Investigation of the presence of Non-carious cervical lesions (NCCLs) in ancient adult skulls: analyzing data from prehistoric and historical samples through a systematic review and meta-analysis.

OBJECTIVES: Historically, the prevalence of caries has undergone significant changes, particularly increasing with the industrialization of sugar consumption. When examining ancient populations, lower caries rates are discovered, attributed in part to dietary factors. These populations consumed abrasive foods, leading to occlusal wear and reduced non-axial occlusal forces, potentially influencing Non-Carious Cervical Lesions (NCCLs). Although some attribute NCCLs to abfraction, the mechanism remains debated. This systematic review aims to evaluate the presence of NCCLs in ancient populations, shedding light on the factors contributing to their occurrence. MATERIALS AND METHODS: The present systematic review was registered on PROSPERO, and the manuscript was prepared following PRISMA guidelines. RESULTS: After the literature search and article screening, data from 6 studies were included in the meta-analysis, with only 2 reporting NCCLs in ancient skulls, encopassing 17 subjects in 805 examined skulls, suggesting their presence even before the widespread use of toothbrushes. This finding indicates a potential etiopathogenic mechanism linked to abfraction, but the cause is complex and involves abrasive and erosive factors closely tied to dietary habits. CONCLUSIONS: In summary, NCCLs were present in ancient populations, albeit with a much lower prevalence. Their occurrence cannot be solely attributed to wear mechanisms but must be connected to abrasive factors related to diet or practices with religious and cultural significance, such as the use of labrets. CLINICAL RELEVANCE: Th the knowledge of NCCLs presence in acient sculls is crucial today for better understand the associated risk factors. In this context, the analysis of ancient skulls allows us to discern the role that tooth brushing and diet played in the formation of NCCLs, over the past century.

Oral lichen planus in children: A systematic review / Liquen plano oral en niños: una revisión sistemática

Background: Oral Lichen Planus is a common chronic inflammatory disease of the oral mucosa. The prevalencein adults ranges between 0.5% and 2%, while in children is reported to be about 0,03%. Clinical features of OralLichen Planus could be variable in both adults and children, ranging from painless white hyperkeratotic lesions topainful erythematous atrophic ones.Actually, there are no systematic reviews in the literature on OLP in children, whereby this paper aims to sum-marize all the pathophysiological aspects and identify all cases described in the literature of Oral Lichen Planusin children, reporting their clinical characteristics.Material and Methods: A systematic review of the literature was performed in online databases including PubMed,Scopus, Web of Science, Science Direct, EMBASE. In addition, in order to identify reports not otherwise identifi-able, an analysis of the gray literature was performed on google scholar and in Open Gray.Results: By literature analysis, it emerged that most cases were reported from India. The mean age at time of diag-nosis of the disease was 11 years, ranging from 3 to 17 years. The most frequent pattern was the reticular patternfollowed by plaque-like, erosive, atrophic, sclerosus, and bullous. The buccal mucosa was the most involved oralsite, followed by the tongue, lips and gingiva.Conclusions: Although Oral Lichen Planus in children is rare, it may cause oral discomfort and need to be dif-ferentiated from other oral white lesions and/or chronic ulcers.(AU)

IL-37 evaluation in chronic periodontitis after periodontal treatment with and without low level laser therapy.

BACKGROUND: Periodontal disease poses a significant global health challenge. Traditional treatments focus on reducing inflammation and bacterial load, yet novel approaches are continually being investigated. Recent research suggests that IL-37, a potent anti-inflammatory cytokine, may play a crucial role in modulating the inflammatory processes associated with periodontal disease. In conjunction with IL-37, low-level laser therapy (LLLT) has gained attention for its potential in promoting tissue repair, reducing inflammation, and enhancing cellular processes. This study aims to investigate the effects of LLLT on IL-37 in periodontal disease management. METHODS: Thirty patients were enrolled: the G1 group patients were treated with only scaling and root planning-SRP, the G2 group was treated with SRP and LLLT. Before treatment (T0) all periodontal probing pocket depth and bleeding on probing were obtained. Before (T0) and 10 (T1), 30 (T2) and 60 (T3) days after treatment, was achieved plaque sample and specimens of gingival crevicular fluid. Diode laser wavelength range was used between 600-1000 nm and 0.04-60 J/cm2 energy density for 3-s spotlights. RESULTS: In all patients PPD, BOP and IL-37 have shown healing improved parameters. CONCLUSIONS: Although LLLT is widely recommended for its biostimulatory and anti-inflammatory roles, it only showed additional short-term merits in reducing the pocket depth after conventional SRP. Its long-term adjunctive benefits remain unclear. Future RCTs with better study designs, adequate sample power and longer durations of follow-up are required to assess the effectiveness of LLLT as an adjunctive treatment strategy in patients with periodontal disease.

Possible uses of Hunter-Schreger bands of dental enamel for automated personal identification.

BACKGROUND: Hunter-Schreger bands (HSB) are optical phenomena observed on tooth surfaces under polarized light, resulting from the intersection of enamel prisms. Anthropological studies demonstrate the prevalence of HSB in large mammals, contributing to enamel resistance. Historically, John Hunter and Schreger depicted HSB in dental literature. In dentistry, HSB play a role in non-carious cervical lesions (NCCL) and internal dental perikymata, suggesting their potential for personal identification. Personal identification, crucial in both daily and professional life, involves biometric characteristics, such as fingerprints or facial recognition. The need for non-invasive, rapid, and user-friendly methods has prompted the exploration of using HSB dental images for personal identification. The review aimed to consolidate studies employing HSB for personal identification. METHODS: The scoping review was carried out strictly following the PRISMA-ScR checklist; the search was carried out on tree databases (PubMed, Scopus, Science Direct,) and a register (Cochrane library). RESULTS: The research produced a number of bibliographic sources totaling 410. With the removal of duplicates, 334 were obtained; potentially eligible articles amounted to 14, of which only 4 fully complied with the criteria of eligibility. CONCLUSIONS: From the data in the literature, we can assert that HSB could be used in personal identification, as they are characteristics that are difficult to change and easily detectable.

Dentistry in the centuries: a historical overview.

The began of the dentistry as medicine's concept has a long history dating back to 7000 BCE, making it one of the earliest medical specialties. In its early days, dental diseases were often attributed to supernatural causes like "evil spirits" and "tooth worms." However, today, dentistry leverages cutting-edge technologies, including artificial intelligence, for diagnosis and treatment. This journey reflects the remarkable progress made in the field. Despite these advancements, there is still room for improvement in integrating dental knowledge and skills with medical science and engineering backgrounds. Bridging these disciplines could lead to even greater advancements in the diagnosis and maintenance of oral health. Thus, over time, it has transformed from a primitive form of medicine into a modern field that emphasizes preventative dental care, advanced diagnostics, and state-of-the-art treatment.

Challenging Differential Diagnosis of Mandible Angle Metastasis from Breast Cancer.

Breast cancer is the most common cancer in women and the second leading cause of cancer-related death. Breast cancer manifestations in the head and neck are relatively rare, and they are mostly bony metastasis to the mandible and maxilla. In this paper, we present a case report of a metastatic tumor in the mandibular angle originating from breast carcinoma. A 32-year-old female patient with a paresthesia/anesthesia in the left mandibular area was referred to us to aid in the differential diagnosis between osteonecrosis and metastasis. Her medical history revealed a radical bimastectomy 3 years ago for invasive lobular carcinoma of the breasts. Additionally, she received chemotherapy and radiotherapy 3 years ago, and intravenous zoledronic acid was administered every 3 weeks. Intraoral examination did not reveal any mucosal ulcer or fistula, and there was no radiological evidence of cyst. The patient demonstrated good oral hygiene. Palpable regional left submandibular lymph nodes and a few swellings on the lateral angular mandibular surface were observed. Cone-beam computed tomography (CBCT) and positron emission tomography (PET) were performed. CBCT showed small poorly diffused radiopacity in proximity to the mandibular angle on both medial and lateral surfaces. PET showed fluoro-2-deoxy-D-glucose uptake in the mandible in the left angle surface area. Based on the patient's clinical history, signs, symptoms, and tomographic evidence, we were able to diagnose mandibular metastasis. This case also highlights the importance of proficiency in reading tomographic examinations, which can be carried out in dental clinics for various purposes. In the absence of symptoms, misdiagnosis can occur, underscoring the significance of accurate interpretation and diagnosis.

Dietary Polyphenols against Oxidative Stress in Head and Neck Cancer: What's New, What's Next.

Head and neck cancers (HNC) are a worldwide health problem, accounting for over 5% of all types of cancers. Their varied nature makes it sometimes difficult to find clear explanations for the molecular mechanisms that underline their onset and development. While chemio- and radiotherapy are clearly not to be dismissed, we cannot undervalue the effect that polyphenols - especially dietary polyphenols - can have in helping us to cope with this medical emergency. By influencing several different proteins involved in numerous different metabolic pathways, polyphenols can have a broad spectrum of biological action and can hopefully act synergistically to tackle down head and neck cancer. Moreover, being natural molecules, polyphenols does not present any side effects and can even enhance drugs efficacy, making our clinical therapy against head and neck cancer more and more effective. Certainly, oxidative stress plays an important role, altering several molecular pathways, lowering the body's defenses, and ultimately helping to create a microenvironment conducive to the appearance and development of the tumor. In this regard, the regular and constant intake of foods rich in polyphenols can help counteract the onset of oxidative stress, improving the health of the general population. In this review, we highlight the role of polyphenols in managing oxidative stress, with such positive effects that they can be considered new tools to use in our anti-head and neck cancer strategy.

Anti-LGALS3BP antibody-drug conjugate treatment induces durable and potent antitumor response in a preclinical model of adenoid cystic carcinoma.

OBJECTIVES: Adenoid cystic carcinoma (ACC) is a rare type of cancer that typically arises from glandular tissues, most commonly in the salivary glands. Although relatively rare, it represents a serious clinical issue as the management of the disease is highly complex being the only therapeutic options represented by invasive surgery and/or radiotherapy. In the present study, we have explored the potential of galectin-3 binding protein (LGALS3BP) as a novel target for antibody-drug conjugate (ADC) therapy in ACC. MATERIALS AND METHODS: RNAseq was conducted on a panel of 10 ACC patient-derived xenografts (PDX)s tissues and 6 normal salivary glands to analyze LGALS3BP gene expression. Protein expression was assessed in ACC PDX and primary tumor tissues using immunohistochemistry. Anti-LGALS3BP ADC named 1959-sss/DM4, was tested in high LGALS3BP expressing ACC PDX model ST1502B. RESULTS: RNAseq analysis revealed that LGALS3BP expression was highly expressed in ACC PDX tissues compared to normal salivary gland tissues. As evaluated by immunohistochemical analysis, LGALS3BP protein was found to be heterogeneously expressed in 10 ACC PDX and in tumor tissues derived from a cohort of 37 ACC patients. Further, treatment with 1959-sss/DM4 ADC led to durable tumor growth inhibition (TGI) in 100% of animals without observed toxicity. CONCLUSIONS: Our study provides strong evidence that LGALS3BP is a promising therapeutic target for ACC, warranting further expedited preclinical and clinical investigation.

Introspection of the Etiopathological Mechanisms Underlying Noncarious Cervical Lesions: Analysis of the Different Theories and Their Impact on the Mineralized Structures of the Tooth.

The noncarious cervical lesions (NCCLs) recognize an etiological framework of onset very different from the carious processes with etiology whose bacteria aggregated in a biofilm play a predominant role, leading in this way to the loss of the mineralized structure of the tooth. The pathological picture of the NCCLs, which manifests itself with a clinical picture of dental wear, differs from caries because it mainly recognizes a series of pathological processes, such as erosion, through the action of generally acidic chemical agents and abrasion, which is basically expressed through repeated mechanical trauma characteristic of tooth brushing. However, in the literature, there is no unanimous agreement in identifying only these two mechanisms, but there are some who propose a more marked role of anomalous occlusal loads, which would be unloaded on some teeth which, in addition to both erosive and abrasive mechanisms, would give rise to abfraction. Therefore, the aim of this review was to collect literature etio-pathological information and discuss the mechanisms underlying NCCLs.

Optimization of Cobalt-Chromium (Co-Cr) Scaffolds for Bone Tissue Engineering in Endocrine, Metabolic and Immune Disorders.

Approximately 50% of the adult global population is projected to suffer from some form of metabolic disease by 2050, including metabolic syndrome and diabetes mellitus. At the same time, this trend indicates a potential increase in the number of patients who will be in need of implant-supported reconstructions of specific bone regions subjected to inflammatory states. Moreover, physiological conditions associated with dysmetabolic subjects have been suggested to contribute to the severity of bone loss after bone implant insertion. However, there is a perspective evidence strengthening the hypothesis that custom-fabricated bioengineered scaffolds may produce favorable bone healing effects in case of altered endocrine or metabolic conditions. This perspective review aims to share a comprehensive knowledge of the mechanisms implicated in bone resorption and remodelling processes, which have driven researchers to develop metallic implants as the cobalt-chromium (Co-Cr) bioscaffolds, presenting optimized geometries that interact in an effective way with the osteogenetic precursor cells, especially in the cases of perturbed endocrine or metabolic conditions.

The Correlation between Mandibular Arch Shape and Vertical Skeletal Pattern.

Background and Objectives: The aim of this study was to evaluate the correlation between the mandibular arch shape and the vertical skeletal pattern in growing patients. Materials and Methods: A total of 73 Caucasian patients (33 males and 40 females; mean age 9.4) were retrospectively enrolled from a pool of patients treated in chronological order at the Department of Orthodontics, University of Foggia, Italy, from April 2018 to December 2021. Each patient received a laterolateral radiograph and a digital scan of the dental arch. Eight cephalometric parameters (lower gonial angle, intermaxillary angle, divergence angle, Wits index, Jarabak ratio, OP-MP angle, PP-OP angle, and ANB) and five dental measurements (posterior mandibular arch width, anterior mandibular arch width, mandibular occlusal angle, posterior width on distobuccal molar cusps, and molar angle) were analyzed and then compared. A Spearman's rho correlation test between the cephalometric measurements and the dental measurements was performed. Statistical significance was set at p < 0.05. Results: A negative statistically significant correlation was found between the Jarabak ratio and the intermolar angle; a statistically significant correlation was also observed between the Wits index, the posterior mandibular width, and the occlusal mandibular angle; the ANB angle and the occlusal mandibular angle; the intermaxillary angle (PP-PM) and the mandibular occlusal angle, posterior mandibular width on the disto-vestibular cusp, and the intermolar angle; and the OP-MP angle and mandibular occlusal angle and the posterior mandibular width on the disto-vestibular cusp. Conclusions: The mandibular arch form may be related to certain predisposing features in craniofacial morphology, such as jaw divergence, the Jarabak ratio, and the intermaxillary angle.

Treatment of Mandibular Impacted Canine in a Patient with Class II Division 1 Malocclusion with "Reverse Pin": A Case Report.

This case report presents an orthodontic treatment conducted on a 13-year-old girl with bilateral Class II malocclusion and a mandibular impacted canine. The presence of an impacted tooth necessitates careful consideration of the timing of orthodontic treatment, the appropriate surgical procedure to expose the tooth, the specific orthodontic mechanics involved, and the potential problems that may arise, all of which depend on the type and location of the canine impaction in the jaw. The treatment plan included a surgical procedure to expose the impacted tooth and orthodontic traction to guide it into position. Correction of the Class II Division 1 malocclusion utilized a specialized technique called the "reverse pin", reducing vertical side effects. The revised version maintains clarity and key information about the case report and treatment.

The Potential microRNA Prognostic Signature in HNSCCs: A Systematic Review.

Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as "signature microRNA OR miR" AND "HNSCC OR LSCC OR OSCC OR oral cancer" were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.

LGALS3BP is a potential target of antibody-drug conjugates in oral squamous cell carcinoma.

OBJECTIVE: The aim of the present study was to evaluate the expression of intracellular and vesicular LGALS3BP in oral squamous cell carcinoma (OSCC) patients and available cell lines to explore its potential as a target for antibody-drug conjugate (ADC) therapy. METHODS: Free and vesicular LGALS3BP expression levels were evaluated in cancer tissues from a cohort of OSCC patients as well as in a panel of OSCC cell lines through immunohistochemistry, qRT-PCR, Western Blot analysis, and ELISA. RESULTS: LGALS3BP resulted in being highly expressed in the cytoplasm of tumour cells in OSCC patient tissues. A strong correlation was found between high LGALS3BP expression levels and aggressive histological features of OSCC. Biochemistry analysis performed on OSCC cell lines showed that LGALS3BP is expressed in all the tested cell lines and highly enriched in cancer-derived extracellular vesicles. Moreover, LGALS3BP high-expressing HOC621 and CAL27 OSCC cell lines showed high sensitivity to the ADC-payload DM4, with an IC50 around 0.3 nM. CONCLUSIONS: The present study highlights that LGALS3BP is highly expressed in OSCC suggesting a role as a potential diagnostic biomarker and therapeutic target for ADC-based therapy.

Attitudes and practices of dentists treating HIV+ patients in the era of new antiretroviral therapy: A 12-year update.

During the first years of the HIV pandemic, the virus diffusion was responsible for discriminatory behavior from medical and dental care workers towards HIV-infected patients, as described by our research group in 2009. The aim of the current study was to provide an update on the previous data, investigating the presence of discriminatory behaviors, evaluating the level of dentists' knowledge about the virus and proposing strategies to be implemented to avoid professional exposure and cross-infections. This study was a cross-sectional, online, national survey on dentists, members of the main national dental associations (ANDI and AIO). The questionnaire was divided into four major sections, with the same structure as the questionnaire administered in 2009. The differences between groups were analyzed using the software program IBM SPSS Statistic, version 21.0. A total of 1054 dentists filled out the questionnaire completely. Among them 0.04% revealed a discriminatory attitude towards HIV-infected patients. The univariate analysis showed that discrimination towards HIV + patients was statistically associated with personal experiences and the level of fear associated with treating them (p = 0.001) and with the type of dental treatments performed (p = 0.01). This cross-sectional study revealed the persistence of dentists who still discriminate against HIV + patients, and the percentage of these dentists was only slightly lower than that in the previous survey (4.3% in the present survey vs. 4.5%). The survey also depicted other information worthy of consideration, such as a perceived ability to detect HIV + patients based on their appearance, complaints about not having received adequate training for treating HIV + individuals, and a lack of scientific knowledge about the virus. From the evidence reported by the present survey, it can be argued that universities, professional boards, and training institutions must increase their efforts in spreading correct knowledge about HIV among all dental care workers.

The Immune Cells in the Development of Oral Squamous Cell Carcinoma.

A still unresolved issue surrounding tumor formation concerns the role that the immune system plays in preventing the formation and progression of neoplasia, including oral squamous cell carcinoma (OSCC). Antitumor immunity has historically been seen as a critical barrier for cancer cells to develop, grow and spread, and this can be modulated using immunotherapies to achieve antitumor clinical responses. However, it has recently become clear that tumor-associated immunity, particularly the inflammatory microenvironment, has the paradoxical effect of enhancing tumorigenesis and progression. In this review, we discuss the multifaceted function of infiltrating immune cells in suppressing or promoting premalignancy and cancer. In particular, we report on the evidence supporting a role for T lymphocytes, dendritic cells, macrophages, and neutrophils in the development and progression of oral potentially malignant disorders (OPMD) and OSCC. We also draw attention to the clinical relevance of immune cell phenotypes and associated molecules for use as biomarkers and to the translatability of current research findings to improve classification systems and precision medicine in patients with OSCC.

High-risk TP53 mutations predict poor primary treatment response of patients with head and neck squamous cell carcinoma.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) poses a diagnostic and therapeutic challenge worldwide and is associated with a poor survival rate. Due to the variability in the efficacy of treatments for HNSCC, new predictive biomarkers of therapy outcomes are needed. Recently, we developed an algorithm that employs the mutational profile of TP53 as an independent prognostic factor in HNSCC. In this study, we investigated its role as a predictive biomarker of treatment outcomes in HNSCC patients. We also tested the usefulness of two classification systems for TP53 mutational landscapes. MATERIALS AND METHODS: Clinical and genomic data were retrieved from The Cancer Genome Atlas database. We built a multivariate stepwise backward binary regression model to assess the role of TP53 mutations in predicting therapeutic outcomes. RESULTS: Cases harbouring high-risk-of-death mutations reported an odds ratio of 3.301 for stable or progressive disease compared to wild-type cases, while no significant difference in treatment outcomes was found between cases with low-risk-of-death mutations and wild-type TP53. Our analysis found that older patients with a history of alcohol consumption had a higher risk of stable/progressive disease. CONCLUSIONS: This study improves current evidence on the role of TP53 mutations in treatment response in HNSCC patients.

COVID-19 and Oral Lichen Planus: Between an "Intriguing Plot" and the "Fata Morgana Effect".

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant morbidity and mortality worldwide since its declaration as a global pandemic in March 2020. Alongside the typical respiratory symptoms, unusual clinical manifestations such as oral lichen planus (OLP) have been observed. OLP is a chronic inflammatory mucocutaneous dermatosis that results from a cell-mediated reaction, and its pathogenesis involves the loss of immunological tolerance. OLP has been associated with several triggering factors, such as certain drugs, stress, smoking, and even some viruses. Exposure to the spike protein antigen of SARS-CoV-2 during an infection can trigger autoimmune reactions and lead to the onset or flare of OLP. The E3 protein ligase TRIM21, which is identified in the lamina propria of OLP lesions, is overexpressed in COVID-19 patients and plays a critical role in autoimmune pathologies. Furthermore, the psychological stress of the lockdown and quarantine can be a trigger for the onset or exacerbation of OLP. However, the diagnosis of OLP is complex and requires a biopsy in order to confirm a clinical diagnosis, rule out other pathologies, and establish the most appropriate therapeutic procedure. Further research is needed to understand the potential link between Co-19 and OLP.

Monkeypox: A New Challenge for Global Health System?

The COVID-19 pandemic, starting in 2020, has presented a major challenge in terms of early diagnosis and the subsequent containment and management of severe cases. The spread of viruses such as monkeypox in non-endemic countries is now creating new difficulties for healthcare professionals. Proper case definition and clinical examination are crucial for the early identification of suspected cases. For this reason, we performed a review of the literature in order to report the first signs, which are useful for healthcare providers for early case identification. Since 2022 to date, 86,930 laboratory-confirmed cases and 1051 probable cases have been reported worldwide, and of these, 116 were fatal cases and, for the first time, most of the cases were registered in countries that have not historically reported monkeypox and that lack direct or immediate epidemiological links to areas of West or Central Africa where the disease is endemic. Patients with Monkeypox experience prodromal symptoms, such as fever, fatigue, headache, muscle aches, and a rash after an incubation period of 5-21 days. The disease is usually self-limiting within 2-4 weeks but can lead to complications, such as pneumonia, encephalitis, kidney injury, and myocarditis in children, pregnant individuals, and those with weakened immune systems. The case-fatality ratio is between 1 and 10%. Today, prevention campaigns and the control of human monkeypox are the best weapons to prevent infection and stop transmission. Prevention strategies, such as avoiding contact with sick or dead animals, and the proper preparation of all foods containing animal meat or parts, should be adopted. Furthermore, close contact with infected people or contaminated materials should be avoided to prevent human-to-human transmission.