Far infrared micro-spectroscopy: an innovative method to detect individual metal-organic framework particles.

The purpose of this study is to extend the spectral range of a differential method of infrared micro-spectroscopy in order to allow the accurate detection of nanoparticles of interest for biomedical applications. Among these, metal-organic framework (MOF) nanoparticles have attracted increasing interest due to their capacity to incorporate high drug payloads, biodegradability, and possibility of tailoring their surfaces by grafting specific ligands. However, MOF particle detection in biological media without grafting or incorporating fluorescent molecules is challenging. We took advantage here of the presence of the specific absorption bands of nanoscale MOFs in far infrared in order to individually discriminate them. Here we show that single MOF nanoparticles can be imaged with a spatial resolution of a few tens of nanometers.

Deep Learning-Based Estimation of Radiographic Position to Automatically Set Up the X-Ray Prime Factors.

Radiation dose and image quality in radiology are influenced by the X-ray prime factors: KVp, mAs, and source-detector distance. These parameters are set by the X-ray technician prior to the acquisition considering the radiographic position. A wrong setting of these parameters may result in exposure errors, forcing the test to be repeated with the increase of the radiation dose delivered to the patient. This work presents a novel approach based on deep learning that automatically estimates the radiographic position from a photograph captured prior to X-ray exposure, which can then be used to select the optimal prime factors. We created a database using 66 radiographic positions commonly used in clinical settings, prospectively obtained during 2022 from 75 volunteers in two different X-ray facilities. The architecture for radiographic position classification was a lightweight version of ConvNeXt trained with fine-tuning, discriminative learning rates, and a one-cycle policy scheduler. Our resulting model achieved an accuracy of 93.17% for radiographic position classification and increased to 95.58% when considering the correct selection of prime factors, since half of the errors involved positions with the same KVp and mAs values. Most errors occurred for radiographic positions with similar patient pose in the photograph. Results suggest the feasibility of the method to facilitate the acquisition workflow reducing the occurrence of exposure errors while preventing unnecessary radiation dose delivered to patients.

Local terahertz microspectroscopy with λ/100 spatial resolution.

We have extended the spectral range of a differential method of infrared microspectroscopy in order to operate in the terahertz spectral region. We show on samples of graphite embedded in a matrix of polymers that the spatial resolution is practically independent of the wavelength and is at least λ/100. This method aims at performing "chemical mapping" of various objects since it is sensitive only to the imaginary part of the index of refraction.

A Porous Media Model for Blood Flow within Reticulated Foam.

A porous media model is developed for non-Newtonian blood flow through reticulated foam at Reynolds numbers ranging from 10-8 to 10. This empirical model effectively divides the pressure gradient versus flow speed curve into three regimes, in which either the non-Newtonian viscous forces, the Newtonian viscous forces, or the inertial fluid forces are most prevalent. When compared to simulation data of blood flow through two reticulated foam geometries, the model adequately captures the pressure gradient within all three regimes, especially that within the Newtonian regime where blood transitions from a power-law to a constant viscosity fluid.

Use of antifungal agents in pediatric and adult high-risk areas.

The purpose of this investigation was to describe the characteristics of the use of systemic antifungal agents (AFAs) and to evaluate their appropriateness of use. A prospective drug-utilisation study was conducted in intensive-care areas: haematology-oncology services and transplant units. Data were collected in three periods over 9 months. The required sample size was determined to be 113 patients (margin of error ±7%, 95% confidence interval [CI]), assuming a variability of 50%. Two different investigator groups evaluated the appropriateness of use separately; Cohen's Kappa index was used to calculate the degree of agreement between groups. A total of 114 patients we included, of which 62 (54.4%) were children. A total of 150 prescriptions were administered; fluconazole was the most frequently prescribed (38%), followed by liposomal amphotericin B (22.7%) and caspofungin (18.7%). The indications were: (1) pre-emptive treatment of Candida in non-neutropaenic critically ill patients (35.1%), (2) treatment of systemic fungal infection (24.6%), (3) prophylaxis for systemic fungal infection (SFI) in immunocompromised patients (16.7%), (4) prophylaxis of SFI in transplant recipients (12.3%), (5) prophylaxis of SFI in preterm infants (5.3%), (6) treatment of SFI in neonates (6.1%). The Kappa index showed a substantial agreement (Kappa = 0.73). The indications were considered to be inappropriate in 71 (47.3%) episodes. The indications or dosages were inappropriate in 79 cases (52.7%). The indications, dosages or duration of treatment were inappropriate in 83 cases (55.3%). We conclude that AFAs are prescribed for a significant number of inappropriate indications.

Arthroscopic tibiotalocalcaneal arthrodesis. Technique, indications and results. / Panartrodesis artroscópica de tobillo. Indicaciones, técnica y resultados.

BACKGROUND: Arthroscopic tibiotalocalcaneal arthrodesis with a retrograde nail is performed as a minimally invasive technique in patients without improvement in conservative treatment of osteoarthritis. Complications and hospital stay after surgery are less using this technique when they are compared with open ones. MATERIALS AND METHODS: We review retrospectively from 2016 to 2019 seven patients subjected to a posterior arthroscopic tibiotalocalcaneal arthrodesis with a retrograde intramedullary nail. AOFAS scale was used to assess functional results and we collected other data as complications, time required for bony union, time of nonweight-bearing and scale of satisfaction. We also made a description of the technique we performed. RESULTS: The mean hospital stay was 3.43±0.53 days, patients have well functional results and complications were very low. It was noticed tibiotalar bony union in about 86% of patients 10 weeks after surgery and subtalar bony union in about 71% 20 weeks after surgery. Nonweight-bearing was made using a cast for 4 weeks and later, it was changed for Walker allowing patients partial weight-bearing until 10 weeks after surgery. One patient had wound complications and he needed later surgery and another presented tibiotalar pseudoarthrosis, although without symptoms. CONCLUSION: Posterior arthroscopic tibiotalocalcaneal arthrodesis offers very good results with a high rate of bony union, few complications, and minimal nonweight-bearing time. This technique could be used in patients without major deformities, especially in those at high risk of complications from the surgical wound.

Amino acids biosynthesis and nitrogen assimilation pathways: a great genomic deletion during eukaryotes evolution.

BACKGROUND: Besides being building blocks for proteins, amino acids are also key metabolic intermediates in living cells. Surprisingly a variety of organisms are incapable of synthesizing some of them, thus named Essential Amino Acids (EAAs). How certain ancestral organisms successfully competed for survival after losing key genes involved in amino acids anabolism remains an open question. Comparative genomics searches on current protein databases including sequences from both complete and incomplete genomes among diverse taxonomic groups help us to understand amino acids auxotrophy distribution. RESULTS: Here, we applied a methodology based on clustering of homologous genes to seed sequences from autotrophic organisms Saccharomyces cerevisiae (yeast) and Arabidopsis thaliana (plant). Thus we depict evidences of presence/absence of EAA biosynthetic and nitrogen assimilation enzymes at phyla level. Results show broad loss of the phenotype of EAAs biosynthesis in several groups of eukaryotes, followed by multiple secondary gene losses. A subsequent inability for nitrogen assimilation is observed in derived metazoans. CONCLUSIONS: A Great Deletion model is proposed here as a broad phenomenon generating the phenotype of amino acids essentiality followed, in metazoans, by organic nitrogen dependency. This phenomenon is probably associated to a relaxed selective pressure conferred by heterotrophy and, taking advantage of available homologous clustering tools, a complete and updated picture of it is provided.

Sequential chemotherapy regimen of induction with panitumumab and paclitaxel followed by radiotherapy and panitumumab in patients with locally advanced head and neck cancer unfit for platinum derivatives. The phase II, PANTERA/TTCC-2010-06 study.

BACKGROUND: Sequential treatment of Panitumumab (Pb) plus Paclitaxel (Px) as induction treatment (IT) followed by concurrent bioradiotherapy (Bio-RT) with Pb may be an alternative for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) in patients ineligible for high-dose cisplatin therapy. METHODS: Phase II, single-arm, multicentre study, with two-stage design, in patients ≥ 18 years with stage III-IVa-b LA-SCCHN unfit for platinum. Patients received Px + Pb (9 weeks) as IT followed by Bio-RT + Pb. Primary endpoint: overall response rate (ORR) after IT, defined as: more than 70% of patients achieving complete response (CR) or partial response (PR) to IT. Secondary end-points: progression-free survival, organ preservation rate, safety profile. RESULTS: Study ended prematurely (51 patients) due to slow recruitment. ORR: 66.7% (95% CI: 53.7-79.6), 8 (15.7%) CR and 26 (51.0%) PR. 39 patients (76%) completed radiotherapy (RT). Pb and/or Px-related adverse events (AEs) grade 3-4: 56.9% during IT and 63.4% during the concomitant phase, of which most common were skin toxicity (33.3%). Five deaths occurred during treatment, two of them (3.9%) were Pb and/or Px-related. CONCLUSIONS: Although underpowered, ORR was higher than the pre-specified boundary for considering the treatment active. Although Px + Pb as IT provides some benefit, the safety profile is worse than expected. To consider Pb + Px as IT as an alternative for platinum-unsuitable LA-SCCHN, further research/investigation would be needed.

Protein dynamics control of electron transfer in photosynthetic reaction centers from Rps. sulfoviridis.

In the cycle of photosynthetic reaction centers, the initially oxidized special pair of bacteriochlorophyll molecules is subsequently reduced by an electron transferred over a chain of four hemes of the complex. Here, we examine the kinetics of electron transfer between the proximal heme c-559 of the chain and the oxidized special pair in the reaction center from Rps. sulfoviridis in the range of temperatures from 294 to 40 K. The experimental data were obtained for three redox states of the reaction center, in which one, two, or three nearest hemes of the chain are reduced prior to special pair oxidation. The experimental kinetic data are analyzed in terms of a Sumi-Marcus-type model developed in our previous paper,1 in which similar measurements were reported on the reaction centers from Rps. viridis. The model allows us to establish a connection between the observed nonexponential electron-transfer kinetics and the local structural relaxation dynamics of the reaction center protein on the microsecond time scale. The activation energy for relaxation dynamics of the protein medium has been found to be around 0.1 eV for all three redox states, which is in contrast to a value around 0.4-0.6 eV in Rps. viridis.1 The possible nature of the difference between the reaction centers from Rps. viridis and Rps. sulfoviridis, which are believed to be very similar, is discussed. The role of the protein glass transition at low temperatures and that of internal water molecules in the process are analyzed.

Chemical mapping of the distribution of viruses into infected bacteria with a photothermal method.

We show that an infrared spectromicroscopy method based on a photo-thermal effect, is able to localize single viruses as well when they are isolated and when they are located inside the bacteria they have infected. In this latter case, although the topography performed by an AFM cannot image the viruses, the AFMIR is able to do so. In addition, we are able to determine different stages of the bacteria infection.

An algorithm to infer similarity among cell types and organisms by examining the most expressed sequences.

Following sequence alignment, clustering algorithms are among the most utilized techniques in gene expression data analysis. Clustering gene expression patterns allows researchers to determine which gene expression patterns are alike and most likely to participate in the same biological process being investigated. Gene expression data also allow the clustering of whole samples of data, which makes it possible to find which samples are similar and, consequently, which sampled biological conditions are alike. Here, a novel similarity measure calculation and the resulting rank-based clustering algorithm are presented. The clustering was applied in 418 gene expression samples from 13 data series spanning three model organisms: Homo sapiens, Mus musculus, and Arabidopsis thaliana. The initial results are striking: more than 91% of the samples were clustered as expected. The MESs (most expressed sequences) approach outperformed some of the most used clustering algorithms applied to this kind of data such as hierarchical clustering and K-means. The clustering performance suggests that the new similarity measure is an alternative to the traditional correlation/distance measures typically used in clustering algorithms.

Essential amino acid usage and evolutionary nutrigenomics of eukaryotes--insights into the differential usage of amino acids in protein domains and extra-domains.

Nutrigenomics studies the effects of nutrients on the genome, transcriptome and proteome of organisms, and here an evolutionary standpoint on this new discipline is presented. It is well known that metazoan organisms are unable to synthesize all amino acids necessary to produce their proteins and that these essential amino acids (EAA) must be acquired from the diet. Here, we tested the hypothesis that conserved regions such as protein domains (DM) have different essentiality indexes and use different sets of amino acids when compared to extra-domains (ED) and proteins without mapped domains (WD). We found that auxotrophic organisms have a tendency to use less EAAs in DM than do prototrophic ones. Looking into the amino acid usage of eukaryotic proteins downloaded from KEGG and COG, we showed that WD have a usage of amino acids closer to DM, which suggests that proteins without mapped domains behave as large domains. Using an ED index that shows the proportion of prevalent amino acids in ED, a differential usage of amino acids in domains versus extra-domains was demonstrated. Protein domains were shown to be enriched with a higher number of EAA, and it may be related to the fact that these amino acids had lost their biosynthetic pathways in metazoans during a great amino acid pathway deletion, followed by a nutritional constraint that may have happened close to the conquest of the terrestrial environment. Thus, the proportion of EAA outside domains could have decreased during evolution due to nutritional constraints.

Testing the performance of automated annotation of ESTs with the Kegg Orthology (KO) database demonstrates lack of completeness of clusters.

The KEGG Orthology (KO) database was tested as a source for automated annotation of expressed sequence tags (ESTs). We used a control experiment where every EST was assigned to its cognate protein, and an annotation experiment where the ESTs were annotated by proteins from other organisms. Analyzing the results, we could assign classes to the annotation: correct, changed and speculated. The correct annotation ranged from 57 (Caenorhabditis elegans) to 81% (Homo sapiens). In spite of the changed annotation being low (1 in H. sapiens to 9% in Arabidopsis thaliana), the speculation was very high (18 in H. sapiens to 38% in C. elegans). We propose eliminating part of the speculated annotation using the KEGG Genes database to enrich KO clusters, decreasing the speculation from 38 to 2% in C. elegans. Thus, the KO database still demands some effort for moving sequences from Kegg GENES to KO, to complement the annotation performance.

A procedure to recruit members to enlarge protein family databases--the building of UECOG (UniRef-Enriched COG Database) as a model.

A procedure to recruit members to enlarge protein family databases is described here. The procedure makes use of UniRef50 clusters produced by UniProt. Current family entries are used to recruit additional members based on the UniRef50 clusters to which they belong. Only those additional UniRef50 members that are not fragments and whose length is within a restricted range relative to the original entry are recruited. The enriched dataset is then limited to contain only genomes from selected clades. We used the COG database - used for genome annotation and for studies of phylogenetics and gene evolution - as a model. To validate the method, a UniRef-Enriched COG0151 (UECOG) was tested with distinct procedures to compare recruited members with the recruiters: PSI-BLAST, secondary structure overlap (SOV), Seed Linkage, COGnitor, shared domain content, and neighbor-joining single-linkage, and observed that the former four agree in their validations. Presently, the UniRef50-based recruitment procedure enriches the COG database for Archaea, Bacteria and its subgroups Actinobacteria, Firmicutes, Proteobacteria, and other bacteria by 2.2-, 8.0-, 7.0-, 8.8-, 8.7-, and 4.2-fold, respectively, in terms of sequences, and also considerably increased the number of species.

[Forestier-Rotes-Querol's disease. Ossification of the anterior cervical longitudinal ligament as a cause of dysphagia]. / Enfermedad de Forestier-Rotes-Querol. Osificación del ligamento longitudinal cervical anterior como causa de disfagia.

Forestier's disease or diffuse idiophatic skeletal hyperostosis is a systemic reumathological abnormality of unknown etiology. It produces calcificationossification of the anterior longitudinal ligament. The low dorsal region is the most affected in the raquis. These patients are tipically asymptomatic or with few symptoms (minimal joint pain, spinal pain, stiffness). Dysphagia is the most common symptom when the disease affects the cervical spine; less frequent is dyspnea, both secondary to extrinsic compression of the esophagus and trachea. Neurological complaints are quite rare. In the 1970s Resnick described specific radiological criteria for the diagnosis of Forestier's disease that are still used today. It affects men more frequently than women (2:1); the peak occurrence is in patients in their 60s. We present two cases diagnosed by severe difficulty with deglution, a 84 years-old woman and a 54 years-old man; we operated on them for surgical decompression of the esophagus with resection of osteophytes C3-C4 and C5-C6 respectively through a conventional anterolateral neck approach. Relief of difficulty in swallowing was immediately ensued.

Analysis of nano-chemical mapping performed by an AFM-based ("AFMIR") acousto-optic technique.

In this paper, we analyze in detail a new method of infrared micro-spectroscopy, which aims at performing "chemical mapping" of various objects with sub-wavelength lateral resolution by using the infrared vibrational signature characterizing different molecular species. Its principle consists in an atomic force microscope tip, probing the local transient deformation induced by an infrared pulsed laser tuned at a sample absorbing wavelength. The cantilever oscillates at resonant frequencies, which amplitudes can be correlated with local absorption. We show that the system acts as an amplifier of extremely small motions induced by optical absorption and that different frequencies provide different informations, leading to a full description of the sample deformation. We estimate also the influence of the light confinement in the sample and exemplify the accuracy of the method by mapping Escherichia coli bacteria at different cantilever frequencies.

Development of SRS.php, a Simple Object Access Protocol-based library for data acquisition from integrated biological databases.

Data integration has become an important task for biological database providers. The current model for data exchange among different sources simplifies the manner that distinct information is accessed by users. The evolution of data representation from HTML to XML enabled programs, instead of humans, to interact with biological databases. We present here SRS.php, a PHP library that can interact with the data integration Sequence Retrieval System (SRS). The library has been written using SOAP definitions, and permits the programmatic communication through webservices with the SRS. The interactions are possible by invoking the methods described in WSDL by exchanging XML messages. The current functions available in the library have been built to access specific data stored in any of the 90 different databases (such as UNIPROT, KEGG and GO) using the same query syntax format. The inclusion of the described functions in the source of scripts written in PHP enables them as webservice clients to the SRS server. The functions permit one to query the whole content of any SRS database, to list specific records in these databases, to get specific fields from the records, and to link any record among any pair of linked databases. The case study presented exemplifies the library usage to retrieve information regarding registries of a Plant Defense Mechanisms database. The Plant Defense Mechanisms database is currently being developed, and the proposal of SRS.php library usage is to enable the data acquisition for the further warehousing tasks related to its setup and maintenance.

Sex-biased gene flow in African Americans but not in American Caucasians.

We have previously shown evidence of strong sex-biased genetic blending in the founding and ongoing history of the Brazilian population, with the African and Amerindian contribution being highest from maternal lineages (as measured by mitochondrial DNA) and the European contribution foremost from paternal lineages (estimated from Y-chromosome haplogroups). The same phenomenon has been observed in several other Latin American countries, suggesting that it might constitute a universal characteristic of the Iberian colonization of the Americas. However, it has also recently been detected in the Black population of the United States. We thus wondered if the same could be observed in American Caucasians. To answer that question, we retrieved 1387 hypervariable I Caucasian mitochondrial DNA sequences from the FBI population database and established their haplogroups and continental geographical sources. In sharp contrast with the situation of the Caucasian population of Latin American countries, only 3.1% of the American Caucasian sequences had African and/or Amerindian origin. To explain this discrepancy we propose that the finding of elevated genomic contributions from European males and Amerindian or African females depends not only on the occurrence of directional mating, but also on the "racial" categorization of the children born from these relations. In this respect, social practices in Latin America and in the United States diverge considerably; in the former socially significant "races" are normally designated according to physical appearance, while in the latter descent appears to be the most important factor.

Effects of sample re-sequencing and trimming on the quality and size of assembled consensus sequences.

The production of nucleic acid sequences by automatic DNA sequencer machines is always associated with some base-calling errors. In order to produce a high-quality DNA sequence from a molecule of interest, researchers normally sequence the same sample many times. Considering base-calling errors as rare events, re-sequencing the same molecule and assembling the reads produced are frequently thought to be a good way to generate reliable sequences. However, a relevant question on this issue is: how many times the sample needs to be re-sequenced to minimize costs and achieve a high-fidelity sequence? We examined how both the number of re-sequenced reads and PHRED trimming parameters affect the accuracy and size of final consensus sequences. Hundreds of single-pool reaction pUC18 reads were generated and assembled into consensus sequences with CAP3 software. Using local alignment against the published pUC18 cloning vector sequence, the position and number of errors in the consensus were identified and stored in MySQL databases. Stringent PHRED trimming parameters proved to be efficient for the reduction of errors; however, this procedure also decreased consensus size. Moreover, re-sequencing did not have a clear effect on the removal of consensus errors, although it was able to slightly increase consensus.

Delayed intracerebral hemorrhage after ventriculoperitoneal shunt insertion. Case report and literature review.

We present another case of delayed intracerebral hemorrhage after a ventriculoperitoneal (VP) shunting procedure. In this case, a right occipital intraparenchymal hematoma and associated intraventricular hemorrhage occurred six days after the operation for hydrocephalus secondary to subarachnoid hemorrhage in a 64 year old woman. It is a rare complication of VP shunting, with few cases reported previously in the literature. The presumed mechanism is the erosion of a cerebral blood vessel secondary to a close contact with the ventricular catheter; bleeding disorder, vascular malformation, head trauma or brain tumor were excluded in this patient.