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Cutaneous leishmaniasis (CL) is a neglected disease caused by an intracellular parasite of the Leishmania genus. CL lacks tools that allow its understanding and treatment follow-up. This article presents the use of metrical and optical tools for the analysis of the temporal evolution of treated skin ulcers caused by CL in an animal model. Leishmania braziliensis and L. panamensis were experimentally inoculated in golden hamsters, which were treated with experimental and commercial drugs. The temporal evolution was monitored by means of ulcers’ surface areas, as well as absorption and scattering optical parameters. Ulcers’ surface areas were obtained via photogrammetry, which is a procedure that allowed for 3D modeling of the ulcer using specialized software. Optical parameters were obtained from a spectroscopy study, representing the cutaneous tissue’s biological components. A one-way ANOVA analysis was conducted to identify relationships between both the ulcers’ areas and optical parameters. As a result, ulcers’ surface areas were found to be related to the following optical parameters: epidermis thickness, collagen, keratinocytes, volume-fraction of blood, and oxygen saturation. This study is a proof of concept that shows that optical parameters could be associated with metrical ones, giving a more reliable concept during the assessment of a skin ulcer’s healing.

Abstract The Nash embedding theorem demonstrates that any compact manifold can be isometrically embedded in a Euclidean space. Assuming the complex brain states form a high-dimensional manifold in a topological space, we propose a manifold learning framework, termed Thought Chart, to reconstruct and visualize the manifold in a low-dimensional space. Furthermore, it serves as a data-driven approach to discover the underlying dynamics when the brain is engaged in a series of emotion and cognitive regulation tasks. EEG-based temporal dynamic functional connectomes are created based on 20 psychiatrically healthy participants’ EEG recordings during resting state and an emotion regulation task. Graph dissimilarity space embedding was applied to all the dynamic EEG connectomes. In order to visualize the learned manifold in a lower dimensional space, local neighborhood information is reconstructed via k-nearest neighbor-based nonlinear dimensionality reduction (NDR) and epsilon distance-based NDR. We showed that two neighborhood constructing approaches of NDR embed the manifold in a two-dimensional space, which we named Thought Chart. In Thought Chart, different task conditions represent distinct trajectories. Properties such as the distribution or average length in the 2-D space may serve as useful parameters to explore the underlying cognitive load and emotion processing during the complex task. In sum, this framework is a novel data-driven approach to the learning and visualization of underlying neurophysiological dynamics of complex functional brain data.

Este artículo presenta el uso de técnicas de adquisición y procesamiento imágenes multi-espectrales para el análisis de tejido biológico, específi camente cardiovascular. Se presentan diferentes tipos de arquitecturas, tales como los basados en fi ltros de interferencia y los que no requieren el uso de estos fi ltros. También se presentan ventajas y desventajas de ambos sistemas, así como técnicas para la calibración del color y fuentes de ruido. Además, se presentan dos tipos de técnicas de procesamiento de imágenes biológicas: análisis de componentes principales (PCA) y análisis de componentes independientes (ICA). Estas técnicas se han utilizado en el análisis de imágenes biológicas tales como piel humana y tejido gástrico. Sin embargo, y hasta nuestro conocimiento, dichas técnicas no han sido ampliamente utilizados en el análisis de tejido cardiovascular, de modo que se hace un enfoque especial en este tipo de tejido. Como resultado, se encontró que los métodos de PCA e ICA permiten la obtención de imágenes con una mejor defi nición de la morfología del tejido cardiovascular.

Intimidated by the scope of possible illness in your AIDS patients? Jump start your diagnosis with a working knowledge of the most frequently encountered syndromes. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is a neglected tropical disease that requires novel tools for its understanding, diagnosis, and treatment follow-up. In the cases of other cutaneous pathologies, such as cancer or cutaneous ulcers due to diabetes, optical diffuse reflectance-based tools and methods are widely used for the investigation of those illnesses. These types of tools and methods offer the possibility to develop portable diagnosis and treatment follow-up systems. In this article, we propose the use of a three-layer diffuse reflectance model for the study of the formation of cutaneous ulcers caused by CL. The proposed model together with an inverse-modeling procedure were used in the evaluation of diffuse-reflectance spectral signatures acquired from cutaneous ulcers formed in the dorsal area of 21 golden hamsters inoculated with Leishmanisis braziliensis. As result, the quantification of the model’s variables related to the main biological parameters of skin were obtained, such as: diameter and volumetric fraction of keratinocytes, collagen; volumetric fraction of hemoglobin, and oxygen saturation. Those parameters show statistically significant differences among the different stages of the CL ulcer formation. We found that these differences are coherent with histopathological manifestations reported in the literature for the main phases of CL formation.

Background :Changes in oxygenation occur during one-lung ventilation (OLV) due to intrapulmonary shunt. Although arterial oxygenation is generally adequate, there are no studies evaluating the effect of these changes on cerebral oxygenation. Materials and Methods :Cerebral oxygenation (rSO 2 ), heart rate (HR), blood pressure (BP), oxygen saturation (SaO 2 ), and end-tidal carbon dioxide (ETCO 2 ) were prospectively monitored during OLV in adults. Cerebral oxygenation was monitored using near infrared spectroscopy. No clinical decisions were made based on the rSO2 value. BP and HR were the inspired oxygen concentration was adjusted as needed to maintain the SaO 2 ≥ 95%. Results :The study cohort included 40 adult patients. 18,562 rSO 2 values were collected during OLV. The rSO 2 was ≥ baseline at 3,593 of the 18,562 data points (19%). The rSO2 was 0-9 ≤ baseline in 7,053 (38%) of the readings, 10-19 ≤ baseline in 4,084 (22%) of the readings, and 20-29 ≤ baseline in 3,898 (21%) of the readings. 2,599 (14%) of the rSO 2 values were less than 75% of the baseline value. Thirteen patients (32.5%) had at least one rSO2 value that was less than 75% of the baseline. Eight patients (20%) had rSO 2 values less than 75% of baseline for ≥ 25% of the duration of OLV. These patients were older (63.7 ± 10.2 vs 54.6 ± 9.8 years, P < 0.025), weighed more (95.8 ± 17.4 vs 82.6 ± 14.6 kgs, P =0.038), and were more likely to be ASA III vs II (7 of 8 versus 25 of 32, relative risk 1.75) than the remainder of the cohort. Conclusions :Significant changes in rSO2 occur during OLV for thoracic surgical procedures. Future studies are needed to determine the impact of such changes on the postoperative course of these patients.

Abstract Background L-2-hydroxyglutaric aciduria is a metabolic repair deficiency characterized by elevated levels of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid. Neurological signs associated with the disease in humans and dogs include seizures, ataxia and dementia. Case presentation Here we describe an 8 month old Yorkshire terrier that presented with episodes of hyperactivity and aggressive behavior. Between episodes, the dog’s behavior and neurologic examinations were normal. A T2 weighted MRI of the brain showed diffuse grey matter hyperintensity and a urine metabolite screen showed elevated 2-hydroxyglutaric acid. We sequenced all 10 exons and intron-exon borders of L2HGDH from the affected dog and identified a homozygous A to G transition in the initiator methionine codon. The first inframe methionine is at p.M183 which is past the mitochondrial targeting domain of the protein. Initiation of translation at p.M183 would encode an N-terminal truncated protein unlikely to be functional. Conclusions We have identified a mutation in the initiation codon of L2HGDH that is likely to result in a non-functional gene. The Yorkshire terrier could serve as an animal model to understand the pathogenesis of L-2-hydroxyglutaric aciduria and to evaluate potential therapies.

Abstract Background The zebrafish Danio rerio is an important model system for drug discovery and to study cardiovascular development. Using a laser-scanning confocal microscope, we have developed a non-invasive method of measuring cardiac performance in zebrafish embryos and larvae that obtains cardiovascular parameters similar to those obtained using Doppler echocardiography in mammals. A laser scan line placed parallel to the path of blood in the dorsal aorta measures blood cell velocity, from which cardiac output and indices of vascular resistance and contractility are calculated. Results This technique, called laser-scanning velocimetry, was used to quantify the effects of pharmacological, developmental, and genetic modifiers of cardiac function. Laser-scanning velocimetry was applied to analyze the cardiovascular effects of morpholino knockdown of osmosensing scaffold for MEKK3 (OSM), which when mutated causes the human vascular disease cerebral cavernous malformations. OSM-deficient embryos had a constricted aortic arch and markedly increased peak cell velocity, a characteristic indicator of aortic stenosis. Conclusion These data validate laser-scanning velocimetry as a quantitative tool to measure cardiovascular performance for pharmacological and genetic analysis in zebrafish, which requires no specialized equipment other than a laser-scanning confocal microscope.

Abstract Background Robot-mediated therapies offer entirely new approaches to neurorehabilitation. In this paper we present the results obtained from trialling the GENTLE/S neurorehabilitation system assessed using the upper limb section of the Fugl-Meyer (FM) outcome measure. Methods We demonstrate the design of our clinical trial and its results analysed using a novel statistical approach based on a multivariate analytical model. This paper provides the rational for using multivariate models in robot-mediated clinical trials and draws conclusions from the clinical data gathered during the GENTLE/S study. Results The FM outcome measures recorded during the baseline (8 sessions), robot-mediated therapy (9 sessions) and sling-suspension (9 sessions) was analysed using a multiple regression model. The results indicate positive but modest recovery trends favouring both interventions used in GENTLE/S clinical trial. The modest recovery shown occurred at a time late after stroke when changes are not clinically anticipated. Conclusion This study has applied a new method for analysing clinical data obtained from rehabilitation robotics studies. While the data obtained during the clinical trial is of multivariate nature, having multipoint and progressive nature, the multiple regression model used showed great potential for drawing conclusions from this study. An important conclusion to draw from this paper is that this study has shown that the intervention and control phase both caused changes over a period of 9 sessions in comparison to the baseline. This might indicate that use of new challenging and motivational therapies can influence the outcome of therapies at a point when clinical changes are not expected. Further work is required to investigate the effects arising from early intervention, longer exposure and intensity of the therapies. Finally, more function-oriented robot-mediated therapies or sling-suspension therapies are needed to clarify the effects resulting from each intervention for stroke recovery.

The U.S. Army recently mandated that soldiers undergo glucose-6-phosphate dehydrogenase (G6PD) testing before deployment to malarious regions. We retrospectively characterize the presence and degree of G6PD deficiency in U.S. military personnel by sex, self-reported ethnicity, and World Health Organization deficiency classification through test results obtained October 1, 2004 through January 17, 2005. Data were available for 63,302 (54,874 males and 8,428 females) subjects; 2.5% of males and 1.6% of females were deficient, with most having only moderate enzyme deficiency. African American males (12.2%) and females (4.1%), along with Asian males (4.3%), had the highest rates of G6PD deficiency. Most males were found to have class III variants while most females were class IV variants. The most severely deficient were Asian males (class II). These results suggest that universal screening for G6PD deficiency is clinically warranted, and particularly essential for those male service members who self-report ethnicity as African American, Asian, or Hispanic. [ABSTRACT FROM AUTHOR]

Fructose and lactate are present in high concentrations in uterine luminal fluid, fetal fluids and fetal blood of ungulates and cetaceans, but their roles have been ignored and they have been considered waste products of pregnancy. This review provides evidence for key roles of both fructose and lactate in support of key metabolic pathways required for growth and development of fetal-placental tissues, implantation and placentation. The uterus and placenta of ungulates convert glucose to fructose via the polyol pathway. Fructose is sequestered within the uterus and cannot be transported back into the maternal circulation. Fructose is phosphorylated by ketohexokinase to fructose-1-PO4 (F1P) by that is metabolized via the fructolysis pathway to yield dihydoxyacetone phosphate and glyceraldehyde-3-PO4 that are downstream of phosphofructokinase. Thus, there is no inhibition of the fructolysis pathway by low pH, citrate or ATP which allows F1P to continuously generate substrates for the pentose cycle, hexosamine biosynthesis pathway, one-carbon metabolism and tricarboxylic acid cycle, as well as lactate. Lactate sustains the activity of hypoxia-inducible factor alpha and its downstream targets such as vascular endothelial growth factor to increase utero-placental blood flow critical to growth and development of the fetal-placental tissues and a successful outcome of pregnancy. Pregnancy has been referred to as a controlled cancer and this review addresses similarities regarding metabolic aspects of tumors and the placenta., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Bazer, Wu and Johnson.)

In pigs, the majority of embryonic mortality occurs when free-floating conceptuses (embryos/fetuses and associated placental membranes) elongate, and the uterine-placental interface undergoes folding and develops areolae. Both periods involve proliferation, migration, and changes in morphology of cells that require adenosine triphosphate (ATP). We hypothesize that insufficient ATP in conceptus and uterine tissues contributes to conceptus loss in pigs. Creatine is stored in cells as phosphocreatine for ATP regeneration through the creatine-creatine kinase- phosphocreatine pathway. However, the expression of components of this pathway in pigs has not been examined throughout gestation. Results of qPCR analyses indicated increases in AGAT, GAMT, CKM, CKB, and SLC6A8 mRNAs in elongating porcine conceptuses, and immunofluorescence microscopy localized guanidinoacetate N-methyltransferase, creatine kinase M, and creatine kinase B proteins to the trophectoderm of elongating conceptuses, to the columnar chorionic epithelial cells at the bottom of chorioallantoic troughs, and to endometrial luminal epithelium at the tops of the endometrial ridges of uterine-placental folds on Days 40, 60, and 90 of gestation. Guanidinoacetate N-methyltransferase protein is expressed in endometrial luminal epithelium at the uterine-placental interface, but immunostaining is more intense in luminal epithelium at the bottoms of the endometrial ridges. Results of this study indicate that key elements of the pathway for creatine metabolism are expressed in cells of the conceptus, placenta, and uterus for potential production of ATP during two timepoints in pregnancy with a high demand for energy; elongation of the conceptus for implantation and development of uterine-placental folding during placentation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Impaired alveolar epithelial regeneration in patients with idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) is attributed to telomere dysfunction in type II alveolar epithelial cells (A 2 Cs). Genetic susceptibility, aging, and toxicant exposures, including tobacco smoke (TS), contribute to telomere dysfunction in A 2 Cs. Here we investigated whether improvement of telomere function plays a role in CSP7-mediated protection of A 2 Cs against ongoing senescence and apoptosis during bleomycin (BLM)-induced pulmonary fibrosis (PF) as well as alveolar injury caused by chronic TS exposure. We found a significant telomere shortening in A 2 Cs isolated from IPF and COPD lungs in line with other studies. These cells showed increased p53 in addition to its post-translational modification with induction of activated caspase-3 and β-galactosidase , suggesting a p53 -mediated loss of A 2 C renewal. Further, we found increased expression of SIAH-1 , a p53 -inducible E3 ubiquitin ligase known to down-regulate telomere repeats binding factor 2 ( TRF2 ). Consistent with the loss of TRF2 and upregulation of TRF1 , telomerase reverse transcriptase ( TERT ) was downregulated in A 2 Cs. A 2 Cs from fibrotic lungs of mice either repeatedly instilled with BLM or isolated from chronic TS exposure-induced lung injury model showed reduced telomere length along with induction of p53 , PAI-1 , SIAH1 and TRF1 as well as loss of TRF2 and TERT , which were reversed in wild-type mice after treatment with CSP7. Interestingly, PAI-1 -/- mice, or those lacking microRNA-34a expression in A 2 Cs, resisted telomere dysfunction, while uPA -/- mice failed to respond to CSP7 treatment, suggesting p53-microRNA-34a feed-forward induction and p53-uPA pathway contributes to telomere dysfunction.

In Brief: The trophectoderm of the elongating conceptuses of cattle, sheep, and pigs secrete high amounts of interferons that increase or induce the expression of interferon-stimulated genes (ISGs) in the endometrium. Research concerning ISGs, performed from 1995 through 2023, is reviewed in this manuscript., Abstract: Expression of the classical interferon (IFN) stimulated genes (ISGs) increases in the endometrial stroma and glandular epithelium (GE) through activation of signal transducer and activator of transcription (STAT) signaling in response to the secretion of IFN tau (IFNT) and IFN gamma (IFNG) by the conceptuses of ruminants, including cattle and sheep, and pigs, respectively. The first of the classical ISGs to be characterized was ISG15 in cattle. Classical ISGs are not expressed by the endometrial luminal epithelium (LE) due to the expression of interferon regulatory factor 2 (IRF2) in the LE that prevents the expression of ISGs in the LE. Classical ISG expression in the endometrium serves as a reliable indicator of conceptus health and elongation in cattle. There are also nonclassical ISGs that are upregulated in endometrial LE in response to progesterone (P4) that are further stimulated by IFNT in sheep, the intracellular signaling pathway responsible for IFN effects on expression is unknown. ISGs are also upregulated in extrauterine tissues including CL and peripheral blood mononuclear cells (PBMCs). The expression of ISGs by the PBMCs of cattle serves as an early prognosticator of pregnancy. The physiological roles of ISGs remain obscure, but evidence suggests that they are at least in part involved in modifying the immune system to support endometrial remodeling necessary for the successful implantation of the conceptus. Our understanding of these ISGs is primarily the result of work from the laboratories of Drs Fuller Bazer, Thomas (Tod) Hansen, Gregory Johnson, Hakhyun Ka, Patrick Lonergan, Troy Ott, and Thomas Spencer.