BACKGROUND: Intranasal administration of respiratory vaccines offers many advantages such as eliciting both systemic and mucosal immunity at the point of viral entry. Immunogenicity of intranasal vaccination can be improved through the use of adjuvants. Bacteria-like particles derived fromLactococcus lactishave the potential to serve as a vaccine adjuvant.This clinical study investigated the safety, reactogenicity and immunogenicity of intranasal seasonal influenza vaccine adjuvanted with gram-positive matrix particles (FluGEM®).
METHODS: This was a first-in-human, randomized, double-blind, controlled, dose-escalation study performed at the Centre for Human Drug Research (CHDR), the Netherlands. Participants aged 18-49 were randomized in a 3:1 ratio to receive FluGem® in ascending doses (two-dose regimens) together with a standard trivalent inactivated influenza vaccine or unadjuvanted TIV only. Primary outcomes were safety and tolerability. Secondary outcomes were serum hemagglutination inhibition (HI) antibody titers and mucosal IgA. The most immunogenic dose was used in an additionalelderly cohort (>65 years).
RESULTS: Ninty participants were included. Intranasal FluGem®was safe and well tolerated. The majority of adverse events were mild (97.4 %) with (un)solicited adverse events comparable across all dose levels and control groups. All groups showed geometric mean increases ≥ 2.5-fold. Seroconversion (≥40 % participants) was achieved at both day 21 (single-dose) and 42 (two-dose) for the 1.25 mg dose and on day 42 (two-dose only) for the 2.5 mg dose. Highest geometric mean IgA increases were observed in the 1.25 mg group on day 21. Immunogenicity was less pronounced in elderly.
CONCLUSIONS: Intranasal vaccination of FluGEM®was safe and tolerable in healthy adult volunteers aged 18-49 years and 65 and older. Highest immunogenicity was observed for 1.25 mg and 2.5 mg doses (compared to 5 mg) suggesting a potential non-linear dose-response relationship.More research is needed to further investigate the capabilities of bacteria-like peptides as adjuvants.

OBJECTIVE: Little information is known about the mentalis nerve course from the lower lip approximation margin (free margin) to the upper lip. Likewise, no difference in nerve distribution has been observed between the cutaneous and mucosal parts of the lip. Therefore, this study reexamined mentalis nerve morphology.
METHODS: For macroscopic observations, three fresh cadavers were dissected (one male and two females; aged 78-93). We also evaluated histological sections obtained from five donated elderly cadavers (two males and three females, aged 82-96 years) and 15 human fetuses (11-40 weeks or crown-rump length 80-372 mm). Immunohistochemical analysis for S100 protein and tyrosine hydroxylase was performed.
RESULTS: In both fetuses and adult cadavers, one to three nerve branches ran upward in the submucosal tissue from the mental foramen. Near the free margin of the lip, some branches passed through the orbicularis oris muscle layer toward the lip skin, whereas others followed a reversed J-shaped course along the free margin. Nerve twigs ran in parallel beneath the mucosa, whereas wavy nerve twigs attached to the basal lamina of the lip epidermis. The difference in nerve endings abruptly occurred at the skin-mucosal junction. Tyrosine hydroxylase-positive sympathetic nerve twigs surrounded arteries and formed a branch composed of S100-negative unmyelinated fibers.
CONCLUSIONS: The lower lip skin was innervated by a perforating branch passing through the orbicularis oris muscle, that was different from the lip mucosa. A sudden change in the nerve ending configuration at the mucocutaneous junction seemed to develop postnatally.

In the present study, we propose the use of swabs in non-lethal sampling procedures to collect the mucosa-adhered gut microbiota from the posterior intestine of fish, and therefore, we compare the bacterial communities collected by conventional scraping and by swabbing methods. For this purpose, samples of the posterior intestine of rainbow trout (Oncorhynchus mykiss) were collected first using the swabbing approach, and after fish euthanasia, by mucosa scraping. Finally, bacterial communities were compared by 16S rRNA gene Illumina sequencing. Results from the current study revealed that similar values of bacterial richness and diversity were found for both sampling procedures. Similarly, there were no differences between procedures when using qualitative metrics (Jaccard and unweighted UniFrac) for estimating inter-individual diversity, but the quantitative metrics (Bray-Curtis and weighted UniFrac) showed a higher dispersion when samples were obtained by swabbing compared to scraping. In terms of bacterial composition, there were differences in abundance for the phyla Firmicutes and Proteobacteria. The cause of these differential abundances may be the inability of the swab to access to certain areas, such as the basal region of the intestinal villi. Moreover, swabbing allowed a higher representation of low abundant taxa, which may also have an important role in host microbiome regardless of their low abundance. Overall, our results demonstrate that the sampling method is a factor to be considered in experimental design when studying gut bacterial communities to avoid potential biases in the interpretation or comparison of results from different studies. In addition, the advantages and disadvantages of each procedure (swabbing vs scraping) are discussed in detail, concluding that swabbing can be implemented as a reliable and non-lethal procedure for posterior gut microbiota studies, which is of particular interest for animal welfare and the 3Rs principle, and may offer a wide range of novel applications.

Gastrointestinal simulations in vitro have only limited approaches to analyze the microbial communities inhabiting the mucosal compartment. Understanding and differentiating gut microbial ecosystems is crucial for a more comprehensive and accurate representation of the gut microbiome and its interactions with the host. Herein is suggested, in a short-term and static set-up (named \"M-batches\"), the analysis of mucosal and luminal populations of inhabitants of the human colon. After varying several parameters, such as the fermentation volume and the fecal inoculum (single or pool), only minor differences in microbial composition and metabolic production were identified. However, the pool created with feces from five donors and cultivated in a smaller volume (300 mL) seemed to provide a more stable luminal ecosystem. The study of commercially available coffee and green tea in the M-batches suggested some positive effects of these worldwide known beverages, including the increase in butyrate-producing bacteria and lactobacilli populations. We hope that this novel strategy can contribute to future advances in the study of intestinal ecosystems and host-microbe relationships and help elucidate roles of the microbiome in health and disease.

BACKGROUND: Given the paucity of current safety studies related to e-cigarettes, there are no definitive studies on whether e-cigarettes cause oral mucosal lesions or even oral cancer. Although it is still undetermined whether e-cigarettes are harmless, an increasing number of teenagers choose to smoke e-cigarettes and believe that they are not harmful to the human body.
OBJECTIVE: This aims to determine whether e-cigarettes cause damage to the oral mucosa. This study also aims to evaluate the association between e-cigarette smoking and oral mucous membrane lesions in young adults. The objectives are to (1) compare the oral mucosal conditions in participants with and without e-cigarette smoking habits, (2) assess the effect of the amount of e-cigarette smoking on oral mucosal conditions, and (3) assess the effect of the duration of e-cigarette smoking on oral mucosal conditions.
METHODS: In this prospective study, 304 youths aged 15 to 24 years (n=152, 50% who smoke only e-cigarettes and n=152, 50% who do not smoke e-cigarettes or cigarettes) will be divided into 2 groups for a controlled study. Whether e-cigarettes cause oral mucosal lesions will be verified by comparing the odds of oral mucosal lesions in the 2 experimental groups. For this experiment, the predefined power is 80% (P=.04), and the predefined proportions of groups 1 and 2 are 11% and 2.5%, respectively.
RESULTS: This experiment is at the conceptualization phase and has not yet been carried out. Experimenters have not been recruited and no data have been collected.
CONCLUSIONS: e-Cigarettes are still an unfamiliar topic to the public, and it is still unknown whether they can cause damage to the oral mucosa. This experiment aims to find out whether there is a link between the 2. There are still many limitations in this study, such as the lack of categorization of e-cigarettes and the lack of testing methods for oral mucosal status. These limitations are expected to be addressed in the future as the experiment is formally conducted and further optimized.
UNASSIGNED: PRR1-10.2196/53644.

Rapid and proper diagnosis of mucocutaneous presentations of COVID-19 which in many cases are representing internal organ damage is a key way to better approach these patients, and it could be even lifesaving. In this original study, we reported consultant critical and non-critical cases of admitted COVID-19 patients and some interesting outpatient cases for 14 months, and some newly encountered vaccine-associated dermatoses. We presented 121 cases divided into 12 categories; all had full multi-aspects photographs attached as an atlas to a Supplementary File. These categories were:1- Generalized papulopustular eruptions (3 patients), 2- Erythroderma (4 patients), 3- Maculopapular lesions(16 patients), 4- Mucosal lesions (8 patients), 5- Urticarial lesions and angioedema (16 patients), 6- Vascular injuries (22 patients), 7- Vesiculobullous lesions (12 patients), 8- The specific new onset of mucocutaneous presentations or aggravation of any especial previous dermatoses (9 patients), 9- Nail changes (3 patients), 10- Hair loss (2 patients), 11- Non-specific mucocutaneous problems (16 patients) and 12-Vaccine-associated dermatoses (10 patients).In the pandemic, if we countered with extensive mucocutaneous lesions with vascular components or vesiculobullous erosive lesions in association with any cutaneous rash that could be an alarming sign of a probable life-threatening systemic event, we would need to approach them as soon as possible.

BACKGROUND: Intensity modulated radiotherapy (IMRT) for head and neck cancer has led to a reduction in radiotherapy doses to normal tissues, like the salivary glands, while maintaining high rates of local control. Oral mucosal and skin toxicity is still a major source of treatment-related morbidity, occurring in most patients.
OBJECTIVE: We conducted a dosimetric feasibility study with the goal of creating a methodology that could theoretically reduce the dose of radiation to skin and oral mucosa, while maintaining comparable avoidance of other organs at risk, and planning target volume (PTV) coverage.
METHODS: The clinical plans of patients treated previously were replanned using coplanar VMAT arcs on a TrueBeam STx using the photon optimizer (PO) version 15.6 and the Acuros XB dose calculation algorithm. Comparisons were made between three methodologies: \"Conventional,\" \"Skin Sparing\" and a skin/mucosa avoiding (\"SMART\") technique, with dose metrics being compared using analysis of variance, with a Bonferroni correction to account for multiple pairwise comparisons. The maximum grade of mucositis and radiation dermatitis during treatment was correlated to different dose-volume metrics to predict what could be clinically meaningful.
RESULTS: Sixteen patients met the study criteria and were replanned using the skin sparing and SMART techniques. Maximum doses to the skin sparing structure were reduced from 64.2 Gy to 56.6 and 55.9 Gy, in the skin sparing and SMART plans (p < 0.0001), and mean doses reduced from 26.7 Gy to 20.0 and 20.2 Gy, respectively (p < 0.0001). Maximum doses to the oral cavity structure were not reduced by either technique, however mean dose to the oral cavity structure was reduced from 39.03 Gy to 33.5 Gy by the SMART technique (p < 0.0001). There was a slight reduction in PTV_High coverage by the V95% in the SMART plans (99.52% vs. 98.79%, p = 0.0073), and a similar slight reduction in PTV_Low coverage by the V95% by both the skin sparing and SMART plans (99.74% vs. 97.89% vs. 97.42%, p < 0.0001). Maximum doses to organs at risk were not statistically different between techniques. Dose to oral cavity and maximum grade experienced during radiotherapy correlated. The Spearman correlation coefficient for dose to 20%, 50%, and 80% of the volume of oral cavity was 0.5 (p = 0.048), 0.64 (p = 0.007), and 0.62 (p = 0.010), respectively. Skin toxicity grade was only found to be correlated with the D20% of the skin sparing structure (Spearman correlation coefficient of 0.58, p = 0.0177).
CONCLUSIONS: The SMART technique appears to be able to reduce maximum and mean skin dose, as well as mean oral cavity doses, while only slightly reducing PTV coverage, with acceptable OAR doses. We feel the improvements warrant investigation in a clinical trial.

OBJECTIVE: The aim was to evaluate peri-implant tissue levels over a 3-year period for implants connected to either convex or concave final abutments at the time of implant placement.
METHODS: In this randomized, double-masked, controlled clinical study, 28 patients with one missing maxillary premolar were assigned to receive one single implant with a permanent abutment of either convex (CONVEX Group) or concave (CONCAVE Group) emergence shape at the time of implant placement. Clinical and radiographic data were collected at the time of implant placement (IP), final prosthesis delivery (PR), 12 months (FU-1), and 36 months (FU-3) following implant placement.
RESULTS: At the FU-3 13 patients were available from the CONCAVE Group (n = 13) and eleven from the CONVEX Group (n = 11). The mean change in buccal peri-implant mucosa position (MP) from IP to FU-3 was -0.54 ± 0.93 mm for the CONVEX Group and - 0.53 ± 0.87 mm for CONCAVE Group (p = .98). The amount of bone remodeling above the implant platform from IP to FU-3 was -0.69 ± 0.48 mm for the CONVEX Group and -0.16 ± 0.22 mm for the CONCAVE Group (p = .005).
CONCLUSIONS: The study failed to support the hypothesis that abutment macro-design has an effect on buccal peri-implant mucosa margin position over time.

Post-weaning diarrhea (PWD) remains a major source of mortality and morbidity in swine production. Transplantation of bacteria-free filtrate of feces (fecal filtrate transplant, FFT) has shown gut protective effects in neonatal pigs, and early postnatal establishment of the gut microbiome is suggested to determine later stability and robustness of the gut. We, therefore, hypothesized that early postnatal transplantation of bacteria-free feces would have a protective effect against PWD. Using fecal filtrates derived from healthy lactating sows, we compared oral administration of fecal filtrate transplantation (FFT, n = 20) and saline (CON, n = 18) in newborn piglets. We assessed growth, diarrhea prevalence, blood parameters, organ measurements, morphology, and gut brush border enzymes and analyzed luminal bacterial composition using 16S rRNA gene amplicon sequencing. The two groups showed similar average daily gain (ADG) during the suckling period, whereas in the post-weaning period, a negative ADG was observed in both groups. While diarrhea was largely absent in both groups before weaning, there was a lower diarrhea prevalence on days 27 (p = 2.07*10-9), 28 (p = 0.04), and 35 (p = 0.04) in the FFT group relative to CON. At weaning on day 27, the FFT group had higher numbers of red blood cells, monocytes, and lymphocytes, while on day 35, i.e., 1 week after weaning, the two groups were similar regarding hematology. The biochemical profile was largely similar between FFT and CON on days 27 and 35, except for a higher level of alanine aminotransferase and a lower level of Mg in the FFT group. Likewise, organ weights relative to body weight were largely similar on day 35, albeit with a lower stomach weight and more colon content in FFT relative to CON. Gut mucosal percentage and mucosal enzyme activity were similar between the two groups on days 27 and 35. Gut bacterial composition was slightly different on day 35 but not on day 27. In conclusion, early postnatal administration of FFT, showed positive clinical effects in post-weaning pigs, albeit with subtle effects on the gut mucosa and microbiome. Prophylactic treatment with FFT may offer a means to reduce morbidity, yet larger studies are required to document effect size.

OBJECTIVE: The purpose of this multicenter retrospective study was to investigate the demographic characteristics and treatment outcomes of patients with mucosal malignant melanoma (MM) of the oral cavity.
METHODS: This was a multicenter study involving 8 Japanese universities. The medical records of 69 patients who were diagnosed with primary oral MM between January 2000 and December 2020 were retrospectively analyzed. Overall survival (OS) and prognostic factors for OS were analyzed statistically.
RESULTS: There were 40 (58.0%) males and 29 (42.0%) females, and their mean (range) age was 69.8 ± 14.6 (22-96) years old. The most common primary site was the palate (30 patients, 43.5%). Stage IVA was the most common disease stage (36 patients, 52.2%). Radical therapy was performed in 55 patients (79.7%). The 2-year and 5-year OS rates of the 69 patients were 64.6% and 42.5%, respectively. The 2-year and 5-year OS rates of the stage III patients were 85.9% and 72.5%, respectively, and those of the stage IVA patients were 56.3% and 26.0%, respectively. The 1-year OS rate of the stage IVB/IVC patients was 26.7%. The 2-year and 5-year OS rates of the radical therapy group were 74.1% and 50.5%, respectively, whereas the 2-year OS rate of the non-radical therapy group was 26.0%. An advanced T classification was the only identified prognostic factor for OS (hazard ratio: 6.312, 95% confidence interval: 1.133-38.522, p < 0.05).
CONCLUSIONS: Early detection and radical treatment are essential for improving the prognosis of oral MM patients.
CONCLUSIONS: Early detection and adequate radical therapy leads to the better prognosis of oral MM patients.