A molecular epidemiological and transmission analysis of Clostridioides difficile using draft whole-genome sequencing in a single hospital.

BACKGROUND: The nosocomial transmission of toxin-producing Clostridioides difficile is a significant concern in infection control. C. difficile, which resides in human intestines, poses a risk of transmission, especially when patients are in close contact with medical staff. METHODS: To investigate the nosocomial transmission of C. difficile in a single center, we analyzed the genetic relationships of the bacteria. This was done using draft whole-genome sequencing (WGS) and examining single nucleotide polymorphisms (SNPs) in core-genome, alongside data regarding the patient's hospital wards and room changes. Our retrospective analysis covered 38 strains, each isolated from a different patient, between April 2014 and January 2015. RESULTS: We identified 38 strains that were divided into 11 sequence types (STs). ST81 was the most prevalent (n = 11), followed by ST183 (n = 10) and ST17 (n = 7). A cluster of strains that indicated suspected nosocomial transmission (SNT) was identified through SNP analysis. The draft WGS identified five clusters, with 16 of 38 strains belonging to these clusters. There were two clusters for ST81 (ST81-SNT-1 and ST81-SNT-2), two for ST183 (ST183-SNT-1 and ST183-SNT-2), and one for ST17 (ST17-SNT-1). ST183-SNT-1 was the largest SNT cluster, encompassing five patients who were associated with Wards A, B, and K. The most frequent room changer was a patient labeled Pt08, who changed rooms seven times in Ward B. Patients Pt36 and Pt10, who were also in Ward B, had multiple admissions and discharges during the study period. CONCLUSIONS: Additional culture tests and SNP analysis of C. difficile using draft WGS revealed silent transmission within the wards, particularly in cases involving frequent room changes and repeated admissions and discharges. Monitoring C. difficile transmission using WGS-based analysis could serve as a valuable marker in infection control management.

Satisfaction of patients with frozen shoulder following silent manipulation: a prospective observation study.

Silent manipulation is a procedure for frozen shoulders that involves manipulating the shoulder while the patient is awake by performing C5, C6, and C7 cervical nerve root block under ultrasound guidance. This retrospective study, conducted at Yokohama City University Hospital, aimed to evaluate the clinical outcomes of silent manipulation and assess whether the experience level of the practitioner influenced treatment efficacy. Between October 2020 and January 2022, 53 patients who met the inclusion criteria underwent silent manipulation for frozen shoulder. The procedure was performed by either an experienced or a less experienced practitioner, and the patients were followed-up for up to 1 year post-treatment. Silent manipulation resulted in significant improvements in shoulder range of motion, as measured by forward flexion, abduction, external rotation, and hand-behind-back, as well as in patient-reported outcomes, including disabilities of the arm, shoulder, and hand and Shoulder 36 scores. These improvements were observed 1 week, 3 months, and 1 year after silent manipulation, indicating the short-term efficacy of the procedure. Furthermore, this study revealed that the practitioners' level of experience played a significant role in the outcomes. The experienced doctor achieved better 1st external rotation and belt tying outcomes, as well as Shoulder 36 pain, muscle strength, and activities of daily living domain scores. This suggests that technical expertise in silent manipulation is crucial to achieve optimal outcomes. Silent manipulation offers an effective therapeutic approach for frozen shoulder, leading to significant improvements in range of motion and patient satisfaction. Practitioner expertise is a vital factor in treatment success, emphasizing the importance of skilled professionals in the performance of this procedure.

Impact of microvascular decompression on wall shear stress in responsible arteries in trigeminal neuralgia and hemifacial spasm.

Microvascular decompression (MVD) has proven efficacy in trigeminal neuralgia (TN) and hemifacial spasm (HFS). This study utilized computational fluid dynamics (CFD) to investigate the impact of MVD on wall shear stress (WSS) of responsible arteries (RAs) at the neurovascular contact (NVC). A total of 21 cases (10 TN, 11 HFS) were analyzed, involving RAs at NVC validated through intraoperative photographs. Hemodynamic parameters (WSS, vessel diameter, flow rate, pressure drop) was calculated using CFD for the RAs based on 3D silent-magnetic resonance angiograms. The NVC was segmented into NVC-proximal, NVC-site, and NVC-distal portions using simulated 3D CFD images that correlated with surgical observations. WSS ratios of NVC-site to NVC-proximal (NVC-site/proximal) was calculated both before and after MVD. Prior to MVD, WSS in the RA at the NVC displayed a peaked curve with a maximum at NVC-site; however, post MVD, it presented a smooth curve without peaks. The WSS ratio exhibited a significant decrease after MVD. The impact of MVD on WSS of RAs at NVC was evaluated in both TN and HFS cases. Analyzing the hemodynamics of RAs through CFD and identifying WSS peaks at NVC portions before MVD provided a more detailed and localized understanding of the morphologically depicted NVC.

Cholecystokinin regulates atrial natriuretic peptide secretion through activation of NOX4-Sirt1-LEF1 signaling in beating rat hypoxic atria.

The mammalian cardiac myocytes not only synthesize and secrete atrial natriuretic peptide (ANP), but also express cholecystokinin (CCK) and its receptors (CCK1R and CCK2R). However, atrial CCK expression patterns and its effects on ANP secretion during hypoxia are unclear. Therefore, this study is aimed to investigate the effect of hypoxia on the expression levels of CCK and its receptors, as well as the underlying mechanisms involved in regulating hypoxia-induced ANP secretion in isolated beating atria. The results of this study showed that acute hypoxia significantly upregulated expression of CCK and CCK1R as well as CCK2R through activation of hypoxia-inducible factor 1α-apelin signaling. Endogenous CCK induced by hypoxia markedly upregulated the expression of silent information regulator factor 2-related enzyme 1 (Sirt1) and its downstream nuclear factor erythroid­2­related factor 2 (Nrf2) via the activation of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), leading to increase of activating T cell factor (TCF) 3 and TCF4/ lymphoid enhancer factor (LEF) 1, ultimately promoting hypoxia-induced ANP secretion. In addition, siRNA-mediated knockdown of LEF1 dramatically attenuated hypoxia-induced increase of ANP expression in HL-1 atrial myocytes. These results indicated endogenous CCK induced by hypoxia promoted hypoxia-induced ANP secretion by activation of NOX4-Sirt1-TCF3/4-LEF1 signaling pathway.

Angiographically silent macular retinoschisis and vitreomacular traction in a patient with same - side Duane retraction syndrome.

Introduction: To report the unusual fundus features of a case with unilateral Duane retraction syndrome (DRS) with same-side extensive macular retinoschisis. Methods: A 75-year-old woman was diagnosed to have DRS type 3 and several multimodal fundus imaging modalities were performed. Results: There was limited abduction and adduction, globe retraction, and narrowing of the palpebral fissure on the adduction of the left eye without a compensatory face turn. Concurrently, spectral domain optical coherence tomography revealed marked macular retinoschisis and severe vitreoretinal traction without any evidence of dye leakage or pooling on fluorescein angiography in the left eye. Discussion: Various ocular abnormalities may rarely accompany DRS and the present case is the first reported case of most likely coincidental macular retinoschisis in association with DRS.

Hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles inhibit neuronal death after spinal cord injury by regulating the SIRT1/Nrf2/HO-1 pathway.

Background: Oxidative stress and apoptosis of neurons significantly contribute to the pathophysiological cascade of spinal cord injury (SCI). However, the role of hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles (H-sEVs) in promoting SCI repair remains unclear. Hence, the present study aims to investigate the regulatory effects of H-sEVs on neuronal oxidative stress and apoptotic responses following SCI. Methods: The administration of H-sEVs of SCI rats was assessed using behavioral evaluations such as Basso-Beattie-Bresnahan (BBB) scores, neuroelectrophysiological monitoring, and Catwalk gait analysis. Indices of oxidative stress (including superoxide dismutase [SOD], total antioxidant capacity [T-AOC], and malondialdehyde [MDA]) were measured. Neuronal survival was evaluated through Nissl staining, while the expression level of sirtuin 1 (SIRT1) was examined using immunohistochemical staining. Additionally, histological evaluation of lesion size was performed using hematoxylin-eosin (HE) staining. Tunel cell apoptosis staining and analysis of apoptosis-associated proteins (B-cell lymphoma-2 [Bcl2] and BCL2-Associated X [Bax]) were conducted through immunofluorescence staining and western blot, respectively. Furthermore, the model of oxidative stress was established using PC12 cells, and apoptosis levels were assessed via flow cytometry and western blot analysis. Importantly, to ascertain the critical role of SIRT1, we performed SIRT1 knockout experiments in PC12 cells using lentivirus transfection, followed by western blot. Results: Using those behavioral evaluations, we observed significant functional improvement after H-sEVs treatment. Nissl staining revealed that H-sEVs treatment promoted neuronal survival. Moreover, we found that H-sEVs effectively reduced oxidative stress levels after SCI. HE staining demonstrated that H-sEVs could reduce lesion area. Immunohistochemical analysis revealed that H-sEVs enhanced SIRT1 expression. Furthermore, Tunel cell apoptosis staining and western blot analysis of apoptosis-related proteins confirmed the anti-apoptotic effects of H-sEVs. The PC12 cells were used to further substantiate the neuroprotective properties of H-sEVs by significantly inhibiting neuronal death and attenuating oxidative stress. Remarkably, SIRT1 knockout in PC12 cells reversed the antioxidant stress effects induced by H-sEVs treatment. Additionally, we elucidated the involvement of the downstream Nrf2/HO-1 signaling pathway. Conclusion: Our study provides valuable insights into the effects of H-sEVs on neuronal oxidative stress and apoptosis after SCI. These findings underscore the potential clinical significance of H-sEVs-based therapies for SCI.

MicroRNAs as Epigenetic Regulators of Obesity.

In obesity, the process of adipogenesis largely determines the number of adipocytes in body fat depots. Adipogenesis is regulated by several adipocyte-selective micro-ribonucleic acids (miRNAs) and transcription factors that modulate adipocyte proliferation and differentiation. However, some miRNAs block the expression of master regulators of adipogenesis. Since the specific miRNAs display different expressions during adipogenesis, in mature adipocytes and permanent obesity, their use as biomarkers or therapeutic targets is feasible. Upregulated miRNAs in persistent obesity are downregulated during adipogenesis. Moreover, some of the downregulated miRNAs in obese individuals are upregulated in mature adipocytes. Induction of adipocyte stress and hypertrophy leads to the release of adipocyte-derived exosomes (AdEXs) that contain the cargo molecules, miRNAs. miRNAs are important messengers for intercellular communication involved in metabolic responses and have very specific signatures that direct the metabolic activity of target cells. While each miRNA targets multiple messenger RNAs (mRNAs), which may coordinate or antagonize each other's functions, several miRNAs are dysregulated in other tissues during obesity-related comorbidities. Deletion of the miRNA-processing enzyme DICER in pro-opiomelanocortin-expressing cells results in obesity, which is characterized by hyperphagia, increased adiposity, hyperleptinemia, defective glucose metabolism, and alterations in the pituitary-adrenal axis. In recent years, RNA-based therapeutical approaches have entered clinical trials as novel therapies against overweight and its complications. Development of lipid droplets, macrophage accumulation, macrophage polarization, tumor necrosis factor receptor-associated factor 6 activity, lipolysis, lipotoxicity, and insulin resistance are effectively controlled by miRNAs. Thereby, miRNAs as epigenetic regulators are used to determine the new gene transcripts and therapeutic targets.

Impact of different energy sources on coagulation biomarkers and silent cerebral events in balloon-based ablation for atrial fibrillation.

Background: Different energy sources of balloon-based ablation for pulmonary vein isolation cause different kinds of endothelial damage and coagulation responses associated with thromboembolic risk. Objectives: The study sought to compare the impact of different balloon-based ablation, cryoballoon ablation (CBA) and laser balloon ablation (LBA), on coagulation/fibrinolysis biomarkers and silent cerebral events (SCEs) in paroxysmal atrial fibrillation. Methods: Paroxysmal atrial fibrillation patients who underwent pulmonary vein isolation using either CBA (n = 52) or LBA (n = 53) without radiofrequency touch-up ablation were eligible. Time course (day 0 [before ablation], day 1, day 2, and day 28) of myocardial enzymes and inflammatory and coagulation/fibrinolysis biomarkers was evaluated during the perioperative period. Brain magnetic resonance imaging was performed within 2 days after the procedure to evaluate SCEs. Results: There was no difference in patient characteristics between CBA and LBA.CBA had greater myocardial injury (troponin I and creatine kinase-MB) and lower inflammatory reaction (white blood cell count and neutrophil/lymphocyte ratio) than LBA. The coagulation biomarkers maximally increased by day 2 and then decreased in both groups. In day 28, the serum prothrombin fragment 1+2 and D-dimer levels in LBA were significantly higher than the values in CBA. The fibrinolysis biomarker (plasmin-α2 plasmin inhibitor complex) did not increase after the procedure in either group. The incidence of SCEs was comparable between CBA and LBA (11% vs 15%; P = .591). No thromboembolic event was observed. Conclusion: CBA and LBA had different effects on myocardial injury, inflammatory reaction, and coagulation activity but did not affect the incidence of thromboembolic events. LBA had significantly higher coagulation activity in day 28 and may require more careful postprocedural anticoagulation than CBA.

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OBJECTIVES: To study the risk factors and prognostic characteristics of pediatric silent lupus nephritis (SLN) with class Ⅲ to V. METHODS: A retrospective study was conducted to collect clinical data from 30 children diagnosed with SLN at the Department of Pediatrics, Second Xiangya Hospital, Central South University, from May 2007 to April 2023. Based on renal pathological classification, the patients were divided into a class Ⅱ group (12 cases) and a class Ⅲ to Ⅴ group (18 cases). The risk factors for the occurrence of class Ⅲ to Ⅴ SLN were analyzed, and the prognostic characteristics were summarized. RESULTS: Among the 30 SLN patients, the median follow-up time was 61.50 months. There were no statistically significant differences in the proportions of patients who discontinued glucocorticoids or achieved low disease activity status, nor in the annual decline rate of estimated glomerular filtration rate (eGFR) between the class Ⅱ and class Ⅲ to V groups (P>0.05). However, three patients in the class Ⅱ group progressed to stage 1 chronic kidney disease (CKD), while eight patients in the class III to V group reached stage 1 CKD, and four patients reached stage 2 CKD. Among the 26 female SLN patients, serum complement C3 levels in the class III to V group were lower than those in the class Ⅱ group (P<0.05). Serum C3 levels in SLN patients, as well as in female SLN patients, were negatively correlated with the fluorescence intensity of IgA, IgG, and C3 immune complexes in the kidneys (P<0.05). Additionally, serum C3 levels in female SLN patients were negatively correlated with the renal pathological activity index (P<0.05). Binary logistic regression analysis indicated that being female and having low serum complement C3 levels were risk factors for the occurrence of class Ⅲ to V SLN in children (P<0.05). CONCLUSIONS: Class Ⅲ to V SLN is not uncommon among SLN children, and there remains a risk of long-term renal function progression. Being female and having low serum complement C3 levels are identified as risk factors for class Ⅲ to V SLN in children.

Evaluation of silent brain injury in patients undergoing aorto-ostial coronary stent implantation.

BACKGROUND: Aorto-ostial (AO) coronary interventions may be associated with multiple problems, including the potential embolization of atherothrombotic debris into the aorta and systemic circulation. Such embolization could theoretically lead to stroke or silent brain injury (SBI). In this study, we aimed to investigate whether there is an increased risk of SBI in patients undergoing AO stent implantation. METHODS: Fifty-five consecutive patients undergoing AO stenting and 55 consecutive patients undergoing non-AO stenting were included. Venous blood samples were obtained before and 12 h after the procedure to measure neuron-specific enolase (NSE), which is a sensitive marker of brain injury. Newly developed NSE elevation after the procedure in an asymptomatic patient was defined as SBI. RESULTS: SBI was detected in 24 (43.6%) patients in the AO stenting group and 17 (30.9%) patients in the non-AO stenting group (p = .167). Although the SBI rates were statistically comparable between the groups, the presence of significant (≥50%) AO stenosis was found to be an independent predictor of SBI in multivariate logistic regression analysis [odds ratio (OR) 2.856; 95% confidence interval (CI) 1.057-7.716; p = .038]. A longer procedure time was another independent predictor for the development of SBI (OR 1.037; 95% CI 1.005-1.069; p = .023). CONCLUSION: This study suggests that AO stenting may be associated with an increased risk of SBI if the lesion in the ostium is significant.

Speech synthesis from three-axis accelerometer signals using conformer-based deep neural network.

Silent speech interfaces (SSIs) have emerged as innovative non-acoustic communication methods, and our previous study demonstrated the significant potential of three-axis accelerometer-based SSIs to identify silently spoken words with high classification accuracy. The developed accelerometer-based SSI with only four accelerometers and a small training dataset outperformed a conventional surface electromyography (sEMG)-based SSI. In this study, motivated by the promising initial results, we investigated the feasibility of synthesizing spoken speech from three-axis accelerometer signals. This exploration aimed to assess the potential of accelerometer-based SSIs for practical silent communication applications. Nineteen healthy individuals participated in our experiments. Five accelerometers were attached to the face to acquire speech-related facial movements while the participants read 270 Korean sentences aloud. For the speech synthesis, we used a convolution-augmented Transformer (Conformer)-based deep neural network model to convert the accelerometer signals into a Mel spectrogram, from which an audio waveform was synthesized using HiFi-GAN. To evaluate the quality of the generated Mel spectrograms, ten-fold cross-validation was performed, and the Mel cepstral distortion (MCD) was chosen as the evaluation metric. As a result, an average MCD of 5.03 ± 0.65 was achieved using four optimized accelerometers based on our previous study. Furthermore, the quality of generated Mel spectrograms was significantly enhanced by adding one more accelerometer attached under the chin, achieving an average MCD of 4.86 ± 0.65 (p < 0.001, Wilcoxon signed-rank test). Although an objective comparison is difficult, these results surpass those obtained using conventional SSIs based on sEMG, electromagnetic articulography, and electropalatography with the fewest sensors and a similar or smaller number of sentences to train the model. Our proposed approach will contribute to the widespread adoption of accelerometer-based SSIs, leveraging the advantages of accelerometers like low power consumption, invulnerability to physiological artifacts, and high portability.

Correlation of silent brain infarcts and leukoaraiosis in middle-aged ischemic stroke patients: a retrospective study.

Background: Cerebrovascular diseases of the brain are usually defined by transient ischemic attacks and strokes. However, they can also cause brain injuries without neurological events. Silent brain infarcts (SBI) and leukoaraiosis are symptoms of both vascular and neurological abnormalities. This study aims to investigate the association between SBI, leukoaraiosis, and middle-aged patients with ischemic stroke. Methods: A single-center retrospective study of 50 middle-aged, ischemic stroke patients were studied from November 2022 and May 2023. The patients were divided into two groups based on the presence or absence of leukoaraiosis. History taking, physical examination, brain CT scan, and MRI were all part of the diagnostic process. Metabolic syndrome (MetS) was also assessed through various factors. The statistical analysis included descriptive statistics, logistic regression analysis, and chi-square test. Results: Out of the cohort comprising 50 patients, characterized by a mean age of 52.26 years (SD 5.29), 32 were male, constituting 64% of the sample. Among these patients, 26 individuals exhibited leukoaraiosis, with 17 of them (65.4%) also presenting with SBI. Moreover, within this cohort, 22 patients were diagnosed with MetS, representing 84.6% of those affected. The Multivariate logistic regression analysis showed a strong and independent association between leukoaraiosis and SBI. Individuals with leukoaraiosis were nearly five times more likely to have SBI compared to those without leukoaraiosis. Conclusion: The study highlights leukoaraiosis as a significant risk factor for SBI, alongside MetS. Advanced imaging techniques have facilitated their detection, revealing a higher prevalence among stroke patients, particularly associated with age and hypertension. Further research is needed to fully understand their complex relationship and develop better management strategies for cerebrovascular diseases, ultimately improving patient outcomes.

Clinical characterization of the silent chronic pancreatitis patient: a single-center retrospective cohort study.

Background: Silent chronic pancreatitis (SCP) is a poorly understood subtype of chronic pancreatitis (CP) in which individuals describe little to no abdominal pain. The risk factors for SCP are unclear, and it is unknown whether there are differences in the clinical outcomes of SCP and painful CP. We set out to investigate the clinical features of SCP and the risk factors associated with this condition. Methods: This was a retrospective cohort study using data from the Penn State Milton S. Hershey Medical Center from 2019-2022. Two patient groups, the SCP cohort (23 patients) and the painful CP cohort (94 patients), were identified from consecutive clinics. Descriptive statistics and bivariate and logistic regression analyses (including variables with a P-value <0.1 on bivariate analysis) were performed to characterize the study cohort and to evaluate for independent associations with SCP. Results: SCP was independently associated with older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.01-1.11; P=0.03) and male sex (OR 5.38, 95%CI 1.38-20.96; P=0.02), and inversely associated with current opioid use (OR 0.18, 95%CI 0.03-0.96; P=0.04). There was no association between SCP and current pain medication or diabetes mellitus. Conclusions: Our study adds to the growing body of literature describing SCP as a condition associated with older age and male sex, and inversely associated with opioid use. We found no greater association of diabetes with SCP. Future larger longitudinal studies are needed to gain a better understanding of SCP.

Mirror movements in multiple sclerosis -a clinical, electrophysiological, and imaging study.

BACKGROUND: Mirror movements (MM) are commonly caused by a defect of interhemispheric pathways also affected in multiple sclerosis (MS), particularly the corpus callosum. We investigated the prevalence of MM in MS in relation to functional and morphological callosal fiber integrity by transcranial magnetic stimulation (TMS), magnetic resonance imaging (MRI), as well as fatigue. METHODS: In 21 patients with relapsing-remitting MS and 19 healthy controls, MM were assessed and graded (Woods and Teuber scale: MM 1-4) using a bedside test. Fatigue was evaluated using the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire. TMS measured ipsilateral silent period latency and duration. MRI assessed callosal atrophy by measuring the normalized corpus callosum area (nCCA), corpus callosum index (CCI), and lesion volume. RESULTS: MS patients had significantly more often and pronounced MM compared to healthy controls (p = 0.0002) and nCCA was significantly lower (p = 0.045) in MRI studies. Patients with higher MM scores (MM > 1 vs. MM 0/1) showed significantly more fatigue (higher FSMC sum score, p = 0.04, motor score, p = 0.01). In TMS and MRI studies, no significant differences were found between patients with MM 0/1 and those with MM > 1 (ipsilateral silent period measurements, CCA, CCI and lesion volume). CONCLUSIONS: MM are common in MS and can easily be detected through bedside testing. As MM are associated with fatigue, they might indicate fatigue in MS. It is possible that other cerebral structures, in addition to the corpus callosum, may contribute to the origin of MM in MS.

Variant-specific antibody profiling for tracking SARS-CoV-2 variant infections in children and adolescents.

Monitoring the seroprevalence of SARS-CoV-2 in children and adolescents can provide valuable information for effective SARS-CoV-2 surveillance, and thus guide vaccination strategies. In this study, we quantified antibodies against the spike S1 domains of several SARS-CoV-2 variants (wild-type, Alpha, Delta, and Omicron variants) as well as endemic human coronaviruses (HCoVs) in 1,309 children and adolescents screened between December 2020 and March 2023. Their antibody binding profiles were compared with those of 22 pre-pandemic samples from children and adolescents using an in-house Luminex®-based Corona Array (CA). The primary objectives of this study were to (i) monitor SARS-CoV-2-specific antibodies in children and adolescents, (ii) evaluate whether the S1-specific antibody response can identify the infecting variant of concern (VoC), (iii) estimate the prevalence of silent infections, and (iv) test whether vaccination or infection with SARS-CoV-2 induce HCoV cross-reactive antibodies. Both SARS-CoV-2 infection and vaccination induced a robust antibody response against the S1 domain of WT and VoCs in children and adolescents. Antibodies specific for the S1 domain were able to distinguish between SARS-CoV-2 VoCs in infected children. The serologically identified VoC was typically the predominant VoC at the time of infection. Furthermore, our highly sensitive CA identified more silent SARS-CoV-2 infections than a commercial ELISA (12.1% vs. 6.3%, respectively), and provided insights into the infecting VoC. Seroconversion to endemic HCoVs occurred in early childhood, and vaccination or infection with SARS-CoV-2 did not induce HCoV S1 cross-reactive antibodies. In conclusion, the antibody response to the S1 domain of the spike protein of SARS-CoV-2 is highly specific, providing information about the infecting VoC and revealing clinically silent infections.

Development of an Innovative Pupillometer Able to Selectively Stimulate the Eye's Fundus Photoreceptor Cells.

Recent advancements in clinical research have identified the need to combine pupillometry with a selective stimulation of the eye's photoreceptor cell types to broaden retinal and neuroretinal health assessment opportunities. Our thorough analysis of the literature revealed the technological gaps that currently restrict and hinder the effective utilization of a method acknowledged to hold great potential. The available devices do not adequately stimulate the photoreceptor types with enough contrast and do not guarantee seamless device function integration, which would enable advanced data analysis. RetinaWISE is an advanced silencing pupillometry device that addresses these deficiencies. It combines a Maxwellian optical arrangement with advanced retinal stimulation, allowing for calibrated standard measurements to generate advanced and consistent results across multiple sites. The device holds a Class 1 CE marking under EU regulation 2017/745, thus facilitating clinical research progress.

Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors.

Elimination of the binding of immunoglobulin Fc to Fc gamma receptors is highly desirable for the avoidance of unwanted inflammatory responses to therapeutic antibodies and fusion proteins. Many different approaches have been used in the clinic, but they have not been systematically compared. We have now produced a matched set of anti-CD20 antibodies with different Fc subclasses and variants and compared their activity for binding to C1q, Fc-gamma receptors and in cell-based assays. Most of the variants still have significant levels of activity in one or more of these assays and many of them have impaired temperature stability compared with the corresponding wild-type antibody.

Diversity of trypanosomes in tsetse fly caught in two "silent" sleeping sickness foci of Bafia and the Manoka Island in Cameroon.

BACKGROUND: Surveillance of "silent" human African Trypanosomiasis (HAT) foci is important for the achievement of the World Health Organization (WHO) goal of interrupting the transmission of this disease by 2030. It is in this context that this study was carried out to determine the trypanosome species circulating in the "silent" HAT foci of Bafia and the Manoka island in Cameroon. METHODS: In the Bafia and Manoka HAT foci, georeferenced pyramidal traps were used to trap tsetse flies. After DNA extraction from each whole fly, molecular tools were used to detect different trypanosome species as well as the origin of tsetse fly blood meals. Geographical information system was used to map the trypanosome infections and entomological data and to localize areas at high risk for trypanosome transmission. RESULTS: For this study, 1683 tsetse flies were caught and the relative apparent densities was 2.96: 0.03 in the Bafia HAT focus and 5.23 in the Manoka island. For the molecular identification of trypanosomes, 708 non-teneral tsetse flies (8 from Bafia and 700 from Manoka) were randomly selected. The overall trypanosome infection rate was 7.34 % with no infection in the Bafia HAT focus. Among the analysed flies, 4.57 % had trypanosomes of the subgenus Trypanozoon while 4.1 % and 1.13 % had respectively T. congolense and T. vivax. The most common mixed infections were the combination of trypanosomes of the subgenus Trypanozoon and T. congolense. Of the 708 tsetse flies analysed, 134 (18.93 %) tsetse flies were found with residual blood meals, 94 % and 6 % were respectively from humans and dogs. The trapping sites of Plateau, Sandje and Hospital appeared as the areas where contact with tsetse flies is most common. CONCLUSION: This study revealed a discrepancy in the abundance tsetse flies as well as the trypanosome infection rates in tsetse of the two "silent" HAT foci of Cameroon. The detection of different trypanosome species in tsetse from the Manoka Island highlights their transmission. The high percentage of human blood meals in tsetse flies indicates an important contact between tsetse flies and human; emphasizing the risk of trypanosome transmission to human in this island.

Incidence and Prognostic Significance of Silent Coronary Disease in Asymptomatic Patients with Severe Aortic Stenosis.

Background and Objectives: The aim of this study was to estimate the prevalence of silent coronary artery disease (CAD) in asymptomatic patients with severe aortic stenosis (AS) and assess long-term prognosis in terms of major adverse cardiovascular event (MACE)-free survival. Materials and Methods: This was a prospective study conducted at the Clinic for Cardiac Surgery, University Clinical Center of Serbia, in asymptomatic patients with severe AS, normal LVEF and stress test without signs of myocardial ischemia. Adverse cardiovascular events (cardiac death, myocardial infarction and any hospitalization due to heart disease) was monitored during one year of follow up. Results: A total of 116 asymptomatic patients with severe AS were included in the study. The average age was 67.3 ± 9.6 years, and 56.9% of patients were men. The most common cause of AS was degenerative valvular disease (83.5%). The incidence of significant CAD was 30 out of 116 patients (25.9%). The median Society for Thoracic Surgeons (STS) predicted risk of mortality score was 1.62% (25th to 75th percentile: 1.15-2.76%). The overall mean gradient across aortic valve (Pmean) was 52.30 mmHg ± 12.16, and the mean indexed AVA (AVAi) was 0.37 ± 0.09 cm2/m2. The mean LVEF was 68.40% ± 8.01%. Early surgery for aortic valve replacement was performed in 55 patients (55.2%), while 52 (44.8%) patients received conservative treatment. Twenty-two patients (42.3%) in the conservative treatment group underwent surgery during follow up. There were a total of 44 (37.9%) patients with MACE during one year of follow up. Univariate Cox regression analyses identified the following significant risk factors for MACE-free survival: presence of CAD and early conservative treatment (p = 0.004), age (p = 0.003), diabetes mellitus (p = 0.016) and STS score (p = 0.039). According to multivariate analysis, the presence of CAD with early conservative treatment was the most important predictor of MACE-free survival in asymptomatic patients with severe aortic stenosis (p ≤ 0.001). Conclusions: Early surgery for aortic valve replacement in asymptomatic patients with severe AS and concomitant CAD is beneficial for long-term survival.

Emergence of silent NDM-1 carbapenemase gene in carbapenem-susceptible Klebsiella pneumoniae: Clinical implications and epidemiological insights.

The global dissemination of carbapenemase genes, particularly blaNDM-1, poses a significant threat to public health. While research has mainly focused on strains with phenotypic resistance, the impact of silent resistance genes has been largely overlooked. This study documents the first instance of silent blaNDM-1 in a cluster of clonally related carbapenem-susceptible K. pneumoniae strains from a single patient. Despite initial effectiveness of carbapenem therapy, the patient experienced four recurrent lung infections over five months, indicating persistent K. pneumoniae infection. Genomic sequencing revealed all strains harbored blaNDM-1 on the epidemic IncX3 plasmid. A deletion within the upstream promoter region (PISAba125) of blaNDM-1 hindered its expression, resulting in phenotypic susceptibility to carbapenems. However, in vitro bactericidal assays and a mouse infection model showed that K. pneumoniae strains with silent blaNDM-1 exhibited significant tolerance to carbapenem-mediated killing. These findings demonstrate that silent blaNDM-1 can mediate both phenotypic susceptibility and antibiotic tolerance. In silico analysis of 1986 blaNDM sequences showed that 1956 (98.5%) retained the original promoter PISAba125. Given that previous genomic sequencing typically targets carbapenem-resistant strains, accurately assessing the prevalence of silent blaNDM remains challenging. This study highlights the hidden threat of silent resistance genes to clinical antimicrobial therapy and calls for enhanced clinical awareness and laboratory detection.