Septal stimulation attenuates hippocampal seizure with subregion specificity.

OBJECTIVE: Deep brain stimulation (DBS) is a promising approach for the treatment of epilepsy. However, the optimal target for DBS and underlying mechanisms are still not clear. Here, we compared the therapeutic effects of DBS on distinct septal subregions, aimed to find the precise targets of septal DBS and related mechanisms for the clinical treatment. METHODS: Assisted by behavioral test, electroencephalography (EEG) recording and analyzing, selectively neuronal manipulation and immunohistochemistry, we assessed the effects of DBS on the three septal subregions in kainic acid (KA)-induced mouse seizure model. RESULTS: DBS in the medial septum (MS) not only delayed generalized seizure (GS) development, but reduced the severity; DBS in the vertical diagonal band of Broca (VDB) only reduced the severity of GS, while DBS in the horizontal diagonal band of Broca (HDB) subregion showed no anti-seizure effect. Notably, DBS in the MS much more efficiently decreased abnormal activation of hippocampal neurons. EEG spectrum analysis indicated that DBS in the MS and VDB subregions mainly increased the basal hippocampal low-frequency (delta and theta) rhythm. Furthermore, ablation of cholinergic neurons in the MS and VDB subregions blocked the anti-seizure and EEG-modulating effects of septal DBS, suggesting the seizure-alleviating effect of DBS was dependent on local cholinergic neurons. SIGNIFICANCE: DBS in the MS and VDB, rather than HDB, attenuates hippocampal seizure by activation of cholinergic neurons-augmented hippocampal delta/theta rhythm. This may be of great therapeutic significance for the clinical treatment of epilepsy with septal DBS. PLAIN LANGUAGE SUMMARY: The optical target of deep brain stimulation in the septum is still not clear. This study demonstrated that stimulation in the medial septum and vertical diagonal band of Broca subregions, but not the horizontal diagonal band of Broca, could alleviate hippocampal seizure through cholinergic neurons-augmented hippocampal delta/theta rhythm. This study may shed light on the importance of precise regulation of deep brain stimulation therapy in treating epileptic seizures.

Mechanisms of cuproptosis and its relevance to distinct diseases.

Copper is a trace element required by the organism, but once the level of copper exceeds the threshold, it becomes toxic and even causes death. The underlying mechanisms of copper-induced death are inconclusive, with different studies showing different opinions on the mechanism of copper-induced death. Multiple investigations have shown that copper induces oxidative stress, endoplasmic reticulum stress, nucleolar stress, and proteasome inhibition, all of which can result in cell death. The latest research elucidates a copper-dependent death and denominates it as cuproptosis. Cuproptosis takes place through the combination of copper and lipoylated proteins of the tricarboxylic acid cycle, triggering agglomeration of lipoylated proteins and loss of iron-sulfur cluster proteins, leading to proteotoxic stress and ultimately death. Given the toxicity and necessity of copper, abnormal levels of copper lead to diseases such as neurological diseases and cancer. The development of cancer has a high demand for copper, neurological diseases involve the change of copper contents and the binding of copper to proteins. There is a close relationship between these two kinds of diseases and copper. Here, we summarize the mechanisms of copper-related death, and the association between copper and diseases, to better figure out the influence of copper in cell death and diseases, thus advancing the clinical remedy of these diseases.

Upconversion nanoparticles doped optical lens: let's see the near-infrared light.

The human cannot detect light with a wavelength exceeding 700 nm, primarily due to limitations in the physiological structure of the human eye. However, in certain specific scenarios, the ability to detect near-infrared (NIR) light proves to be extremely valuable. To attain this desired capability, NIR up conversion nanoparticles (UCNPs) were prepared and doped in the optical lens materials, aiming to obtain a NIR light "visible" optical lens. It is demonstrated that the doping of UCNPs in the optical lens materials does not significantly impact on their mechanical properties, optical properties, surface properties and it exhibits excellent biocompatibility in cell and animal experiments. More importantly, the UCNPs doping can convert NIR light into visible light within the material effectively and stably. The eyes can "see" the NIR light after wearing such UCNPs doped optical lens. Such NIR light visible optical lens could have great potential in actual applications.

[Differences and drivers of leaf stable carbon and nitrogen isotope in herbs under different vegetation types on the eastern Qinghai-Tibet Plateau]. / é’è—é«˜åŽŸä¸œç¼˜ä¸åŒæ¤è¢«ç±»åž‹ä¸‹è‰æœ¬æ¤ç‰©å¶ç‰‡ç¢³æ°®ç¨³å®šåŒä½ç´ å·®å¼‚åŠå ¶é©±åŠ¨å› ç´ .

The natural abundance of stable carbon and nitrogen isotopes (δ13C and δ15N) in leaves can provide comprehensive information on the physiological and ecological processes of plants and has been widely used in ecological research. However, recent studies on leaf δ13C and δ15N have focused mainly on woody species, few studies have been conducted on herbs in different vegetation types, and their differences and driving factors are still unclear. In this study, we focused on the herbs in subalpine coniferous forests, alpine shrublands, and alpine mea-dows on the eastern Qinghai-Tibet Plateau, and investigated the differences in leaf δ13C and δ15N of herbs and the driving factors. The results showed that there were significant differences in leaf δ13C and δ15N values of herbs among different vegetation types, with the highest δ13C and δ15N values in alpine meadows, followed by alpine shrublands, and the lowest in subalpine coniferous forests. Using variation partitioning analysis, we revealed that differences in leaf δ13C and δ15N of herbs among various vegetation types were driven by both leaf functional traits and climate factors, with the contribution of leaf functional traits being relatively higher than that of climate factors. Hierarchical partitioning results indicated that mean annual temperature (MAT), chlorophyll content index, leaf nitrogen content per unit area (Narea), and leaf mass per area were the main drivers of leaf δ13C variations of herbs across different vegetation types, while the relative importance of Narea and MAT for variation in leaf δ15N of herbs was much higher than those other variables. There was a strong coupling relationship between leaf δ13C and δ15N as indicated by the result of the ordinary least squares regression. Our findings could provide new insights into understanding the key drivers of leaf δ13C and δ15N variations in herbs across different vegetation types.

Molecule Crowding Strategy in Polymer Electrolytes Inducing Stable Interfaces for All-Solid-State Lithium Batteries.

All-solid-state lithium batteries with polymer electrolytes suffer from electrolyte decomposition and lithium dendrites because of the unstable electrode/electrolyte interfaces. Herein, a molecule crowding strategy is proposed to modulate the Li+ coordinated structure, thus in situ constructing the stable interfaces. Since 15-crown-5 possesses superior compatibility with polymer and electrostatic repulsion for anion of lithium salt, the anions are forced to crowd into a Li+ coordinated structure to weaken the Li+ coordination with polymer and boost the Li+ transport. The coordinated anions prior decompose to form LiF-rich, thin, and tough interfacial passivation layers for stabilizing the electrode/electrolyte interfaces. Thus, the symmetric Li-Li cell can stably operate over 4360 h, the LiFePO4||Li full battery presents 97.18% capacity retention in 700 cycles at 2 C, and the NCM811||Li full battery possesses the capacity retention of 83.17% after 300 cycles. The assembled pouch cell shows excellent flexibility (stand for folding over 2000 times) and stability (89.42% capacity retention after 400 cycles). This work provides a promising strategy to regulate interfacial chemistry by modulating the ion environment to accommodate the interfacial issues and will inspire more effective approaches to general interface issues for polymer electrolytes.

In situ real-time pathway to study the polyethylene long-term degradation process by a marine fungus through confocal Raman quantitative imaging.

Since plastic waste has become a worldwide pollution problem, studying the ability of marine microorganisms to degrade plastic waste is important. However, conventional methods are unable to in situ real-time study the ability of microorganisms to biodegrade plastics. In recent years, Raman spectroscopy has been widely used in the characterization of plastics as well as in the study of biological metabolism due to its low cost, rapidity, label-free, non-destructive, and water-independent features, which provides us with new ideas to address the above limitations. Here, we have established a method to study the degradation ability of microorganisms on plastics using confocal Raman imaging. Alternaria alternata FB1, a recently reported polyethylene (PE) degrading marine fungus, is used as a model to perform a long-term (up to 274 days) in situ real-time nondestructive inspection of its degradation process. We can prove the degradation of PE plastics from the following two aspects, visualization and analysis of the degradation process based on depth imaging and quantification of the degradation rate by crystallinity calculations. The findings also reveal unprecedented degradation details. The method is important for realizing high-throughput screening of microorganisms with potential to degrade plastics and studying the degradation process of plastics in the future.

Machine-Learning-Assisted Rational Design of Si─Rhodamine as Cathepsin-pH-Activated Probe for Accurate Fluorescence Navigation.

High-performance fluorescent probes stand as indispensable tools in fluorescence-guided imaging, and are crucial for precise delineation of focal tissue while minimizing unnecessary removal of healthy tissue. Herein, machine-learning-assisted strategy to investigate the current available xanthene dyes is first proposed, and a quantitative prediction model to guide the rational synthesis of novel fluorescent molecules with the desired pH responsivity is constructed. Two novel Si─rhodamine derivatives are successfully achieved and the cathepsin/pH sequentially activated probe Si─rhodamine─cathepsin-pH (SiR─CTS-pH) is constructed. The results reveal that SiR─CTS-pH exhibits higher signal-to-noise ratio of fluorescence imaging, compared to single pH or cathepsin-activated probe. Moreover, SiR─CTS-pH shows strong differentiation abilities for tumor cells and tissues and accurately discriminates the complex hepatocellular carcinoma tissues from normal ones, indicating its significant application potential in clinical practice. Therefore, the continuous development of xanthene dyes and the rational design of superior fluorescent molecules through machine-learning-assisted model broaden the path and provide more advanced methods to researchers.

A non-lipid nucleic acid delivery vector with dendritic cell tropism and stimulation.

Rationale: Nucleic acid constructs are commonly used for vaccination, immune stimulation, and gene therapy, but their use in cancer still remains limited. One of the reasons is that systemic delivery to tumor-associated antigen-presenting cells (dendritic cells and macrophages) is often inefficient, while off-target nucleic acid-sensing immune pathways can stimulate systemic immune responses. Conversely, certain carbohydrate nanoparticles with small molecule payloads have been shown to target these cells efficiently in the tumor microenvironment. Yet, nucleic acid incorporation into such carbohydrate-based nanoparticles has proven challenging. Methods: We developed a novel approach using cross-linked bis succinyl-cyclodextrin (b-s-CD) nanoparticles to efficiently deliver nucleic acids and small-molecule immune enhancer to phagocytic cells in tumor environments and lymph nodes. Our study involved incorporating these components into the nanoparticles and assessing their efficacy in activating antigen-presenting cells. Results: The multi-modality immune stimulators effectively activated antigen-presenting cells and promoted anti-tumor immunity in vivo. This was evidenced by enhanced delivery to phagocytic cells and subsequent immune response activation in tumor environments and lymph nodes. Conclusion: Here, we describe a new approach to incorporating both nucleic acids and small-molecule immune enhancers into cross-linked bis succinyl-cyclodextrin (b-s-CD) nanoparticles for efficient delivery to phagocytic cells in tumor environments and lymph nodes in vivo. These multi-modality immune stimulators can activate antigen-presenting cells and foster anti-tumor immunity. We argue that this strategy can potentially be used to enhance anti-tumor efficacy.

Interplay between mesenchymal stem cells and macrophages: Promoting bone tissue repair.

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space, a focus and difficulty in orthopedic treatment. In recent years, the success of mesenchymal stem cells (MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine. MSCs are closely related to macrophages. On one hand, MSCs regulate the immune regulatory function by influencing macrophages proliferation, infiltration, and phenotype polarization, while also affecting the osteoclasts differentiation of macrophages. On the other hand, macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment. The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration. Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair, and will also provide a reference for further application of MSCs in other diseases.

Computational evaluation of wire position using separate vertical wire technique and candy box technique for the fixation of inferior pole patellar fractures: a finite element analysis.

The separate vertical wire (SVW) technique and the improved candy box (CB) technique have been proposed for treating inferior pole patellar fractures. However, there is still a lack of clear explanation regarding the location of the wire passing through the patella. Five models of SVW techniques were established in different positions. Finite element analysis was then conducted to determine the optimal bone tunnel position for the SVW technique. Based on these findings, six groups of finite element models were created for CB techniques. The maximum displacement and stress on both the patella and steel wire were compared among these groups under 100-N, 200-N, 300-N, 400-N, and 500-N force loads. The results indicated that, in the SVW technique, the steel wire group near the fracture end of the longitudinal bone tunnel showed minimal displacement and stress on the patella when subjected to different forces. On the other hand, in the CB technique, both the patella and wire experienced minimal stress when a transverse bone tunnel wire was placed near the upper posterior aspect of patella. In conclusion, the SVW technique may require the bone tunnel wire to be positioned near the fractured end of the lower pole of the patella. On the other hand, in CB technique, the transverse bone tunnel wire passing through the patella may be close to its upper posterior aspect. However, further validation is necessary through comprehensive finite element analysis and additional biomechanical experiments.

Single cell analysis reveals the roles and regulatory mechanisms of type-I interferons in Parkinson's disease.

The pathogenesis of Parkinson's disease (PD) is strongly associated with neuroinflammation, and type I interferons (IFN-I) play a crucial role in regulating immune and inflammatory responses. However, the specific features of IFN in different cell types and the underlying mechanisms of PD have yet to be fully described. In this study, we analyzed the GSE157783 dataset, which includes 39,024 single-cell RNA sequencing results for five PD patients and six healthy controls from the Gene Expression Omnibus database. After cell type annotation, we intersected differentially expressed genes in each cell subcluster with genes collected in The Interferome database to generate an IFN-I-stimulated gene set (ISGs). Based on this gene set, we used the R package AUCell to score each cell, representing the IFN-I activity. Additionally, we performed monocle trajectory analysis, and single-cell regulatory network inference and clustering (SCENIC) to uncover the underlying mechanisms. In silico gene perturbation and subsequent experiments confirm NFATc2 regulation of type I interferon response and neuroinflammation. Our analysis revealed that microglia, endothelial cells, and pericytes exhibited the highest activity of IFN-I. Furthermore, single-cell trajectory detection demonstrated that microglia in the midbrain of PD patients were in a pro-inflammatory activation state, which was validated in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model as well. We identified transcription factors NFATc2, which was significantly up-regulated and involved in the expression of ISGs and activation of microglia in PD. In the 1-Methyl-4-phenylpyridinium (MPP+)-induced BV2 cell model, the suppression of NFATc2 resulted in a reduction in IFN-ß levels, impeding the phosphorylation of STAT1, and attenuating the activation of the NF-κB pathway. Furthermore, the downregulation of NFATc2 mitigated the detrimental effects on SH-SY5Y cells co-cultured in conditioned medium. Our study highlights the critical role of microglia in type I interferon responses in PD. Additionally, we identified transcription factors NFATc2 as key regulators of aberrant type I interferon responses and microglial pro-inflammatory activation in PD. These findings provide new insights into the pathogenesis of PD and may have implications for the development of novel therapeutic strategies.

Linc-NSC affects cell differentiation, apoptosis and proliferation in mouse neural stem cells and embryonic stem cells in vitro and in vivo.

BACKGROUND: Stem cell therapy is a promising therapeutic strategy. In a previous study, we evaluated tumorigenicity by the stereotactic transplantation of neural stem cells (NSCs) and embryonic stem cells (ESCs) from experimental mice. Twenty-eight days later, there was no evidence of tumor formation or long-term engraftment in the NSCs transplantation group. In contrast, the transplantation of ESCs caused tumor formation; this was due to their high proliferative capacity. Based on transcriptome sequencing, we found that a long intergenic non-coding RNA (named linc-NSC) with unknown structure and function was expressed at 1100-fold higher levels in NSCs than in ESCs. This finding suggested that linc-NSC is negatively correlated with stem cell pluripotency and tumor development, but positively correlated with neurogenesis. In the present study, we investigated the specific role of linc-NSC in NSCs/ESCs in tumor formation and neurogenesis. METHODS: Whole transcriptome profiling by RNA sequencing and bioinformatics was used to predict lncRNAs that are widely associated with enhanced tumorigenicity. The expression of linc-NSC was assessed by quantitative real-time PCR. We also performed a number of in vitro methods, including cell proliferation assays, differentiation assays, immunofluorescence assays, flow cytometry, along with in vivo survival and immunofluorescence assays to investigate the impacts of linc-NSC on tumor formation and neurogenesis in NSCs and ESCs. RESULTS: Following the knockdown of linc-NSC in NSCs, NSCs cultured in vitro and those transplanted into the cortex of mice showed stronger survival ability (P < 0.0001), enhanced proliferation(P < 0.001), and reduced apoptosis (P < 0.05); the opposite results were observed when linc-NSC was overexpressed in ESCs. Furthermore, the overexpression of linc-NSC in ECSs induced enhanced apoptosis (P < 0.001) and differentiation (P < 0.01), inhibited tumorigenesis (P < 0.05) in vivo, and led to a reduction in tumor weight (P < 0.0001). CONCLUSIONS: Our analyses demonstrated that linc-NSC, a promising gene-edited target, may promote the differentiation of mouse NSCs and inhibit tumorigenesis in mouse ESCs. The knockdown of linc-NSC inhibited the apoptosis in NSCs both in vitro and in vivo, and prevented tumor formation, revealing a new dimension into the effect of lncRNA on low survival NSCs and providing a prospective gene manipulation target prior to transplantation. In parallel, the overexpression of linc-NSC induced apoptosis in ESCs both in vitro and in vivo and attenuated the tumorigenicity of ESCs in vivo, but did not completely prevent tumor formation.

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission.

Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1-/- mice but partially terminated SE in IL1R1-/- mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1ß pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.

An overview and comprehensive analysis of interdisciplinary clinical research in endometriosis based on trial registry.

Endometriosis is a chronic multisystem disease associated with immunological, genetic, hormonal, psychological, and neuroscientific factors, leading to a significant socioeconomic impact worldwide. Though multidisciplinary management is the ideal approach, there remains a scarcity of published interdisciplinary clinical trials at present. Here, we have conducted a comprehensive analysis of the characteristics and issues of interdisciplinary trials on endometriosis based on the clinical registration database ClinicalTrials.gov. Among all 387 endometriosis trials, 30% (116) were identified as interdisciplinary, mostly conducted in Europe and North America, and fully funded by non-industrial sources. We documented growth in both patient-centered multidisciplinary comprehensive management and collaboration between fundamental biomedical science and applied medicine. However, compared to traditional obstetric-gynecological trials, interdisciplinary studies exhibited negative characteristics such as less likely to be randomized and less likely to report results. Our study provides insights for future trial investigators and may contribute to fostering greater collaboration in medical research.

New multi-source waste co-incineration and clustering park operating model for small- and medium-sized city: A case study in China.

With improvements in urban waste management to promote sustainable development, an increasing number of waste types need to be sorted and treated separately. Due to the relatively low amount of waste generated in small- and medium-sized cities, separate treatment facilities for each waste type lack scale, waste is treated at a high cost and low efficiency. Therefore, industrial symbiosis principles are suggested to be used to guide collaborative waste treatment system of multi-source solid wastes, and co-incineration is the most commonly used technology. Most existing studies have focused on co-incineration of one certain waste type (such as sludge or medical waste) with municipal solid waste (MSW), but the systematic design and the comprehensive benefits on a whole city and park level have not been widely studied. Taking the actual operation of a multi-source waste co-incineration park in south-central China as an example, this study conducted a detailed analysis of the waste-energy-water metabolism process of MSW, sludge, food waste, and medical waste co-incineration. The environmental and economic benefits were evaluated and compared with the single decentralized waste treatment mode. The results showed that the multi-source waste co-incineration and clustering park operating model was comprehensively superior to the single treatment mode, greenhouse gases and human toxicity indicators were decreased by 11.87% and 295.74%, respectively, and the internal rate of return of the project was increased by 29.35%. This mainly benefits from the synergy of technical system and the economies of scale. Finally, this research proposed policy suggestions from systematic planning and design, technical route selection, and an innovative management mode in view of the potential challenges.

Diagnosis, isolation and description of a novel amnoonvirus recovered from diseased fancy guppies, Poecilia reticulata.

The guppy, Poecilia reticulata, is one of the most common cultured ornamental fish species, and a popular pet fish highly desired by hobbyists worldwide due to its availability of many brilliantly coloured fish of many varieties. The susceptibility of guppies to diseases presents a remarkable concern for both breeders and hobbyists. In this study, we report the emergence of disease in fancy guppies caused by a previously uncharacterized virus in the USA. This virus was isolated from moribund guppies in two separate outbreaks in California and Alabama, from December 2021 to June 2023. The infected guppies presented with acute morbidity and mortality shortly after shipping, displaying nonspecific clinical signs and gross changes including lethargy, anorexia, swimming at the water surface, gill pallor, mild to moderate coelomic distension and occasional skin lesions including protruding scales, skin ulcers and hyperaemia. Histological changes in affected fish were mild and nonspecific; however, liver and testes from moribund fish were positive for Tilapia lake virus (TiLV), the single described member in the family Amnoonviridae, using immunohistochemistry and in situ hybridization, although the latter was weak. A virus was successfully recovered following tissue inoculation on epithelioma papulosum cyprini and snakehead fish cell lines. Whole genome sequencing and phylogenetic analyses revealed nucleotide and amino acid homologies from 78.3%-91.2%, and 78.2%-97.7%, respectively, when comparing the guppy virus genomes to TiLV isolates. Based on the criteria outlined herein, we propose the classification of this new virus, fancy tailed guppy virus (FTGV), as a member of the family Amnoonviridae, with the name Tilapinevirus poikilos (from the Greek 'poikilos', meaning of many colours; various sorts, akin to 'poecilia').

Assessing Severity of Low Anterior Resection Syndrome After Intersphincteric Resection for Ultralow Rectal Cancer: A Pilot Study Using an Exploratory Instrument.

BACKGROUND: The Delphi consensus identified 8 symptoms and 8 consequences as the highest priorities for defining low anterior resection syndrome. OBJECTIVE: To describe an exploratory scoring instrument correlating the Delphi consensus on low anterior resection syndrome with functional and quality-of-life scores following intersphincteric resection for ultralow rectal cancer. DESIGN: This was a prospective pilot study. In accordance with the Wexner incontinence score, 5 frequency responses ranging from never (score 0) to always (score 4) were used to measure the severity of symptom- and consequence-specific variables. SETTINGS: Colorectal surgery referral center. PATIENTS: Among 161 eligible patients, 137 participants (85%) completed an electronic self-assessment survey regarding function and quality of life at scheduled follow-up, including 3 to 6, 12, and ≥24 months after ileostomy reversal. MAIN OUTCOME MEASURES: Outcome measures included patient-reported severity of the identified priorities, and their correlation with condition-specific quality of life. RESULTS: The most frequent symptom and consequence were "emptying difficulties" and "dissatisfaction with the bowels," respectively. Aside from "emptying difficulties," the proportions of negative symptom domains increased after reversal. In particular, neither the frequency responses nor the severity scores of "emptying difficulties" differed between groups. The percentages of "always" selection for consequence domains improved at 12-month follow-up, whereas a higher rate was observed at 24 months, except for "toilet dependence" and "dissatisfaction with the bowels." We found significant improvements in the summary score of the Fecal Incontinence Quality-of-Life Scale ( p = 0.04) and our exploratory instrument ( p = 0.009) but not in functional scores measured by traditional questionnaires. Furthermore, the condition-specific quality of life strongly correlated with the Delphi consensus severity score ( rs = -0.73). LIMITATIONS: Single-institution data and limited sample size. CONCLUSIONS: The important priorities identified by the Delphi consensus might enable a comprehensive overview and a better assessment of low anterior resection syndrome after intersphincteric resection. See Video Abstract . EVALE LA GRAVEDAD DEL SNDROME DE RESECCIN ANTERIOR BAJA DESPUS DE LA RESECCIN INTERESFINTRICA PARA EL CNCER DE RECTO ULTRABAJO UN ESTUDIO PILOTO QUE UTILIZA UN INSTRUMENTO EXPLORATORIO: ANTECEDENTES:El consenso Delphi identificó ocho síntomas y ocho consecuencias como las máximas prioridades para definir el síndrome de resección anterior baja.OBJETIVO:Describir un instrumento de puntuación exploratorio que correlaciona el consenso Delphi sobre el síndrome de resección anterior baja con puntuaciones funcionales y de calidad de vida después de la resección interesfinteriana para el cáncer de recto ultrabajo.DISEÑO:Este fue un estudio piloto prospectivo. De acuerdo con la puntuación de incontinencia de Wexner, se utilizaron cinco respuestas de frecuencia que van desde nunca (puntuación 0) hasta siempre (puntuación 4) para medir la gravedad de las variables específicas de los síntomas y las consecuencias.AJUSTES:Centro de referencia de cirugía colorrectal.PACIENTES:Entre 161 pacientes elegibles, 137 (85%) participantes completaron una encuesta electrónica de autoevaluación sobre la función y la calidad de vida en el seguimiento programado, incluidos 3 a 6, 12 y ≥ 24 meses después de la reversión de la ileostomía.MEDIDAS PRINCIPALES DE RESULTADO:Las medidas de resultado incluyeron la gravedad de estas prioridades informada por los pacientes, así como su correlación con la calidad de vida específica de la afección.RESULTADOS:El síntoma y la consecuencia más frecuentes fueron "dificultades para vaciar" e "insatisfacción con las deposiciones", respectivamente. Aparte de las "dificultades de vaciado", las proporciones de dominios de síntomas negativos aumentaron después de la reversión. En particular, tanto las respuestas de frecuencia como las puntuaciones de gravedad de las "dificultades para vaciar" no difirieron entre los grupos. Los porcentajes de "opción siempre" para los dominios de consecuencias mejoraron a los 12 meses de seguimiento, mientras que se observó una tasa más alta a los 24 meses después, excepto para "dependencia del baño" e "insatisfacción con los intestinos". Encontramos mejoras significativas en la puntuación resumida de la Escala de calidad de vida de incontinencia fecal ( p = 0,04) y nuestro instrumento exploratorio ( p = 0,009), pero no en las puntuaciones funcionales medidas con los cuestionarios tradicionales. Además, la calidad de vida específica de la condición se correlacionó fuertemente con la puntuación de gravedad del consenso Delphi (rs = -0,73).LIMITACIONES:Datos de una sola institución y tamaño de muestra limitado.CONCLUSIONES:Las importantes prioridades identificadas por el consenso Delphi podrían permitir una visión global y una mejor evaluación del síndrome de resección anterior baja después de la resección interesfintérica. (Traducción-Dr. Yesenia Rojas-Khalil ).

Surveillance for Acute Flaccid Myelitis - United States, 2018-2022.

Acute flaccid myelitis (AFM) is a serious neurologic condition primarily affecting children; AFM can cause acute respiratory failure and permanent paralysis. AFM is a rare but known complication of various viral infections, particularly those of enteroviruses (EVs). Increases in AFM cases during 2014, 2016, and 2018 were associated with EV-D68 infection. This report examines trends in confirmed AFM cases during 2018-2022 and patients' clinical and laboratory characteristics. The number of AFM cases was low during 2019-2022 (28-47 cases per year); the number of cases remained low in 2022 despite evidence of increased EV-D68 circulation in the United States. Compared with cases during the most recent peak year (2018), fewer cases during 2019-2021 had upper limb involvement, prodromal respiratory or febrile illness, or cerebrospinal fluid pleocytosis, and more were associated with lower limb involvement. It is unclear why EV-D68 circulation in 2022 was not associated with an increase in AFM cases or when the next increase in AFM cases will occur. Nonetheless, clinicians should continue to suspect AFM in any child with acute flaccid limb weakness, especially those with a recent respiratory or febrile illness.

Low-frequency Stimulation at the Subiculum Prevents Extensive Secondary Epileptogenesis in Temporal Lobe Epilepsy.

Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus. It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy, but still lacks effective treatments. Here, we aimed to test the effects of low-frequency stimulation (LFS) at the subiculum for secondary epileptogenesis in a mouse model. Here, secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling stimuli. Mice kindled at the right CA3 showed higher seizure susceptibilities at both the contralateral CA3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive mice. LFS at the ipsilateral subiculum during the primary kindling progress at the right CA3 effectively prevented secondary epileptogenesis at both the contralateral CA3 and the ipsilateral entorhinal cortex, characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary foci. Only application along with the primary epileptogenesis was effective. Notably, the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary foci. These results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.

Brain development in newborns and infants after ECMO.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) not only significantly improves survival rates in severely ill neonates but also is associated with long-term neurodevelopmental issues. To systematically review the available literature on the neurodevelopmental outcomes of neonates and infants who have undergone ECMO treatment, with a focus on motor deficits, cognitive impairments, sensory impairments, and developmental delays. This review aims to understand the incidence, prevalence, and risk factors for these problems and to explore current nursing care and management strategies. DATA SOURCES: A comprehensive literature search was performed across PubMed, EMBASE, and Web of Science using a wide array of keywords and phrases pertaining to ECMO, neonates, infants, and various facets of neurodevelopment. The initial screening involved reviewing titles and abstracts to exclude irrelevant articles, followed by a full-text assessment of potentially relevant literature. The quality of each study was evaluated based on its research methodology and statistical analysis. Moreover, citation searches were conducted to identify potentially overlooked studies. Although the focus was primarily on neonatal ECMO, studies involving children and adults were also included due to the limited availability of neonate-specific literature. RESULTS: About 50% of neonates post-ECMO treatment exhibit varying degrees of brain injury, particularly in the frontal and temporoparietal white matter regions, often accompanied by neurological complications. Seizures occur in 18%-23% of neonates within the first 24 hours, and bleeding events occur in 27%-60% of ECMO procedures, with up to 33% potentially experiencing ischemic strokes. Although some studies suggest that ECMO may negatively impact hearing and visual development, other studies have found no significant differences; hence, the influence of ECMO remains unclear. In terms of cognitive, language, and intellectual development, ECMO treatment may be associated with potential developmental delays, including lower composite scores in cognitive and motor functions, as well as potential language and learning difficulties. These studies emphasize the importance of early detection and intervention of potential developmental issues in ECMO survivors, possibly necessitating the implementation of a multidisciplinary follow-up plan that includes regular neuromotor and psychological evaluations. Overall, further multicenter, large-sample, long-term follow-up studies are needed to determine the impact of ECMO on these developmental aspects. CONCLUSIONS: The impact of ECMO on an infant's nervous system still requires further investigation with larger sample sizes for validation. Fine-tuned management, comprehensive nursing care, appropriate patient selection, proactive monitoring, nutritional support, and early rehabilitation may potentially contribute to improving the long-term outcomes for these infants.