p53 Genetics and Biology in Lung Carcinomas: Insights, Implications and Clinical Applications.

The TP53 gene is renowned as a tumor suppressor, playing a pivotal role in overseeing the cell cycle, apoptosis, and maintaining genomic stability. Dysregulation of p53 often contributes to the initiation and progression of various cancers, including lung cancer (LC) subtypes. The review explores the intricate relationship between p53 and its role in the development and progression of LC. p53, a crucial tumor suppressor protein, exists in various isoforms, and understanding their distinct functions in LC is essential for advancing our knowledge of this deadly disease. This review aims to provide a comprehensive literature overview of p53, its relevance to LC, and potential clinical applications.

Establishing Normal Serum Values of Neurofilament Light Chains and Glial Fibrillary Acidic Protein Considering the Effects of Age and Other Demographic Factors in Healthy Adults.

Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains [sNfL]) or astroglia activation (serum glial fibrillary acidic protein [sGFAP]) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers. A cross-sectional study was conducted including 116 healthy controls with ages between 18 and 69 years (67.5% females; n = 79). sNfL and sGFAP concentrations were measured using single-molecule arrays. Age and body mass index affected sNfL values, and age was found to be the most important factor. The normal values changed with age, and we established normal values for individuals younger than 45 years as <10 pg/mL and for controls older than 45 years as <15 pg/mL. We established normal values at <10 pg/mL for individuals younger than 45 years and <15 pg/mL for older individuals. Alternatively, a Z-score of 1.5 was relevant for all controls. sGFAP was only affected by age. Differences in normal values were evident by 55 years. The highest normality limit for sGFAP was 140 pg/mL for controls under 55 years and 280 for older controls. We defined normal levels for sNfL and sGFAP and their corresponding age-associated changes. These data may contribute to the application of such variables in clinical practice.

Switching and Frequency Response Assessment of Photovoltaic Drivers and Their Potential for Different Applications.

Newly introduced Photovoltaic (PV) devices, featuring a built-in chip with an illuminating Light Emitting Diode (LED), have emerged in the commercial market. These devices are touted for their utility as both low- and high-side power switch drivers and for data acquisition coupling. However, comprehensive knowledge and experimentation regarding the limitations of these Photovoltaic Drivers in both switching and signal processing applications remain underexplored. This paper presents a detailed characterization of a Photovoltaic Driver, focusing on its performance under resistive and capacitive loads. Additionally, it delineates the device's constraints when employed in signal processing. Through the analysis of switching losses across various power switches (Silicon and Silicon Carbide) in both series and parallel driver configurations, this study assesses the driver's efficacy in operating Junction Field-Effect Transistors (JFETs). Findings suggest that Photovoltaic Drivers offer a low-cost, compact solution for specific applications, such as high-voltage, low-bandwidth measurements, and low-speed turn-on with fast turn-off power switching scenarios, including solid-state switches and hot-swap circuits. Moreover, they present a straightforward, cost-effective method for driving JFETs, simplifying the circuit design and eliminating the need for an additional negative power source.

Influence of Sonication on the Molecular Characteristics of Carbopol® and Its Rheological Behavior in Microgels.

In this work, the effect of sonication on the molecular characteristics of polyacrylic acid (Carbopol® Ultrez 10), as well as on its rheological behavior in aqueous dispersions and microgels, was analyzed for the first time by rheometry, weight-average molecular weight (Mw) measurements via static light scattering (SLS), Fourier transform infrared (FTIR) spectroscopy and confocal microscopy. For this, the precursor dispersion and the microgels containing 0.25 wt.% of Ultrez 10 were sonicated in a commercial ultrasound bath at constant power and at different times. The main rheological properties of the microgel, namely, shear modulus, yield stress and viscosity, all decreased with increasing sonication time, while the microgel's Herschel-Bulkley (H-B) behavior, without thixotropy, was preserved. Also, Mw of Ultrez 10 decreased up to almost one-third (109,212 g/mol) of its original value (300,860 g/mol) after 180 min of sonication. These results evidence a softening of the gel microstructure, which results from the reduction in the Mw of polyacrylic acid with sonication time. Separately, FTIR measurements show that sonication produces scission in the C-C links of the Carbopol® backbone, which results in chains with the same chemistry but lower molecular weight. Finally, confocal microscopy observations revealed a diminution of the size of the microsponge domains and more free solvent with sonication time, which is reflected in a less compact and softer microstructure. The present results indicate that both the microstructure and the rheological behavior of Carbopol® microgels, in particular, and complex fluids, in general, may be manipulated or tailored by systematic high-power ultrasonication.

Photocatalytic Synthesis and Functionalization of Sulfones, Sulfonamides and Sulfoximines.

Sulfur(VI)-based functional groups are popular scaffolds in a wide variety of research fields including synthetic and medicinal chemistry, as well as chemical biology. The growing interest in sulfur(VI)-containing molecules has motivated the scientific community to explore new methods to synthesize and modify them. Here, photocatalysis plays a key role granting access to new types of reactivity under mild reaction conditions. In this Perspective, we present a selection of works reported in the last six years focused on the photocatalytic assembly and reactivity of sulfones, sulfonamides, and sulfoximines. We addressed the key synthetic intermediates for each transformation, while discussing limitations and strength points of the protocols. Future directions of the field are finally presented.

Transcriptomic Analysis Reveals Early Alterations Associated with Intrinsic Resistance to Targeted Therapy in Lung Adenocarcinoma Cell Lines.

Lung adenocarcinoma is the most prevalent form of lung cancer, and drug resistance poses a significant obstacle in its treatment. This study aimed to investigate the overexpression of long non-coding RNAs (lncRNAs) as a mechanism that promotes intrinsic resistance in tumor cells from the onset of treatment. Drug-tolerant persister (DTP) cells are a subset of cancer cells that survive and proliferate after exposure to therapeutic drugs, making them an essential object of study in cancer treatment. The molecular mechanisms underlying DTP cell survival are not fully understood; however, long non-coding RNAs (lncRNAs) have been proposed to play a crucial role. DTP cells from lung adenocarcinoma cell lines were obtained after single exposure to tyrosine kinase inhibitors (TKIs; erlotinib or osimertinib). After establishing DTP cells, RNA sequencing was performed to investigate the differential expression of the lncRNAs. Some lncRNAs and one mRNA were overexpressed in DTP cells. The clinical relevance of lncRNAs was evaluated in a cohort of patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA). RT-qPCR validated the overexpression of lncRNAs and mRNA in the residual DTP cells and LUAD biopsies. Knockdown of these lncRNAs increases the sensitivity of DTP cells to therapeutic drugs. This study provides an opportunity to investigate the involvement of lncRNAs in the genetic and epigenetic mechanisms that underlie intrinsic resistance. The identified lncRNAs and CD74 mRNA may serve as potential prognostic markers or therapeutic targets to improve the overall survival (OS) of patients with lung cancer.

Outcomes of Corneal Compound Hyperopic Astigmatism With Presbyopia by Zeiss PRESBYOND Laser Blended Vision LASIK Using Default Custom Refractive Software Master Target Refractions for Reduced Anisometropia.

PURPOSE: To evaluate the effectiveness, safety, and stability of a modified PRESBYOND Laser Blended Vision protocol (Carl Zeiss Meditec AG) for correcting hyperopic astigmatism and presbyopia, using Custom Refractive Software Master (CRSM) targeting over a 6-month period. METHODS: A total of 636 eyes of 318 patients with a mean age of 51.05 ± 4.71 years (range: 40 to 60 years) met the inclusion and exclusion criteria. All patients completed a 6-month follow-up. CRSM software was used to generate ablation profiles for the MEL90 excimer laser (Carl Zeiss Meditec AG). The target refraction was emmetropic for the dominant eyes and between -0.75 and -1.12 diopters (D) for the near eyes. RESULTS: Visual and refractive results were studied separately by the dominant and non-dominant eyes. The mean attempt to correct for spherical equivalent refraction was +2.17 ± 1.16 D (range: -1.00 to +5.37 D). The mean attempted cylinder was -0.60 ± 0.75 D (range: -4.00 to 0.00 D). All eyes monocularly achieved uncorrected distance visual acuity (UDVA) of 20/25 or better after refractive treatment and 88% achieved 20/20. Binocularly all eyes achieved UDVA of 20/25 or better and 96.54% achieved 20/20. Ninety-eight percent of the patients maintained their corrected distance visual acuity before surgery and UDVA 6 months after surgery. CONCLUSIONS: This hyperopic micro-anisometropia protocol with PRESBYOND Laser Blended Vision was an effective, safe, and well-tolerated refractive treatment. It was an effective procedure with excellent results for UDVA and uncorrected near visual acuity and demonstrates that binocular summation exists. [ J Refract Surg. 2024;40(7):e480-e489.].

Desert plants, arbuscular mycorrhizal fungi and associated bacteria: Exploring the diversity and role of symbiosis under drought.

Desert plants, such as Agave tequilana, A. salmiana and Myrtillocactus geometrizans, can survive harsh environmental conditions partly due to their symbiotic relationships with microorganisms, including arbuscular mycorrhizal fungi (AMF). Interestingly, some of these fungi also harbour endosymbiotic bacteria. Our research focused on investigating the diversity of these AMFs and their associated bacteria in these plants growing in arid soil. We found that agaves have a threefold higher AMF colonization than M. geometrizans. Metabarcoding techniques revealed that the composition of AMF communities was primarily influenced by the plant host, while the bacterial communities were more affected by the specific plant compartment or niche they inhabited. We identified both known and novel endofungal bacterial taxa, including Burkholderiales, and confirmed their presence within AMF spores using multiphoton microscopy. Our study also explored the effects of drought on the symbiosis between A. tequilana and AMF. We discovered that the severity of drought conditions could modulate the strength of this symbiosis and its outcomes for the plant holobiont. Severe drought conditions prevented the formation of this symbiosis, while moderate drought conditions promoted it, thereby conferring drought tolerance in A. tequilana. This research sheds light on the diversity of AMF and associated bacteria in Crassulacean Acid Metabolism (CAM) plants and underscores the crucial role of drought as a factor modulating the symbiosis between A. tequilana and AMF. Further research is needed to understand the role of endofungal bacteria in this response.

Pseudoaneurysm as an unusual complication in bone lengthening.

One of the risks of distraction osteogenesis-based techniques is the development of vascular complications, such as pseudoaneurysms associated with the osteotomies performed or the fixation elements of the external fixator used in the procedure. Pseudoaneurysm are formed when the tunica adventitia of the artery is injured, resulting in a gradual and persistent blood extravasation into the surrounding tissues that is encapsulated and connected to the arterial lumen. This report describes a rare case of a late-presentation pseudoaneurysm in the anterior tibial artery resulting from a tibial lengthening procedure aimed at addressing a leg length discrepancy in a 57-year-old female with severe peripheral neuropathy resulting from long-standing poorly controlled diabetes mellitus. We describe the diagnostic process, the treatment options and confirm how the shape of the bony callus can be a reliable indicator of this pathology, as has already been described in the literature.

Influence of the COVID-19 pandemic on the defined daily dose of antimicrobials in patients requiring elective and emergency surgical procedures.

BACKGROUND: The COVID-19 pandemic has resulted in great incertitude and overwhelming changes in healthcare that have had a direct impact on antibiotic prescription. However, the influence of this pandemic on antibiotic consumption in patients undergoing surgery has not yet been analysed. The goal of this study was to analyse antimicrobial consumption and prescription in the same period of 2019 (pre-COVID-19), 2020 (beginning of the COVID-19 pandemic) and 2021 (established COVID-19) according to the DDD system in surgical patients at a tertiary-level hospital. METHODS: A prospectively maintained database was analysed. All patients who underwent elective or emergency gastrointestinal surgery during the same period (2019, 2020 and 2021) were included. Those who received at least 1 of the 10 most frequently prescribed antimicrobials during those periods were analysed. RESULTS: A total of 2975 patients were included in this study. In 2020, the number of procedures performed decreased significantly (653 versus 1154 and 1168 in 2020 versus 2019 and 2021, respectively; P = 0.005). Of all patients who underwent surgery during these periods, 45.08% received at least one of the antimicrobials studied (45.8% in 2020 versus 22.9% and 22.97% in 2019 and 2021, respectively; P = 0.005). Of these, 22.97% of the patients received a combination of these antimicrobials, with ceftriaxone/metronidazole being the most frequent. Hepato-Pancreato-Biliary and Liver Transplant, Emergency Surgery and Colorectal Surgery units had higher antibiotic consumption. CONCLUSIONS: The COVID-19 pandemic has resulted in a significant decrease in surgical activity and higher post-operative antimicrobial prescription compared with previous and subsequent years.

Algorithm for the Bronchoscopic Diagnosis of Alveolar-Pleural Fistula.

Alveolar-pleural fistulas (APF) are a clinical entity that represents a diagnostic and therapeutic challenge. OBJECTIVE: The objective of this work is to design a diagnostic algorithm for the anatomical detection of APF in patients who are not candidates for surgical treatment. METHOD: Prospective non-randomized study of 47 patients. Diagnostic procedures were performed: (a) prior to bronchoscopy: computed axial tomography (CT) and implantation of electronic pleural drainage system (EPD) and (b) endoscopic: endobronchial occlusion (EO) by balloon, selective endobronchial oxygen insufflation (OI) (2l) and selective bronchography (BS) (instillation of iodinated radiological contrast using continuous fluoroscopy). RESULTS: The sample was predominantly male (81%). The diagnostic methods revealed: (a) Determination of the anatomical location of APF by CT in 15/46 patients (31.9% of sample), and variations in the pattern (intermittent or continuous air leak) and quantification after drug administration sedatives using EPD, (b) endoscopic: anatomical determination of APF was achieved in 57.1, 81 and 63.4% respectively using EO, OI and BS. The combination of the diagnostic tests allowed us to determine the anatomical location of the APF in 91.5% of the sample. No complications were recorded in 85.1% of cases. CONCLUSIONS: The diagnosis of APF by flexible bronchoscopy is a useful method, with an adequate safety and efficacy profile. The proposed diagnostic algorithm includes the use of EPD and performing a CT scan. Regarding endoscopic diagnosis: in case of continuous air leak, the first option is OE; and if the leak is intermittent, we recommend endobronchial OI, with BS as a secondary option (respective sensitivity 81% vs 63.4% and complications 8.1% vs 7.3%).

Intracranial hypertension secondary to unruptured pial arteriovenous malformation. Suitability of isolated endovascular treatment with ethylene vinyl alcohol/dimethyl sulfoxide (Onyx®). Case report and literature review.

A 36-year-old male presented to the Emergency Department with clinical symptoms of blurred vision of progressive onset of two years of evolution. The ophthalmological examination revealed the existence of bilateral papilledema. Using cranial computed tomography and magnetic resonance imaging, the presence of a right occipital pial arteriovenous malformation was certified. Arteriographically, pial arterial contributions dependent on the right middle cerebral artery and the right posterior cerebral artery were identified. Venous drainage was located at the level of the superior sagittal sinus. An associated right transverse sinus stenosis was also identified. The existence of secondary intracranial hypertension was corroborated by monitoring with an intracranial pressure sensor. An interventional procedure was carried out consisting of embolization of the arterial supplies of the lesion using Onyx®. The clinical-radiological findings after the procedure were favorable: the papilledema disappeared and complete exclusion of the malformation was achieved. A new intracranial pressure measurement showed resolution of intracranial hypertension. Subsequent regulated radiological controls showed complete exclusion of the malformation up to 5 years later.

Elucidating Black α-CsPbI3 Perovskite Stabilization via PPD Bication-Conjugated Molecule Surface Passivation: Ab Initio Simulations.

The cubic α-CsPbI3 phase stands out as one of the most promising perovskite compounds for solar cell applications due to its suitable electronic band gap of 1.7 eV. However, it exhibits structural instability under operational conditions, often transforming into the hexagonal non-perovskite δ-CsPbI3 phase, which is unsuitable for solar cell applications because of the large band gap (e.g., ∼2.9 eV). Thus, there is growing interest in identifying possible mechanisms for increasing the stability of the cubic α-CsPbI3 phase. Here, we report a theoretical investigation, based on density functional theory calculations, of the surface passivation of the α-, γ-, and δ-CsPbI3(100) surfaces using the C6H4(NH3)2 [p-phenylenediamine (PPD)] and Cs species as passivation agents. Our calculations and analyses corroborate recent experimental findings, showing that PPD passivation effectively stabilizes the cubic α-CsPbI3 perovskite against the cubic-to-hexagonal phase transition. The PPD molecule exhibits covalent-dominating bonds with the substrate, which makes it more resistant to distortion than the ionic bonds dominant in perovskite bulks. By contrasting these results with the natural Cs passivation, we highlight the superior stability of the PPD passivation, as evidenced by the negative surface formation energies, unlike the positive values observed for the Cs passivation. This disparity is due to the covalent characteristics of the molecule/surface interaction of PPD, as opposed to the purely ionic interaction seen with the Cs passivation. Notably, the PPD passivation maintains the optoelectronic properties of the perovskites because the electronic states derived from the PPD molecules are localized far from the band gap region, which is crucial for optoelectronic applications.

A Primary Health Care Program and COVID-19. Impact in Hospital Admissions and Mortality.

BACKGROUND: Most patients with mild or moderate COVID infection did not require hospital admission, but depending on their personal history, they needed medical supervision. In monitoring these patients in primary care, the design of specific surveillance programs was of great help. Between February 2021 and March 2022, EDCO program was designed in Tenerife, Spain, to telemonitor patients with COVID infection who had at least one vulnerability factor to reduce hospital admissions and mortality. OBJECTIVE: The aim of this study is to describe the clinical course of patients included in the EDCO program and to analyze which factors were associated with a higher probability of hospital admission and mortality. DESIGN: Retrospective cohort study. PATIENTS: We included 3848 patients with a COVID-19 infection age over 60 years old or age over 18 years and at least one vulnerability factor previously reported in medical history. MAIN MEASURES: Primary outcome was to assess risk of admission or mortality. KEY RESULTS: 278 (7.2%) patients required hospital admission. Relative risks (RR) of hospital admission were oxygen saturation ≤ 92% (RR: 90.91 (58.82-142.86)), respiratory rate ≥ 22 breaths per minute (RR: 20.41 (1.19-34.48), obesity (RR: 1.53 (1.12-2.10), chronic kidney disease (RR:2.31 (1.23-4.35), ≥ 60 years of age (RR: 1.44 (1.04-1.99). Mortality rate was 0.7% (27 patients). Relative risks of mortality were respiratory rate ≥ 22 breaths per minute (RR: 24.85 (11.15-55.38), patients with three or more vulnerability factors (RR: 4.10 (1.62-10.38), oxygen saturation ≤ 92% (RR: 4.69 (1.70-15.15), chronic respiratory disease (RR: 3.32 (1.43-7.69) and active malignancy (RR: 4.00 (1.42-11.23). CONCLUSIONS: Vulnerable patients followed by a primary care programme had admission rates of 7.2% and mortality rates of 0.7%. Supervision of vulnerable patients by a Primary Care team was effective in the follow-up of these patients with complete resolution of symptoms in 91.7% of the cases.

Explainable machine learning on baseline MRI predicts multiple sclerosis trajectory descriptors.

Multiple sclerosis (MS) is a multifaceted neurological condition characterized by challenges in timely diagnosis and personalized patient management. The application of Artificial Intelligence (AI) to MS holds promises for early detection, accurate diagnosis, and predictive modeling. The objectives of this study are: 1) to propose new MS trajectory descriptors that could be employed in Machine Learning (ML) regressors and classifiers to predict patient evolution; 2) to explore the contribution of ML models in discerning MS trajectory descriptors using only baseline Magnetic Resonance Imaging (MRI) studies. This study involved 446 MS patients who had a baseline MRI, at least two measurements of Expanded Disability Status Scale (EDSS), and a 1-year follow-up. Patients were divided into two groups: 1) for model development and 2) for evaluation. Three descriptors: ß1, ß2, and EDSS(t), were related to baseline MRI parameters using regression and classification XGBoost models. Shapley Additive Explanations (SHAP) analysis enhanced model transparency by identifying influential features. The results of this study demonstrate the potential of AI in predicting MS progression using the proposed patient trajectories and baseline MRI scans, outperforming classic Multiple Linear Regression (MLR) methods. In conclusion, MS trajectory descriptors are crucial; incorporating AI analysis into MRI assessments presents promising opportunities to advance predictive capabilities. SHAP analysis enhances model interpretation, revealing feature importance for clinical decisions.

Extensive folliculitis and abscesses with a sporotrichoid distribution in a parenteral drug user.

We present the case of a 53-year-old Caucasian man with a history of intravenous drug use who presented with fever and multiple pustules predominantly affecting hairy areas of the body, with no clinical improvement despite previous antibiotic treatment. Culture of the pustules confirmed Candida albicans infection and histological examination of skin biopsies revealed suppurative granulomas compatible with candidomycetic folliculitis. The patient was successfully treated with systemic antifungals and discharged with resolution of symptoms. Candidomycetic folliculitis is a condition typically associated with brown heroin consumption due to the use of acidic solvent that promotes Candida growth. Clinical manifestations include fever followed by skin lesions, with possible systemic involvement if untreated. Extensive folliculitis with associated fever in an IVDU should raise suspicion of this pathology since early diagnosis and appropriate treatment are crucial to prevent complications.

"You have to be mentally prepared for that moment": Attitudes of the adolescent population to death and their educational implications.

This article deals with the opinions and attitudes of the adolescent population toward death and its possible treatment in formal education at a public secondary school in Spain. To do so, we use a mixed methodology - DEA-S scale (n = 366) and three focus groups (n = 23), using descriptive statistical analysis, cluster analysis and qualitative thematic analysis. As in other studies, these students show moderately positive attitudes toward the inclusion of death education at their school, but their position is not unanimous, and above all, they admit its inclusion with certain reservations and conditions that reveal a limited conception of the educational potential of death education: they do not consider it appropriate at all educational stages and are critical of the way in which similar topics are usually dealt with at school. The analysis provides important didactic guidelines for the promotion of death awareness in secondary education.

Microglia mitochondrial complex I deficiency during development induces glial dysfunction and early lethality.

Primary mitochondrial diseases (PMDs) are associated with pediatric neurological disorders and are traditionally related to oxidative phosphorylation system (OXPHOS) defects in neurons. Interestingly, both PMD mouse models and patients with PMD show gliosis, and pharmacological depletion of microglia, the innate immune cells of the brain, ameliorates multiple symptoms in a mouse model. Given that microglia activation correlates with the expression of OXPHOS genes, we studied whether OXPHOS deficits in microglia may contribute to PMDs. We first observed that the metabolic rewiring associated with microglia stimulation in vitro (via IL-33 or TAU treatment) was partially changed by complex I (CI) inhibition (via rotenone treatment). In vivo, we generated a mouse model deficient for CI activity in microglia (MGcCI). MGcCI microglia showed metabolic rewiring and gradual transcriptional activation, which led to hypertrophy and dysfunction in juvenile (1-month-old) and adult (3-month-old) stages, respectively. MGcCI mice presented widespread reactive astrocytes, a decrease of synaptic markers accompanied by an increased number of parvalbumin neurons, a behavioral deficit characterized by prolonged periods of immobility, loss of weight and premature death that was partially rescued by pharmacologic depletion of microglia. Our data demonstrate that microglia development depends on mitochondrial CI and suggest a direct microglial contribution to PMDs.

Increasing culturally relevant science media coverage: exploring the outcomes of a collaboration in Puerto Rico.

CienciaPR, a nonprofit that brings together the largest network of Puerto Rican scientists and one of the largest networks of Hispanic/Latine scientists in the world, has collaborated with El Nuevo Día (END), Puerto Rico's newspaper of record, to increase culturally relevant stories in their science section. This Practice Insight quantifies and compares the presence of culturally relevant elements (e.g., referring to Puerto Rico, local landmarks, historic figures, slang) and other content information (e.g., topics, location, focus, protagonist) in articles authored by CienciaPR members versus articles by END, news agencies, and other organizations. Results demonstrate that CienciaPR-authored articles published in END featured culturally relevant elements more often (e.g., mentioned Puerto Rico, used Puerto Rican slang, stories located in Puerto Rico) than those by other sources.