[Pharmacological profiles and clinical findings of nemolizumab as treatment for pruritus associated with atopic dermatitis].

Nemolizumab (Mitchga® syringes) is a biologic with a novel mechanism of action that was first approved in Japan in March 2022 for pruritus associated with atopic dermatitis (AD) only when existing treatments were insufficiently effective. Nemolizumab is a humanized antihuman interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that targets the receptor for IL-31, the major pruritogen in AD. Nemolizumab inhibits IL-31 signaling and suppresses pruritus by competitively preventing IL-31 from binding to IL-31RA. In the phase III study, nemolizumab, 60 |mg, was administered subcutaneously once every 4 weeks, in combination with topical therapy, to patients aged 13 years or older who had AD and inadequately controlled moderate-to-severe pruritus. The efficacy of the treatment was verified by mean percentage change in the pruritus visual analogue scale score from baseline to 16 weeks. Skin symptoms and quality of life (QOL) were improved after 16 weeks. Furthermore, data for up to 68 weeks revealed continuous improvement and/or maintenance of itching, skin symptoms, and QOL. The most common adverse effects were worsening of AD, skin infection, and upper respiratory tract infection. Because skin symptoms may worsen during treatment with this product, patients must be monitored carefully and managed appropriately (e.g., by intensifying treatment with topical anti-inflammatory drugs or withdrawal of medication as needed). Nemolizumab effectively suppresses itching, the most distressing symptom of AD, and improves skin symptoms. It is also expected to help improve QOL, including sleep.This review describes the pharmacological properties of nemolizumab, pharmacokinetics, efficacy and safety in clinical trials in Japan.

Self-biasing of carrier depletion based silicon microring modulators.

We report on the self-biasing effect of carrier depletion based silicon microring modulators (MRM) by demonstrating that a silicon MRM can generate open eye diagrams for non-return-to-zero (NRZ) on-off keying (OOK) modulation without an external reverse bias supplied to it. Two modulator configurations are investigated namely single-ended drive in a ground-signal-ground and differential drive in a ground-signal-signal-ground pad configurations. The single-ended modulator is designed with an on photonic integrated circuit (PIC) 50 Ω termination. Open eye diagrams are obtained at 25 Gbit/s and 36 Gbit/s NRZ OOK modulations. We carry-out thorough experimental characterization of the self-biasing of single-ended MRM under various operating conditions of input optical power, carrier wavelength, ring quality factor and extinction ratio as well as modulation speeds, driving voltage swing and pattern length. We demonstrate that the self-biasing is robust and works well in almost all tested conditions. The differential drive MRM is designed with a high impedance without an on-PIC 50 Ω termination. Open eye diagrams are obtained at 30 Gbit/s and 60 Gbit/s NRZ OOK modulations for modulating voltage swing of ∼2.5 Vpp. As demonstrated, the self-biasing works well in both single-ended and differential drive configurations as well as for on-PIC 50 Ω terminated and non-terminated MRMs. The electrical passive parts are all co-designed and fabricated on the same silicon chip as the PIC. The reported self-biasing eliminates the need of having bipolar DC biases supplied to the anode and cathode of the differential drive modulator and allows for simpler driver / modulator interfaces without inductive bias tees.

Optical filter requirements in an EML-based single-sideband PAM4 intensity-modulation and direct-detection transmission system.

The feasibility of a single sideband (SSB) PAM4 intensity-modulation and direct-detection (IM/DD) transmission based on a CMOS ADC and DAC is experimentally demonstrated in this work. To cost effectively build a >50 Gb/s system as well as to extend the transmission distance, a low cost EML and a passive optical filter are utilized to generate the SSB signal. However, the EML-induced chirp and dispersion-induced power fading limit the requirements of the SSB filter. To separate the effect of signal-signal beating interference, filters with different roll-off factors are employed to demonstrate the performance tolerance at different transmission distance. Moreover, a high resolution spectrum analysis is proposed to depict the system limitation. Experimental results show that a minimum roll-off factor of 7 dB/10GHz is required to achieve a 51.84Gb/s 40-km transmission with only linear feed-forward equalization.

Prediction of percutaneous absorption in human using three-dimensional human cultured epidermis LabCyte EPI-MODEL.

The objective of this study is to establish a relationship of the skin penetration parameters between the three-dimensional cultured human epidermis LabCyte EPI-MODEL (LabCyte) and hairless mouse (HLM) skin penetration in vitro and to predict the skin penetration and plasma concentration profile in human. The skin penetration experiments through LabCyte and HLM skin were investigated using 19 drugs that have a different molecular weight and lipophilicity. The penetration flux for LabCyte reached 30 times larger at maximum than that for HLM skin. The human data can be estimated from the in silico approach with the diffusion coefficient (D), the partition coefficient (K) and the skin surface concentration (C) of drugs by assuming the bi-layer skin model for both LabCyte and HLM skin. The human skin penetration of ß-estradiol, prednisolone, testosterone and ethynylestradiol was well agreed between the simulated profiles and in vitro experimental data. Plasma concentration profiles of ß-estradiol in human were also simulated and well agreed with the clinical data. The present alternative method may decrease human or animal skin experiment for in vitro skin penetration.