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Oral mucositis is highly prevalent among the elderly, for whom oral care is often difficult. Oral mucositis, such as candidiasis, can induce systemic fungemia. Antifungal prophylaxis may be useful in such cases to prevent systemic fungemia; however, studies on this are limited. The objective of this study was to demonstrate the effectiveness of antifungal prophylaxis to prevent systemic Candida dissemination compared to oral care using a mice model. Oral candidiasis was induced using chemotherapy and inoculation with C. albicans in 8-week-old male mice. Group A was given oral care, Group B was orally administered an antifungal drug, Group C was intravenously administered an antifungal drug, and Group D was used as the negative control group. Macroscopic features of the tongue surface, colony forming units (CFU) on the tongue, and blood culture for C. albicans were evaluated. CFU was significantly higher in Group A than in Groups B and C. The oral care group, but not the groups administered antifungal agents, showed significantly higher positive numbers of animals with C. albicans in the blood as compared to the control group, indicating the effectiveness of antifungal prophylaxis over oral care. Antifungal prophylaxis may be an option for the prevention of systemic fungemia in individuals with difficulty in oral care.

Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru.Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021.From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18-24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20-2·14), participants aged 18-24 years (1·80, 1·49-2·18), and participants with primary education (2·18, 1·29-3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46-0·70), participants aged 18-24 years (0·52, 0·46-0·58), and those with primary education (0·60, 0·40-0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45-0·71), participants aged 18-24 years (0·56, 0·49-0·64), and those with secondary education (0·74, 0·68-0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70-1·03) and was higher for transgender women, participants from Peru, those aged 18-24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP.Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP.Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru.For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Atopic dermatitis (AD) is a chronic and relapsing multifactorial inflammatory skin disease that also affects dogs. The oral and gut microbiota are associated with many disorders, including allergy. Few studies have addressed the oral and gut microbiota in dogs, although the skin microbiota has been studied relatively well in these animals. Here, we studied the AD-associated oral and gut microbiota in 16 healthy and 9 AD dogs from a purebred Shiba Inu colony. We found that the diversity of the oral microbiota was significantly different among the dogs, whereas no significant difference was observed in the gut microbiota. Moreover, a differential abundance analysis detected the Family_XIII_AD3011_group (Anaerovoracaceae) in the gut microbiota of AD dogs; however, no bacterial taxa were detected in the oral microbiota. Third, the comparison of the microbial co-occurrence patterns between AD and healthy dogs identified differential networks in which the bacteria in the oral microbiota that were most strongly associated with AD were related to human periodontitis, whereas those in the gut microbiota were related to dysbiosis and gut inflammation. These results suggest that AD can alter the oral and gut microbiota in dogs.

OBJECTIVE To establish the pharmacokinetics of a single 2-mg oral dose of chlorambucil in cats with indolent lymphoproliferative malignancies. ANIMALS 24 client-owned cats. PROCEDURES Cats were assigned to 1 of 4 groups, with each group having a total of 3 sample collection time points over 12 hours after receiving a single 2-mg oral dose of chlorambucil. Each time point combined to generate 6 full patient plasma chlorambucil concentration-time curves from the 24 cats. Chlorambucil treatment was continued every other day and a single, variably timed sample collection was obtained on day 14. Population parameter estimates were obtained by nonlinear mixed-effects modeling. Covariates investigated included age, sex, baseline serum cobalamin, study location, weight, and body condition score. RESULTS Chlorambucil administered orally to cats was found to have a peak plasma concentration of approximately 170 ng/mL (SE, 31.1 ng/mL), percent coefficient of variation (%CV) of 18.4% within 15 minutes, and a terminal half-life of 1.8 hours (SE, 0.21 hour; %CV, 12.4). At the 4-hour mark, a smaller secondary peak in plasma chlorambucil was found. Day 14 samples were similar to those of the initial dose. No covariates showed a significant effect in the population model. CLINICAL RELEVANCE In these cats, chlorambucil at a 2-mg dose administered every other day undergoes rapid gastrointestinal absorption and plasma clearance with no drug accumulation between doses. These data are critical to inform future work investigating the association of chlorambucil drug exposure with adverse events and outcome of cats with lymphoproliferative diseases.

Histoplasmosis, also known as Darling's disease, is a fungal infection caused by Histoplasma capsulatum and is common among patients with AIDS and is mainly found in North, Central and South America and sub-Saharan Africa. It manifests as pulmonary, progressive disseminated histoplasmosis involving reticuloendothelial system, liver, spleen, lymph node, bone marrow, adrenal glands and primary cutaneous histoplasmosis. In HIV infection, 10% cases of histoplasmosis have cutaneous manifestations. Only 12 reports of AIDS associated histoplasmosis are described in the Indian literature. In this report, we describe an additional case of histoplasmosis in 19-year-old male in Kutch district of Gujarat state.

ObjectiveTo assess the relationship of adherence and pregnancy in participants using an estetrol and drospirenone combined oral contraceptive.MethodsWe performed a secondary analysis for which we pooled data from two parallel, multicenter, phase 3 trials (United States and Canada, Europe and Russia) that enrolled participants 16-50 years of age to receive estetrol 15 mg and drospirenone 3 mg in a 24 hormone and four placebo pills regimen for up to 13 cycles. Participants reported pill intake, sexual intercourse, and other contraceptive use on paper diaries. We limited this efficacy analysis to at-risk cycles (one or more reported acts of intercourse and no other contraceptive use) in participants 16-35 years of age at screening. We excluded cycles with other contraceptive use unless pregnancy occurred in that cycle. We assessed primarily the relationship between number of pills not taken per cycle and pregnancies and, secondarily, when pregnancies occurred during product use with a test for trend and χ 2 analyses as appropriate.ResultsAmong 2,837 participants in this analysis, 31 on-treatment pregnancies occurred during 26,455 at-risk cycles. Pregnancies occurred in 0.09%, 0.25%, 0.83%, and 1.6% of cycles in which participants reported they took all hormone pills (n=25,613 cycles) or did not take one (n=405 cycles), two (n=121 cycles), and more than two (n=314 cycles) hormone-containing pills, respectively ( P

Background Oral anticoagulants (OACs) mitigate stroke risk in patients with atrial fibrillation (AF). The study aim was to analyze prevalence and predictors of OAC underutilization. Methods Newly diagnosed AF patients with a CHA2DS2-VASc score ≥ 2 were identified from the US CMS Database (January 1, 2013–December 31, 2017). Patients were stratified based on having an OAC prescription versus not and the OAC prescription group was stratified by direct OAC (DOACs) versus warfarin. Multivariable logistic regression models were used to examine predictors of OAC underutilization. Results Among 1,204,507 identified AF patients, 617,611 patients (51.3%) were not prescribed an OAC during follow-up (mean: 2.4 years), and 586,896 patients (48.7%) were prescribed an OAC during this period (DOAC: 388,629 [66.2%]; warfarin: 198,267 [33.8%]). Age ≥ 85 years (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.55–0.56), female sex (OR 0.96, 95% CI 0.95–0.96), Black race (OR 0.78, 95% CI 0.77–0.79) and comorbidities such as gastrointestinal (GI; OR 0.43, 95% CI 0.41–0.44) and intracranial bleeding (OR 0.29, 95% CI 0.28–0.31) were associated with lower utilization of OACs. Furthermore, age ≥ 85 years (OR 0.92, 95% CI 0.91–0.94), Black race (OR 0.78, 95% CI 0.76–0.80), ischemic stroke (OR 0.77, 95% CI 0.75–0.80), GI bleeding (OR 0.73, 95% CI 0.68–0.77), and intracranial bleeding (OR 0.72, 95% CI 0.65–0.80) predicted lower use of DOACs versus warfarin. Conclusions Although OAC therapy prescription is the standard of care for stroke prevention in AF patients, its overall utilization is still low among Medicare patients ≥ 65 years old, with specific patient characteristics that predict underutilization.

The ongoing SARS-CoV-2 evolution has resulted in many variants, contributing to the striking drop in vaccine efficacy and necessitated the development of next-generation vaccines to tackle antigenic diversity. Herein we developed a multivalent Semliki Forest virus replicon-based mRNA vaccine targeting the receptor binding domain (RBD), heptad repeat domain (HR), membrane protein (M) and epitopes of nsp13 of SARS-CoV-2. The bacteria-mediated gene delivery offers the rapid production of large quantities of vaccine at a highly economical scale and notably allows the needle-free mass vaccination. A favourable Th1 dominated potent antibody and cellular immune responses were detected in the immunized mice. Further, immunization induced strong cross-protective neutralizing antibodies (NAbs) against the B.1.617.2 delta variant (Clade G). We recorded a difference in induction of IgA response by the immunization route with the oral route eliciting a strong mucosal sIgA response, which possibly has contributed to the enhanced protection conferred by the oral immunization. Hamsters immunized orally were completely protected against the viral replication in the lungs and the nasal cavity. Importantly, the vaccine protected the hamsters against SARS-CoV-2-induced pneumonia. The study provides proof-of-principle findings for the development of a feasible and efficacious oral mRNA vaccine against SARS-CoV-2 and its variants., Graphical Abstract, Exploiting Semliki Forest virus replicon allows the development of bacteria-mediated oral mRNA vaccine. The vaccine induces potent Th1 polarized humoral and cellular immune responses. Oral administration elicits robust mucosal IgA response in lung and intestine. Oral replicon-based mRNA vaccine protects hamsters against parental and delta variant SARS-CoV-2 challenge.

Background: Evidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an individual’s negative treatment expectations, is growing across a multitude of medical fields. However, little attention has been paid to patients’ negative expectations and the nocebo effect within dentistry. Aim: This review summarises essential evidence of the nocebo phenomenon especially in relation to pain and drug administration. Subsequently, an overview of the current evidence of the nocebo phenomenon in the dental field is presented. Methods: A PubMed search was performed using keywords related to “nocebo,” “placebo,” “expectations,” and “dentistry.” In addition to the articles selected from the search, placebo/nocebo researchers and dental researchers added important references from their respective fields. Results: Although research on the nocebo effect in dentistry is limited, available current evidence suggests that the factors, which is related to the nocebo effect are likely to play a role in dental practice. Conclusion: Preliminary evidence from the review warrants further investigation into the nocebo effect in dentistry. Finally, based on the general knowledge of the nocebo effect, the review indicates fruitful arrays of research into the nocebo effect in dentistry.

Aims: Comparing actual management costs in patients with non-valvular atrial fibrillation (AF) treated with percutaneous left atrial appendage closure (LAAC) or OAC only. Methods and results: Patients undergoing percutaneous LAAC and AF patients treated with OAC only were matched for gender, age, and diagnosis related groups (DRG) clinical complexity level (CCL). Costs for cardiovascular outpatient clinic visits and hospitalizations were derived from the actual reimbursement records. Between 1/2012 and 12/2016, 8478 patients were referred: 7801 (92%) managed with OAC and 677 (8%) with percutaneous LAAC. Matching resulted in 558 patients (279 per group) for final analysis. Age was 74.9 +/- 7.5 years, 244 were female (43.7%), and DRG CCL was 1.8 +/- 1.1.Annualized management cost before percutaneous LAAC was (sic) 3110 (IQR: (sic) 1281-8127). After 4.5 +/- 1.4 years follow-up, annualized management cost was (sic) 1297 (IQR: (sic) 607-2735) in OAC patients and (sic) 1013 (IQR: (sic) 0-4770) in patients after percutaneous LAAC (p = 0.003). Percutaneous LAAC was the strongest independent determinant to reduce follow-up costs (B =-0.8; CI: 1.09-0.6; p < 0.0001). Estimated 3-year survival was 92% in percutaneous LAAC and 90% in OAC patients (p = 0.7). Conclusion: Percutaneous LAAC significantly reduces management costs. Management costs are significantly higher for patients treated with only OAC compared to patients after percutaneous LAAC. In spite of their complex comorbid profile, percutaneous LAAC patients show a follow-up survival rate similar to patients solely treated with OAC. Future studies are necessary to investigate the potential net economic and clinical benefit of percutaneous LAAC in patients treated with OAC only.

ObjectiveThe pharmacokinetics of oral diazepam are affected by food, but food-effect studies have not been conducted for diazepam nasal spray because it is believed that most absorption occurs via the nasal mucosa. However, gastrointestinal side effects reported with nasal diazepam suggest that at least a portion of the drug may be absorbed enterally and thus subject to food effects. The objective of this study was to evaluate the possible effects of food on the pharmacokinetics of diazepam nasal spray in healthy adults.MethodsThis randomized, open-label crossover study compared equal doses of diazepam nasal spray after an overnight fast and after a standardized high-fat, high-calorie breakfast. Each participant served as their own control, and there was a washout period of at least 21 days between treatments.ResultsTwenty-four healthy adults enrolled in this study. Two participants withdrew consent, and two had pre-dose diazepam concentrations that exceeded the protocol-defined minimum after the washout period and were excluded from the final analysis population of 20 participants. Under fed conditions, the mean maximum plasma diazepam concentration was decreased by 48% (p

This article will focus on the types and history of written translation and the history, classification and differences of human-machine translation.

ObjectivesMobility (international/internal migration, and localized mobility) is a key driver of the HIV epidemic. While mobility is associated with higher-risk sexual behavior in women, a possible association with condom, modern contraceptive, and dual method use among women living with HIV (WLHIV), is unknown. In addition, HIV status and sexual behaviors such as relationship concurrency may also affect condom, modern contraceptive, and dual method use.Study designWe surveyed sexually active women (N=1067) aged 15 to 49 in 12 communities in Kenya and Uganda participating in a test-and-treat trial in 2015 to 2016. Generalized (unordered) multinomial logistic regression models accounting for community clustering examined associations between mobility (overnight travel away from home in past 6 months and any migration within past 2 years) and condom, modern contraceptive (i.e., oral contraceptive pills, injectables, intrauterine devices, implants, vasectomy, tubal ligation; excluding male/female condoms), and dual method use within past 6 months, adjusting for key covariates such as HIV status and relationship concurrency.ResultsWLHIV relative to HIV-negative women (ratios of relative risk [RRR]=3.76, 95% confidence interval [CI]: 2.40-5.89), and women in concurrent relative to monogamous relationships (RRR=4.03, 95% CI 1.9-8.50) had higher odds of condom use alone. In contraceptive use models, WLHIV relative to HIV-negative women were less likely to use modern contraceptive methods alone (RRR=0.51, 95% CI 0.36-0.73). Relationship concurrency (RRR=4.51, 95% CI 2.10-9.67) and HIV status (RRR=3.97, 95% CI 2.43-6.50) were associated with higher odds of dual method use while mobility was marginally associated with higher odds of dual method use (RRR=1.65, 95% CI 0.99-2.77, p=0.057).ConclusionsMobility had a potential impact on dual method use in Kenya and Uganda. In addition, our findings highlight that WLHIV were using condoms and dual methods more, but modern contraceptives less, than HIV-negative women. Those in concurrent relationships were also more likely to use condoms or dual methods. These findings suggest that in a context of high mobility, women may be appropriately assessing risks and taking measures to protect themselves and their partners from unintended pregnancies and acquisition and transmission of HIV.ImplicationsOur findings point to a need to strengthen accessibility of sexual and reproductive health services for both mobile and residentially stable women in settings of high mobility and high HIV prevalence.

Cystic conditions of the jaw cause bony destruction and may cause resorption or displacement of adjacent teeth. Odontogenic cysts have developmental or inflammatory origins. To describe in detail the inflammatory odontogenic cysts, a manual search was done in hard copy books of oral and maxillofacial pathology, and an electronic search was done in the google website, oral and maxillofacial pathology E-books, PubMed, Research Gate, Academia, and Google scholar using the keywords "odontogenic cysts," "classification of the odontogenic cysts," "radicular cyst," "periapical cyst," "lateral inflammatory cyst," "residual cyst," "paradental cyst," "collateral inflammatory cyst," "treatment of inflammatory odontogenic cysts," and matching each odontogenic inflammatory cyst subtype with these words "gross description," "pathogenesis," "microscopical," clinical," "radiographical" appearance. Articles published till February 2021 were included in this review. In conclusion, an accurate diagnosis of an inflammatory odontogenic cyst requires information relative to its clinical, radiographical, macro- and microscopical findings. In many instances, two cysts that are classified differently may exhibit similar histopathological features. In such cases, clinical and radiographic findings are necessary to make a precise diagnosis.

Increasing trend in oral cancer (0.6% per year) and its related mortality has been reported worldwide since 2010. The United States alone reports an increase of 57% within the past 10 years. This emphasizes the need not only for designing strategies of prevention and planning but also for an effective treatment regime for the various oral cancers. Cancers of the lips, tongue, cheeks, floor of the mouth, and hard palate have been primarily classified under the category of oral cancers. If left undiagnosed, these cancers can be life threatening. Amongst these, the most undesignated and understudied cancer type is the lip carcinoma, which is either categorized under oral cancer or/as well as skin cancer or head and neck cancer. However, lip cancer corresponds to 25–30% of all diagnosed oral cancers. Though the etiology of lip cancer is not yet fully understood, numerous risk factors involved in its development are now being studied. The cells in the lip region are continuously exposed to various DNA damaging agents from endogenous as well as exogenous sources. Flaws in DNA repair mechanisms involved in eliminating these damages may be linked to the origin of carcinogenesis. Accumulation of DNA damage and defect in repair mechanisms may play a role in lip carcinogenesis and progression. This literature review is an exhaustive compilation of the research work performed on the role of DNA damage and repair responses in lip carcinoma which will pave a path for researchers to identify predictive DNA repair biomarker/s for lip cancer, and its diagnosis, prevention, and treatment.

We investigate the variation in oral and written language in terms of anaphoric distance (i.e., the textual distance between anaphors and their antecedents), expanding corpus-based research with experimental evidence. Contrastive corpus studies demonstrate that oral genres include longer average anaphoric distance than written genres, if the distance is measured in terms of clauses (Fox, 1987; Aktaş & Stede, 2020). We designed an experiment in order to examine the contrasts in oral and written mediums, using the same genre. We aim to gain more insight about the impact of the medium, in a situation where both mediums convey a similar level of spontaneity, informality and interactivity. We designed a story continuation study, where the participants are recruited via crowdsourcing. To our knowledge, this is the first study of its kind, where anaphoric distance is manipulated systematically in a language production experiment in order to examine medium distinctions. We observed that participants use more pronouns in oral medium than in written medium if the anaphoric distance is long. This result is in line with the implications of the earlier corpus-based research. In addition, our results indicate that anaphoric distance has a larger effect in referential choice for the written medium.

ObjectiveTo evaluate the bleeding patterns of a new combined oral contraceptive containing estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg in a 24/4-day regimen.Study designWe pooled bleeding data from two parallel, open-label, 13-cycle phase 3 trials that enrolled participants 16 to 50 years old with body mass index (BMI) ≤35 kg/m2. Participants reported vaginal bleeding/spotting in daily diaries. For this bleeding analysis, we included participants with at least one evaluable cycle. We calculated mean frequencies of scheduled and unscheduled bleeding/spotting episodes and median duration of bleeding/spotting episodes, and assessed associations between treatment compliance, BMI and recent hormonal contraceptive use on bleeding/spotting outcomes.ResultsWe included 3409 participants with 33,815 cycles. Scheduled bleeding/spotting occurred in 87.2% to 90.4% of participants/cycle, with a median duration of 4 to 5 days. Unscheduled bleeding/spotting decreased from 27.1% in Cycle 1 to 20.6% in Cycle 2 to ≤17.5% from Cycle 5 onwards. Most (66.5%) unscheduled bleeding/spotting episodes were spotting-only. Between 5.8% and 7.8% of users/cycle experienced absence of any scheduled or unscheduled bleeding/spotting. Missing one or more active pills resulted in a higher occurrence of unscheduled bleeding/spotting (adjusted odds ratio [aOR] 2.13 [95% confidence interval 1.68-2.70]) and absence of scheduled bleeding/spotting (aOR 2.36 [1.82-3.07]). Participants with a BMI ≥30 kg/m2 reported more absence of scheduled bleeding/spotting (aOR 1.68 [1.37-2.05]). Switchers and starters reported similar frequencies of unscheduled bleeding/spotting (aOR 0.94 [0.83-1.07]) and absence of scheduled bleeding/spotting (aOR 1.00 [0.85-1.19]). Three percent of participants discontinued for a bleeding-related adverse event.ConclusionE4/DRSP use results in a predictable bleeding pattern with limited unscheduled bleeding/spotting. Noncompliance and BMI affect bleeding patterns.Implications statementMost estetrol/drospirenone users experience a predictable and regular bleeding pattern. Providers can educate patients about the expected bleeding patterns and should advise users that they may infrequently experience no scheduled bleeding/spotting. This information may improve user acceptability and continuation of this new oral contraceptive.

Made available in DSpace on 2022-04-29T08:35:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Background: Fixed drug eruption is a drug reaction characterized by the recurrent occurrence of erosive or ulcerative lesions in skin or mucosa surfaces upon the use of a specific drug. The occurrence of fixed drug eruption in oral mucosa is rare and ill documented. Case report: A 37-year-old woman who presented with recurrent erosive lesions in the palatal marginal gingiva of the upper first molars for 3 consecutive months. In anamnesis and follow-up, the time association with the intake of piroxicam to treat menstrual pain led us to the diagnosis of fixed drug eruption. Conclusion: Piroxicam is a rare culprit drug to fixed drug eruption, especially in oral mucosa. Department of Stomatology AC Camargo Cancer Center Dental School Department of Conservative Dentistry Federal University of Rio Grande do Sul Department of Oral Diagnosis Piracicaba Dental School University of Campinas (UNICAMP) Oral Oncology Center School of Dentistry of Araçatuba São Paulo State University Serviço de Odontologia Oncológica Instituto do Câncer do Estado de São Paulo ICESP-FMUSP Faculdade de Medicina da Universidade de São Paulo Dental School University Brasil Oral Oncology Center School of Dentistry of Araçatuba São Paulo State University

Objective To analyze the medication rules of traditional Chinese medicine (TCM) oral prescriptions for the prevention of COVID-19. Methods The preventive oral prescriptions for COVID-19 published by national and provincial health and wellness committees, administrations of TCM, medical institutions at all levels, and medical masters and Chinese medicine experts were collected to establish a database, manual screening was carried out according to the inclusion and exclusion criteria, and frequency statistics, association rule analysis. The mutual information method, entropy hierarchical clustering and other methods were improved through Excel and the TCM inheritance auxiliary platform V2.5 to mine the rules and characteristics of medication. Results The selected 157 prescriptions contained a total of 130 TCMs. The top five TCMs with the highest use frequency were Glycyrrhizae Radix et Rhizoma (86), Astragali Radix (80), Lonicerea Japonicae Flos (70), Atractylodis Macrocephalae Rhizoma (62), Saposhnikoviae Radix (60). In accordance with TCM efficacy classification, most of them were medicines for qi-tonifying (279), followed by medicines for clearing heat and drying dampness (163), dispelling pathogenic wind-cold (126), resolving dampness (111), as well as dispelling pathogenic wind-heat (99). The characteristics of four-natures of the selected medicines are as follows: most of them were cold (59), followed by warm (38) and mild (21). In terms of five-taste, most of them were sweet (26) and acrid-and-bitter (24), followed by sweet-and-bitter (20), bitter (20) and acrid (15). For the meridian attribution, the five-zang organs and six-fu organs were all involved, most of them attributed to lung meridian (80), followed by stomach meridian (57) and spleen meridian (40). Based on association rule analysis, 12 commonly used medicine combinations with two or three TCMs were found. The commonly used medicinal pairs included Astragali Radix and Saposhnikoviae Radix (51), Astragali Radix and Atractylodis Macrocephalae Rhizoma (46), Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (43), Astragali Radix and Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (38), Forsythiae Fructus and Astragali Radix (37), and so on. In addition, 14 core combinations of medicines were obtained by complex system entropy cluster analysis, on this basis, six new prescriptions were screened out based on unsupervised entropy hierarchical clustering analysis. According to The Catalogue of Edible Traditional Chinese Medicinal Materials, Traditional Chinese Medicinal Materials for Health Food, and New Resources of Food published by National Health Commission of the People's Republic of China, there are 35 species belonging to the group of edible traditional Chinese medicinal materials, 20 species belonging to the group of new resources of food, 31 species belonging to the group of traditional Chinese medicinal materials for health food, 19.11% of the preventive oral prescriptions for COVID-19 were composed of the medicines belonging to the above three groups. Besides, there are 11 toxic species, and 24.84% of the preventive oral prescriptions for COVID-19 contained toxic traditional Chinese medicines. Conclusion We found that invigorating qi and resolving dampness were the main treatment used to prevent for COVID-19, combined with the methods for strengthening vital energy and eliminating pathogenic factors. Most of the preventive oral prescriptions for COVID-19 were treated in lung, spleen and stomach meridians. In the process of selecting prescriptions and using TCMs to prevent for COVID-19, the safety of preventive medicines was also emphasized. And the theory of "Preventive Treatment of Disease" was embodied in these preventive oral prescriptions for COVID-19. For the prescriptions containing toxic TCMs, special attention should be paid to their safety in clinical application.

Agomelatine is a novel melatonergic antidepressant, with a non-monoaminergic mechanism of action. The aim of this study was to evaluate its plasma concentrations after a single oral dose of 300 mg/dog in fasted and fed status. The research was carried out in 6 adult healthy Labrador dogs according to a randomized open, single-dose, two-treatment, two-phase, paired 2 × 2 cross-over study. At the end of the study all the animals had received the drug in fasted and fed conditions. The drug concentrations were detected in plasma by a validated LC-MS/MS analytical method. The plasma concentrations of agomelatine were found to be extremely variable in both groups as well as the pharmacokinetic profiles. Due to these variable findings the only reliable pharmacokinetic parameters were assessed as Cmax (31.8 vs 15.7 ng/mL), Tmax (0.75 vs 4 h) and AUC (155 vs 52 ng h/mL) in fasted and fed status, respectively. Unfortunately, as a pioneer study, the small animal sample size used along with the unanticipated variability did not allow to neither statistically estimate if food can affect the pharmacokinetics of agomelatine nor recommend agomelatine for off-label therapies in canine species. Further studies are warranted to clarify this issue.

Invasive fungus infection affects about six people out of every 100,000 people each year. Only half of these infections are detected throughout the patient's lifetime, making it one of the most common causes of death among intensive-care patients. The low detection rate is due to the diagnostic work's complexity, which comprises clinical, radiographic, and microbiological results. Antimycotic drug-resistant fungi are on the rise all over the world. Guidelines for identifying and treating invasive fungous infections caused by Candida spp., Aspergillus spp., Mucorales, and Fusarium spp. are the topic of this review. In typical hospital care, intrusive fungous infections are frequently ignored. They must include it as a necessary component of antimicrobial stewardship programmes. There is also a great need for novel antimycotic medication classes to be developed

Purpose Patients undergoing head and neck surgery are often elderly and frail with significant comorbidities. Discussion and documentation of what patients would desire for end‐of‐life care and decision‐making is, therefore, essential for delivering patient‐centered care. Materials and Methods This was a retrospective, cross‐sectional study of patients undergoing surgery for head and neck cancer at two large, academic, tertiary care centers in Canada. Advance care planning was defined as any documentation of advance directives, resuscitation orders, or end‐of‐life care preferences. Results Among 301 patients, advance care planning was documented for 31 (10.3%). Patients with locally advanced disease (T3+) were twice as likely to have advance care planning documentation compared to those with early disease (RR 1.97, 95%CI [0.98, 3.97]). Conclusions In this multi‐institutional cross‐sectional study of two large academic centers, we have demonstrated that advance care planning and documentation is overall poor in patients undergoing surgery for oral cancer. These findings may have health policy implications, as advance care planning is associated with increased patient and provider satisfaction and improved alignment of patient goals and care delivered. Future work will investigate barriers and facilitators to advance care‐planning documentation in this setting.

Objective To assess efficacy, cycle control, and safety of an oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg. Study design Women aged 16 to 50 years with a body mass index ≤35 kg/m2 enrolled in this multicenter, open-label, 13-cycle, phase 3 trial evaluating E4/DRSP in a 24-active/4-placebo regimen. Follow-up was scheduled at Cycles 2, 4, 7, and 10 and within 3 weeks of completing Cycle 13. Participants used daily diaries to record pill use and vaginal bleeding. We evaluated efficacy outcomes in women 16 to 35 years and bleeding patterns and safety (adverse events [AEs]) in all participants. We assessed overall and method-failure pregnancy rates using the Pearl index (PI) and life-table analysis. Scheduled bleeding included spotting or bleeding starting during the 4-day placebo period or first 3 days of the next cycle. Results We enrolled 1864 women of whom 1674 were 16 to 35 years. Women 16 to 35 years had a PI of 2.65 (95% CI 1.73–3.88), method-failure PI of 1.43 (95% CI 0.7–2.39) and 13-cycle life-table pregnancy rate of 2.1%. Scheduled bleeding occurred in 82.9% to 87.0% of women per cycle; median duration was 4.5 days. Unscheduled bleeding decreased from 30.3% in Cycle 1 to 21.3% to 22.1% during Cycles 2 to 4 and remained stable (15.5% to 19.2%) thereafter. The most frequently reported AEs were headache (5.0%) and metrorrhagia (4.6%). One-hundred thirty-two (7.1%) women discontinued the study early for an AE, most commonly for metrorrhagia (0.9%) and menorrhagia (0.8%). No thromboembolic events occurred. Conclusion E4/DRSP is an effective oral contraceptive with a predictable bleeding pattern for most women and low AE rates. Implications statement A new oral contraceptive with a novel estrogen, estetrol, combined with drospirenone has efficacy and safety within the range of other available oral contraceptives. Large phase 4 studies will be needed to confirm if this combination is associated with an improved adverse event profile or lower thrombosis risk.

Background Limited data are available on the role of direct oral anticoagulants (DOACs) for the treatment of upper extremities deep vein thrombosis (UEDVT). Objectives The aim of this study was to assess the effectiveness and safety of DOACs in the treatment of UEDVT. Methods Patients with an objectively confirmed acute UEDVT treated with DOACs were merged from prospective cohorts to a collaborative database. Primary study outcomes were recurrent venous thromboembolism (VTE) and major bleeding occurring during DOAC treatment. Results Overall, 188 patients were included in the study: mean age 52.4 ± 20.4 years, males 43.6%, patients with active cancer 29.2%. Twenty-nine percent of patients had 2 or more risk factors for VTE, 33.0% had catheter-related or pacemaker-related UEDVT. In 13.8% of patients, DOACs were started one month after UEDVT diagnosis or later. Active cancer was an independent predictor for delayed initiation of DOACs (OR 8.1, 95% CI 3.0–22.2). Mean duration of treatment with DOACs was 5.1 ± 2.8 months. During treatment with DOACs, recurrent VTE occurred in 0.9 per 100 patient-year, major bleeding in 1.7 and all-cause deaths in 6.0 per 100 patient-year. No fatal bleeding or fatal VTE recurrence were observed. During 232.1 patient-years of follow-up after DOAC withdrawal, recurrent VTE occurred in 3.0 per 100 patient-year. The 2019 ESC categories for risk of VTE recurrences were able to discriminate patient groups at different risk of events in the on and off-treatment periods. Conclusions Our data support the feasibility as well as the effectiveness and safety of DOACs for the treatment of acute UEDVT.

RESUMO INTRODUÇÃO: Os hormônios presentes no anticoncepcional afetam a coagulação sanguínea e podem favorecer a formação de coágulos. Quando esses coágulos obstruem uma veia tem-se uma trombose venosa profunda, geralmente nas pernas. O risco maior é esse coágulo se soltar e chegar aos pulmões, causando uma embolia pulmonar. OBJETIVOS: realizar uma revisão do tipo integrativa sobre a trombose causada pelo uso irregular de anticoncepcionais orais. MÉTODOS: O presente estudo foi desenvolvido através de uma pesquisa de revisão integrativa, realizada pela minuciosa seleção de artigos completos e gratuitos, nas bases de dados Scientific Electronic Library Online – SCIELO; PUBMED; e Literatura Latino-Americana e do Caribe em Ciências da Saúde – LILACS, com um recorte temporal de 2016 a 2022. RESULTADOS: Conforme os critérios metodológicos empregados, de forma inicial, foram encontrados nas bases de dados SciELO; PuBmed e LILACS, 980 artigos na primeira triagem feita, 572 artigos foram excluídos por estarem em duplicidade; em outro idioma; fora da faixa temporal; e não ser gratuito. Em seguida 408 artigos permaneceram, logo após 353 foram excluídos por fugir da metodologia, sendo eles relatórios de estágios, resumos expandidos e pappers. Dos 55 artigos científicos restantes, foram excluídos 24 tendo a mesma temática, porém contendo informações que não estavam concernentes ao tema proposto, seguidamente retirados 20 por não possuir os objetivos semelhantes ao trabalho em questão, restando apenas os 11 selecionados. CONCLUSÃO: A trombose causada pelo uso irregular de anticoncepcionais orais ocorrerá na presença de determinados fatores, como, tabagismo; obesidade; doenças cardiovasculares e diversos outros. Os hormônios presentes nesses medicamentos afetam diretamente a coagulação sanguínea, podendo favorecer a formação de coágulos, gerando alterações como a trombose venosa profunda ou embolia pulmonar. Assim é necessária uma indicação clínica particularizada, no que diz respeito a essas drogas e uma avaliação diagnóstica detalhada de possíveis registros de eventos trombóticos, a fim de que essas terapias hormonais possam ser utilizadas da forma mais exitosa e segura possíveis para cada paciente., Combined Oral Contraceptives. Clot. Thromboembolism

Epithelial cells are known to produce mediators which can influence the behaviour of neighbouring immune cells. Although the oral mucosa has gained increased interest as a route to induce allergy desensitisation and mucosal pathogen immunisation in dogs, there is only limited knowledge on the factors which impact mediator secretion by canine oral epithelial cells. The study’s objective was to enlarge the knowledge on the stimuli that can influence the secretion of some pro- and anti-inflammatory cytokines and the chemokine CXCL8 by canine buccal epithelial cells. To investigate this, buccal epithelial cells were isolated from a biopsy of a dog and immortalised by lentiviral transduction of the SV40 large T antigen. The cells were stained with a CD49f and cytokeratin 3 antibody to confirm their epithelial origin. Cells were incubated with allergen extracts, Toll-like receptor ligands (TLRL), recombinant cytokines and vitamin A and D metabolites. Subsequently, the secretion of the cytokines interleukin (IL)-4, IL-6, IL-10, IL-17A, IFN-γ, TGF-β1 and the chemokine CXCL8 was assayed by ELISA. Immortalised canine buccal epithelial cells stained positive for CD49f but not for cytokeratin 3. The cells produced detectable amounts of CXCL8 and TGF-β1. ADermatophagoides farinaeextract, anAlternaria alternataextract, Pam3CSK4, heat-killedListeria monocytogenes, FSL-1, flagellin and canine recombinant IL-17A significantly increased CXCL8 secretion, while the vitamin D metabolite calcitriol significantly suppressed the production of this chemokine. This study showed that certain allergens, TLRL, IL-17A and calcitriol modulate CXCL8 secretion in a cell line of canine buccal epithelial cells.

Computer-assisted surgery (CAS) allows clinicians to personalize treatments and surgical interventions and has therefore become an increasingly popular treatment modality in maxil-lofacial surgery. The current maxillofacial CAS consists of three main steps: (1) CT image reconstruction, (2) bone segmentation, and (3) surgical planning. However, each of these three steps can introduce errors that can heavily affect the treatment outcome. As a consequence, tedious and time-consuming manual post-processing is often necessary to ensure that each step is performed adequately. One way to overcome this issue is by developing and implementing neural networks (NNs) within the maxillofacial CAS workflow. These learning algorithms can be trained to perform specific tasks without the need for explicitly defined rules. In recent years, an extremely large number of novel NN approaches have been proposed for a wide variety of applications, which makes it a difficult task to keep up with all relevant developments. This study therefore aimed to summarize and review all relevant NN approaches applied for CT image reconstruction, bone segmentation, and surgical planning. After full text screening, 76 publications were identified: 32 focusing on CT image reconstruction, 33 focusing on bone segmentation and 11 focusing on surgical planning. Generally, convolutional NNs were most widely used in the identified studies, although the multilayer perceptron was most commonly applied in surgical planning tasks. Moreover, the drawbacks of current approaches and prom-ising research avenues are discussed.Dentomaxillofacial Radiology (2022) 51, 20210437. doi: 10.1259/dmfr.20210437

Author(s): Gemzell-Danielsson, K; Apter, D; Zatik, J; Weyers, S; Piltonen, T; Suturina, L; Apolikhina, I; Jost, M; Creinin, MD; Foidart, J-M | Abstract: ObjectivesTo assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15nmg and drospirenone (DRSP) 3nmg.DesignMulticenter, open-label, phase 3 trial.SettingSixty-nine sites in Europe and Russia.PopulationSexually active women aged 18-50nyears with regular menstrual cycles and body mass index ≤35nkg/m2 .MethodsE4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary.Main outcome measuresPearl Index (PI) for women 18-35nyears (overall and method-failure), bleeding pattern and AEs.ResultsA total of 1553 women aged 18-50nyears, including 1353 from 18 to 35nyears old, received the study medication. PI was 0.47 pregnancies/100 woman-years (95% CI 0.15-1.11); method failure PI was 0.29 pregnancies/100 woman-years (95% CI 0.06-0.83). Scheduled bleeding/spotting occurred in 91.9-94.4% of women over Cycles 1 to 12 and lasted a median of 4-5ndays per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to l16% from Cycle 6 onwards. The most common AEs were headache (7.7%), metrorrhagia (5.5%), vaginal haemorrhage (4.8%) and acne (4.2%). One treatment-related serious AE was reported, a lower extremity venous thromboembolism. One-hundred and forty-one (9.1%) women discontinued study participation because of treatment-related adverse events.ConclusionE4/DRSP provides effective contraception, a predictable bleeding pattern and a favourable safety profile.Tweetable abstractA phase 3 trial with E4/DRSP shows high contraceptive efficacy, a predictable bleeding pattern and favourable safety profile.

Orally administered drug entities have to survive the harsh gastrointestinal environment, penetrate the enteric epithelia and circumvent hepatic metabolism before reaching the systemic circulation. Whereas the gastrointestinal stability can be well maintained by taking proper measures, hepatic metabolism presents as a formidable barrier to drugs suffering from first-pass metabolism. The pharmaceutical academia and industries are seeking alternative pathways for drug transport to circumvent problems associated with the portal pathway. Intestinal lymphatic transport is emerging as a promising pathway to this end. In this review, we intend to provide an updated overview on the rationale, strategies, factors and applications involved in intestinal lymphatic transport. There are mainly two pathways for peroral lymphatic transport—the chylomicron and the microfold cell pathways. The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.

The interdisciplinary nature of food studies lends itself to the study of food through many avenues, most notably in this research, through folklore and the oral history transcripts of the Schools’ Collection made by the Irish Folklore Commission in 1937–1938. Folklore can give us an insight into sometimes overlooked features of society and how people’s lives can be studied and highlighted through their relationship with food. The Christmas period was an extremely important time in Irish tradition, and food was a main aspect of that celebration. This paper, therefore, at first delves into the literature surrounding Christmas, folklore, and food; diet and social class; gender, and food in rural Ireland, before comparing it with the oral history transcripts of the National Folklore Collection’s online archive, to unearth a better understanding of the relation[1]ship and the role of food in the Christmas festival in Ireland’s recent past

Introduction: Selenomonas noxia (SN) is an important periodontal pathogen, associated with gingivitis and periodontitis. Many studies have found associations between SN and indicators of poor health outcomes, such as smoking, low socioeconomic status and obesity. However, less is known about the prevalence of this organism and more specifically about other oral site-specific locations that may harbor this organism. Methods: Using an existing patient repository (n = 47) of DNA isolated from saliva and other oral sites (n = 235), including the dorsum of the tongue, lower lingual incisor, upper buccal molar and gingival crevicular fluid (GCF), molecular screening for SN was performed. Screening results were analyzed for associations between demographic variables (age, sex, race/ethnicity) and clinical information (body mass index or BMI, presence of orthodontic brackets, primary/mixed/permanent dentition). Results: qPCR screening revealed a total of n = 62/235 sites or 26.3% harboring SN with saliva and GCF (either alone or in combination with one or more sites) most often observed (Saliva, n = 23/27 or 85.18%, GCF, n = 14/27 or 51%). Analysis of site-specific data revealed most positive results were found among saliva and GCF alone or in combination, with fewer positive results observed among the tongue (33.3%), lower lingual incisor (29.6%), and upper buccal molar (25.9%). No significant associations were found between demographic or clinical variables and presence of SN at any site. Conclusions: These results may be among the first to describe site-specific locations of S. noxia among various additional oral biofilm sites. These data may represent a significant advancement in our understanding of the sites and locations that harbor this organism, which may be important for our understanding of the prevalence and distribution of these organisms among patients of different ages undergoing different types of oral treatments, such as orthodontic treatment or therapy.

Amphotericin B is an effective polyene antifungal considered as a “gold standard” in the management of fungal infections. Currently, it is administered mainly by IV due to poor aqueous solubility, which precludes its delivery orally. Paradoxically, IV administration is akin to side effects that have not been fully eliminated even with more recent IV formulations. Thus, the need for alternative formulations/route of administration for amphotericin B remains crucial. The oral route offers the possibility of delivering amphotericin B systemically and with diminished side effects; however, enterocyte permeation remains a constraint. Cellular phagocytosis of submicron particles can be used to courier encapsulated drugs. In this regard, nanoparticulate delivery systems have received much attention in the past decade. This review examines the trajectory of orally delivered amphotericin B and discusses key physical factors of nanoformulations that impact bioavailability. The review also explores obstacles that remain and gives a window into the possibility of realizing an oral nanoformulation of amphotericin B in the near future. The research was funded by grant number Qatar University Grant: IRCC-2021-006.

Objective: In dentistry, systemic diseases are extremely important in terms of taking the required precautions for overall health and preventing complications before they emerge. Many clinicians are aware of the oral symptoms of systemic diseases; nevertheless, the major source of the problem must be addressed in order to limit the rate of misdiagnosis due to systemic origins and establish an appropriate treatment strategy. The purpose of this study is to investigate whether there is a relationship between systemic diseases and dental health. Methods: The study included 200 individuals, 100 women and 100 men, all between the ages of 25 and 75, who had at least one systemic disease. The patients’ medical records and panoramic radiography were examined. In the panoramic radiographs of the patients, the existence of existing teeth, caries, restorations, prostheses, and endodontic conditions were documented, taking into consideration the presence of systemic disorders, gender, and age of the patients. Results: Caries rates were significantly higher in the 25-40 age group (43.3%) than in the 41-60 age group (20.7%) (p0.05). The prevalence of prosthesis was statistically significantly greater in patients with cardiovascular disease (64.3%) than in patients without cardiovascular disease (47.7%) (p

(1) Background: Odontogenic keratocysts (OKCs) are enigmatic developmental cysts that deserve special attention due to their heterogeneous appearance in histopathological characteristics and high recurrence rate. Despite several nomenclatures for classification, clinicians still confront challenges in its diagnosis and predicting its recurrence. This paper proposes an ensemble deep-learning-based prognostic and prediction algorithm, for the recurrence of sporadic odontogenic keratocysts, on hematoxylin and eosin stained pathological images of incisional biopsies before treatment. (2) Materials and Methods: In this study, we applied a deep-learning algorithm to an ensemble approach integrated with DenseNet-121, Inception-V3, and Inception-Resnet-V3 classifiers. Around 1660 hematoxylin and eosin stained pathologically annotated digital images of OKC-diagnosed (60) patients were supplied to train and predict recurrent OKCs. (3) Results: The presence of SEH (p = 0.004), an incomplete epithelial lining, (p = 0.023), and a corrugated surface (p = 0.049) were the most significant histological parameters distinguishing recurrent and non-recurrent OKCs. Amongst the classifiers, DenseNet-121 showed 93% accuracy in predicting recurrent OKCs. Furthermore, integrating and training the traditional ensemble model showed an accuracy of 95% and an AUC of 0.9872, with an execution time of 192.9 s. In comparison, our proposed model showed 97% accuracy with an execution time of 154.6 s. (4) Conclusions: Considering the outcome of our novel ensemble model, based on accuracy and execution time, the presented design could be embedded into a computer-aided design system for automation of risk stratification of odontogenic keratocysts.

IntroductionRecent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines' pathogen-specific effects, but less than a handful focus on NSE. This paper addresses that gap by reporting economic evaluations of the NSE of oral polio vaccine (OPV) against under-five mortality and COVID-19.Materials and methodsWe studied two settings: (1) reducing child mortality in a high-mortality setting (Guinea-Bissau) and (2) preventing COVID-19 in India. In the former, the intervention involves three annual campaigns in which children receive OPV incremental to routine immunization. In the latter, a susceptible-exposed-infectious-recovered model was developed to estimate the population benefits of two scenarios, in which OPV would be co-administered alongside COVID-19 vaccines. Incremental cost-effectiveness and benefit-cost ratios were modeled for ranges of intervention effectiveness estimates to supplement the headline numbers and account for heterogeneity and uncertainty.ResultsFor child mortality, headline cost-effectiveness was $650 per child death averted. For COVID-19, assuming OPV had 20% effectiveness, incremental cost per death averted was $23,000–65,000 if it were administered simultaneously with a COVID-19 vaccine DiscussionEconomic evaluation suggests the potential of OPV to efficiently reduce child mortality in high mortality environments. Likewise, within a broad range of assumed effect sizes, OPV (or another vaccine with NSE) could play an economically attractive role against COVID-19 in countries facing COVID-19 vaccine delays.FundingThe contribution by DTJ was supported through grants from Trond Mohn Foundation (BFS2019MT02) and Norad (RAF-18/0009) through the Bergen Center for Ethics and Priority Setting.

Danofloxacin is a fluoroquinolone developed for veterinary medicine and used in avian species for the treatment of numerous bacterial infections. However, no pharmacokinetic data have been reported in geese. The aim of the study was three-fold: (i) to evaluate the pharmacokinetics of danofloxacin in geese after single oral (PO) and intravenous (IV) administrations; (ii) to define its residue depletion profile in different goose tissues, and (iii) to recreate a multiple-dose simulation in the practical context of large-scale breeding. Twenty-four healthy geese were randomly divided in three groups each composed of eight animals. Group 1 received danofloxacin IV (5 mg/kg) and groups 2 and 3 were treated PO with the same dose. Blood was collected until 24 h (IV; group 1) and 48 h (PO; group 2) after administration. Two animals from group 3 were sacrificed at 6, 10, 24 and 48 h to collect samples of muscle, heart, kidney, liver, and lung. Danofloxacin was quantified in each matrix using a validated high-performance liquid chromatography method with spectrofluorimetric detection and the pharmacokinetic analysis was performed using non-compartmental and compartmental approaches. Danofloxacin showed a moderate elimination half-life (6.61 h), a slow clearance (0.35 mL/g*h) and a large volume of distribution (1.46 mL/g). The peak plasma concentration after PO administration and the time to reach it were 0.96 μg/mL and 1.70 h, respectively. The oral bioavailability was moderate (58%). Higher residue concentration was found in liver and kidney, compared to the other tissues. If the AUC(0–24) value found in the present study is included in the pharmacokinetic/pharmacodynamic index (AUC(0–24)/MIC) for the prediction of fluoroquinolones' efficacy, danofloxacin seems to be effective in geese against gram-negative bacteria with a minimum inhibitory concentration (MIC)

Background Coronavirus disease 2019 (COVID-19) global pandemic has strikingly high mortality rate with hypercoagulability state being part of the imputed mechanisms. We aimed to compare the rates of in hospital mortality in propensity score matched cohorts of COVID-19 patients in chronic anticoagulation versus those that were not. Methods In this population-based study in the Veneto Region, we retrospectively reviewed all patients aged 65 years or older, with a laboratory-confirmed COVID-19 diagnosis. We compared, after propensity score matching, those who received chronic anticoagulation for atrial fibrillation with those who did not. Results Overall, 4697 COVID-19 patients fulfilled inclusion criteria, and the propensity score matching yielded 559 patients per arm. All-cause mortality rate ratio was significantly higher among non-anticoagulated patients (32.2% vs 26.5%, p = 0.036). On time to event analysis, all-cause mortality was found lower among anticoagulated patients, although the estimate was not statistically significant. (HR 0.81, 95%CI 0.65–1.01, p = 0.054). Conclusion Among elderly patients with COVID-19, those on chronic oral anticoagulant treatment for atrial fibrillation seem to be at lower risk of all-cause mortality compared to their propensity score matched non-anticoagulated counterpart. This finding needs to be confirmed in further studies., Highlights • COVID-19 infection has strikingly high mortality rate. • Hypercoagulability has been imputed as one of the pathological mechanisms. • Anticoagulation may improve outcomes in COVID-19 infection. • We found chronic anticoagulation to be related to lower mortality in COVID-19 patients.

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

Background: Atrial Fibrillation (AF) represents a major cause of mortality and morbidity in older people; however, oldest-old frail patients are usually excluded from clinical trials. Aim of the study is to evaluate the impact of oral anticoagulation (OAC) therapy on long-term overall survival and clinically relevant bleedings in a large cohort of hospitalised frail, oldest-old patients with AF. Patients and methods: Prospective, observational, cohort study, evaluating patients consecutively hospitalized for acute illnesses in our Geriatrics Unit (January 2013-July 2017). Participants were divided in two groups, AF and sinus rhythm (SR). Besides recording demographic characteristics and clinical history, comprehensive geriatric assessment (CGA) was obtained. Results: AF patients [1808/5093 (35.5%), 58.5% women] were older, with higher burden of comorbidity than those with SR. At discharge, HAS-BLED [OR 0.77 (95%CI 0.67-0.90), cognitive impairment [OR 0.92 (95%CI 0.90-0.95)], malnutrition [OR 0.74 (95%CI 0.57-0.97)] and CHA2DS2VASc [OR 1.33 (95%CI 1.20-1.47)] emerged as significant independent predictors of anticoagulant prescription. AF patients showed significantly reduced overall survival (OS) than those with SR (11.4 vs 19.4 months, p

Background: Psoriasis is an autoimmune disease that affects the skin and mucous membranes and the Oral manifestations of psoriasis are not well recognized like skin lesions. As Psoriasis may be a rare oral manifestation but it is very important to know about it. Aim: To carry on a survey to know about the knowledge of Psoriasis among the general population. Materials And Methods: 100 students were chosen and a questionnaire including 6 questions were surveyed and the results are obtained. The questionnaire included questions concentrating on the knowledge of the students about the knowledge of Psoriasis. Results and Conclusion: The awareness of Psoriasis disease among the general population was taken as a study and it was found that upto 90% have a knowledge of this disease. But the knowledge on the diagnosis, treatment and prevention was minimum which has to be improved.

ObjectiveAntenatal anaemia is associated with increased peripartum transfusion requirement in South Africa. We studied whether HIV was associated with the response to treatment of iron-deficiency anaemia.DesignProspective cohort study.SettingHospital-based antenatal anaemia clinic in South Africa.SampleEqual-sized cohorts of pregnant women testing positive for HIV (HIV+) and testing negative for HIV (HIV-) with iron-deficiency anaemia.MethodsHaemoglobin trajectories of women with confirmed iron-deficiency anaemia (ferritin&nbsp

Objective:The aim of this study was to determine the effects of vitamin D supplementation on kidney function, blood concentrations of 25-hydroxyvitamin D, and parathyroid hormone levels.Methods:The 25-hydroxyvitamin D levels of approximately 4,000 participants between the ages of 18 and 75 years were investigated retrospectively. Inclusion criteria included screening 25-hydroxyvitamin D

The aim of this study was to fabricate celecoxib-loaded chitosan/guar gum (CS/GG) single (SC) and dual (DC) crosslinked hydrogel beads using the ionotropic gelation approach. The prepared formulations were evaluated for entrapment efficiency (EE%), loading efficiency (LE%), particle size and swelling studies. The performance efficiency was assessed by in vitro drug release, ex-vivo mucoadhesion, permeability, ex-in vivo swelling and in vivo anti-inflammatory studies. The EE% was found to be ~55% and ~44% for SC5 and DC5 beads, respectively. The LE% was ~11% and ~7% for SC5 and DC5 beads, respectively. The beads showed a matrix-like network with thick fibers. The particle size of beads ranged from ~2.74 to 1.91 mm. About 74% and 24% celecoxib was released from SC and DC hydrogel beads, respectively, within 24 h. The SC formulation showed higher %swelling and permeability than the DC counterpart, while the %mucoadhesion was relatively higher for DC beads. During the in vivo study, a significant decrease in the inflammation of the rat paw and inflammatory markers including C-reactive proteins (CRP) and interleukin-6 (IL-6) was observed following treatment with the prepared hydrogel beads; however, the SC formulation showed better therapeutic efficiency. In conclusion, celecoxib-loaded crosslinked CS/GG hydrogel beads can provide sustained drug release and act as potential candidates for managing inflammatory conditions.

Background: This study describes the management protocol for capillary-venous malformations in pediatric patients and reports the epidemiology of diagnosed and treated cases at the Unit of Odontostomatology of the Aldo Moro University of Bari from 2014 to 2022. Methods: The authors classified the intraoral and perioral capillary-venous malformations by superficial diameter (3 cm) and ultrasonographical depth extension (≤5 mm, >5 mm). All patients underwent pulsed-mode diode laser transmucosal photocoagulation (8–12 W/cm2); those with malformations that were wide (>3 cm) and deep (>5 mm) received intralesional photocoagulation, too (13 W/cm2). The children received general anesthesia based on their compliance and lesions’ extension. The follow-up lasted six months. Results: A total of 22 females and 14 males (age range 4–18 years) presented 63 capillary-venous malformations. Five patients with Sturge–Weber syndrome, seven with hereditary hemorrhagic telangiectasia, and five with angiomatosis showed multiple malformations. The authors found no intraoperative or postoperative complications. Seventeen patients with lesions >1 cm and >5 mm deep required multiple laser sessions to heal. Conclusion: The results of the current study support diode laser photocoagulation as the gold standard for the treatment of intraoral and perioral capillary-venous malformations in pediatric patients.

Plant-derived extracellular vesicles (EVs) may represent a platform for the delivery of RNA-based vaccines, exploiting their natural membrane envelope to protect and deliver nucleic acids. Here, EVs extracted from orange (Citrus sinensis) juice (oEVs) were investigated as carriers for oral and intranasal SARS-CoV-2 mRNA vaccine. oEVs were efficiently loaded with different mRNA molecules (coding N, subunit 1 and full S proteins) and the mRNA was protected from degrading stress (including RNase and simulated gastric fluid), delivered to target cells and translated into protein. APC cells stimulated with oEVs loaded with mRNAs induced T lymphocyte activation in vitro. The immunization of mice with oEVs loaded with S1 mRNA via different routes of administration including intramuscular, oral and intranasal stimulated a humoral immune response with production of specific IgM and IgG blocking antibodies and a T cell immune response, as suggested by IFN-γ production by spleen lymphocytes stimulated with S peptide. Oral and intranasal administration also triggered the production of specific IgA, the mucosal barrier in the adaptive immune response. In conclusion, plant-derived EVs represent a useful platform for mRNA-based vaccines administered not only parentally but also orally and intranasally.

Glucagon-like peptide-1 (GLP-1) receptor agonists are efficacious glucose-lowering medications with salient benefits for body weight and cardiovascular events. This class of medications is now recommended as the top priority for patients with established cardiovascular disease or indicators of high risk. Until the advent of oral semaglutide, however, GLP-1 receptor agonists were available only in the form of subcutaneous injections. Aversion to needles, discomfort with self-injection, or skin problems at the injection site are commonly voiced problems in people with diabetes, and thus, attempts for non-invasive delivery strategies have continued. Herein, we review the evolution of GLP-1 therapy from its discovery and the development of currently approved drugs to the unprecedented endeavor to administer GLP-1 receptor agonists via the oral route. We focus on the pharmacokinetic and pharmacodynamic properties of the recently approved oral GLP-1 receptor agonist, oral semaglutide. Small molecule oral GLP-1 receptor agonists are currently in development, and we introduce how these chemicals have addressed the challenge posed by interactions with the large extracellular ligand binding domain of the GLP-1 receptor. We specifically discuss the structure and pharmacological properties of TT-OAD2, LY3502970, and PF-06882961, and envision an era where more patients could benefit from oral GLP-1 receptor agonist therapy.

BACKGROUND Oral lichen planus (OLP) is a chronic inflammatory disorder, and it can affect normal oral function. The conventional treatments for OLP are not always effective, and relapse easily occurs. Therefore, treatment of OLP is difficult and challenging. In this study, we evaluated over a long period the clinical efficacy of surgical excision and acellular dermal matrix (ADM) grafting in patients with refractory OLP. CASE SUMMARY Eleven patients with refractory OLP underwent a standardized protocol of surgical excision and ADM grafting. The condition of the area of the grafted wound, the intraoperative maximum mouth opening, pain, and clinical healing were assessed at postoperative follow-up visits. All patients had a flat surgical area with similar mucosal tissue coverage and local scar formation. Patients had no irritation and pain in their mucous membranes when eating acidic and spicy food. All patients’ mouth openings returned to normal within 2-6 mo after surgery. During follow-up, none of the patients had recurrence of OLP after surgery. The longest follow-up was 11 yr and the shortest was 6 mo, and none of the patients relapsed during follow-up. CONCLUSION Surgical excision and ADM grafting could be an effective method to treat refractory OLP.

The potential of nanoemulsions for the oral administration of peptides is still in its early stage. The aim of the present work was to rationally design, develop, and fully characterize a new nanoemulsion (NE) intended for the oral administration of hydrophobically modified insulin (HM-insulin). Specific components of the NE were selected based on their enhancing permeation properties as well as their ability to improve insulin association efficiency (Miglyol 812, sodium taurocholate), stability in the intestinal fluids, and mucodiffusion (PEGylated phospholipids and poloxamer 407). The results showed that the NE co-existed with a population of micelles, forming a mixed system that exhibited a 100% of HM-insulin association efficiency. The nanosystem showed good stability and miscibility in different bio-relevant media and displayed an acceptable mucodiffusive behavior in porcine mucus. In addition, it exhibited a high interaction with cell mono-cultures (Caco -2 and C2BBe1 human colon carcinoma Caco-2 clone cells) and co-cultures (C2BBe1 human colon carcinoma Caco-2 clone/HT29-MTX cells). The internalization in Caco-2 monolayers was also confirmed by confocal microscopy. Finally, the promising in vitro behavior of the nanosystem in terms of overcoming the biological barriers of the intestinal tract was translated into a moderate, although significant, hypoglycemic response (≈ 20–30%), following intestinal administration to both healthy and diabetic rat models. Overall, this information underlines the crucial steps to address when designing peptide-based nanoformulations to successfully overcome the intestinal barriers associated to the oral modality of administration. Graphical abstract