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.

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.

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.

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.

OBJECTIVE: The prevalence of root caries is increasing globally, especially in the elderly population, and even though the number of patients with root caries lesions is augmenting, there are still many discrepancies in how dentists manage this condition. The present study aimed to develop and validate a questionnaire to evaluate how dentists diagnose, record and manage root caries lesions, and to verify the validity and reliability of this questionnaire.
METHODS: An expert panel developed a self-administered questionnaire survey with three domains: (1) dentists\' knowledge on diagnosis, recording, and managing root caries; (2) information about their current general clinical routines; (3) their demographics. The original English [E] version was translated into three different languages (French [F], German [G], Italian [I]), and subsequently back-translated into English by independent dentists. For the validation, 82 dentists (20-22 for each of the translated versions) accepted to answer the questionnaire at two different time-points (with 1-week interval). The data was quality checked. Construct validity, internal reliability, and intra-class correlation (ICC) were assessed.
RESULTS: Seventy-seven dentists completed the questionnaire twice [E: 17; F: 19; G: 19; I: 22]. The mean ICC (standard deviation) was 0.98(0.03) for E, 0.90(0.12) for F, 0.98 (0.04) for G, and 0.98 (0.01) for I. Overall, the test-retest reliability was excellent (mean ICC (SD): 0.96 (0.08)). Furthermore, the questionnaire demonstrated good internal reliability (inter-observer reliability; Fleiss kappa: overall:0.27(fair); E:0.30 (fair); F: 0.33(fair); G: 0.33(fair); I: 0.89 (almost perfect)).
CONCLUSIONS: The questionnaire was validated and is suitable to be used in the four languages to assess the knowledge of dentists on diagnosing, recording and managing root caries.
CONCLUSIONS: The present questionnaire was validated and seems to be a good tool to evaluate how dentists diagnose, record, and manage root caries lesions both in its original (English) and its translated (French, German, and Italian) versions.

A systematic review and meta-analysis were carried out to evaluate the efficacy of silver diamine fluoride (SDF) in controlling caries progression in cavitated primary molars. A search for randomized and non-randomized trials with follow-up > 6 months was performed using PubMed, Scopus and Embase. The Cochrane risk of bias tools were used for the quality assessment. The success rate and odds ratios were chosen to calculate the effect size for the meta-analysis. A total of 792 papers were identified and 9 were selected. A high variability regarding SDF application protocol was found; otherwise, caries arrest was always recorded using visual/tactile methods. Two studies were judged at low risk of bias, six at moderate risk and one at high risk. Data from five studies were aggregated for meta-analysis. Heterogeneity was found moderate (I2 = 35.69%, p = 0.18). SDF application was found to be overall effective (fixed effect model) in arresting caries progression (ES = 0.35, p < 0.01). In a total of 622 arrested lesions, out of 1205 considered, the caries arrest rate was 51.62% ± 27.40% (Confidence = 1.55) using SDF ≥ 38% applied annually or biannually. In conclusion, when applied to active cavitated caries lesions in primary molars, SDF appears to be effective in arresting dental caries progression, especially if applied biannually.

UNASSIGNED: Recent studies have shown that specific cases of post-appendectomy abscess (PAA) in children could be treated conservatively. However, due to the lack of high-quality evidence, choice of treatment still depends on preferences of the treating surgeon, leading to heterogeneity in clinical practice. Therefore, we aimed to provide an update of recent literature on the management of PAA in children and subsequently evaluate the outcomes of a large multicenter cohort of children treated for PAA.
UNASSIGNED: A literature search was performed in Pubmed and Embase, selecting all randomized controlled trials, prospective and retrospective cohort studies, and case series published from 2014 and onward and reporting on children (<18 years) treated for a PAA. Subsequently, a historical cohort study was performed, including all children (<18 years) treated for a radiologically confirmed PAA between 2014 and 2021 in a tertiary referral center and two large peripheral centers. Medical charts were reviewed to compare non-invasive (i.e., antibiotics) and invasive (i.e., drainage procedures) treatment strategies. Primary outcome was the success rate of treatment, defined as no need for further interventions related to PAA or its complications.
UNASSIGNED: The search yielded 1,991 articles, of which three were included. Treatment success ranged between 69-88% and 56-100% for non-invasive and invasive strategies, respectively. Our multicenter cohort study included 70 children with a PAA, of which 29 (41%) were treated non-invasively and 41 (59%) invasively. In the non-invasive group, treatment was effective in 21 patients (72%) compared to 25 patients (61%) in the invasive group. Non-invasive treatment was effective in 100% of unifocal small (<3 cm) and 80% of unifocal medium size PAA (3-6 cm), but not effective for multiple abscesses.
UNASSIGNED: Non-invasive treatment of especially unifocal small and medium size (<6 cm) PAA in children seems to be safe and effective. Based on these results, a standardized treatment protocol was developed. Prospective validation of this step-up approach-based treatment protocol is recommended.

Conventional transcranial electrical stimulation (tES) is a non-invasive method to modulate brain activity and has been extensively used in the treatment of Parkinson\'s disease (PD). Despite promising prospects, the efficacy of conventional tES in PD treatment is highly variable across different studies. Therefore, many have tried to optimize tES for an improved therapeutic efficacy by developing novel tES intervention strategies. Until now, these novel clinical interventions have not been discussed or reviewed in the context of PD therapy. In this review, we focused on the efficacy of these novel strategies in PD mitigation, classified them into three categories based on their distinct technical approach to circumvent conventional tES problems. The first category has novel stimulation modes to target different modulating mechanisms, expanding the rang of stimulation choices hence enabling the ability to modulate complex brain circuit or functional networks. The second category applies tES as a supplementary intervention for PD hence amplifies neurological or behavioral improvements. Lastly, the closed loop tES stimulation can provide self-adaptive individualized stimulation, which enables a more specialized intervention. In summary, these novel tES have validated potential in both alleviating PD symptoms and improving understanding of the pathophysiological mechanisms of PD. However, to assure wide clinical used of tES therapy for PD patients, further large-scale trials are required.

Neonatal retropharyngeal abscess (RPA) is a rare and life-threatening entity. Most of the cases are idiopathic in nature. We encountered a case of RPA in a newborn secondary to extravasation injury. The presence of neck swelling with clinical deterioration following extravasation of total parenteral nutrition (TPN) infused via a peripherally inserted central catheter at the right upper limb raised the suspicion of neck abscess. This was later confirmed to be RPA based on magnetic resonance imaging of the neck. She was treated with prolonged intravenous antibiotics in the Neonatal Intensive Care Unit (NICU). Her condition gradually improved, evidenced by resolution of the collection on serial imaging. Early recognition and prompt management are crucial to reduce the morbidity and mortality from RPA.