Light-sheet microscopy in a glass capillary: feedback holographic control for illumination beam correction.

Light-sheet microscopy enables fast 3D, high-contrast imaging in biology and colloidal sciences. Recently, the controlled transport of living embryos or small colloids through stable glass capillaries is manifold interesting. Although they hardly impair the sample, glass capillaries spoil the image by generating significant aberrations of the illumination and detection light. Here, we analyze the deflection of illuminating Bessel beams at the capillary by k-spectral shifting, and correct for it by a beam deflector. Using cylindrical lenses for astigmatism compensation on the detection side, we demonstrate 3D line-confocal imaging inside a glass capillary over an axial range of ±400 µm.

Where are the inequalities in colorectal cancer care in a country with universal healthcare? A systematic review and narrative synthesis.

OBJECTIVE: Patients diagnosed with colorectal cancer living in more deprived areas experience worse survival than those in more affluent areas. Those living in more deprived areas face barriers to accessing timely, quality healthcare. These barriers may contribute to socioeconomic inequalities in survival. We evaluated the literature for any association between socioeconomic group, hospital delay and treatments received among patients with colorectal cancer in the UK, a country with universal healthcare. DESIGN: MEDLINE, EMBASE, CINAHL, CENTRAL, SCIE, AMED and PsycINFO were searched from inception to January 2023. Grey literature, including HMIC, BASE and Google Advanced Search, and forward and backward citation searches were conducted. Two reviewers independently reviewed titles, abstracts and full-text articles. Observational UK-based studies were included if they reported socioeconomic measures and an association with either hospital delay or treatments received. The QUIPS tool assessed bias risk, and a narrative synthesis was conducted. The review is reported to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. RESULTS: 41 of the 7209 identified references were included. 12 studies evaluated 7 different hospital intervals. There was a significant association between area-level deprivation and a longer time from first presentation in primary care to diagnosis. 32 studies evaluated treatments received. There were socioeconomic inequalities in surgery and chemotherapy but not radiotherapy. CONCLUSION: Patients with colorectal cancer face inequalities across the cancer care continuum. Further research is needed to understand why and what evidence-based actions can reduce these inequalities in treatment. Qualitative research of patients and clinicians conducted across various settings would provide a rich understanding of the complex factors that drive these inequalities. Further research should also consider using a causal approach to future studies to considerably strengthen the interpretation. Clinicians can try and mitigate some potential causes of colorectal cancer inequalities, including signposting to financial advice and patient transport schemes. PROSPERO REGISTRATION NUMBER: CRD42022347652.

Deep neural networks predict class I major histocompatibility complex epitope presentation and transfer learn neoepitope immunogenicity.

Identifying neoepitopes that elicit an adaptive immune response is a major bottleneck to developing personalized cancer vaccines. Experimental validation of candidate neoepitopes is extremely resource intensive and the vast majority of candidates are non-immunogenic, creating a needle-in-a-haystack problem. Here we address this challenge, presenting computational methods for predicting class I major histocompatibility complex (MHC-I) epitopes and identifying immunogenic neoepitopes with improved precision. The BigMHC method comprises an ensemble of seven pan-allelic deep neural networks trained on peptide-MHC eluted ligand data from mass spectrometry assays and transfer learned on data from assays of antigen-specific immune response. Compared with four state-of-the-art classifiers, BigMHC significantly improves the prediction of epitope presentation on a test set of 45,409 MHC ligands among 900,592 random negatives (area under the receiver operating characteristic = 0.9733; area under the precision-recall curve = 0.8779). After transfer learning on immunogenicity data, BigMHC yields significantly higher precision than seven state-of-the-art models in identifying immunogenic neoepitopes, making BigMHC effective in clinical settings.

Monocyte chemoattractant protein 1 as a potential biomarker for immune checkpoint inhibitor-associated neurotoxicity.

BACKGROUND: Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors (ICI). However, there is a growing awareness of immune-related adverse events (irAE). Especially ICI-mediated neurological adverse events (nAE(+)), are tough to diagnose and biomarkers to identify patients at risk are missing. METHODS: A prospective register with prespecified examinations was established for ICI treated patients in December 2019. At the time of data cut-off, 110 patients were enrolled and completed the clinical protocol. Herein, cytokines and serum neurofilament light chain (sNFL) from 21 patients were analyzed. RESULTS: nAE of any grade were observed in 31% of the patients (n = 34/110). In nAE(+) patients a significant increase in sNFL concentrations over time was observed. Patients with higher-grade nAE had significantly elevated serum-concentrations of monocyte chemoattractant protein 1 (MCP-1) and brain-derived neurotrophic factor (BDNF) at baseline compared to individuals without any nAE (p < 0.01 and p < 0.05). CONCLUSION: Here, we identified nAE to occur more frequently than previously reported. Increase of sNFL during nAE confirms the clinical diagnosis of neurotoxicity and might be a suitable marker for neuronal damage associated with ICI therapy. Furthermore, MCP-1 and BDNF are potentially the first clinical-class nAE predictors for patients under ICI therapy.

Conversations With Individuals on the Fence about CV-19 Vaccination: Analysis of Lives Saved by Vaccine vs. Natural Infection Mortality and Other Reflections.

As of June 15, 2021, from 672,000 to 912,000 deaths have been averted through vaccination of 48% of the US population. Because 52% remain unvaccinated, 728,000 to 988,000 lives remain at risk. These deaths can be spared, and the pandemic stopped in its tracks provided a final national vaccination rate of 84% is achieved. We aim to demonstrate in our analysis the number of lives saved that can be attributed to CV-19 vaccination vs the mortality rate of natural infection seen in unvaccinated individuals. However, time is short given the recent exponential rise of the highly contagious SARS-CoV-2 Delta variant. Delta infection results in a thousand-fold increase in viral load and a transmissibility 2.25x that of the original SARS-CoV-2 strain. Predominance of the Delta variant has already resulted in Covid-19 surges in area with low vaccination rates. An aggressive and timely vaccination campaign is being attempted. We hope our analysis helps convince individuals 'on the fence' that vaccination is essential if the pandemic is to be ended in the United States.

A Case Report and Review of the Literature: Infectious Aneurysm Formation in the Pulmonary Arteries-A Rare but Perilous Sequela of Persisting Infection With Klebsiella pneumoniae.

Septic aneurysms of the pulmonary artery are rare conditions, with few cases having been reported worldwide. They are assumed to result from septic emboli that cause a local inflammatory reaction of the arterial wall, ultimately leading to degenerative changes. We report the case of a 63-year-old female patient presenting with Klebsiella pneumoniae urosepsis and first diagnosis of diabetes mellitus, who developed a life-threatening infectious pulmonary artery aneurysm secondary to bacteremia with Klebsiella pneumoniae. The patient required a lobectomy due to pulmonary hemorrhage. We review the clinical hallmarks of Klebsiella pneumoniae related septic pulmonary embolic disease and summarize currently known risk factors for the development of infectious aneurysmatic disease including diabetes mellitus and other states of immunosuppression. The featured case aims to increase the awareness for this seldom but life-threatening complication of infectious diseases such as Klebsiella pneumoniae urosepsis.

Design and Rationale of the HANSE Study: A Holistic German Lung Cancer Screening Trial Using Low-Dose Computed Tomography.

Despite the high prevalence and mortality of lung cancer and proven effectiveness of low-dose computed tomography (LDCT) to reduce mortality, Germany still lacks a national screening program. The German Institute for Quality and Efficiency in Health Care (IQWiG) and the Federal Office for Radiation Protection (BfS) both published positive scientific evaluations recommending a quality-controlled national screening program. IQWiG underlined the importance of a clear risk definition, integrated smoking cessation programs, and quality assurance, highlighting the necessity of procedural optimization.In the HANSE study, former and current smokers aged 55-79 years are assessed for their lung cancer risk by the NELSON and PLCOM2012 risk scores. 5000 high-risk participants, defined as PLCOM2012 6-year risk ≥ 1.58 % or fulfilling NELSON risk inclusion criteria, will be screened by LDCT at baseline and after 12 months. Lung nodules are analyzed by a modified Lung-RADS 1.1 score of the HANSE study, and values of emphysema and coronary calcium are determined and randomly reported to the participants. 7100 low-risk participants serve as a control. All patients are followed-up for up to 10 years. The sensitivity and specificity of the two risk assessments and LDCT screening, effects of the randomized LDCT reporting, efficiency of lung nodule management, and several other factors are assessed to analyze the success and quality of the holistic screening program.The HANSE study is designed as a holistic lung cancer screening study in northern Germany to answer pressing questions for a successful implementation of an effective German lung cancer screening program. · HANSE is designed to address pressing questions for the implementation of lung cancer screening in Germany.. · HANSE compares NELSON and PLCOM2012 risk assessments for optimal definition of the high-risk group. . · HANSE integrates cardiac calcium and pulmonary emphysema scoring in a holistic screening approach.. CITATION FORMAT: · Vogel-Claussen J, Lasch F, Bollmann B et al. Design and Rationale of the HANSE Study: A Holistic German Lung Cancer Screening Trial Using Low-Dose Computed Tomography. Fortschr Röntgenstr 2022; 194: 1333 - 1345.

Mesoporous Strontium-Doped Phosphate-Based Sol-Gel Glasses for Biomedical Applications.

Mesoporous phosphate-based glasses have great potential as biomedical materials being able to simultaneously induce tissue regeneration and controlled release of therapeutic molecules. In the present study, a series of mesoporous phosphate-based glasses in the P2O5-CaO-Na2O system, doped with 1, 3, and 5 mol% of Sr2+, were prepared using the sol-gel method combined with supramolecular templating. A sample without strontium addition was prepared for comparison. The non-ionic triblock copolymer EO20PO70EO20 (P123) was used as a templating agent. Scanning electron microscopy (SEM) images revealed that all synthesized glasses have an extended porous structure. This was confirmed by N2 adsorption-desorption analysis at 77 K that shows a porosity typical of mesoporous materials. 31P magic angle spinning nuclear magnetic resonance (31P MAS-NMR) and Fourier transform infrared (FTIR) spectroscopies have shown that the glasses are mainly formed by Q1 and Q2 phosphate groups. Degradation of the glasses in deionized water assessed over a 7-day period shows that phosphate, Ca2+, Na+, and Sr2+ ions can be released in a controlled manner over time. In particular, a direct correlation between strontium content and degradation rate was observed. This study shows that Sr-doped mesoporous phosphate-based glasses have great potential in bone tissue regeneration as materials for controlled delivery of therapeutic ions.

Enoximone in status asthmaticus.

In a patient with severe status asthmaticus, enoximone, a phosphodiesterase-3 inhibitor, caused immediate bronchodilation http://bit.ly/38UYpUn.

Response to Checkpoint Inhibition in Non-Small Cell Lung Cancer with Molecular Driver Alterations.

AIMS: Non-small cell lung cancer (NSCLC) patients with EGFR mutations do not respond well to checkpoint inhibitors. However, little is known about the activity of immunotherapy in NSCLC with other driver mutations. The increasing use of next-generation sequencing (NGS) leads to molecular findings that face the clinician with problems while choosing the best treatment. This study aims at analyzing response of NSCLC with driver mutations to immunotherapy. PATIENTS AND METHODS: We retrospectively included 84 NSCLC patients diagnosed and treated at 2 German tertiary-care lung cancer centers using NGS and treatment with immunotherapy. Response to immunotherapy was analyzed in correlation to molecular findings. RESULTS: 51 patients harbored at least 1 driver mutation. PIK3CA, EGFR, and STK11 mutations did not respond to immunotherapy. KRAS, TP53, and MET exon 14 skipping mutations responded well. One patient with NF-1 mutation showed durable response. CONCLUSIONS: Molecular testing may be of use in guiding treatment decision making in NSCLC.

Infected chronic sinus secondary to a retained fragment of radial artery introducer sheath following percutaneous coronary intervention (PCI).

Coronary angiography and percutaneous coronary intervention (PCI) are frequently performed procedures in the UK and the developed world, with the radial artery becoming the preferred route of access. A chronically retained macroscopic fragment of radial artery introducer sheath is a very rare complication that has not, to our knowledge, been reported. We report the case of a 62-year-old woman who underwent PCI and developed a persisting infected sinus and abscess at the cannulation site despite multiple courses of antibiotics. Surgical exploration of the forearm recovered a foreign body that was found in the brachioradialis muscle and resembled a fragment of hydrophilic sheath. In conclusion, this case highlights that it is possible to leave macroscopic fragments of hydrophilic sheaths in situ. This is likely to be encountered during difficult access, especially during arterial spasm, and it is advised that the sheath and any other vascular access device is thoroughly inspected following removal.

Development and testing of a patient-centered dental home assessment for low-income families.

OBJECTIVES: The purpose of this study was to develop an instrument in English (ENG) and Spanish (SPA) for use in assessing perceptions of dental home characteristics among low-income adults. METHODS: An expert panel selected 21 items from a pool of 81 items mapped to domains in the American Academy of Pediatrics' medical home. Pilot testing with mothers (n = 795) of children in Early Head Start (EHS) resulted in an expanded 36-item scale, which was field-tested in interviews with ENG- (NENG = 665) and SPA-speakers (NSPA = 116). An exploratory factor analysis of 23 usable items was carried out in an EHS reference group (NENG-EHS = 272). The selected model was evaluated by confirmatory factor analysis (CFA) in two other subgroups (NENG-NonEHS = 393; NSPA = 116). We tested measurement and structural invariances using a multiple-group approach. Known-groups validity was examined by testing factor mean differences between two groups defined by whether or not the mother used a single dental office. RESULTS: A three-factor CFA model with 10 items was retained for its close fit for all three subgroups. Invariance tests found the two ENG subgroups to be homogenous and were combined. Several item and factor parameters in the SPA group differed from the combined ENG group. The proposed dental home measure demonstrated good known-group validity in that people who used the same dental office reported better dental care experiences. CONCLUSIONS: An instrument to measure the dental home concept among low-income adults was developed with three domains (accessible-comprehensive, compassionate, and health literate care) that demonstrated good validity and reliability.

Genetic and phenotypic differentiation of lumpfish (Cyclopterus lumpus) across the North Atlantic: implications for conservation and aquaculture.

Demand for lumpfish (Cyclopterus lumpus) has increased exponentially over the last decade, both for their roe, which is used as a caviar substitute, and increasingly also as cleaner fish to control sea lice in salmon farming. The species is classified as Near Threatened by the IUCN and there are growing concerns that over-exploitation of wild stocks and translocation of hatchery-reared lumpfish may compromise the genetic diversity of native populations. We carried out a comparative analysis of genetic and phenotypic variation across the species' range to estimate the level of genetic and phenotypic differentiation, and determined patterns of gene flow at spatial scales relevant to management. We found five genetically distinct groups located in the West Atlantic (USA and Canada), Mid Atlantic (Iceland), East Atlantic (Faroe Islands, Ireland, Scotland, Norway and Denmark), English Channel (England) and Baltic Sea (Sweden). Significant phenotypic differences were also found, with Baltic lumpfish growing more slowly, attaining a higher condition factor and maturing at a smaller size than North Atlantic lumpfish. Estimates of effective population size were consistently low across the North East Atlantic (Iceland, Faroe Islands and Norway), the area where most wild lumpfish are fished for their roe, and also for the aquaculture industry. Our study suggests that some lumpfish populations are very small and have low genetic diversity, which makes them particularly vulnerable to over-exploitation and genetic introgression. To protect them we advocate curtailing fishing effort, closing the breeding cycle of the species in captivity to reduce dependence on wild stocks, restricting the translocation of genetically distinct populations, and limiting the risk of farm escapes.

Principales patologías diagnosticadas por el servicio de Neurología en urgencias e internación en un hospital universitario en Colombia 2020 - 2021 / Main pathologies diagnosed by the Neurology service in emergencies and hospitalization in a university hospital in Colombia 2020 - 2021

RESUMEN INTRODUCCIÓN: Las enfermedades neurológicas constituyen gran parte de las urgencias médicas (10 %-15%). Por ende, se hace necesario el reconocimiento de la distribución de las principales condiciones tanto en urgencias como en hospitalización. Se decidió caracterizar la distribución real de la enfermedad neurológica atendida en un hospital universitario de tercer nivel en Boyacá. MATERIALES Y MÉTODOS: Estudio descriptivo de corte transversal. RESULTADOS: 1203 pacientes con edad promedio de 56,2 (± 21,2) años, la mayoría de sexo masculino, casi la mitad de ellos nivel de educación básica primaria. De un total de 81 diagnósticos, se caracterizaron clínica y sociodemográficamente los 12 primeros, encontrando que en el área de urgencias prevalece la enfermedad cerebrovascular, epilepsia, cefalea, polineuropatia y vértigo. CONCLUSIONES. Los principales motivos de interconsulta del servicio son la enfermedad cerebrovascular y el delirio en urgencias e internación respectivamente, siendo generadas principalmente por medicina general, medicina interna y unidad de cuidado intensivo.

ABSTRACT INTRODUCTION: Neurological diseases constitute a large proportion of medical emergencies (10%-15%). Knowledge of the distribution of the main neurological conditions both in the emergency room and in hospitalization is necessary. The real distribution of neurological disease treated in a tertiary university hospital in Boyacá can be characterized. METHODOLOGY: Descriptive cross-sectional study. Results: 1203 patients with a mean age of 56.2 (± 21.2) years, most of them male, almost half of them with basic primary education. From a total of 81 diagnoses, the first 12 were characterized clinically and socio demographically, we found that in the emergency department, cerebrovascular disease, epilepsy, headache, polyneuropathy and vertigo prevailed. CONCLUSIONS. The main reasons for consultation were cerebrovascular disease and delirium in the emergency department and hospitalization, respectively, being mainly generated by internal medicine and the intensive care unit.

Afecciones, manifestaciones y repercusiones neurológicas del COVID-19 / COVID-19 conditions, manifestations, and neurological repercussions

Resumen Inetroducción: El Síndrome Respiratorio Agudo Severo (SARS-CoV-2) es la entidad patológica responsable de la actual pandemia que no solo genera un cuadro respiratorio distintivo sino que también se ha asociado con múltiples mecanismos de invasión al sistema nervioso central (SNC). Objetivo: Determinar las afecciones, manifestaciones y repercusiones neurológicas que puede generar la infección por SARS-CoV-2. Métodos: Revisión de la literatura científica de pacientes con infección por SARS-CoV-2, en quienes se evaluó desarrollo de afecciones, manifestaciones y repercusiones neurológicas, desenlace seleccionado en los estudios, presencia de afecciones micro y macroscópicas del SNC y periférico (SNP). Resultados: Se estudiaron 40 artículos que analizaban la familia y estructura del SARS-CoV-2, mecanismos fisiopatológicos, manifestaciones clínicas neurológicas y las posibles repercusiones a nivel sistema nervioso central. Conclusiones: El SARS-CoV-2 es una entidad patológica que se asocia a distintos mecanismos de intervención neurológica, por medio de infección directa al SNC, secundario a un proceso parainfeccioso y postinfeccioso, relacionado con el síndrome de tormenta de citoquinas, daño endotelial, trastornos trombóticos, adicionalmente de secundario a hipoxia, hipoxemia y fallo multiorgánico.

Abstract Introduction: Severe Acute Respiratory Syndrome (SARS-CoV-2) is the pathological entity responsible for the current pandemic that not only generates a distinctive respiratory pattern but has also been associated with multiple mechanisms of invasion of the central nervous system (CNS). Objective: To determine the affections, manifestations and neurological repercussions that SARS-CoV-2 infection can generate. Methods: Review of the scientific literature of patients with SARS-CoV-2 infection, in whom the development of conditions, manifestations and neurological repercussions, selected outcome in the studies, presence of micro and macroscopic conditions of the CNS and peripheral (PNS) were evaluated. Results: 40 articles were included where the family and structure of SARS-CoV-2, pathophysiological mechanisms, neurological clinical manifestations, and possible repercussions at the central nervous system level were analyzed. Conclusions: SARS-CoV-2 is a pathological entity that is associated with different mechanisms of neurological intervention, through direct infection to the CNS, secondary to a parainfectious and postinfectious process, related to cytokine storm syndrome, endothelial damage, thrombotic disorders, in addition to secondary to hypoxia, hypoxemia and multiple organ failure.

The Neviaser portal for superior glenoid anchor insertion: an anatomic study.

PURPOSE: To measure the angular relationship between the Neviaser portal and the superior glenoid labrum in 60 cadaveric specimens to determine whether this portal can be used for reliable anchor placement. METHODS: The Neviaser portal of 30 left and 30 right unpaired dry cadaveric scapulae with clavicles were measured by a single observer using an analogue vernier caliper. The angular relationship between the Neviaser portal and the 12 o'clock position of the glenoid labrum was calculated. RESULTS: 13 of the 60 scapulae were excluded from analysis, because the Neviaser portal was medial to the glenoid rim making safe anchor insertion unfeasible. For the remaining 47 scapulae, the mean angles α and ß were 58.2º and 57.9º, respectively. Compared with the ideal angles α and ß of 30º and 0º, respectively, all the 47 Neviaser portals were more posterior (relative to the 12 o'clock position) and closer to the transverse plane, making insertion of suture anchors in the optimum position unfeasible, except for one that was within 10º of the ideal angles in both planes. CONCLUSION: Reliable insertion of suture anchors at the 12 o'clock position of the glenoid labrum through the Neviaser portal is unfeasible in most patients.

Absceso encefálico secundario a estafilococcemia: caso clínico / Brain abscess secondary to staphylococcemia: Case report

RESUMEN Los abscesos encefálicos son enfermedades infecciosas poco frecuentes. El Staphylococcus aureus tiene un papel importante como causa de infecciones intrahospitalaria y extrahospitalarias; la presentación más común es la infección de piel y tejidos blandos, aunque también puede afectar otros órganos, como corazón y cerebro. CASO: Una mujer de 19 años presentó artralgia de rodilla derecha, vómitos, petequias de 3 días de evolución. Se diagnosticó septicemia por S. aureus que había producido secundariamente un absceso cerebral en región parietal izquierda con sintomatología similar a un accidente cerebrovascular, por hemiparesia derecha. DISCUSION: El absceso encefálico es poco frecuente, y puede presentar sintomatología similar a una lesión vascular. Se asocia a varios factores de riesgo, y se debe tener en cuenta que hay tres mecanismos de entrada del microorganismo al sistema nervioso central. El diagnóstico en imagenológico y su tratamiento dependerá del antibiograma.

SUMMARY Brain abscesses are infrequent. Staphylococcus aureus has an important role as cause of intrahospital and extra hospital infections; the most common nosological entity is infection of soft tissues, although it can also affect other organs such as heart or brain. CASE: A 19-year-old woman presented with a 3-day course of arthralgia in the right knee, vomiting, and petechiae. S. aureus septicemia was diagnosed, presenting as an abscess with a stroke-like right hemiparesis. DISCUSSION: Brain abscesses are uncommon; presenting symptoms might be similar to a stroke. They are associated with several risk factors, three mechanisms of entry of the microorganism into the central nervous system have been recognized. The diagnosis is radiologic and its treatment will depend on the antibiogram.