Knowledge, Attitudes, and Practices of Dental Students from Romania Regarding Self-Perceived Risk and Prevention of Infectious Diseases.

University education is a leading source of information for dental practitioners. Particular emphasis should be given to determining the extent to which students acquire positive knowledge, attitudes, and practices (KAP) and positive metacompetences beyond the scope of each studied dental discipline. We performed a cross-sectional questionnaire-based study among dentistry students from Romania to assess self-perceived risk of infectious diseases and their KAP on topics related to infectious disease prevention. The surveyed students presented good knowledge regarding personal protective equipment (PPE), and their PPE practices significantly correlated with the perceived usefulness of PPE. Only 45.1% correctly recognized all vaccine-preventable diseases (VPDs), but knowledge regarding VPDs significantly improved with increasing year of study (τb = 0.298, p = 0.001), confirming a positive education effect. Awareness regarding the need for screening for bloodborne viruses is poor; the majority of students had never performed a test for hepatitis C virus infection (HCV) (59.4%) or for human immunodeficiency virus (HIV) infection (60.4%). Furthermore, most respondents incorrectly considered themselves at high or very high risk of acquiring BBV, and perceived risk was inversely correlated with willingness to treat patients with hepatitis B virus (HBV) infection (τb = -0.214, p = 0.018), HCV infection (τb = -0.234, p = 0.013), or HIV infection (τb = -0.242, p = 0.006). This led to 3.0% of respondents stating that they would hypothetically deny dental treatment to a patient with HBV infection, 5.0% for HCV infection, and 10.9% for HIV infection, the proportion being significantly higher for HIV (z = -2.2, p = 0.026). In conclusion, better knowledge is needed among dental students regarding their own vaccination history, screening for bloodborne viruses, accurate estimates for their risk of acquiring bloodborne viruses during routine dental practice, and the existence of post-exposure measures following occupational exposure. Improving student knowledge and awareness could translate into a higher willingness to treat patients with chronic viral infections and into a safer and more inclusive dental practice. We propose an adaptation to the university curriculum to cover these key areas for targeted focus to empower future dental practitioners and to facilitate the improvement of across-discipline metacompetences for infection prevention and control.

Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates.

SARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there's a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.5 variant of SARS-CoV-2. A prime-boost regimen using GRAd followed by adjuvanted S-2P (GRAd+S-2P) accelerated viral clearance in both the lower and upper airways. GRAd delivered via aerosol (GRAd(AE)+S-2P) modestly improved protection compared to its matched intramuscular regimen, but showed dramatically superior boosting by mRNA and, importantly, total virus clearance in the upper airway by day 4 post infection. GrAd vaccination regimens elicited robust and durable systemic and mucosal antibody responses to multiple SARS-CoV-2 variants, but only GRAd(AE)+S-2P generated long-lasting T cell responses in the lung. This research underscores the flexibility of the GRAd vaccine platform to provide durable immunity against SARS-CoV-2 in both the lower and upper airways.

Bacterial species associated with peri-implant disease - a literature review.

Peri-implantitis is a pathological condition in dental medicine that manifests as an inflammatory process affecting the tissues surrounding dental implants. Peri-implantitis occurs when the soft and hard tissues surrounding these implants become inflamed, leading to progressive destruction of the supporting bone. The etiology of peri-implantitis is multifactorial, involving microbial, host-related, and environmental factors. Microbial involvement in peri-implantitis can be explained either by direct in-situ virulence activation leading to pathogenicity, or by induction of low-grade chronic immune activation, leading to long-term persistence of a pro-inflammatory status. Understanding peri-implantitis is pivotal in maintaining the long-term success of dental implants and improving patient outcomes in implant-supported restorations. Recognizing the etiological factors, including particular bacterial species, genetic predispositions, and environmental influences, is very important for devising effective preventive strategies and targeted interventions.

Mucosal administration of a live attenuated recombinant COVID-19 vaccine protects nonhuman primates from SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein spike for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live, attenuated, recombinant human respiratory syncytial virus expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200-fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunoglobulin A in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against virus variants of concern Alpha, Beta, and Delta. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in Phase 1 clinical trials as an intranasal COVID-19 vaccine.

mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron.

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.

Vaccine protection against the SARS-CoV-2 Omicron variant in macaques.

The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. In this study, we show that the mRNA-based BNT162b2 vaccine and the adenovirus-vector-based Ad26.COV2.S vaccine provide robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in cynomolgus macaques. We vaccinated 30 macaques with homologous and heterologous prime-boost regimens with BNT162b2 and Ad26.COV2.S. Following Omicron challenge, vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs. However, 4 vaccinated animals that had moderate Omicron-neutralizing antibody titers and undetectable Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Moreover, virologic control correlated with both antibody and T cell responses. These data suggest that both humoral and cellular immune responses contribute to vaccine protection against a highly mutated SARS-CoV-2 variant.

Vaccine Protection Against the SARS-CoV-2 Omicron Variant in Macaques.

BACKGROUND: The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. Immune correlates of vaccine protection against Omicron are not known. METHODS: 30 cynomolgus macaques were immunized with homologous and heterologous prime-boost regimens with the mRNA-based BNT162b2 vaccine and the adenovirus vector-based Ad26.COV2.S vaccine. Following vaccination, animals were challenged with the SARS-CoV-2 Omicron variant by the intranasal and intratracheal routes. RESULTS: Omicron neutralizing antibodies were observed following the boost immunization and were higher in animals that received BNT162b2, whereas Omicron CD8+ T cell responses were higher in animals that received Ad26.COV2.S. Following Omicron challenge, sham controls showed more prolonged virus in nasal swabs than in bronchoalveolar lavage. Vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs, showing that current vaccines provide substantial protection against Omicron in this model. However, vaccinated animals that had moderate levels of Omicron neutralizing antibodies but negligible Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Virologic control correlated with both antibody and T cell responses. CONCLUSIONS: BNT162b2 and Ad26.COV2.S provided robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in macaques. Protection against this highly mutated SARS-CoV-2 variant correlated with both humoral and cellular immune responses.

Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine.

The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 µg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates.

Effect of repeated sodium valproate and topiramate administration on mania­like behaviors induced by methylphenidate in mice.

Novel and effective treatments for mania are needed, and well­validated animal models are important to reach this goal. The psychostimulant­induced hyperactivity is the most frequently animal model of mania used. Although this model is validated pharmacologically using mood stabilizers, data about its predictive validity with negative controls (i.e., drugs that are clinically ineffective in treating mania) are lacking. The present study evaluated the effects of the repeated administration of a clinically effective drug (sodium valproate) and clinically ineffective drug (topiramate) on methylphenidate (MPH)­induced manic­like behaviors in Swiss mice in the behavioral pattern monitor (BPM). Methylphenidate increased locomotor activity and center activity in the BPM. Valproate attenuated the effect of MPH on locomotor and general activity, with no effect on center activity. Topiramate did not affect any MPH­induced manic­like behaviors. Methylphenidate did not change exploratory activity (rearing or nose poking). These results support the predictive validity of MPH­induced hyperactivity for screening antimanic­like drugs.

Protection against SARS-CoV-2 Beta variant in mRNA-1273 vaccine-boosted nonhuman primates.

Neutralizing antibody responses gradually wane against several variants of concern (VOCs) after vaccination with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine messenger RNA-1273 (mRNA-1273). We evaluated the immune responses in nonhuman primates that received a primary vaccination series of mRNA-1273 and were boosted about 6 months later with either homologous mRNA-1273 or heterologous mRNA-1273.ß, which encompasses the spike sequence of the B.1.351 Beta variant. After boost, animals had increased neutralizing antibody responses across all VOCs, which was sustained for at least 8 weeks after boost. Nine weeks after boost, animals were challenged with the SARS-CoV-2 Beta variant. Viral replication was low to undetectable in bronchoalveolar lavage and significantly reduced in nasal swabs in all boosted animals, suggesting that booster vaccinations may be required to sustain immunity and protection.

Prior infection with SARS-CoV-2 WA1/2020 partially protects rhesus macaques against reinfection with B.1.1.7 and B.1.351 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that result in increased transmissibility and partial evasion of neutralizing antibodies have recently emerged. Whether natural immunity induced by the original SARS-CoV-2 WA1/2020 strain protects against rechallenge with these SARS-CoV-2 variants remains a critical unresolved question. In this study, we show that natural immunity induced by the WA1/2020 strain leads to partial but incomplete protection against the SARS-CoV-2 variants B.1.1.7 (alpha) and B.1.351 (beta) in rhesus macaques. We challenged rhesus macaques with B.1.1.7 and B.1.351 and showed that infection with these variants resulted in high viral replication in the upper and lower respiratory tract. We then infected rhesus macaques with the WA1/2020 strain and rechallenged them on day 35 with the WA1/2020, B.1.1.7, or B.1.351 variants. Natural immunity to WA1/2020 led to robust protection against rechallenge with WA1/2020 but only partial protection against rechallenge with B.1.351. An intermediate degree of protection was observed in rhesus macaques against rechallenge with B.1.1.7. These data demonstrate partial but incomplete protective efficacy of natural immunity induced by WA1/2020 against SARS-CoV-2 variants of concern. Our findings have important implications for both vaccination and public health strategies in the context of emerging SARS-CoV-2 variants of concern.

Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates.

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 µg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti­S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273­induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine­induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.

Protection against SARS-CoV-2 Beta Variant in mRNA-1273 Boosted Nonhuman Primates.

Neutralizing antibody responses gradually wane after vaccination with mRNA-1273 against several variants of concern (VOC), and additional boost vaccinations may be required to sustain immunity and protection. Here, we evaluated the immune responses in nonhuman primates that received 100 µg of mRNA-1273 vaccine at 0 and 4 weeks and were boosted at week 29 with mRNA-1273 (homologous) or mRNA-1273.ß (heterologous), which encompasses the spike sequence of the B.1.351 (beta or ß) variant. Reciprocal ID 50 pseudovirus neutralizing antibody geometric mean titers (GMT) against live SARS-CoV-2 D614G and the ß variant, were 4700 and 765, respectively, at week 6, the peak of primary response, and 644 and 553, respectively, at a 5-month post-vaccination memory time point. Two weeks following homologous or heterologous boost ß-specific reciprocal ID 50 GMT were 5000 and 3000, respectively. At week 38, animals were challenged in the upper and lower airway with the ß variant. Two days post-challenge, viral replication was low to undetectable in both BAL and nasal swabs in most of the boosted animals. These data show that boosting with the homologous mRNA-1273 vaccine six months after primary immunization provides up to a 20-fold increase in neutralizing antibody responses across all VOC, which may be required to sustain high-level protection against severe disease, especially for at-risk populations. ONE-SENTENCE SUMMARY: mRNA-1273 boosted nonhuman primates have increased immune responses and are protected against SARS-CoV-2 beta infection.

Protective efficacy of Ad26.COV2.S against SARS-CoV-2 B.1.351 in macaques.

The emergence of SARS-CoV-2 variants that partially evade neutralizing antibodies poses a threat to the efficacy of current COVID-19 vaccines1,2. The Ad26.COV2.S vaccine expresses a stabilized spike protein from the WA1/2020 strain of SARS-CoV-2, and has recently demonstrated protective efficacy against symptomatic COVID-19 in humans in several geographical regions-including in South Africa, where 95% of sequenced viruses in cases of COVID-19 were the B.1.351 variant3. Here we show that Ad26.COV2.S elicits humoral and cellular immune responses that cross-react with the B.1.351 variant and protects against B.1.351 challenge in rhesus macaques. Ad26.COV2.S induced lower binding and neutralizing antibodies against B.1.351 as compared to WA1/2020, but elicited comparable CD8 and CD4 T cell responses against the WA1/2020, B.1.351, B.1.1.7, P.1 and CAL.20C variants. B.1.351 infection of control rhesus macaques resulted in higher levels of virus replication in bronchoalveolar lavage and nasal swabs than did WA1/2020 infection. Ad26.COV2.S provided robust protection against both WA1/2020 and B.1.351, although we observed higher levels of virus in vaccinated macaques after B.1.351 challenge. These data demonstrate that Ad26.COV2.S provided robust protection against B.1.351 challenge in rhesus macaques. Our findings have important implications for vaccine control of SARS-CoV-2 variants of concern.

Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates.

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 - 100 µg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP. ONE-SENTENCE SUMMARY: mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

Isolated De Novo Headache as the Presenting Symptom of Listeria Meningitis: A Report of 2 Cases.

BACKGROUND: Headache is a frequent symptom at the onset of Listeria meningitis, accompanied by others such as fever, altered mental status and meningeal signs, but never reported so far as an isolated symptom. METHODS AND RESULTS: Two immunocompetent males, with no history of primary headaches, went to the emergency department because of headache. The first after a sudden severe, holocranial headache without other associated symptoms, and the second after a subacute, moderate oppressive headache in temples, which 8 days later added a mild left hemiparesis. None of them had fever or meningeal signs. The initial cranial CT was unremarkable in both cases. Lumbar puncture was diagnostic for Listeria meningitis serotype IVb. CONCLUSIONS: Listeria meningitis may present as an isolated headache, with different clinical patterns, which should be taken into account when evaluating de novo unclassified headaches according to the ICHD-3 criteria.

A rare tumor in a rare location: giant cell tumor of the sacrum and ilium - case report and current perspectives.

Giant cell tumor (GCT) is considered a locally aggressive, intermediate grade benign bone neoplasm. In rare cases, GCT undergoes malignant degeneration or may cause distant metastasis, mainly in the pulmonary area. Most bone GCTs are situated in the epiphysis or metaphysis of long bones, while GCTs of the pelvis are quite rare. There is no standard treatment protocol for the GCT of pelvic bones. This paper presents the therapeutic management of a rare case of a stage III GCT, situated on the iliac tuberosity, sacral wing and partially the left iliac wing. The chosen treatment consisted in intralesional curettage, high-speed burring, phenolization and hydrogen peroxide lavage. At the six-week follow-up, the patient reported minimal disability. No complications and no local infections were revealed. Healing was confirmed by the two-year postoperative follow-up. This case report demonstrates that intralesional curettage complemented with adjuvant therapies is a viable alternative to wide resection surgery for the treatment of aggressive GCT.

Morphological assessment of the mandibular canal trajectory in edentate subjects.

BACKGROUND: The mandibular canal and its content represent the vital structure, which can complicate dentoalveolar surgical procedures in the posterior region of the mandible. The purpose of the present study was to determine the path the mandibular canal takes in relation to the horizontal and the vertical anatomical reference planes in edentate subjects, in order to minimize the risk of affecting its neurovascular content during various oral surgery procedures. MATERIALS AND METHODS: Morphometric evaluations were performed on 12 dried fully edentulous human mandibles and on cone-beam computed tomography (CBCT) cross-sectional images of the mandible, from 20 patients with either partial or complete edentulism. Both methods were utilized, in three target areas (corresponding to the second premolar, to the first molar and to the second molar regions), in order to measure the distance between the mandibular canal and the following reference points: (i) the lateral (buccal) surface of the mandible (MC-BS distance); (ii) the medial (lingual) surface of the mandible (MC-LS distance); (iii) the alveolar surface of the mandible (MC-AS distance). The results were statistically processed in Stata MP/13 software package using analysis of variance (ANOVA) test. RESULTS: The mandibular canal crossed the trabecular bone from the posterior towards the anterior, and from the lingual towards the buccal, reaching the premolar region, distal to the mental foramen, where it was located in the centre of the trabecular bone, main topographic pattern encountered in 27 (84.37%) of the cases. In five (15.63%) of the cases, in the premolar region, the mandibular canal was located near the buccal cortical plate. The mandibular canal descended from the second molar region towards the premolar region, main topographic pattern found in 28 (87.5%) of the cases. In four (12.5%) cases, the mandibular canal had a descending trajectory in the molar regions and it took a slightly ascending course in the premolar region. CONCLUSIONS: According to the results, the second molar region represents the highest risk area in the accidental injury to the content of the mandibular canal, during various oral surgery procedures.

Morphological assessment of the mandibular canal trajectory in dentate subjects.

BACKGROUND: The mandibular canal is the most important vital structure within the mandibular body. The aim of the present study was to determine the course of mandibular canal in relation to external surfaces of the mandible (buccal, lingual) and to root apices of the lateral teeth, in order to minimize the risk of its content being injured during either conservative or radical treatment of the mandibular lateral teeth. MATERIALS AND METHODS: Morphometric evaluations were performed on 11 dried dentate human mandibles and on cone-beam computed tomography (CBCT) cross-sectional images of the mandible, from 18 dentate patients. By means of both methods, the following parameters were assessed: (i) the distance between the mandibular canal and the buccal (lateral) surface of the mandible (MC-BS distance); (ii) the distance between the mandibular canal and the lingual (medial) surface of the mandible (MC-LS distance); (iii) the distance between the mandibular canal and the root apices of the second premolar, the first and second molars (MC-T distance). The results were statistically processed in Stata MP÷13 software package using analysis of variance (ANOVA). RESULTS: With respect to buccal-lingual location, the mandibular canal passed horizontally through the mandibular trabecular bone, from posterior to anterior, and from lingual to lateral (buccal), and so at premolar level it approached the lateral (buccal) cortical bone plate, main topographic pattern found in 26 (89.65%) of the cases. The mandibular canal had a descending trajectory from the second molar to the first molar, after which it ascended slightly towards the second premolar, main topographic pattern found in 24 (82.75%) of the cases. CONCLUSIONS: According to the results, the second mandibular molar is the most common tooth involved in the accidental damaging of the content of the mandibular canal, during various therapeutic procedures. Overlooking the location of the mandibular canal can lead to complications in endodontic therapy and in dentoalveolar surgical procedures in the posterior region of the mandible.