Search Results (14)

Background: Early neurovascular unit (NVU) impairment plays a critical role in the pathogenesis of diabetic retinopathy (DR), often preceding clinically detectable changes. Butyrate, a short-chain fatty acid (SCFA) derived from gut microbiota, has shown promising metabolic and anti-inflammatory effects. Methods: This study investigated the protective potential of oral butyrate supplementation in a mouse model of early type 2 diabetes mellitus (T2DM) induced by a high-fat diet and streptozotocin. Mice (C57BL/6J) received sodium butyrate (5 g/L in drinking water) for 12 weeks. Retinal NVU integrity was assessed using widefield swept-source optical coherence tomography angiography (WF SS-OCTA), alongside evaluations of systemic glucose and lipid metabolism, hepatic steatosis, visual function, and gut microbiota composition via 16S rRNA sequencing. Results: Butyrate supplementation significantly reduced body weight, fasting glucose, serum cholesterol, and hepatic lipid accumulation. Microbiome analysis demonstrated a partial reversal of gut dysbiosis, characterized by increased SCFA-producing taxa (Ruminococcaceae, Oscillibacter, Lachnospiraceae) and decreased pro-inflammatory, lipid-metabolism-related genera (Rikenella, Ileibacterium). KEGG pathway analysis further revealed enrichment in microbial lipid metabolism functions (fabG, ABC.CD.A, and transketolase). Retinal vascular and neurodegenerative alterations—including reduced vessel density and retinal thinning—were markedly attenuated by butyrate, as revealed by WF SS-OCTA. OKN testing indicated partial improvement in visual function, despite unchanged ERG amplitudes. Conclusions: Butyrate supplementation mitigates early NVU damage in the diabetic retina by improving glucose and lipid metabolism and partially restoring gut microbial balance. This study also underscores the utility of WF SS-OCTA as a powerful noninvasive tool for detecting early neurovascular changes in DR. Full article

Pupil responses and optokinetic nystagmus (OKN) are known to vary with the brightness and direction of motion of attended stimuli, as well as gaze position. However, whether these processes are controlled by a common mechanism remains unclear. In this study, we investigated how OKN latency relates to pupil response latency under two conditions: gaze shifts (eye movement) and attention shifts (covert attention without eye movement). As a result, while OKN showed consistent temporal changes across both gaze and attention conditions, pupillary responses exhibited distinct patterns. Moreover, the results revealed no significant correlation between pupil latency and OKN latency in either condition. These findings suggest that, although OKN and pupillary responses are influenced by similar attentional processes, their underlying mechanisms may differ. Full article

Optokinetic reflex (OKR) assays in zebrafish models are a valuable tool for studying a diverse range of ophthalmological and neurological conditions. Despite its increasing popularity in recent years, there are no clear reporting guidelines for the assay. Following reporting guidelines in research enhances reproducibility, reduces bias, and mitigates underreporting and poor methodologies in published works. To better understand optimal reporting standards for an OKR assay in zebrafish, we performed a systematic literature review exploring the animal, environmental, and technical factors that should be considered. Using search criteria from three online databases, a total of 109 research papers were selected for review. Multiple crucial factors were identified, including larval characteristics, sample size, fixing method, OKR set-up, distance of stimulus, detailed stimulus parameters, eye recording, and eye movement analysis. The outcome of the literature analysis highlighted the insufficient information provided in past research papers and the lack of a systematic way to present the parameters related to each of the experimental factors. To circumvent any future errors and champion robust transparent research, we have created the zebrafish optokinetic (ZOK) reflex minimal reporting guideline. Full article

Background and Objectives: In Peru, the presence of antimicrobial-resistant bacteria is a constant concern in hospitals and has likely increased in frequency during the pandemic. The objective of the study was to analyze the frequency of carbapenemase-producing bacteria resistant to two carbapenems (Imipenem and Meropenem), which were isolated from Peruvian patients in the intensive care unit of the Victor Lazarte Echegaray Hospital in Trujillo (Peru) during the COVID-19 pandemic. Materials and Methods: The biological samples of the patients hospitalized in the ICU were processed in the Microbiology Diagnostic Laboratory of the Víctor Lazarte Echegaray Hospital between May 2021 and March 2022. Antimicrobial sensitivity was determined with the automated system AutoScan-4, and for the identification of the type of carbapenemase, the RESISIT-3 O.K.N K-SET cassettes were used. Results: The results show that 76 cultures (76/129) had resistance to the two carbapenems (imipenem or meropenem), where the most frequent were Klebsiella pneuomoniae (31.6%), Pseudomonas aeruginosa (26.3%), and Acinetobacter baumannii (14.5%). Pseudomonas aeruginosa cultures showed at least three carbapenemase types (KPC, NDM, and OXA-48), while A. baumannii, Escherichia coli, and Burkholderia cepacia complex presented at least two carbapenemases (NDM and OXA-48). The carbapenemase NDM was detected in Enterobacter cloacae, Morganella morganii, and Proteus mirabilis, while KPC was present in all Klebsiella pneumoniae and Klebsiella oxytoca cultures. Conclusions: The samples from patients hospitalized in the Victor Lazarte Echegaray Hospital ICU showed a high prevalence of imipenem- and meropenem-resistant bacteria. These findings are relevant and concerning from the perspective of antibiotic-resistant bacteria monitoring, control, and disinfection. Thus, an appropriate antibiotic policy must be implemented. Full article

Studies on contrast sensitivity (CS) testing using optokinetic nystagmus (OKN) proposed adjusting the stimulus presentation duration based on its contrast, to increase the time efficiency of such measurement. Furthermore, stimulus-specific limits of the least OKN gain might reduce false negatives in OKN detection procedures. Therefore, we aimed to test the effects of various stimulus characteristics on OKN and to propose the stimulus-specific limits for the OKN gain and stimulus presentation duration. We tested the effect of contrast (C), spatial frequency ($SF$), and color on selected parameters of robust OKN response, namely its onset and offset time, amplitude, and gain. The right eyes of fifteen emmetropes were tracked with an infrared eye tracker during monocular observations of sinusoidal gratings moving over the horizontal plane with a velocity of ($21{}^{\circ }/s$). The available contrast levels were C: 0.5%, 2.0%, 8.2%, 16.5%, 33.0%, and 55.5% presented in a random order for ten times in all measurements of $SF$: 0.12, 0.25, 0.5, and 1.00 cycles per degree and grating type: luminance, red-green, and blue-yellow. This study showed a significant effect of the stimulus characteristics on the OKN onset, offset and gain. The effect of $SF$ was insignificant in OKN amplitude; however, it indicated significance for the C and grating type. Furthermore, the OKN gain and offset limits were proposed as functions of contrast for the luminance and chromatic gratings. This study concludes the characteristics of a visual stimulus have an effect on the OKN gain and onset and offset time, yet do not affect the eye-movement amplitude considerably. Moreover, the proposed limits are expected to improve the time efficiency and eye-movement detection in OKN-based contrast sensitivity measurements. Full article

Objective: Most neurological diseases are usually accompanied by changes in the oculomotor nerve. Analysis of different types of eye movements will help provide important information in ophthalmology, neurology, and psychology. At present, many scholars use optokinetic nystagmus (OKN) to study the physiological phenomenon of eye movement. OKN is an involuntary eye movement induced by a large moving surrounding visual field. It consists of a slow pursuing eye movement, called “slow phase” (SP), and a fast re-fixating saccade eye movement, called “fast phase” (FP). Non-invasive video-oculography has been used increasingly in eye movement research. However, research-grade eye trackers are often expensive and less accessible to most researchers. Using a low-cost eye tracker to quantitatively measure OKN eye movement will facilitate the general application of eye movement research. Methods & Results: We design an analytical algorithm to quantitatively measure OKN eye movements on a low-cost eye tracker. Using simple conditional filtering, accurate FP positions can be obtained quickly. The high-precision FP recognition rate is of great help for the subsequent calculation of eye movement analysis parameters, such as mean slow phase velocity (MSPV), which is beneficial as a reference index for patients with strabismus and other eye diseases. Conclusions: Experimental results indicate that the proposed method achieves faster and better results than other approaches, and can provide an effective algorithm to calculate and analyze the FP position of OKN waveforms. Full article

Diabetes, a metabolic disease in which the blood glucose level rises over time, is one of the most common chronic diseases at present. It is critical to accurately predict and classify diabetes to reduce the severity of the disease and treat it early. One of the difficulties that researchers face is that diabetes datasets are limited and contain outliers and missing data. Additionally, there is a trade-off between classification accuracy and operational law for detecting diabetes. In this paper, an algorithm for diabetes classification is proposed for pregnant women using the Pima Indians Diabetes Dataset (PIDD). First, a preprocessing step in the proposed algorithm includes outlier rejection, imputing missing values, the standardization process, and feature selection of the attributes, which enhance the dataset’s quality. Second, the classifier uses the fuzzy KNN method and modifies the membership function based on the uncertainty theory. Third, a grid search method is applied to achieve the best values for tuning the fuzzy KNN method based on uncertainty membership, as there are hyperparameters that affect the performance of the proposed classifier. In turn, the proposed tuned fuzzy KNN based on uncertainty classifiers (TFKNN) deals with the belief degree, handles membership functions and operation law, and avoids making the wrong categorization. The proposed algorithm performs better than other classifiers that have been trained and evaluated, including KNN, fuzzy KNN, naïve Bayes (NB), and decision tree (DT). The results of different classifiers in an ensemble could significantly improve classification precision. The TFKNN has time complexity O(kn²d), and space complexity O(n²d). The TFKNN model has high performance and outperformed the others in all tests in terms of accuracy, specificity, precision, and average AUC, with values of 90.63, 85.00, 93.18, and 94.13, respectively. Additionally, results of empirical analysis of TFKNN compared to fuzzy KNN, KNN, NB, and DT demonstrate the global superiority of TFKNN in precision, accuracy, and specificity. Full article

Current therapies for high-grade gliomas, particularly glioblastomas (GBM), do not extend patient survival beyond 16–22 months. OKN-007 (OKlahoma Nitrone 007), which is currently in phase II (multi-institutional) clinical trials for GBM patients, and has demonstrated efficacy in several rodent and human xenograft glioma models, shows some promise as an anti-glioma therapeutic, as it affects most aspects of tumorigenesis (tumor cell proliferation, angiogenesis, migration, and apoptosis). Combined with the chemotherapeutic agent temozolomide (TMZ), OKN-007 is even more effective by affecting chemo-resistant tumor cells. In this study, mass spectrometry (MS) methodology ESI-MS, mass peak analysis (Leave One Out Cross Validation (LOOCV) and tandem MS peptide sequence analyses), and bioinformatics analyses (Ingenuity^® Pathway Analysis (IPA^®)), were used to identify up- or down-regulated proteins in the blood sera of F98 glioma-bearing rats, that were either untreated or treated with OKN-007. Proteins of interest identified by tandem MS-MS that were decreased in sera from tumor-bearing rats that were either OKN-007-treated or untreated included ABCA2, ATP5B, CNTN2, ITGA3, KMT2D, MYCBP2, NOTCH3, and VCAN. Conversely, proteins of interest in tumor-bearing rats that were elevated following OKN-007 treatment included ABCA6, ADAMTS18, VWA8, MACF1, and LAMA5. These findings, in general, support our previous gene analysis, indicating that OKN-007 may be effective against the ECM. These findings also surmise that OKN-007 may be more effective against oligodendrogliomas, other brain tumors such as medulloblastoma, and possibly other types of cancers. Full article

Vestibular migraine (VM) is the most common cause of episodic vertigo in children. Vertigo, nausea, dizziness and unsteadiness are often complained of by children with migraine, which can precede, follow or be present simultaneously with headache. The aim of this study was to use posturography to investigate the visually evoked postural responses (VEPRs) of children with VM and compare them to data obtained from children with primary headache (M) and controls (C). Twenty children diagnosed as affected by VM, nineteen children with M without aura and twenty healthy subjects were recruited in this cross-sectional study. Posturography was performed by a standardized stabilometric force-platform (Svep-Politecnica) in the following conditions: open eyes (OE), closed eyes (CE) and during full-field horizontal optokinetic stimulation (OKN-S). Electronystagmography was performed simultaneously to analyze optokinetic reflex parameters. In the OE condition, no difference was found between groups with respect to body sway area. In contrast, this parameter increased in the two pathological groups with respect to controls in the CE condition. The optokinetic stimulations also induced a similar increase of body sway area in the M group relative to controls, but a further increase was elicited in the VM group. Electronystagmographic recording also revealed different optokinetic reflex parameters in the latter groups. This study disclosed an abnormal sensitivity of children with M and VM to full-field moving scenes and a consequent destabilization of posture, as documented by the abnormal VEPRs. Children with VM were particularly exposed to this risk. Possible clinical implications of these findings are discussed. Full article

Rapid and accurate detection can help optimize patient treatment and improve infection control against nosocomial carbapenemase-producing organisms (CPO). In this study, a total of 217 routine clinical isolates (Enterobacterales and A. baumannii), including 178 CPOs and 39 non-CPOs, were tested to evaluate the performance of six phenotypic carbapenemase detection and classification assays, i.e., BD Phoenix CPO detect panel, Rapidec Carba-NP, O.K.N detection kit, and three carbapenem inactivation methods (CIMs; mCIM, eCIM, sCIM). The overall detection sensitivity and specificity were 98.78% (95.21–99.79%) and 79.49% (63.06–90.13%), respectively, for the BD phoenix CPO P/N test; 91.93% (86.30–95.45%) and 100% (88.83–100%), respectively, for the Rapidec Carba-NP; 98.06% (94.00–99.50%) and 97.44% (84.92–99.87%), respectively, for mCIM; and 96.89% (92.52–98.85%) and 94.87% (81.37–99.11%), respectively, for sCIM. The classification sensitivity and specificity for the BD phoenix CPO Ambler test, the O.K.N detection kit, and the mCIM and eCIM were 56.71% (48.75–64.34%) and 94.87% (81.37–99.11%), 99.28% (95.43–99.96%) and 100% (88.83–100%), and 92.90% (87.35–96.23%) and 97.44% (84.92–99.87%), respectively. All detection assays were reliable in detecting carbapenemase. However, the Rapidec Carba-NP and mCIM were insufficient in detecting OXA-48-like enzymes. The BD phoenix CPO detect panel had a strong ability to detect carbapenemase but failed to classify 48/59 (81.36%) KPC, 8/52 (15.38%) NDM, 8/22 (36.36%) OXA-23-like, and 6/11 (54.55%) dual enzymes. The O.K.N detection kit accurately detected and differentiated KPC, NDM, and OXA-48-like enzymes existing alone or in combination. The results of this study will support reliable laboratory work tools and promote therapeutic and infection control decisions. Full article

Optokinetic nystagmus (OKN) is an involuntary eye movement induced by motion of a large proportion of the visual field. It consists of a “slow phase (SP)” with eye movements in the same direction as the movement of the pattern and a “fast phase (FP)” with saccadic eye movements in the opposite direction. Study of OKN can reveal valuable information in ophthalmology, neurology and psychology. However, the current commercially available high-resolution and research-grade eye tracker is usually expensive. Methods & Results: We developed a novel fast and effective system combined with a low-cost eye tracking device to accurately quantitatively measure OKN eye movement. Conclusions: The experimental results indicate that the proposed method achieves fast and promising results in comparisons with several traditional approaches. Full article

OKN corresponding to the motion of the fixating area occurs when a stimulus has two areas separated in depth containing motion in different directions. However, when attention and vergence are separately directed to areas with different motions and depths, it remains unclear which property of attention and vergence is prioritized to initiate OKN. In this study, we investigated whether OKN corresponding to motion in the attending or fixating area occurred when two motions with different directions were presented in the central and peripheral visual fields separated in depth. Results show that OKN corresponding to attended motion occurred when observers maintained vergence on the peripheral stimulus and attended to the central stimulus. However, OKN corresponding to each motion in the attending area and in the fixating area occurred when observers maintained vergence on the central stimulus and attended to the peripheral stimulus. The accuracy rate of the target detection task was the lowest in this condition. These results support the idea that motion in the attended area is essential for occurrence of OKN, and vergence and retinal position affect the strength of attention. Full article

Base on the sequence of S genes, which encode spike proteins, we previously identified three different types (North American, S INDEL, and S large-DEL types) of porcine epidemic diarrhea virus (PEDV) that have re-emerged in Japan since 2013. Based on experimental infections with the North American and S large-DEL types, we also hypothesized that PEDV virulence may be linked to the S1 subunit of the S protein. To test this hypothesis, we have now assayed in gnotobiotic piglets various recombinant PEDVs generated by reverse genetics. Piglets inoculated with CV777 maintained in National Institute of Animal Health, along with piglets infected with a recombinant form of the same virus, developed subclinical to mild diarrhea. In contrast, severe watery diarrhea, dehydration, weight loss, astasia, and high mortality were observed in piglets inoculated with recombinant strains in which the S gene was partially or fully replaced with corresponding sequences from the highly virulent Japanese PEDV isolate OKN-1/JPN/2013. Indeed, symptoms resembled those in piglets inoculated with the OKN-1/JPN/2013, and were especially pronounced in younger piglets. Collectively, the data demonstrate that the S1 subunit of the S protein is an important determinant of PEDV virulence, and advance development of new vaccine candidate. Full article

Existing algorithms for learning Boolean networks (BNs) have time complexities of at least O(N · n^0:7(k+1)), where n is the number of variables, N is the number of samples and k is the number of inputs in Boolean functions. Some recent studies propose more efficient methods with O(N · n²) time complexities. However, these methods can only be used to learn monotonic BNs, and their performances are not satisfactory when the sample size is small. In this paper, we mathematically prove that OR/AND BNs, where the variables are related with logical OR/AND operations, can be found with the time complexity of O(k·(N+ logn)·n²), if there are enough noiseless training samples randomly generated from a uniform distribution. We also demonstrate that our method can successfully learn most BNs, whose variables are not related with exclusive OR and Boolean equality operations, with the same order of time complexity for learning OR/AND BNs, indicating our method has good efficiency for learning general BNs other than monotonic BNs. When the datasets are noisy, our method can still successfully identify most BNs with the same efficiency. When compared with two existing methods with the same settings, our method achieves a better comprehensive performance than both of them, especially for small training sample sizes. More importantly, our method can be used to learn all BNs. However, of the two methods that are compared, one can only be used to learn monotonic BNs, and the other one has a much worse time complexity than our method. In conclusion, our results demonstrate that Boolean networks can be learned with improved time complexities. Full article