Explore the vast range of titles available.

Demyelinating optic neuritis (DON) is a rare but sight-threatening ophthalmic condition which occasionally occurs after human papilloma virus (HPV) vaccination. We herein report a case of previously healthy 13-year-old girl who developed a bilateral refractory DON three days after the first dose of bivalent HPV vaccine. The patient experienced bilateral severe visual loss three days after HPV vaccination, and her vision was quickly deteriorated to no light perception one day after the onset of DON. Ophthalmic examination revealed sluggish pupillary light reflex and swollen optic disc in both eyes, and an emergent orbital MRI examination revealed bilateral hyperintensity and enlargement of the intraorbital optic nerve with contrast enhancement. Serological tests for aquaporin-4 IgG antibody, myelin oligodendrocyte glycoprotein IgG antibody, and other common autoantibodies were all negative. The patient showed poor response to 10 days of intravenous methylprednisolone pulse therapy (500 mg, 250 mg, and 125 mg twice per day for 4, 4, and 2 days, respectively). Hence, three-dosed subcutaneous satralizumab was used in the acute stage of DON as an adjunct therapy. Her vision gradually improved after satralizumab therapy, and increased to 20/20 and 20/32 in the right and left eye at the 3-month follow-up. To the best of our knowledge, this is the first case report of satralizumab therapy in the AQP-4 Ab and MOG-Ab dual seronegative isolated DON. Our study indicates that satralizumab may be a safe and efficient adjunct therapy which can be used in the acute stage of the refractory DON poorly responding to steroid pulse therapy.

Input saturation and disturbances often exist in hydraulic systems, reducing internal state stability and tracking response performances of the system as well as complicating the design of advanced non‐linear controllers. A practical method named active disturbance rejection controller is proposed by backstepping method for full‐state constrained hydraulic systems to constrain tracking errors in the desired boundaries and deal with input saturation as well as disturbances. To achieve the previously mentioned objectives, the disturbance compensation strategy and dynamic auxiliary systems are integrated into the barrier Lyapunov theory for the first time. It is proved that all states of hydraulic systems are kept within the ultimate boundaries with satisfactory dynamic performance and high steady‐state accuracy. In addition, when disturbances are constants, asymptotic tracking is theoretically achieved. The performance of the control strategy is verified by experimental results.

The treatment of demyelinating optic neuritis (DON) in pregnant patients is challenging, especially when there is poor or no response to intravenous methylprednisolone pulse (IVMP) therapy or adjunctive treatments such as intravenous immunoglobulin (IVIG) therapy. We herein report a case of a 28-year-old pregnant woman who experienced sequential severe vision loss in both eyes. She presented to a local hospital with the main complaint of sudden, painless vision loss in the left eye and was diagnosed with DON in the left eye. However, she did not receive orbital MRI or IVMP therapy due to safety concerns. Upon admission to our hospital, her visual acuity was 20/30 in the right eye and there was no light perception in the left eye. Her right eye vision deteriorated rapidly, declining to 20/1,000 one day after the admission. The ophthalmic examination revealed a normal anterior segment and a swollen optic disk in the right eye and a dilated pupil with a relative afferent pupillary defect and a swollen optic disk in the left eye. The serological tests for common pathogens, including the aquaporin-4 antibody (AQP-4 Ab), myelin oligodendrocyte glycoprotein antibody (MOG-Ab), and other common autoantibodies, were all negative. The patient was clinically diagnosed with DON in both eyes and received 7 days of IVMP therapy and 4 days of IVIG therapy, but showed no visual improvement. A three-dose regimen of satralizumab 120 mg was then administered subcutaneously during the acute stage of DON, in combination with a slowly tapered oral methylprednisolone regimen. Moreover, 2 months after the first injection of satralizumab, the patient naturally gave birth to a healthy female infant weighing 2,305 g at 36 weeks and 1 day of gestation. Her visual acuity improved to 20/500 in both eyes and slightly increased to 20/320 in both eyes 2 months later. Her visual acuity remained stable during subsequent follow-up visits. The infant was fed formula milk powder and developed normally. No systemic or ocular side effects related to satralizumab therapy were observed in the patient or her fetus during the 9-month follow-up. Our findings in this case suggest that satralizumab may be a safe and efficient adjunctive therapy for pregnant patients with DON who poorly respond to IVMP and IVIG therapy, even in cases of dual-negative AQP-4 Ab and MOG-Ab.

The study aims to explore the characteristics of the impact load of a ship under the influence of a harsh marine environment. The horizontal excitation test platform is established to analyze the response law of the external excitation frequency of the sloshing load. Moreover, nonlinear liquid sloshing impact load characteristics are analyzed under porous baffling with different solids ratios and tanks with different liquid depths. It is found that the resonance frequency of the tank without baffling is 0.93 ω 0 , and that of the tank with a porous baffle is 0.96ω0. With the solid ratios of 0.4 to 0.8, the transient and steady state pressure peaks decrease by 66% and 71%, respectively. The liquid depths of H to H/4, for both transients and steady state pressure peaks, decreased by about 36%. It shows that the resonant frequency is closer to the natural frequency when the amplitude of liquid sloshing is reduced. When the solid ratio is smaller or the liquid depth increases, the impact load of liquid on the wall is stronger, and the double peak of impact load is more obvious. This provides a reference for the engineering design of the liquid tank and the study of fluid sloshing damping.

ObjectivesThis study aimed to evaluate the suitability of the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) for measuring vision-related quality of life (VRQoL) in patients with Leber hereditary optic neuropathy receiving lenadogene nolparvovec gene therapy in three Phase III randomised controlled clinical trials.MethodsVRQoL was assessed using the NEI-VFQ-25 at baseline (n=174) and 2 years after treatment (n=152). All participants received lenadogene nolparvovec in at least one eye. The scoring structure of the original NEI-VFQ-25 was evaluated for fit to the Rasch model, and a post hoc revision was created and psychometrically reevaluated. Stacked analysis was conducted to compare Rasch-revised scores at baseline and 2 years after treatment.ResultsThe original NEI-VFQ-25 exhibited multiple issues including limitations in response functioning and scale dimensionality. These issues were rectified by revising the NEI-VFQ25 into two separate unidimensional scales measuring ‘Vision-related Activity Limitation’ (VAL) and ‘Socioemotional Functioning’ (SEF). Participants’ mean VAL score at baseline on a Rasch-transformed 0–100 scale was 46.1 (11.7), improving to 48.4 (13.7) after treatment (F(1, 324) = 2.67, p=0.103). On the SEF scale, there was a significant difference 2 years after treatment, with participants improving from a mean score of 40.1 (14.1) at baseline to 49.6 (17.6) (F(1, 324) = 29.1, p<0.001).ConclusionsThe scoring structure of the original NEI-VFQ-25 has limitations that undermine its psychometric validity as a measure of VRQoL. Using the Rasch-revised NEI-VFQ-25, we determined that improvement in VRQoL after treatment with lenadogene nolparvovec was driven predominantly by an improvement in socioemotional functioning.

ObjectiveREFLECT is the first randomised, double-masked, placebo-controlled multicentre phase 3 clinical trial that evaluated the efficacy and safety of bilateral intravitreal (IVT) injection of lenadogene nolparvovec in subjects with Leber hereditary optic neuropathy carrying the m.11778G>A mutation.Methods and analysisA total of 98 subjects were enrolled with vision loss of ≤12 months. The subjects were randomised to one of two treatment arms with all subjects receiving an intravitreal (IVT) injection of lenadogene nolparvovec in their first affected eye and the second-affected eye randomised to receive IVT of either lenadogene nolparvovec or placebo.ResultsThe majority of subjects were male with a mean duration of vision loss of 8.3 months. All but one subject experienced bilateral loss of vision at the time of injection. The mean best-corrected visual acuity of first-affected eyes was worse compared with second/not-yet-affected eyes. Analysis of retinal anatomical parameters showed increased thinning in the first-affected eyes when compared with the second/not-yet-affected eyes with both treatment arms showing significant changes compared with unaffected individuals.ConclusionThe REFLECT trial is the third and the largest phase 3 clinical study evaluating lenadogene nolparvovec in m.11778G>A Leber hereditary optic neuropathy (LHON) subjects. The observed demographics in REFLECT are consistent with previous reports in LHON subjects in the acute and dynamic phases of LHON disease. Combined with the visual function and anatomical parameters obtained in the previous RESCUE and REVERSE trials, REFLECT has provided a uniformly collected data set that should help direct future LHON clinical trials.

[Objective] The paper was to develop genetic engineering vaccine that can express α exotoxin antigen protein efficiently without destroying its immunogenicity for preventing and controlling the diseases caused by Clostridium perfringens. [Method] Efficiently expressed soluble recombinant α protein was obtained from Escherichia coli expression system by optimizing codon, removing signal peptide, selecting sequences with better hydrophilicity and antigenicity, and optimizing expression conditions. [Result] Mice obtained higher serum antibody level when immunized by α protein, and the immune protection rates against type A, type B, type C and type D C. perfringens were 100%, 90%, 85% and 90%, respectively. The antibody titer of mice within 7-14 d after the third immunization reached the peak. [Conclusion]The α protein has good immunogenicity, and can be further used to develop genetic engineering subunit vaccines for preventing C. perfringens.

The foodborne pathogen Listeria monocytogenes (Lm) is a highly heterogeneous species and currently comprises of 4 evolutionarily distinct lineages. Here, we characterize isolates from severe ovine listeriosis outbreaks that represent a hybrid sub-lineage of the major lineage II (HSL-II) and serotype 4h. HSL-II isolates are highly virulent and exhibit higher organ colonization capacities than well-characterized hypervirulent strains of Lm in an orogastric mouse infection model. The isolates harbour both the Lm Pathogenicity Island (LIPI)-1 and a truncated LIPI-2 locus, encoding sphingomyelinase (SmcL), a virulence factor required for invasion and bacterial translocation from the gut, and other non-contiguous chromosomal segments from another pathogenic species, L . ivanovii . HSL-II isolates exhibit a unique wall teichoic acid (WTA) structure essential for resistance to antimicrobial peptides, bacterial invasion and virulence. The discovery of isolates harbouring pan-species virulence genes of the genus Listeria warrants global efforts to identify further hypervirulent lineages of Lm. Listeria monocytogenes isolates are highly heterogeneous and exhibit different levels of virulence. Here, the authors identify hypervirulent isolates that represent a hybrid sub-lineage of the major lineage II harbouring virulence factors from Listeria ivanovii and wall teichoic acids found in major lineage I.

When antibiotic-resistant pathogenic bacteria pose a high threat to human health, bacterial multidrug efflux pumps become major contributors to the high-level antibiotic resistance in most microorganisms. Since traditional antibiotics are still indispensable currently, we report a dual drug delivery system to maximize the antibacterial efficacy of antibiotics by inhibiting efflux pumps in bacteria before their exposure to antibiotics. In this research, a microsphere/hydrogel composite was constructed from ciprofloxacin (Cip)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres and ginsenoside Rh2 (G-Rh2) dispersed thermo-sensitive hydrogel to treat skin infections. In vitro drug release studies indicated that while G-Rh2 in hydrogel presented a faster and short-term release manner to rapidly inhibit the NorA efflux pumps, Cip showed a sustained and long-term release behavior to provide a local high concentration gradient for facilitating drug percutaneous penetration. The combination of Cip and G-Rh2 demonstrated a high degree of synergism against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), hence significantly improving their in vitro antibacterial activity and efficiency. Moreover, the antibacterial performance of the microsphere/hydrogel composite with a sequential release profile is superior to that of other formulations in mouse model of MRSA skin infections, indicating its great potential to treat antibiotic-resistant skin infections.

Cerebral malaria (CM) is a severe encephalopathy caused by Plasmodium parasite infection, resulting in thousands of annual deaths and neuro-cognitive sequelae even after anti-malarial drugs treatment. Despite efforts to dissect the mechanism, the cellular transcriptomic reprogramming within the spatial context remains elusive. Here, we constructed single-cell and spatial transcriptome atlases of experimental CM (ECM) male murine brain tissues with or without artesunate (ART) treatment. We identified activated inflammatory endothelial cells during ECM, characterized by a disrupted blood-brain barrier, increased antigen presentation, and leukocyte adhesion. We also observed that inflammatory microglia enhance antigen presentation pathway such as MHC-I to CD8 + cytotoxic T cells. The latter underwent an inflammatory state transition with up-regulated cytokine expression and cytotoxic activity. Multi-omics analysis revealed that the activated interferon-gamma response of injured neurons during ECM and persisted after ART treatment. Overall, our research provides valuable resources for understanding malaria parasite-host interaction mechanisms and adjuvant therapy development. By integrating single-cell and spatial transcriptomic analysis, Chen et al. profile the cellular disruptions in the murine brain during cerebral malaria and after artemisinin treatment.