Digital matching of palatal rugae patterns for forensic identification in edentulous denture wearers.

Identifying edentulous victims in forensic contexts poses a significant challenge. It has been reported that having a denture to reproduce and compare Palatal Rugae (PR) patterns is crucial for identifying edentulous individuals, yet there are no validated protocols for conducting this procedure. In this study, a new method was developed and validated for plaster molding of the internal surface of upper dentures, along with a protocol involving focus-stacked photographs and reference scales. Thirty-eight edentulous subjects participated in the study, obtaining plaster models of the patients (PM), and their dentures (AM) were standardized. The AM/PM model was highlighted and photographed with ten shots in different z-focuses for each model, using standard lighting and aligning the position of the PR perpendicular to the photographic axis using tubular spirit levels and modeling clay. The images were processed using the stacking technique and analyzed by three observers through the proposed protocol using Adobe® Photoshop®. The results were analyzed based on the intra-observer and inter-observer agreement levels, with a 95% confidence interval. This study demonstrated high-precision intra-observer and inter-observer agreement (k = 1) in the matching of Palatal Rugae (PR) and maxillary morphology obtained from participants and their dentures. The protocol is simple, cost-effective, and precise. It enables standardization of the technique for obtaining plaster models, and the exposure of PR and photographic protocol minimizes the presence of artifacts in the images, thereby reducing the likelihood of errors and promoting the reproducibility of both the recording technique and the comparison of the PR.

Artificial Diets with Altered Levels of Sulfur Amino Acids Induce Anticancer Activity in Mice with Metastatic Colon Cancer, Ovarian Cancer and Renal Cell Carcinoma.

Sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricted diets is poorly understood. In this work, we screened the in vivo anticancer activity of several Met-deficient artificial diets supplemented with Cys, Tau or both. Diet B1 (6% casein, 2.5% leucine, 0.2% Cys and 1% lipids) and diet B2B (6% casein, 5% glutamine, 2.5% leucine, 0.2% Tau and 1% lipids) showed the highest activity and were selected for further studies. Both diets induced marked anticancer activity in two animal models of metastatic colon cancer, which were established by injecting CT26.WT murine colon cancer cells in the tail vein or peritoneum of immunocompetent BALB/cAnNRj mice. Diets B1 and B2B also increased survival of mice with disseminated ovarian cancer (intraperitoneal ID8 Tp53-/- cells in C57BL/6JRj mice) and renal cell carcinoma (intraperitoneal Renca cells in BALB/cAnNRj mice). The high activity of diet B1 in mice with metastatic colon cancer may be useful in colon cancer therapy.

Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents-In Vitro Evaluation against Breast Cancer Cells.

Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents.

Undergraduate dental students and their potential role in disaster victim identification procedures: A scoping review under a Chilean perspective.

BACKGROUND: A mass fatality incident is an unexpected event that can cause the death of many people, which has motivated careful analysis and development of appropriate strategies for planning and response with all available resources. As these events involve multiple victims, their identities must be confirmed using the highest possible quality standards. Forensic Odontology (FO) has proven to be a scientific resource for disaster victim identification (DVI) procedures; however, it is highly dependent on the proper management not only of material resources but also of human resources. Chile is a country recognised as prone to natural disasters, but an insufficient number of forensic odontologists has been reported. The aim of the study was to review the literature on a dental undergraduate (UG) student's potential value in a DVI process. METHODOLOGY: A scoping review was performed using a specific search strategy in PubMed/Medline, Web of Science, Scopus, SciELO and EBSCO databases. RESULTS: The search identified 27 articles in which the basic dental degree, the necessary training and the need for human resources are variables considered in different priorities by those articles. DISCUSSION: It is vital to assess the local needs of Chile based on its UGs, considering that FO is an underestimated resource that should be included early on in dental curriculums. Furthermore, it should align with public policies to ensure viability and inclusion in standardised protocols. CONCLUSION: Although there is "potential" usage of UG dental students in DVI is not ideal, circumstances will dictate their use. The better trained they are as students, the more valuable their "potential" contribution will be.

Forensic odontology and dental age estimation research: a scoping review a decade after the NAS report on strengthening forensic science.

Dental age estimation (DAE) is one of the most reliable and useful scientific methods employed by forensic odontology (FO) for human identification. In 2009, the US National Academy of Sciences (NAS) report highlighted the need to deepen research in many disciplines, among which FO received strong criticism for specific expertise. The aim of this review is to provide a comprehensive overview in order to systematically map the latest original research done in FO, as well as identify DAE within this field. A systematic search was performed from 2014 to 2019. In total, 644 studies were identified for qualitative analysis: DAE was the most studied topic (41.30%). Asia was the most productive continent with 58.27% of the global production on DAE; India was the most productive Asian country, with 32.33% and 55.48% of global and Asian production, respectively. The University of Macerata (Italy), KU Leuven (Belgium), University of Split (Croatia), and University of São Paulo (Brazil) led DAE research. Authors from leading countries on DAE research demonstrated great individual productivity, which is evidence of their scientific efforts, but also possible risks if the continuity of this line of research depends on them. Although FO has significantly focused its research on DAE, the absence of publications on controversial topics but necessary for research according to the NAS report shows the possible lack of interest of authors or journals to address them.

Age estimation by evaluation of obliteration of the palatine sutures: a scoping review.

The age estimation (AE) of human remains is a challenging task since it is dependent on the state in which these remains are found. Since the macroscopic evaluation of palatal sutures has been proposed as a method for AE, the aim of this study was to review the literature on this method, considering that the cases of edentulous elderly are among the greatest challenges in anthropological and forensic contexts. A scoping review was performed using a specific search strategy in PubMed, Web of Science, SciELO, LILACS, and Google Scholar. The search identified 13 articles, among which the USA yielded the most information with 3 articles. Only 1 study was identified in Latin America (Peru). There was great diversity regarding the origin of samples, and the studies were carried out on both historical and modern populations. Only 6 articles exceeded the average sample size (168.08) and 4 articles studied samples of fewer than 100 individuals. Although 6 different methods were identified, Mann et al.'s revised method was the most used. The selection of appropriate methods for AE depends on what skeletal elements are present and the general age of the specimens. Although evaluation of the obliteration of the palatal sutures has been found to be simple and promising for AE in individuals over 60 years of age, this method has been reported to have less precision than other more complex methods, which makes the use of a combination of methods necessary to increase the level of confidence and the percentage of success. Further research could resolve this weakness, and methodological refinement (perhaps the digitization and automation of processes, or the application of Bayesian methodology) could provide the necessary solidity to comply with international standards in the forensic scenario.

Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we screened 18 artificial diets for anticancer activity in a challenging animal model of renal cell carcinoma. The model was established by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine, and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential and mechanism of action of this simple and inexpensive anticancer strategy.

Recovery of impregnated hydrocarbon in drill cuttings using supercritical carbon dioxide.

Pollution due to waste generated by the oil industry has led to serious damage to ecosystems and the environment. Therefore, preventive and corrective actions must be taken to mitigate the ecological impact of waste resulting from oil-related activities, to explore and implement environment-friendly approaches, and achieve sustainable development. In this study, an alternative treatment for cuttings generated during the drilling of oil wells was investigated by extracting the hydrocarbons present in such cuttings through the use of carbon dioxide under supercritical conditions. The extractions were performed in a Supercritical Fluid Technologies Inc. Model SFT-150 extractor, under varying pressure (2300-6600 psi) and temperature (52-109 °C), while maintaining constant carbon dioxide flow rate and extraction time, to analyse the effect of these two thermodynamic variables on the extraction efficiency. During supercritical extraction, 21.51 g of total hydrocarbons from drill cuttings (oil/kg) were recovered at 6000 psi and 100 °C. The results indicated that pressure had the strongest effect on the extraction yield, with only a small amount of hydrocarbons recovered at the lowest pressure for all fractions. At <3000 psi pressure, increasing the temperature led to a decrease in the amount of recovered hydrocarbons; at >3000 psi pressure, increasing the temperature led to an increase in the extraction yield.

Early Oligocene chinchilloid caviomorphs from Puerto Rico and the initial rodent colonization of the West Indies.

By their past and present diversity, rodents are among the richest components of Caribbean land mammals. Many of these became extinct recently. Causes of their extirpation, their phylogenetic affinities, the timing of their arrival in the West Indies and their biogeographic history are all ongoing debated issues. Here, we report the discovery of dental remains from Lower Oligocene deposits (ca 29.5 Ma) of Puerto Rico. Their morphology attests to the presence of two distinct species of chinchilloid caviomorphs, closely related to dinomyids in a phylogenetic analysis, and thus of undisputable South American origin. These fossils represent the earliest Caribbean rodents known thus far. They could extend back to 30 Ma the lineages of some recently extinct Caribbean giant rodents (Elasmodontomys and Amblyrhiza), which are also retrieved here as chinchilloids. This new find has substantial biogeographic implications because it demonstrates an early dispersal of land mammals from South America to the West Indies, perhaps via the emergence of the Aves Ridge that occurred ca 35-33 Ma (GAARlandia hypothesis). Considering both this new palaeontological evidence and recent molecular divergence estimates, the natural colonization of the West Indies by rodents probably occurred through multiple and time-staggered dispersal events (chinchilloids, then echimyid octodontoids (spiny rats/hutias), caviids and lastly oryzomyin muroids (rice rats)).

Meroterpenoids from the Brown Alga Cystoseira usneoides as Potential Anti-Inflammatory and Lung Anticancer Agents.

The anti-inflammatory and anticancer properties of eight meroterpenoids isolated from the brown seaweed Cystoseira usneoides have been evaluated. The algal meroterpenoids (AMTs) 1-8 were tested for their inhibitory effects on the production of the pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), and the expression of cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in LPS-stimulated THP-1 human macrophages. The anticancer effects were assessed by cytotoxicity assays against human lung adenocarcinoma A549 cells and normal lung fibroblastic MRC-5 cells, together with flow cytometry analysis of the effects of these AMTs on different phases of the cell cycle. The AMTs 1-8 significantly reduced the production of TNF-α, IL-6, and IL-1ß, and suppressed the COX-2 and iNOS expression, in LPS-stimulated cells (p < 0.05). The AMTs 1-8 displayed higher cytotoxic activities against A549 cancer cells than against MRC-5 normal lung cells. Cell cycle analyses indicated that most of the AMTs caused the arrest of A549 cells at the G2/M and S phases. The AMTs 2 and 5 stand out by combining significant anti-inflammatory and anticancer activities, while 3 and 4 showed interesting selective anticancer effects. These findings suggest that the AMTs produced by C. usneoides may have therapeutic potential in inflammatory diseases and lung cancer.

Cancer etiology: Variation in cancer risk among tissues is poorly explained by the number of gene mutations.

Recent evidence indicates that the risk of being diagnosed with cancer in a tissue is strongly correlated (0.80) with the number of stem cell divisions accumulated by the tissue. Since cell division can generate random mutations during DNA replication, this correlation has been used to propose that cancer is largely caused by the accumulation of unavoidable mutations in driver genes. However, no correlation between the number of gene mutations and cancer risk across tissues has been reported. Because many somatic mutations in cancers originate prior to tumor initiation and the number of cell divisions occurring during tumor growth is similar among tissues, I use whole genome sequencing information from 22 086 cancer samples and incidence data from the largest cancer registry in each continent to study the relationship between the number of gene mutations and the risk of cancer across 33 tissue types. Results show a weak positive correlation (mean = 0.14) between these 2 parameters in each of the 5 cancer registries. The correlation became stronger (mean = 0.50) when gender-related cancers were excluded. Results also show that 1003 samples from 29 cancer types have zero mutations in genes. These data suggest that cancer etiology can be better explained by the accumulation of stem cell divisions than by the accumulation of gene mutations. Possible mechanisms by which the accumulation of cell divisions in stem cells increases the risk of cancer are discussed.

A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin® (EU and US) in healthy male subjects.

AIM: The aim of this study was to compare the pharmacokinetics (PK) of DRL_BZ with that of EU-approved (reference medicinal product; RMP) and US-licensed (reference product; RP) bevacizumab (Avastin® ) in healthy male subjects. METHODS: In this double-blind, parallel-group, Phase 1 study (BZ-01-001), men aged 20-45 years were randomized 1:1:1 to receive a single intravenous infusion of 1 mg kg-1 of bevacizumab as DRL_BZ, RMP or RP. A total of 149 subjects were randomized (DRL_BZ, 50; RMP, 50; RP, 49). Primary endpoints included maximum observed serum concentration (Cmax ), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinity (AUC(0-∞) ), and area under the concentration-time curve from time zero (pre-dose) to last quantifiable concentration (AUC(0-t) ). Secondary objectives were to compare the safety and immunogenicity of DRL_BZ with those of the reference products. RESULTS: Primary PK parameters were comparable across groups, and 90% confidence intervals for the geometric mean ratios of the primary PK endpoints were within the pre-specified equivalence margins (80-125%) for all pairwise comparisons (DRL_BZ vs. RMP, DRL_BZ vs. RP and RMP vs. RP). No deaths or serious adverse events were reported. Similar numbers of subjects reported similar numbers of treatment-emergent adverse events in the three treatment groups. One subject who received DRL_BZ had anti-drug antibodies at the Day 85 visit; however, no anti-drug antibodies were detected in this subject at the 12-month follow-up visit. CONCLUSIONS: PK, safety and immunogenicity of DRL_BZ were comparable to EU-approved and US-licensed bevacizumab in healthy male subjects.

Correction to: Sex estimation of infants through geometric morphometric analysis of the ilium.

After publication of the original article, it was brought to authors' attention two errors that were included in the final publication.

A 30-s exposure to ethanol 20% is cytotoxic to human keratinocytes: possible mechanistic link between alcohol-containing mouthwashes and oral cancer.

OBJECTIVES: To provide mechanistic evidence for the epidemiological link between long-term use of alcohol-containing mouthwashes and oral cancer. MATERIAL AND METHODS: Human epithelial keratinocytes were exposed for 30 s to concentrations of ethanol commonly present in mouthwashes. After a recovery period, cell viability was assessed with the MTT assay. RESULTS: A marked cytotoxic effect was observed for ethanol concentrations of 20% and above. CONCLUSIONS: The cytotoxicity of ethanol may explain the epidemiological association between mouthwash use and oral cancer. Evidence suggests that the risk of developing cancer in a tissue is strongly determined by the number of stem cell divisions accumulated by the tissue during a person's lifetime; cell division is a major source of mutations and other cancer-promoting errors. Since cell death activates the division of stem cells, the possible cytotoxicity of ethanol on the cells lining the oral mucosa will promote the division of the stem cells located in deeper layers to produce new cells to regenerate the damaged epithelium. If we regularly use mouthwashes containing cytotoxic concentrations of ethanol, the stem cells of the oral cavity may need to divide more often than usual and our risk of developing oral cancer may increase. CLINICAL RELEVANCE: Many mouthwashes contain percentages of ethanol above 20%. Because ethanol is not crucial to prevent and reduce gingivitis and plaque, members of the dental team should consider the potential risk of oral cancer associated with frequent use of alcohol-containing mouthwashes when advising their patients.

Selective cytotoxic activity and DNA damage by an epoxyalkyl galactopyranoside.

Preclinical Research & Development Several clinically useful anticancer drugs selectively kill cancer cells by inducing DNA damage; the genomic instability and DNA repair defects of cancer cells make them more vulnerable than normal cells to the cytotoxicity of DNA-damaging agents. Because epoxide-containing compounds can induce DNA damage, we have used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate the selective cytotoxicity of three epoxyalkyl galactopyranosides against A549 lung cancer cells and MRC-5 lung normal cells. Compound (2S,3S)-2,3-epoxydecyl 4,6-O-(S)-benzylidene-ß-d-galactopyranoside (EDBGP) showed the highest selective anticancer activity and was selected for mechanistic studies. After observing that EDBGP induced cellular DNA damage (comet assay), we found that cells deficient in nucleotide excision repair were hypersensitive to the cytotoxicity of this compound; this suggests that EDBGP may induce bulky DNA adducts. EDBGP did not inhibit glycolysis (glucose consumption and lactate production). Pretreatment of lung cancer cells with several antioxidants did not reduce the cytotoxicity of EDBGP, thereby indicating that reactive oxygen species do not participate in the anticancer activity of this compound. Finally, EDBGP was screened against a panel of cancer cells and normal cells from several tissues, including three genetically modified skin fibroblasts with increasing degree of malignancy. Our results suggest that epoxyalkyl galactopyranosides are promising lead compounds for the development of new anticancer agents.

Sex estimation of infants through geometric morphometric analysis of the ilium.

In archeology or forensics, the analysis of the ilia is often used to determine the age and sex of unknown individuals. However, sex determination using the skeletal remains of individuals who did not develop secondary sexual characteristics remains controversial. Accurately estimating the sex of subadults is hampered by a small number of studies based on identified skeletal collections of juvenile individuals. Here, we analyzed the sexual dimorphism of the subadult ilia using geometric morphometric techniques and individuals from the osteological collection of identified subadults from San José's graveyard (Granada). Seventy-one left ilia from 40 males and 31 females aged between birth and 1 year were included in the analysis. Three landmarks and 27 semi-landmarks of the ilia were placed. By principal component analysis, we found that the size and shape of the ilia could be used to differentiate males and females.

A novel tetravalent formulation combining the four aggregated domain III-capsid proteins from dengue viruses induces a functional immune response in mice and monkeys.

Our group developed a subunit vaccine candidate against dengue virus based on two different viral regions: the domain III of the envelope protein and the capsid protein. The novel chimeric protein from dengue-2 virus [domain III-capsid (DIIIC-2)], when presented as aggregated incorporating oligodeoxynucleotides, induced anti-viral and neutralizing antibodies, a cellular immune response and conferred significant protection to mice and monkeys. The remaining constructs were already obtained and properly characterized. Based on this evidence, this work was aimed at assessing the immune response in mice of the chimeric proteins DIIIC of each serotype, as monovalent and tetravalent formulations. Here, we demonstrated the immunogenicity of each protein in terms of humoral and cell-mediated immunity, without antigen competition on the mixture forming the formulation tetra DIIIC. Accordingly, significant protection was afforded as measured by the limited viral load in the mouse encephalitis model. The assessment of the tetravalent formulation in non-human primates was also conducted. In this animal model, it was demonstrated that the formulation induced neutralizing antibodies and memory cell-mediated immune response with IFN-γ-secreting and cytotoxic capacity, regardless the route of immunization used. Taken together, we can assert that the tetravalent formulation of DIIIC proteins constitutes a promising vaccine candidate against dengue virus, and propose it for further efficacy experiments in monkeys or in the dengue human infection model, as it has been recently proposed.

The PARP inhibitor Olaparib disrupts base excision repair of 5-aza-2'-deoxycytidine lesions.

Decitabine (5-aza-2'-deoxycytidine, 5-azadC) is used in the treatment of Myelodysplatic syndrome (MDS) and Acute Myeloid Leukemia (AML). Its mechanism of action is thought to involve reactivation of genes implicated in differentiation and transformation, as well as induction of DNA damage by trapping DNA methyltranferases (DNMT) to DNA. We demonstrate for the first time that base excision repair (BER) recognizes 5-azadC-induced lesions in DNA and mediates repair. We find that BER (XRCC1) deficient cells are sensitive to 5-azadC and display an increased amount of DNA single- and double-strand breaks. The XRCC1 protein co-localizes with DNMT1 foci after 5-azadC treatment, suggesting a novel and specific role of XRCC1 in the repair of trapped DNMT1. 5-azadC-induced DNMT foci persist in XRCC1 defective cells, demonstrating a role for XRCC1 in repair of 5-azadC-induced DNA lesions. Poly (ADP-ribose) polymerase (PARP) inhibition prevents XRCC1 relocation to DNA damage sites, disrupts XRCC1-DNMT1 co-localization and thereby efficient BER. In a panel of AML cell lines, combining 5-azadC and Olaparib cause synthetic lethality. These data suggest that PARP inhibitors can be used in combination with 5-azadC to improve treatment of MDS and AML.

Alterations of skull bones found in anencephalic skeletons from an identified osteological collection. Two case reports.

One of the most common conditions during fetal development is anencephaly, which often involves many identification difficulties in the context of physical anthropology, as it causes severe skull challenges. In this paper, we describe the alterations found in the skulls of two perinatal individuals with anencephaly from the osteological collection of identified infants in the Anthropology Laboratory of the University of Granada, Spain. Both subjects of study are in perfect state of preservation. Despite the severe malformations, all skull bones have been targeted and identified, as the possibility of studying a subject with a complete, articulated, and partially mummified skull; the other was disjointed and well preserved. The skull bones of these two individuals affected with anencephaly have been described in detail, allowing this pathological condition to be identified in skeletonized individuals in archaeological or forensic contexts, in cases where these bones did not have anatomical connection or when these were taphonomically altered.