Inhibiting IL-4 and IL-13 are critical cytokines that induce the pathogenic responses of allergic airway diseases. Currently, monoclonal antibodies targeting IL-4Rα are administered subcutaneously to treat eosinophilic rhinosinusitis and allergic asthma. However, these treatments have several drawbacks. To address these issues, we have developed a novel IL-4Rα-targeting nanobody designed for non-invasive delivery to local inflammatory sites in allergic airway diseases. H5, selected via the ribosomal display applied screening from synthetic nanobody library, underwent dimerization and in-silico affinity maturation using AlphaFold2 and GROMACS resulting in a substantial/dramatic enhancement of its binding affinity. H5 effectively controlled inflammatory markers such as MUC5AC, CCL26, and FOXJ1 in human nasal epithelial cells (HNECs) by inhibiting IL-4 and IL-13 signaling. The bivalent form of H5 showed efficacy in easily accessible cells, such as multi-ciliated cells, while the monovalent variant targeted hard-to-reach cells, such as basal cells of HNECs. In summary, we developed a nanobody that could effectively inhibit inflammatory signaling in HNECs via intranasal administration, showing promise as a non-invasive rhinitis treatment.

Urinary incontinence, characterized by the involuntary leakage of urine, significantly impacts millions globally, affecting their quality of life, social interactions, and psychological well-being. Traditional diagnostic methods and treatments often fall short, especially for refractory urinary incontinence, due to their invasive nature and limited scope for continuous, real-time assessment. This narrative review critically examines current approaches to diagnosing and managing urinary incontinence, highlights significant gaps in practice, and underscores the urgent need for innovative solutions. We explore the evolution of diagnostic and treatment modalities and introduce a preliminary method involving a conceptual catheter device that promises to shift toward non-invasive, real-time monitoring and management. This review synthesizes prevailing research and provides a visionary outlook on how emerging technologies could revolutionize urinary incontinence care, offering a future of personalized, patient-centered strategies. Our discussion extends to the limitations of conventional urodynamic studies, which are often uncomfortable and fail to capture the dynamic nature of urinary incontinence in everyday settings. The proposed preliminary method features an advanced, smart-device solution integrating sensors and artificial intelligence to offer precise, real-time insights into bladder activity. This device, still in the conceptual stages, has the potential to transform the landscape of urinary incontinence management by enhancing diagnostic accuracy and therapeutic efficacy. By bridging the gap between current limitations and future possibilities, this paper aims to inspire ongoing innovation and research in the field of urogynecology.

Plants offer a cost-effective and scalable pharmaceutical platform devoid of host-derived contamination risks. However, their medical application is complicated by the potential for acute allergic reactions to external proteins. Developing plant-based protein therapeutics for localized diseases with non-invasive treatment modalities may capitalize on the benefits of plant proteins while avoiding their inherent risks. Dupilumab, which is effective against a variety of allergic and autoimmune diseases but has systemic responses and injection-related side effects, may be more beneficial if delivered locally using a small biological form. In this study, we engineered a single-chain variable fragment (scFv) of dupilumab, termed Dup-scFv produced by Nicotiana benthamiana, and evaluated its tissue permeability and anti-inflammatory efficacy in air-liquid interface cultured human nasal epithelial cells (HNECs). Despite showing 3.67- and 17-fold lower binding affinity for IL-4Ra in surface plasmon resonance assays and cell binding assays, respectively, Dup-scFv retained most of the affinity of dupilumab, which was originally high, with a dissociation constant (KD) of 4.76 pM. In HNECs cultured at the air-liquid interface, Dup-scFv administered on the air side inhibited the inflammatory marker CCL26 in hard-to-reach basal cells more effectively than dupilumab. In addition, Dup-scFv had an overall permeability of 0.8% across cell layers compared to undetectable levels of dupilumab. These findings suggest that plant-produced Dup-scFv can be delivered non-invasively to cultured HNESc to alleviate inflammatory signaling, providing a practical approach to utilize plant-based proteins for topical therapeutic applications.

UNASSIGNED: The use of nebulized tranexamic acid (TXA) in massive pulmonary hemorrhage is well-described. Published utilization in post-tonsillectomy bleeding (PTB) is limited to a single case. This study examines whether TXA resulted in change of operative intervention necessity and narcotic utilization.
UNASSIGNED: This was a retrospective cohort study at a single, urban academic medical center in the United States. Chart review was conducted of all patients who presented to the hospital for post-tonsillectomy bleed (PTB) between 3/1/2018 and 7/1/2020. Demographic data, intervention modality, need for control under general anesthesia, and opioid use were collected and analyzed.
UNASSIGNED: Twenty-one patients underwent a total of 23 visits for PTB over the study period. Control of hemorrhage without need for operating room intervention for PTB was 100% (6/6) for patients receiving TXA nebulizer and 53% (9/17) for those receiving other treatment modalities. Opioid usage in hospital and on discharge was also lower in patients receiving TXA nebulizers. All results were statistically significant.
UNASSIGNED: Our study supports nebulized TXA as an effective, non-invasive mode of hemostasis in patients presenting to the emergency department for post-tonsillectomy hemorrhage. Nebulized TXA may prevent the need for general anesthesia and operative intervention. Otolaryngologists should consider addition of this novel treatment appropriation of TXA to their management options for postoperative tonsillar hemorrhage.

The aging population warrants the increase of mild cognitive impairment (MCI) prevalence, a condition that could progress to dementia. Efforts have been made to improve the MCI and prevent its progression, including the introduction of Tai Chi, a Chinese traditional exercise. The aim of this systematic review and meta-analysis was to evaluate the efficacy of Tai Chi in attenuating MCI among the elderly population. Records investigating the effect of Tai Chi exercise intervention on cognitive function among elderly patients were searched systematically from PubMed, ScienceDirect, Google Scholar, and Europe PMC as of April 13, 2023. The risk of bias (RoB 2.0) quality assessment was employed in the quality appraisal of the studies included. Review Manager 5.4.1 was used for data extraction and meta-analysis, where the standard mean difference (SMD) and 95% confidence interval (95%CI) were computed. Eight randomized control trials with a total of 1379 participants were included in this meta-analysis. Six trials assessed Montreal Cognitive Assessment scores, where its pooled analysis suggested that Tai Chi was as effective as conventional exercise (SMD=0.15, 95%CI: -0.11 to 0.40, p=0.26). However, pooled analysis of the Mini-Mental Status Examination suggested that Tai Chi intervention more effectively improved cognitive function and reduced the rate of cognitive impairment in elderly patients (SMD=0.36, 95%CI: 0.18 to 0.54, p<0.01) as compared to the control group. This systematic review and meta-analysis suggest that, in some extent, Tai Chi is efficacious in improving cognitive function and slowing down the rate of cognitive impairment among elderly patients.

Bladder dysfunction, particularly neurogenic detrusor overactivity (DO), poses a substantial challenge in multiple sclerosis (MS) patients, detrimentally impacting their quality of life (QoL). Conventional therapies often fall short, necessitating alternative approaches like posterior tibial nerve stimulation (PTNS) for effective management. This narrative review critically examines the application of PTNS in treating DO among MS patients, aiming to provide a comprehensive synthesis of its efficacy, underlying mechanisms, and clinical outcomes. By evaluating a spectrum of studies, including randomized controlled trials and long-term follow-up research, the review elucidates PTNS\'s role in enhancing bladder control and ameliorating symptoms of urgency and incontinence, thereby improving patient well-being. Despite its potential, the review acknowledges the limited scope of existing research specific to MS-induced neurogenic DO and calls for further investigation to optimize PTNS protocols and understand its long-term benefits. Highlighting PTNS\'s minimal invasiveness and favorable safety profile, the review advocates for its consideration as a viable third-line treatment option in MS-related bladder dysfunction management. Through this analysis, the review contributes to the broader narrative of seeking effective, patient-centered therapeutic strategies for MS-related complications, underscoring the importance of personalized care in improving patient outcomes.

Despite the increase in the root caries prevalence, little is still known about how dentists manage this condition. The present study aimed to evaluate the knowledge of dentists on diagnosing and recording root caries lesions (RCL).
The survey consisted of three domains: (1) dentists\' knowledge on diagnosing, recording and managing RCL; (2) information about their current general clinical routines; and (3) their demographics. The four Swiss Universities distributed the survey via e-mail lists for alumni or professionals participating in continuing education. The data was quality checked. Construct validity, internal reliability and intraclass correlation (ICC) were assessed.
The survey was answered by 383 dentists from 25(out of 26) cantons [mean(SD) working experience: 22.5(12) years]. The majority replied that they see less than 5 patients with RCL per week, whereas 41 have at least 5 per week, and 40 % (157 dentists) do not distinguish RCL from coronal caries in their patients\' medical records. When diagnosing active RCL, tactile sensation was the most predominant criterion (n = 380), whereas color (n = 224) and visual appearance (n = 129) of the lesion were less often selected. The most often chosen risk factors for RCL were poor oral hygiene and presence of biofilm.The responses were significantly influenced by the participants\' place of education, their age and working area.
The present survey highlights the huge diversity in diagnosing, recording and assessing risk factors of RCL. The benefits of an appropriate diagnosis, recording and management of risk factors of RCL should be highlighted in under- and postgraduate dental education.
A great diversity in diagnosing, recording and assessing risk factors of RCL was observed, which migh strongly impact how dentists manage RCL. The study emphasizes the necessity for intensive efforts to bridge the gap between guideline recommendations and their implementation in private dental practices.

OBJECTIVE: Skin laxity and wrinkling are common signs of the aging process. This physiological condition of the skin is often accompanied by psychological and social concerns, especially for females, entailing considerable expenses for cosmetics and pharmaceuticals to cease or slow down its advancement. The objective of this study was to evaluate the short-term impact of a new non-ablative radiofrequency device available in the skin face cosmetic field.
METHODS: A randomized study was run on 62 healthy subjects with normal-age related-grade skin laxity, subdivided into two groups. Group 1 received one treatment with Modula RF device (Wavemed, San Cesareo RM, Italy) over the whole face surface. Group 2 received three monthly treatments.
RESULTS: Clinical improvements of the exposed areas were detected by measuring skin parameters, such as total water content, elasticity, and sebum levels at baseline and 1 h after the treatment. Data showed significant effects of Med-RF treatment on skin hydration (p < 0.001), skin elasticity (p < 0.0001), and sebum (p = 0.0009). Moreover, a negative linear correlation was obtained between women\'s age and hydration.
CONCLUSIONS: In conclusion, the results of this study suggest that radiofrequency significantly improves the subjective and objective judgment of patients and doctors, supported by the positive results obtained on the skin quality parameters evaluated. These results confirm that Med-RF technology represents an important tool to achieve face rejuvenation in the field of non-invasive procedures.

Peyronie\'s disease (PD) is a connective tissue disorder affecting the tunica albuginea. It can cause pain and penile deformation, and its prevalence increases with age. Although surgery is the gold standard for the chronic phase of the disease, there are several conservative treatment methods available, and the optimal management of the acute phase of the disease remains a matter of debate. In this article, we aim to summarize the recent trends in research on the subject of non-surgical treatment of PD. The search was performed in PubMed, Scopus, and Web of Science databases and included studies in English published between 2012 and 2022 investigating the clinical outcomes of non-surgical PD management in humans. We have identified 20 distinct conservative treatment strategies. Among the oral therapeutics, only the use of phosphodiesterase type 5 inhibitors is currently recommended for clinical use in patients with concomitant erectile dysfunction. The use of collagenase from Clostridium histolyticum is supported by the best quality evidence in terms of intralesional injections for patients suffering from significant penile curvature; however, interferon alpha-2b can also be an option in such patients. Among other non-invasive methods, extracorporeal shockwaves can be useful for pain reduction, and penile traction therapy can lead to a reduction in penile curvature and plaque size. Despite a wide range of non-surgical methods available for PD treatment, the majority are not supported by sufficient scientific evidence, and the treatment efficacy is underwhelming. Further research on the subject of non-surgical management of PD is highly warranted.

Most of embryos fail to produce live offspring during In Vitro Fertilization-Embryo Transfer (IVF-ET) procedure. There is a dearth of research activity addressing this problem despite the significant population of women suffering from repeated implantation failure after transfer of high-quality of embryos. As a clinically accessible option, granulocyte colony stimulating factor (G-CSF) is often used for the treatment to improve the rates of embryo implantation. However, there are currently no evidence-based standardized protocol for the clinical use of G-CSF. G-CSF was administered into one side of mouse uterine horns and saline was infused into the other side of horns as a control. Intrauterine G-CSF administration showed maximal effects 24 h after administration in enhancing endometrial receptivity and subsequent increase of angiogenesis by demonstrating elevated integrin β3 and OPN and reduced cytotoxicity of NK cells. Furthermore, G-CSF administration 24 h prior to embryo transfer promoted the stability of attached embryos at the early stage of implantation in vitro. Our findings suggest as new consensus criteria providing a potential therapeutic strategy of the clinical use of G-CSF to achieve maximal effects of IVF-ET for patients who are suffering from repeated implantation failure with the problems with endometrial receptivity.