MetSCORE: a molecular metric to evaluate the risk of metabolic syndrome based on serum NMR metabolomics.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. METHODS: We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. RESULTS: We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920-0.952, p < 0.001). MetSCORE is also able to discriminate the intermediate phenotypes, identifying the early risk of MetS in a quantitative way and ranking individuals according to their risk of undergoing MetS (for general population) or according to the severity of the syndrome (for MetS patients). CONCLUSIONS: We believe that MetSCORE may be an insightful tool for early intervention and lifestyle modifications, potentially preventing the aggravation of metabolic syndrome.

Postural tremor and sexual chromosome aneuploidies: case report and review of literature.

PURPOSE: To examine the link between tremor and sex chromosome abnormalities, emphasizing the necessity of comprehensive physical examination. CASE DESCRIPTION: An 18-year-old man exhibited an isolated action tremor in both hands. Despite having no familial history of tremors and no identifiable secondary causes, his tall stature and learning difficulties suggested a genetic origin. His karyotype confirmed the diagnosis of Jacob's syndrome (XYY syndrome). Therapies with primidone and propranolol were ineffective for his tremor. CONCLUSIONS: Tremor can be caused by various conditions, and aneuploidies might often be overlooked as a cause. They should be considered in young patients with concrete phenotypes and negative familiar history of tremors. Karyotyping is a cost-effective diagnostic tool crucial for genetic counselling. Common treatments for tremors often yield unsatisfactory results in these cases.

The Expression of Alamandine Receptor MrgD in Clear Cell Renal Cell Carcinoma Is Associated with a Worse Prognosis and Unfavorable Response to Antiangiogenic Therapy.

Renal cell carcinoma (RCC) ranks among the most prevalent malignancies in Western countries, marked by its notable heterogeneity, which contributes to an unpredictable clinical trajectory. The insufficiency of dependable biomarkers adds complexity to assessing this tumor progression. Imbalances of several components of the intrarenal renin-angiotensin system (iRAS) significantly impact patient prognoses and responses to first-line immunotherapies. In this study, we analyzed the immunohistochemical expression of the Mas-related G-protein-coupled receptor D (MrgD), which recognizes the novel RAS peptide alamandine (ALA), in a series of 87 clear cell renal cell (CCRCCs), 19 papillary (PRCC), 7 chromophobe (ChRCC) renal cell carcinomas, and 11 renal oncocytomas (RO). MrgD was expressed in all the renal tumor subtypes, with a higher mean staining intensity in the PRCCs, ChRCCs, and ROs. A high expression of MrgD at the tumor center and at the infiltrative front of CCRCC tissues was significantly associated with a high histological grade, large tumor diameter, local invasion, and locoregional node and distant metastasis. Patients with worse 5-year cancer-specific survival and a poorer response to antiangiogenic tyrosine-kinase inhibitors (TKIs) showed higher MrgD expression at the center of their primary tumors. These findings suggest a possible role of MrgD in renal carcinogenetic processes. Further studies are necessary to unveil its potential as a novel biomarker for CCRCC prognosis and response to frontline therapies.

Modelling and testing forest ecosystems condition account.

We developed an application model based on the System of Environmental Economic Accounting-Ecosystem Accounting (SEEA-EA) framework, endorsed by the United Nations Statistical Commission in 2021. This model enables mapping condition accounts for forest ecosystems using automated computation. We applied the model nationally in Spain between 2000 and 2015 to test its effectiveness. Our model follows five methodological steps to generate forest condition accounts: (i) definition and spatial delimitation of forest ecosystem types; (ii) selection of variables using the ecosystem condition typology encompassing physical, chemical, compositional, structural, functional, and landscape characteristics; (iii) establishment of reference levels, including lower (collapse) and upper (high ecosystem integrity) thresholds; (iv) aggregation of variables into condition index; and (v) calculation of a single condition index by rescaling the aggregated indicators between 0 and 1. The results obtained from the model provide valuable insights into the status and trends of individual condition indicators, as well as aggregated condition index values for forest ecosystems, in a spatially explicit manner. Overall, the condition of the forest ecosystems in Spain showed a slight increase, from 0.56 in 2000 to 0.58 in 2015. However, distinct trends were observed for each ecosystem type. For example, mixed Alpine and Macaronesia forests exhibited a significant improvement, while the continental Mediterranean coniferous forests did not show any change. This innovative approach to monitoring forest condition accounts has important potential applications in policy and decision-making processes. It can contribute to effective evidence-based nature conservation, ecosystem service management, and identifying restoration areas.

Percutaneous ablation of malignant and locally aggressive solid tumors in pediatric patients.

Image-guided percutaneous ablation is an accepted treatment modality for common adult cancers. Unfortunately, its use in patients younger than 18 years is rare. This retrospective review presents our series of pediatric patients treated with ablation at our institution. From January 2002 to December 2021, a total of 14 patients (17 lesions) younger than 18 years were treated with percutaneous image-guided ablation. Estimated overall survival at 5 years was 58%; median survival of this group was not reached. Estimated local tumor progression-free survival at 5 years was 62%. One major complication was recorded.

Abnormal photoplethysmography waveforms are associated with chemotherapy induced neuropathy.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-dependent adverse event of many chemotherapy agents that affects autonomic, motor, and sensory nerve fibers. The purpose of this study is to describe abnormal photoplethysmography waveforms (PPGs) in the setting of CIPN in cancer patients screened for peripheral arterial disease (PAD), which to our knowledge has not been previously described. Patients and methods: 147 patients who underwent vascular physiologic testing in evaluation for PAD with an ankle brachial index (ABI) or toe brachial index (TBI), segmental pressures, pulse volume recordings, and toe PPGs, in a tertiary cancer center's vascular lab between January 1, 2019 and January 31, 2021 were included in the study. Results: Odds ratio analysis demonstrates 3 times increased odds of abnormal PPGs in patients with PAD (OR 3.2256 95% CI 1.523-6.832, p=0.002), 7 times increased odds of abnormal PPGs in patients with CIPN (OR 7.802 95% CI 3.606-16.880, p<0.001), 9 times increased odds of abnormal PPGs in patients with both CIPN and PAD (9.895 95% CI 2.643-37.043, p=0.001), and 7 times increased odds of abnormal PPGs in patients with chemotherapy agent known to cause CIPN (7.821 95% CI 3.619-16.902, p<0.001). Logistic regression demonstrated that PAD (coefficient 1.171 std. error 0.383 wald 9.354 p=0.002), CIPN (coefficient 2.054 std. error 0.394 wald 27.227 p<0.001), and chemo agent known to cause CIPN (coefficient 2.057 std. error 0.393 wald 27.370 p<0.001) were all predictors of abnormal PPGs. Conclusions: CIPN had greater odds for abnormal PPGs than PAD. Additional larger studies are needed to assess if PPG analysis could be utilized to assess for early diagnosis of CIPN.

The effect of cannabidiol on sevoflurane minimum alveolar concentration reduction produced by morphine in rats.

OBJECTIVE: To investigate the effect of cannabidiol (CBD) on sevoflurane minimum alveolar concentration (MACSEV) reduction produced by morphine in rats. STUDY DESIGN: Randomized, blinded trial. ANIMALS: A total of 75 male Wistar Han rats weighing 276 ± 23 g (mean and standard deviation), aged 3 months. METHODS: Cannabidiol (CBD) was prepared in an ethanol-solutol-saline vehicle. Animals were randomly divided into 15 groups and given an intraperitoneal bolus of 1, 3, 5, 6.5, 7.5 or 10 mg kg-1 of CBD alone (CBD1, CBD3, CBD5, CBD6.5, CBD7.5 and CBD10 respectively) or combined with 5 mg kg-1 of morphine (MOR+CBD1, MOR+CBD3, MOR+CBD5, MOR+CBD6.5, MOR+CBD7.5 and MOR+CBD10). While three controls groups: MOR+saline, MOR+vehicle and vehicle were given an intraperitoneal bolus of morphine with saline, morphine with vehicle or vehicle alone respectively. The MACSEV was determined from alveolar gas samples at the time of tail clamp application. The MACSEV reduction was analyzed using a one-way ANOVA followed by Tukey's test. Additionally, Kruskal-Wallis test for non-normally-distributed data was performed. Data are presented as mean ± standard deviation. P < 0.05 RESULTS: The mean MACSEV was not reduced by the action of CBD administered alone, but the addition of morphine to the different doses of CBD significantly reduced the MACSEV. That reduction was greatest in the MOR+CBD1, MOR+CBD7.5 and MOR+CBD10 groups (29 ± 5%, 32 ± 5% and 30 ± 6% respectively), less in MOR+CBD3 and MOR+CBD6.5 groups (24 ± 3% and 26 ± 4% respectively) and least in MOR+CBD5 group (17 ± 2%). However, only the MOR+CBD5 group was statistically significantly different from MOR+CBD1, MOR+CBD7.5 and MOR+CBD10 groups. CONCLUSIONS AND CLINICAL RELEVANCE: MACSEV in rat was unaltered by the action of CBD alone, the reduction in MACSEV produced by morphine was not enhanced by the addition of CBD at the doses studied.

Cannabidiol reduces lung injury induced by hypoxic-ischemic brain damage in newborn piglets.

BackgroundBrain hypoxic-ischemic (HI) damage induces distant inflammatory lung damage in newborn pigs. We aimed to investigate the effects of cannabidiol (CBD) on lung damage in this scenario.MethodsNewborn piglets received intravenous vehicle, CBD, or CBD+WAY100635 (5-HT1A receptor antagonist) after HI brain damage (carotid flow interruption and FiO2 0.10 for 30 min). Total lung compliance (TLC), oxygenation index (OI), and extravascular lung water content (EVLW) were monitored for 6 h. Histological damage, interleukin (IL)-1ß concentration, and oxidative stress were assessed in brain and lung tissue. Total protein content was determined in bronchoalveolar lavage fluid (BALF).ResultsCBD prevented HI-induced deleterious effects on TLC and OI and reduced lung histological damage, modulating inflammation (decreased leukocyte infiltration and IL-1 concentration) and reducing protein content in BALF and EVLW. These effects were related to CBD-induced anti-inflammatory changes in the brain. HI did not increase oxidative stress in the lungs. In the lungs, WAY100635 blunted the beneficial effects of CBD on histological damage, IL-1 concentration, and EVLW.ConclusionsCBD reduced brain HI-induced distant lung damage, with 5-HT1A receptor involvement in these effects. Whether the effects of CBD on the lungs were due to the anti-inflammatory effects on the brain or due to the direct effects on the lungs remains to be elucidated.

Hypoxic-ischemic brain damage induces distant inflammatory lung injury in newborn piglets.

BACKGROUND: We aimed to investigate whether neonatal hypoxic-ischemic (HI) brain injury induces inflammatory lung damage. METHODS: Thus, hypoxic (HYP, FiO2 10% for 30 min), ischemic (ISC, bilateral carotid flow interruption for 30 min), or HI event was performed in 1-2-d-old piglets. Dynamic compliance (Cdyn), oxygenation index (OI), and extravascular lung water (EVLW) were monitored for 6 h. Then, histologic damage was assessed in brain and lung (lung injury severity score). Total protein content (TPC) was determined in broncoalveolar lavage fluid (BALF), and IL-1ß concentration was measured in lung and brain tissues and blood. RESULTS: Piglets without hypoxia or ischemia served as controls (SHM). HI-induced brain damage was associated with decreased Cdyn, increased OI and EVLW, and histologic lung damage (interstitial leukocyte infiltration, congestive hyperemia, and interstitial edema). BALF TPC was increased, suggesting inflammatory damage. In agreement, tissue IL-1ß concentration increased in the brain and lung, in correspondence with increased IL-1ß serum concentration. Neither HYP nor ISC alone led to brain or lung damage. CONCLUSION: HI brain damage in newborn piglets led to inflammatory lung damage, suggesting an additional mechanism accounting for the development of lung dysfunction after neonatal HI encephalopathy.

Effect of the I/E ratio on CO2 removal during high-frequency oscillatory ventilation with volume guarantee in a neonatal animal model of RDS.

UNLABELLED: The objective of this study was to analyze the effect of I/E ratio on carbon dioxide (CO2) elimination during high-frequency oscillatory ventilation (HFOV) combined with volume guarantee (VG). Five 2-day-old piglets were studied before and after a bronchoalveolar lavage (BAL). The effect of an I/E ratio of 1:1 and 1:2 with (VG-ON) and without VG (VG-OFF) on PaCO2, as well as delta and mean airway pressures at the airway opening (∆Phf-ao, mPaw-ao) and at the tracheal level (∆Phf-t, mPaw-t) were evaluated at frequencies of 5, 8, 11, and 14 Hz. With the VG-ON, PaCO2 was significant lower with the I/E ratio of 1:2 at 5 Hz compared with the 1:1. mPaw-t was higher than mPaw-ao, with 1:1 I/E ratio, and on VG-ON, this difference was statistically significant. CONCLUSION: "In this animal study and with this ventilator, the I/E ratio of 1:1 compared to 1:2 in HFOV and VG-ON did not produce a higher CO2 lavage as when HFOV was used without the VG modality. Even more, a lower PaCO2 was found when using the lower frequency and 1:2 ratio compared to 1:1. So in contrast to non-VG HFOV mode, using a fixed tidal volume, no significant changes on CO2 elimination are observed during HFOV when the I/E ratios of 1:1 and 1:2 are compared at different frequencies." WHAT IS KNOWN: •The tidal volume on HFOV is determinant in CO 2 removal, and this is generated by delta pressure and the length of the inspiratory time. What is New: •HFOV combined with VG, an I/E ratio of 1:2 is more effective to remove CO 2 , and this is not related to the tidal volume.

Single-syringe ketamine-propofol for induction of anaesthesia in rabbits.

OBJECTIVE: To evaluate and compare three intravenous (IV) doses of a ketamine-propofol admixture (ketofol) for induction of anaesthesia in unpremedicated rabbits. STUDY DESIGN: Prospective, randomized 'blinded' trial. ANIMALS: Twenty-one healthy female New Zealand rabbits weighing 2.7 ± 0.1 kg. METHODS: Animals were allocated randomly into three groups of seven animals and received 1 (KP1), 3 (KP3) or 5 (KP5) mg kg(-1) of both ketamine and propofol in a 1:1 mg kg(-1) ratio admixture. Cardiorespiratory parameters and arterial blood gases were measured at baseline, 2 and 5 minutes after drug administration. The time to loss of the righting reflex (LORR) and the duration of action and apnoea were recorded. The quality of induction and intubation were scored. Data were compared using a two-way anova or a t-test for unpaired data, as relevant. RESULTS: The time to LORR was the shortest (11 ± 5 seconds) and the duration of action the longest (374 ± 26 seconds) in group KP5. Group KP1 did not lose the righting reflex; instead mild to moderate sedation was observed in this group. The quality of induction in group KP5 was smooth, but ranged from smooth to fair in group KP3. Intubation was not possible in the KP1 group, and 10 animals in the other two groups showed some resistance to intubation. At 2 and 5 minutes, the pulse rate was significantly higher in all three groups compared with baseline, but no statistical differences were seen in arterial blood pressures. Hypoxaemia and dose-dependent respiratory depression were observed in all groups, with periods of apnoea in the KP5 group. CONCLUSIONS AND CLINICAL RELEVANCE: The IV ketamine-propofol admixture had a dose-dependent effect. Haemodynamic function was well maintained in all groups but hypoxemia was observed at the highest doses and oxygen administration is recommended. Addition of premedication or topical lidocaine is advisable to make intubation easier.

Effects of intramuscular dexmedetomidine in combination with ketamine or alfaxalone in swine.

OBJECTIVE: To evaluate and compare the use of intramuscular (IM) premedication with dexmedetomidine in combination with ketamine or alfaxalone in pigs. STUDY DESIGN: Prospective, randomized, 'blinded' trial. ANIMALS: Fourteen healthy 2-month-old Landrace × Large White pigs weighing 21.5 ± 0.6 kg. METHODS: Animals were distributed randomly into two groups: group KD (n = 7) was given 10 mg kg(-1) IM ketamine + 10 µg kg(-1) IM dexmedetomidine; and group AD (n = 7) was given 5 mg kg(-1) IM alfaxalone + 10 µg kg(-1) IM dexmedetomidine mixed in the same syringe. Pain on injection, degree of sedation and quality of induction were scored. The time from induction of anaesthesia to recumbency was recorded. Once pigs were recumbent, reflexes were evaluated. Pulse and respiratory rates, end-tidal carbon dioxide and arterial oxygen saturation were recorded at 5 and 10 minutes after drug administration. Data were compared using a two-way anova or a t-test for unpaired data as relevant. Data are presented as the mean ± standard deviation (range). RESULTS: Two animals in both groups showed slight pain on drug injection. The time to lateral recumbency in group KD [187 ± 34 seconds (153-230)] was similar to group AD [206 ± 36 seconds (150-248)]. In group AD, sedation was deeper, and the quality of anaesthetic induction was smoother. When moved for anaesthesia, five pigs in group KD vocalized. There were no differences between groups in pulse rates, arterial oxygen saturation and end-tidal carbon dioxide; however, the respiratory rate at 10 minutes was significantly higher in group KD than in group AD. CONCLUSIONS AND CLINICAL RELEVANCE: IM dexmedetomidine in combination with ketamine in pigs induced moderate to deep sedation and fair to smooth induction of anaesthesia. When dexmedetomidine was combined with alfaxalone, sedation was deeper, and induction was of a better quality.

Exploring the Capacity of Water Framework Directive Indices to Assess Ecosystem Services in Fluvial and Riparian Systems: Towards a Second Implementation Phase.

We explored the capacity of the biological and hydromorphological indices used in the Water Framework Directive (WFD) to assess ecosystem services by evaluating the ecological status of Spanish River Basins. This analysis relies on an exhaustive bibliography review which showed scientific evidence of the interlinkages between some ecosystem services and different hydromorphological and biological elements which have been used as indices in the WFD. Our findings indicate that, of a total of 38 ecosystem services analyzed, biological and hydromorphological indices can fully evaluate four ecosystem services. In addition, 18 ecosystem services can be partly evaluated by some of the analyzed indices, while 11 are not related with the indices. While Riparian Forest Quality was the index that was able to assess the largest number of ecosystem services (N = 12), the two indices of macrophytes offered very poor guarantees. Finally, biological indices related to diatoms and aquatic invertebrates and the Fluvial Habitat Index can be related with 7, 6, and 6 ecosystem services, respectively. Because the WFD indices currently used in Spain are not able to assess most of the ecosystem services analyzed, we suggest that there is potential to develop the second phase of the WFD implementation taking this approach into consideration. The incorporation of the ecosystem services approach into the WFD could provide the framework for assess the impacts of human activities on the quality of fluvial ecosystems and could give insights for water and watershed management in order to guarantee the delivery of multiple ecosystem services.

[Interventional radiology: current problems and new directions]. / Radiología intervencionista. Problemas actuales y nuevos caminos.

In recent years, vascular and interventional radiology has become one of the fastest growing diagnostic and therapeutic specialties. This growth has been based on a fundamental concept: performing minimally invasive procedures under imaging guidance. This attractive combination has led to the interest of professionals from other clinical specialties outside radiology in performing this type of intervention. The future of vascular and interventional radiology, although uncertain, must be linked to clinical practice and multidisciplinary teamwork.

Modeling the cortical response elicited by wrist manipulation via a nonlinear delay differential embedding.

Regarding motor processes, modeling healthy people's brains is essential to understand the brain activity in people with motor impairments. However, little research has been undertaken when external forces disturb limbs, having limited information on physiological pathways. Therefore, in this paper, a nonlinear delay differential embedding model is used to estimate the brain response elicited by externally controlled wrist movement in healthy individuals. The aim is to improve the understanding of the relationship between a controlled wrist movement and the generated cortical activity of healthy people, helping to disclose the underlying mechanisms and physiological relationships involved in the motor event. To evaluate the model, a public database from the Delft University of Technology is used, which contains electroencephalographic recordings of ten healthy subjects while wrist movement was externally provoked by a robotic system. In this work, the cortical response related to movement is identified via Independent Component Analysis and estimated based on a nonlinear delay differential embedding model. After a cross-validation analysis, the model performance reaches 90.21% ± 4.46% Variance Accounted For, and Correlation 95.14% ± 2.31%. The proposed methodology allows to select the model degree, to estimate a general predominant operation mode of the cortical response elicited by wrist movement. The obtained results revealed two facts that had not previously been reported: the movement's acceleration affects the cortical response, and a common delayed activity is shared among subjects. Going forward, identifying biomarkers related to motor tasks could aid in the evaluation of rehabilitation treatments for patients with upper limbs motor impairments.

Trispecific anti-CD3/BCMA/CD38 antibodies for multiple myeloma: a patent evaluation of US20240132615.

INTRODUCTION: CD38 and BCMA are proteins expressed at high levels in multiple myeloma cells, so they are targets for the development of mono- or multispecific antibodies. AREAS COVERED: patent US20240132615 describes anti-CD3/BCMA/CD38 trispecific antibodies and a method of treating relapsed/refractory multiple myeloma pharmaceutically. In vitro and preclinical results show that anti-CD3/BCMA/CD38 trispecific antibodies have stronger binding affinity and killing potency compared to daratumumab, isatuximab, and teclistamab antibodies. EXPERT OPINION: the trispecific structure and a silenced Fc is a pharmaceutical advantage of the anti-CD3/BCMA/CD38 antibody for the treatment of relapsed or refractory multiple myeloma.

Patenting trends in the pharmaceutical field of Mexican universities.

Aim: pharmaceutical patenting activity in developing countries, including Mexico, is unknown. Objective: determine the activity of pharmaceutical patents by Mexican universities. Method: using 'university' as keyword and A61K, A61P and C07 as International Patent Classification codes, was searched to generate a perspective of pharmaceutical patent applications by Mexican universities. Results: 227 patents (186 granted patents + 41 not-granted patents) were claimed in the period 2000-2018. The leading university was the National Autonomous University of Mexico, followed by the Instituto Politecnico Nacional, Universidad Autonoma de Nuevo León and Universidad Autonoma de Puebla. The pharmaceutical concerns addressed were led by the fields of infectious, cancer and diabetes. Conclusion: in Mexican universities, the licensing of pharmaceutical patents is still in its early stages.

Comprehensive and High-Throughput Method for Quantitative Fingerprinting of Phenolic Compounds.

Accurate, robust, and wide-coverage analytical tools are needed in polyphenol research to deal with the high physicochemical complexity of the secondary plant metabolome. In this chapter, a novel method based on reversed-phase ultrahigh-performance liquid chromatography coupled with a diode array detector and mass spectrometry is presented, which enables high-throughput, comprehensive, and quantitative fingerprinting of a broad spectrum of phenolic compounds and related metabolites in different food products. The simplicity, low-cost, and excellent analytical performance of this method would facilitate its implementation in food science for quality control and authenticity purposes.

Drug repurposing of rimantadine for treatment of cancer.

Repurposing of approved drugs allows strong savings in time and investment. Rimantadine is an FDA-approved drug for prevention and treatment of influenza A infection. Patent US2021330605 describes the use of rimantadine, an adamantane derivative, for the treatment of melanoma, breast cancer and head and neck squamous cell carcinoma. Rimantadine inhibited proliferation of cell lines of melanoma, breast cancer, and head and neck squamous cell carcinoma, increased the survival of mice injected with cancer cell lines and restores the expression of MHC class I. Rimantadine has the potential to be used successfully in the treatment of head and neck squamous cell carcinoma.