Emergence of Quantum Dots as Innovative Tools for Early Diagnosis and Advanced Treatment of Breast Cancer.

Quantum dots (QDs) semiconducting nanomaterials, have garnered attention due to their distinctive properties, including small size, high luminescence, and biocompatibility. In the context of triple-negative breast cancer (TNBC), notorious for its resistance to conventional treatments, QDs exhibit promising potential for enhancing diagnostic imaging and providing targeted therapies. This review underscores recent advancements in the utilization of QDs in imaging techniques, such as fluorescence tomography and magnetic resonance imaging, aiming at the early and precise detection of tumors. Emphasis is placed on the significance of QD design, synthesis and functionalization processes as well as their use in innovative strategies for targeted drug delivery, capitalizing on their ability to selectively deliver therapeutic agents to cancer cells. As the research in this field advances rapidly, this review covers a classification of QDs according to their composition, the characterization techniques than can be used to determine their properties and, subsequently, emphasizes recent findings in the field of TNBC-targeting, highlighting the imperative need to address challenges, like potential toxicity or methodologies standardization. Collectively, the findings explored thus far suggest that QDs could pave the way for early diagnosis and effective therapy of TNBC, representing a significant stride toward precise and personalized strategies in treating TNBC.

Modelling the spatial risk of malaria through probability distribution of Anopheles maculipennis s.l. and imported cases.

Malaria remains one of the most important infectious diseases globally due to its high incidence and mortality rates. The influx of infected cases from endemic to non-endemic malaria regions like Europe has resulted in a public health concern over sporadic local outbreaks. This is facilitated by the continued presence of competent Anopheles vectors in non-endemic countries.We modelled the potential distribution of the main malaria vector across Spain using the ensemble of eight modelling techniques based on environmental parameters and the Anopheles maculipennis s.l. presence/absence data collected from 2000 to 2020. We then combined this map with the number of imported malaria cases in each municipality to detect the geographic hot spots with a higher risk of local malaria transmission.The malaria vector occurred preferentially in irrigated lands characterized by warm climate conditions and moderate annual precipitation. Some areas surrounding irrigated lands in northern Spain (e.g. Zaragoza, Logroño), mainland areas (e.g. Madrid, Toledo) and in the South (e.g. Huelva), presented a significant likelihood of A. maculipennis s.l. occurrence, with a large overlap with the presence of imported cases of malaria.While the risk of malaria re-emergence in Spain is low, it is not evenly distributed throughout the country. The four recorded local cases of mosquito-borne transmission occurred in areas with a high overlap of imported cases and mosquito presence. Integrating mosquito distribution with human incidence cases provides an effective tool for the quantification of large-scale geographic variation in transmission risk and pinpointing priority areas for targeted surveillance and prevention.

Landscape and mosquito community impact the avian Plasmodium infection in Culex pipiens.

Avian malaria parasites provide an important model for studying host-pathogen interactions, yet understanding their dynamics in vectors under natural conditions is limited. We investigated the effect of vector abundance, species richness and diversity, and habitat characteristics on avian Plasmodium prevalence and lineage richness in Culex pipiens across 45 urban, natural, and rural localities in southern Spain. Analyzing 16,574 mosquitoes grouped in 768 mosquito pools, 32.7% exhibited parasite presence. 13 different Plasmodium lineages were identified, with the lineage SYAT05 being the most commonly found. Parasite prevalence positively correlated with the distance to saltmarshes and rivers, but negatively with the distance to total water source. Parasite lineage diversity was higher in natural than in rural areas and positively correlated with mosquito species richness. These results emphasize the complex dynamics of avian Plasmodium in the wild, with habitat characteristics and vector community driving the parasite transmission by mosquito vectors.

Efficacy of radiofrequency in lumbar facet joint pain: a systematic review and meta-analysis of placebo-controlled randomized controlled trials.

BACKGROUND: Lumbar facet joint pain (LFJP) is one of the main causes of chronic low back pain (LBP) and can be treated using radiofrequency (RF) sensory denervation. The aim of this work is to analyze the efficacy of RF in LFJP through a systematic review and meta-analysis of randomized controlled trials (RCTs) with placebo control. MATERIALS AND METHODS: A systematic search was conducted in the Medline (PubMed), Scopus, Web of Science databases, and the Cochrane Central Register of Controlled Trials (CENTRAL). The variables of interest were pain, functional status, quality of life (QoL), and global perceived effect (GPE) measured at different time intervals: short (< 3 months), medium (> 3 and < 12 months), and long term (> 12 months). RESULTS: Eight RCTs with placebo control were included. RF showed significant benefits over placebo in pain relief in the short (MD - 1.01; 95% CI - 1.98 to -0.04; p = 0.04), medium (MD - 1.42; 95% CI - 2.41 to - 0.43; p = 0.005), and long term (MD - 1.12; 95% CI - 1.57 to - 0.68; p < 0.001), as well as improvement in functional disability in the short (SMD - 0.94; 95% CI - 1.73 to - 0.14; p = 0.02) and long term (SMD - 0.74; 95% CI - 1.09 to - 0.39; p < 0.001). No statistically significant differences were observed in QoL or quantitative GPE, but benefits for RF were observed in dichotomous GPE in the medium (OR 0.19; 95% CI 0.07-0.52; p = 0.001) and long term (OR 0.22; 95% CI 0.06-0.78; p = 0.02). Subgroup analyses showed more benefits for RF in LBP < 1 year in the short term and in RCTs that did not require performing an MRI for patient selection. CONCLUSIONS: RF demonstrated significant improvement in pain and functionality, but the benefits in terms of QoL and GPE are inconclusive. Future clinical trials should investigate the long-term effects of RF, its impact on quality of life, and define appropriate criteria for patient selection.

Clinical practice guideline on the management of vestibular schwannoma.

INTRODUCTION: Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. The greater accessibility to radiological tests has increased its diagnosis. Taking into account the characteristics of the tumour, the symptoms and the age of the patient, three therapeutic strategies have been proposed: observation, surgery or radiotherapy. Choosing the most appropriate for each patient is a frequent source of controversy. MATERIAL AND METHODS: This paper includes an exhaustive literature review of issues related to VS that can serve as a clinical guide in the management of patients with these lesions. The presentation has been oriented in the form of questions that the clinician usually asks himself and the answers have been written and/or reviewed by a panel of national and international experts consulted by the Otology Commission of the SEORL-CCC. RESULTS: A list has been compiled containing the 13 most controversial thematic blocks on the management of VS in the form of 50 questions, and answers to all of them have been sought through a systematic literature review (articles published on PubMed and Cochrane Library between 1992 and 2023 related to each thematic area). Thirty-three experts, led by the Otology Committee of SEORL-CCC, have analyzed and discussed all the answers. In Annex 1, 14 additional questions divided into 4 thematic areas can be found. CONCLUSIONS: This clinical practice guideline on the management of VS offers agreed answers to the most common questions that are asked about this tumour. The absence of sufficient prospective studies means that the levels of evidence on the subject are generally medium or low. This fact increases the interest of this type of clinical practice guidelines prepared by experts.

Vanadocene-functionalized mesoporous silica nanoparticles: platforms for the development of theranostic materials against breast cancer.

Nanoscale materials have demonstrated a very high potential in anticancer therapy by properly adjusting their functionalization and physicochemical properties. Herein, we report the synthesis of some novel vanadocene-loaded silica-based nanomaterials incorporating four different S-containing amino acids (penicillamine, methionine, captopril, and cysteine) and different fluorophores (rhodamine B, coumarin 343 or Alexa Fluor™ 647), which have been characterized by diverse solid-state spectroscopic techniques viz; FTIR, diffuse reflectance spectroscopies,13C and51V solid-state NMR spectroscopy, thermogravimetry and TEM. The analysis of the biological activity of the novel vanadocene-based nanostructured silicas showed that the materials containing cysteine and captopril aminoacids demonstrated high cytotoxicity and selectivity against triple negative breast cancer cells, making them very promising antineoplastic drug candidates. According to the biological results it seems that vanadium activity is connected to its incorporation through the amino acid, resulting in synergy that increases the cytotoxic activity against cancer cells of the studied materials presumably by increasing cell internalization. The results presented herein hold significant potential for future developments in mesoporous silica-supported metallodrugs, which exhibit strong cytotoxicity while maintaining low metal loading. They also show potential for theranostic applications highlighted by the analysis of the optical properties of the studied systems after incorporating rhodamine B, coumarin 343 (possible)in vitroanticancer analysis, or Alexa Fluor™ 647 (in vivostudies of cancer models).

Melatonin Derivative-Conjugated Formulations of Pd(II) and Pt(II) Thiazoline Complexes on Mesoporous Silica to Enhance Cytotoxicity and Apoptosis against HeLa Cells.

The search for alternatives to cisplatin has led to the development of new metal complexes where thiazoline derivatives based on platinum(II) and palladium(II) stand out. In this sense, the Pt(II) and Pd(II) complexes coordinated with the thiazoline derivative ligand 2-(3,4-dichlorophenyl)imino-N-(2-thiazolin-2-yl)thiazolidine (TdTn), with formula [PtCl2(TdTn)] and [PdCl2(TdTn)], have previously shown good results against several cancer lines; however, in this work, we have managed to improve their activity by supporting them on mesoporous silica nanoparticles (MSN). The incorporation of metal compounds with a melatonin derivative (5-methoxytryptamine, 5MT), which is a well-known antioxidant and apoptosis inducer in different types of cancer, has been able to increase the cytotoxic activity of both MSN-supported and isolated complexes with only a very low amount (0.35% w/w) of this antioxidant. The covalently functionalized systems that have been synthesized are able to increase selectivity as well as accumulation in HeLa cells. The final materials containing the metal complexes and 5MT (MSN-5MT-PtTdTn and MSN-5MT-PdTdTn) required up to nine times less metal to achieve the same cytotoxic activity than their corresponding non-formulated counterparts did, thus reducing the potential side effects caused by the use of the free metal complexes.

The Educational Impact of Radiology in Anatomy Teaching: A Field Study Using Cross-Sectional Imaging and 3D Printing for the Study of the Spine.

INTRODUCTION: Cross-sectional imaging and 3D printing represent state-of-the-art approaches to improve anatomy teaching compared to traditional learning, but their use in medical schools remains limited. This study explores the utility of these educational tools for teaching normal and pathological spinal anatomy, aiming to improve undergraduate medical education. MATERIALS AND METHODS: A field study was conducted on a cohort of undergraduate medical students who were exposed to anatomy lessons of the spine considering three learning paradigms: traditional learning, cross-sectional imaging examinations, and 3D printed models. 20 students (intervention group) received the three approaches, and other 20 students (control group) received the conventional (traditional) approach. The students were examined through a multiple-choice test and their results were compared to those of a control group exposed to traditional learning matched by age, sex and anatomy grades. In addition, students in the experimental group were assessed for their satisfaction with each learning method by means of an ad hoc questionnaire. RESULTS: Students exposed to cross-sectional imaging and 3D printing demonstrated better knowledge outcomes compared to the control group. They showed high satisfaction rates and reported that these technologies enhanced spatial understanding and facilitated visualization of specific pathologies. However, limitations such as the representativeness of non-bone conditions in 3D printed models and the need for further knowledge on imaging fundamentals were highlighted. CONCLUSION: Cross-sectional imaging and 3D printing offer valuable tools for enhancing the teaching of spinal anatomy in undergraduate medical education. Radiologists are well positioned to lead the integration of these technologies, and further research should explore their potential in teaching anatomy across different anatomical regions.

Ultrasound guided injections in ankle and foot.

Ultrasound guidance is particularly useful for percutaneous injections in the diagnosis and management of painful conditions of the ankle and foot. The injectates used include steroids and local anesthetics, such as lidocaine, mepivacaine, bupivacaine, ropivacaine, and platelet-rich plasma. Osteoarthritis is the main indication for joint injections. Joints amenable to being injected include the tibiotalar, subtalar, midtarsal, and metatarsophalangeal joints. Tendon injections mainly involve the Achilles, peroneus, extensors, and tibialis tendons, while plantar fascia injections are useful for treating plantar fasciitis and plantar fibromatosis. Forefoot injections include joint arthritis, intermetatarsal bursitis, and Morton neuroma. The standardized approaches and doses reviewed in this paper are based on the authors' experience and can lead to high success in symptomatic relief for various conditions. These injections can be curative or serve as a guide to identify the source of pain when surgery or other therapeutic options are planned.

Factors influencing vertebral collapse in osteoporotic vertebral fractures: a case-control study of symptomatic patients attended in the emergency department.

This study aimed to identify risk factors for the collapse of osteoporotic vertebral fractures (OVFs). We analyzed data from conventional radiography and computed tomography in patients with OVFs and found that older age and two radiological measurements were predictive for vertebral collapse. These factors can be useful for clinical practice. PURPOSE: To identify risk factors for collapse of osteoporotic vertebral fractures (OVF) on computed tomography (CT) and conventional radiography (CR). METHODS: This is a retrospective case-control study including a series of patients with OVF diagnosed at the emergency department of our institution from January to September 2019. Inclusion criteria were to have standing CR and supine CT within 2 weeks after the diagnosis of OVF and a follow-up CR at 6 months or later. We evaluated different imaging measurements at the initial diagnostic examinations, including vertebral height loss, local kyphosis, vertebral density, and fracture type according to the grading systems of Genant, Sugita, Association of Osteosynthesis (AO) Spine, and the German Society for Orthopaedics and Trauma. Vertebral collapse was defined as loss of ≥ 50% of vertebral area or height. Cases and controls were defined as OVFs which collapse and do not collapse, respectively, on follow-up. RESULTS: Fifty-six patients were included in the study, with a mean age of 72.6 ± 1.2 years, including 48 women. Twenty-five (44.6%) OVFs developed collapse on follow-up. None of the fracture classification systems were found to be predictive of collapse. Multivariate analysis showed that older age, increased density ratio (≥ 2) between the fractured and non-fractured vertebral bodies, and a ≥ 6% difference in posterior vertebral height (PVH) loss between standing CR and supine CT exhibited 88% discriminative power in predicting vertebral collapse. CONCLUSIONS: Age over 72.5 years, a density ratio ≥ 2 between the fractured and non-fractured vertebral bodies, and a difference equal to or higher than 6% in PVH loss between standing CR and supine CT, are risk factors for developing vertebral collapse after OVF.

Re-Emergence of a West Nile Virus (WNV) Variant in South Spain with Rapid Spread Capacity.

West Nile Virus (WNV) is a mosquito vector-borne zoonosis with an increasing incidence in Europe that has become a public health concern. In Spain, although local circulation has been known for decades, until 2020, when a large outbreak occurred, West Nile Virus cases were scarce and mostly occurred in southern Spain. Since then, there have been new cases every year and the pathogen has spread to new regions. Thus, monitoring of circulating variants and lineages plays a fundamental role in understanding WNV evolution, spread and dynamics. In this study, we sequenced WNV consensus genomes from mosquito pools captured in 2022 as part of a newly implemented surveillance program in southern Spain and compared it to other European, African and Spanish sequences. Characterization of WNV genomes in mosquitoes captured in 2022 reveals the co-circulation of two WNV lineage 1 variants, the one that caused the outbreak in 2020 and another variant that is closely related to variants reported in Spain in 2012, France in 2015, Italy in 2021-2022 and Senegal in 2012-2018. The geographic distribution of these variants indicates that WNV L1 dynamics in southern Europe include an alternating dominance of variants in some territories.

Automated software for counting and measuring Hyalella genus using artificial intelligence.

Amphipods belonging to the Hyalella genus are macroinvertebrates that inhabit aquatic environments. They are of particular interest in areas such as limnology and ecotoxicology, where data on the number of Hyalella individuals and their allometric measurements are used to assess the environmental dynamics of aquatic ecosystems. In this study, we introduce HyACS, a software tool that uses a model developed with the YOLOv3's architecture to detect individuals, and digital image processing techniques to extract morphological metrics of the Hyalella genus. The software detects body metrics of length, arc length, maximum width, eccentricity, perimeter, and area of Hyalella individuals, using basic imaging capture equipment. The performance metrics indicate that the model developed can achieve high prediction levels, with an accuracy above 90% for the correct identification of individuals. It can perform up to four times faster than traditional visual counting methods and provide precise morphological measurements of Hyalella individuals, which may improve further studies of the species populations and enhance their use as bioindicators of water quality.

First-Row Transition 7-Oxo-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidine Metal Complexes: Antiparasitic Activity and Release Studies.

Leishmaniasis and Chagas disease are still considered neglected illnesses due to the lack of investment in research, despite the fact that almost one million new cases are reported every year. Four 7-oxo-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidine (HftpO) first-row transition complexes (Cu, Co, Ni, Zn) have been studied for the first time in vitro against five different species of Leishmania spp. (L. infantum, L. braziliensis, L. donovani, L. peruviana and L. mexicana) as well as Trypanosoma cruzi, showing higher efficacy than the reference commercial drugs. UV and luminescence properties were also evaluated. As a proof of concept, anchoring of a model high-effective-metal complex as an antiparasitic agent on silica nanoparticles was carried out for the first time, and drug-release behaviour was evaluated, assessing this new approach for drug vehiculation.

Influence of Age and Cardiovascular Risk Factors in Vestibular Neuritis: Retrospective Cohort Study.

To analyze the influence of age and cardiovascular risk factors (CVRFs) in the evolution of vestibular neuritis (VN). METHODS: Retrospective cohort study. VN-diagnosed patients were included and divided into two groups: those with and without CVRFs. We analyzed the mean vestibular-ocular reflex (VOR) gain, measured through the video head impulse test (vHIT) at the diagnosis and one-year follow-up. We conducted a factorial analysis of variance (ANOVA) to evaluate the effect of age, sex, and CVRFs in the mean VOR gain. RESULTS: Sixty-three VN-diagnosed patients were included. There were no statistically significant differences in the mean VOR gain between both groups. However, in the subgroup analysis, there were statistically significant differences when comparing the mean VOR gain at the one-year follow-up between the group over 55 years of age 0.77 ± 0.20 and the group under 55 years 0.87 ± 0.15 (p = 0.036). Additionally, the factorial ANOVA demonstrated a significant main effect of age group on the mean VOR gain at the one-year follow-up (p = 0.018), and it also found a significant interaction between the factors of gender, age group, HTN (p = 0.043). CONCLUSIONS: CVRFs do not independently affect the mean VOR gain in VN patients' follow-ups. However, age significantly impacts VOR gain in VN and could be modulated by gender and hypertension.

CDK6-mediated endothelial cell cycle acceleration drives arteriovenous malformations in hereditary hemorrhagic telangiectasia.

Increased endothelial cell (EC) proliferation is a hallmark of arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT). The underlying mechanism and disease relevance of this abnormal cell proliferative state of the ECs remain unknown. Here, we report the identification of a CDK6-driven mechanism of cell cycle progression deregulation directly involved in EC proliferation and HHT vascular pathology. Specifically, HHT mouse liver ECs exhibited defects in their cell cycle control characterized by a G1/S checkpoint bypass and acceleration of cell cycle speed. Phosphorylated retinoblastoma (p-RB1)-a marker of G1/S transition through the restriction point-significantly accumulated in ECs of HHT mouse retinal AVMs and HHT patient skin telangiectasias. Mechanistically, ALK1 loss of function increased the expression of key restriction point mediators, and treatment with palbociclib or ribociclib, two CDK4/6 inhibitors, blocked p-RB1 increase and retinal AVMs in HHT mice. Palbociclib also improved vascular pathology in the brain and slowed down endothelial cell cycle speed and EC proliferation. Specific deletion of Cdk6 in ECs was sufficient to protect HHT mice from AVM pathology. Thus, CDK6-mediated endothelial cell cycle acceleration controls EC proliferation in AVMs and is a central determinant of HHT pathogenesis. We propose that clinically approved CDK4/6 inhibitors have repurposing potential in HHT.

Organotin(IV)-Decorated Graphene Quantum Dots as Dual Platform for Molecular Imaging and Treatment of Triple Negative Breast Cancer.

The pharmacological activity of organotin(IV) complexes in cancer therapy is well recognized but their large applicability is hampered by their poor water solubility. Hence, carbon dots, in particular nitrogen-doped graphene quantum dots (NGQDs), may be a promising alternative for the efficient delivery of organotin(IV) compounds as they have a substantial aqueous solubility, a good chemical stability, and non-toxicity as well as a bright photoluminescence that make them ideal for theranostic applications against cancer. Two different multifunctional nanosystems have been synthesized and fully characterized based on two fragments of organotin-based cytotoxic compounds and 4-formylbenzoic acid (FBA), covalently grafted onto the NGQDs surface. Subsequently, an in vitro determination of the therapeutic and theranostic potential of the achieved multifunctional systems was carried out. The results showed a high cytotoxic potential of the NGQDs-FBA-Sn materials against breast cancer cell line (MDA-MB-231) and a lower effect on a non-cancer cell line (kidney cells, HEK293T). Besides, thanks to their optical properties, the dots enabled their fluorescence molecular imaging in the cytoplasmatic region of the cells pointing towards a successful cellular uptake and a release of the metallodrug inside cancer cells (NGQDs-FBA-Sn).

Use of Skull Vibration-Induced Nystagmus in the Follow-up of Patients With Ménière Disease Treated With Intratympanic Gentamicin.

OBJECTIVES: Ménière disease (MD) is an idiopathic disorder that affects hearing and inner ear balance. Intratympanic gentamicin (ITG) is recognized as an effective treatment for uncontrolled MD characterized by persistent vertigo attacks despite therapy. The video head impulse test (vHIT) and skull vibration-induced nystagmus (SVIN) are validated. METHODS: for evaluating vestibular function. A progressive linear relationship has been identified between the slow-phase velocity (SPV) of SVIN determined using a 100-Hz skull vibrator and the gain difference (healthy ear/affected ear) measured by vHIT. The aim of this study was to ascertain whether the SPV of SVIN was associated with the recovery of vestibular function following ITG treatment. Consequently, we sought to determine whether SVIN could predict the onset of new vertigo attacks in patients with MD who were treated with ITG. METHODS: A prospective longitudinal case-control study was conducted. Several variables were recorded post-ITG and throughout the follow-up period, followed by statistical analyses. Two groups were compared: patients who experienced vertigo attacks 6 months after ITG and those who did not. RESULTS: The sample comprised 88 patients diagnosed with MD who underwent ITG treatment. Of the 18 patients who experienced recurring vertigo attacks, 15 demonstrated gain recovery in the affected ear. However, all 18 patients exhibited a decrease in the SPV of SVIN. CONCLUSION: The SPV of SVIN may be more sensitive than vHIT in identifying the recovery of vestibular function following ITG administration. To our knowledge, this is the first study to illustrate the link between a reduction in SPV and the likelihood of vertigo episodes in patients with MD who have been treated with ITG.