 11 años analizados. Existe un aumento anual en la polaridad media positiva a lo largo de los años, sobre todo entre 2017, 2018 y 2022. La cantidad de tweets disminuyó con el tiempo.

Diagnostic Yield of Patients Undergoing Evaluation of Possible Superior Canal Dehiscence.

OBJECTIVE: To characterize the diagnostic yield of patients undergoing evaluation for superior canal dehiscence syndrome (SCDS), and identify alternative conditions diagnosed in patients suspected of, but not ultimately diagnosed with, SCDS. METHODS: Diagnostically undifferentiated adult patients suspected of having SCDS were identified between 2016 and 2021 at a tertiary academic medical system. Patients were categorized by diagnostic testing, radiographic superior semicircular canal (SSC) abnormality, symptoms, evaluating clinician specialty, operative intervention, and diagnosis. Differences among groups were assessed for statistical significance. RESULTS: Of 1242 candidate patients, 477 met inclusion criteria-evaluation by a clinician with SCDS on their differential diagnosis prior to diagnostic imaging. The mean (SD) age was 53.0 (15.0) years and 70.6% were female. A total of 364 patients underwent subsequent diagnostic imaging, and among these, 164 (45.1%) had a radiographic SSC abnormality with 99 (27.2%) receiving a diagnosis of SCDS (two cases of "near dehiscence syndrome"). One third (33.3%) of patients with SCDS underwent operative repair. Most clinicians with the initial suspicion for SCDS were otolaryngologists (90.6%), who had greater diagnostic yield than clinicians from other specialties (22.2% vs. 6.7%, p = 0.012). Patients not diagnosed with SCDS alternatively received 21 unique diagnoses and 52.1% (138/265) were not definitively diagnosed with any condition. CONCLUSIONS: This study characterizes the diagnostic incidence, or yield, of newly identified radiographic SSC abnormalities (45.1%) and SCDS (27.2%) among people suspected of having SCDS. Considerable overlap in presentation between SCDS and other conditions exists, and there is need for improvement in efficiently diagnosing patients with SCDS and audio-vestibular complaints in general. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

Ocular Mucous Membrane Pemphigoid: The Effect of Risk Factors at Presentation on Treatment Outcomes.

PURPOSE: Analyze the influence of risk factors at presentation in the long-term immunosuppressive therapy (IMT) outcomes of ocular mucous membrane pemphigoid (OMMP). DESIGN: Retrospective multicenter study. PARTICIPANTS: Patients with OMMP seen at the Duke Eye Center, Tecnologico de Monterrey, and Hospital Clinic of Barcelona from 1990 to 2022. METHODS: Data at presentation on demographics, direct immunofluorescence, ocular findings, sites of extraocular manifestations (EOMs), and previous treatments in patients with a clinical or laboratory diagnosis of OMMP, were analyzed with multivariable analysis and Kaplan-Meier plots to identify factors associated with adverse outcomes. MAIN OUTCOME MEASURES: (1) Inflammatory control (no conjunctival inflammation in both eyes at 3 months on IMT); (2) relapse (new-onset inflammation after absolute control in either eye); (3) progression (≥ 1 cicatrizing stage progression in either eye); and (4) vision loss (≥ 2 Snellen lines). RESULTS: A total of 117 patients (234 eyes), 61% (71/117) of whom were women, with a mean age of 66.6 (SD: 12.4) years (range: 37-97 years) and median follow-up of 34 months (interquartile range: 16-66 months; range: 3-265 months), were enrolled. Inflammatory control was achieved in 57% of patients (67/117), with high-risk EOM (HR-EOM), including esophageal, nasopharyngeal, and/or genital involvement (adjusted odds ratio [aOR]: 12.51; 95% confidence interval [CI]: 2.61-59.99; P = 0.002) and corneal scarring (aOR: 3.06; 95% CI, 1.15-8.14; P = 0.025), as significant risk factors for persistent inflammation. Disease relapse, progression, and vision loss occurred in 20% of patients (23/117), 12% of patients (14/117), and 27% of patients (32/117), respectively. Baseline corneal scarring was a risk factor for relapse (adjusted hazard ratio: 4.14; 95% CI: 1.61-10.62; P = 0.003), progression (aOR: 11.46; 95% CI: 1.78-73.75; P = 0.010), and vision loss (aOR: 3.51; 95% CI: 1.35-9.10; P = 0.010). HR-EOM was associated with stage progression (aOR, 34.57; 95% CI, 6.57-181.89; P<0.001) and vision loss (aOR, 8.42; 95% CI, 2.50-28.42; P = 0.001). No significant differences were found between IMT regimes and relapse (P = 0.169). CONCLUSIONS: Ocular mucous membrane pemphigoid presenting with HR-EOMs and corneal scarring has an increased risk of stage progression and vision loss. Corneal scarring and severe inflammation at baseline were associated with an increased risk of relapse. A disease progression staging system incorporating both the HR-EOMs and corneal involvement is required to predict the visual outcome of OMMP better. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.