Serum Extracellular Vesicles Cargo Approach in Bitches with Mammary Tumors.

This study investigated serum extracellular vesicles (EVs) in bitches with mammary neoplasms, in order to understand their size, shape, and concentration, as well as their association with tumor malignancy. Thirty bitches were categorized into control (n = 10), mammary tumor grades I and II (GI, n = 13), and grade III (GII, n = 7). Serum was separated from blood collected during mastectomy, and EVs were isolated using size exclusion chromatography. The analysis revealed no significant differences in EV concentrations among groups, with similar concentrations for control, GI, and GII. Ninety-one proteins were identified in EV-enriched samples, with six showing varied abundance across groups. Notably, keratin 18 was highly abundant in GI, while sushi domain-containing protein, EvC ciliary subunit 2, and the joining chain of multimeric IgM and IgA were increased in GII. Additionally, protocadherin 17 and albumin were upregulated in both GI and GII. ROC curves identified potential biomarkers for differentiating tumor grades. Enrichment pathway analysis revealed AFP gene upregulation in the GI. Mass spectrometry proteomics data were deposited in Mendeley Data. The study provides valuable insights into serum EV characterization in bitches, suggesting keratin 18 and protocadherin 17 as potential biomarkers for canine mammary neoplasia, with implications for future diagnostic and therapeutic strategies.

Bioactivity of hydroalcoholic extracts from tropaeolum majus L. (tropaeolaceae) on the germination, initial plant development and cell cycle of Lactuca sativa L.

Natural products are usually considered harmless; however, these substances need to be consumed with caution. Biological assays with plant models are a suitable alternative for prospective studies to assess natural product-initiated toxicity. The aim of this study was to examine the toxic potential of leaf and flower extracts derived from Tropaeolum majus L. a widely used plant in traditional medicine. Seeds of Lactuca sativa L. were exposed to T. majus extracts and based upon the seedling growth curve values, the 50% Inhibition Concentration (IC50) was calculated and applied for cell cycle analysis exposure. Both extracts contained organic acids, proteins, amino acids, and terpene steroids. Sesquiterpene lactones and depside were detected in leaf extracts. The higher concentration tested exhibited a marked phytotoxic effect. The extracts induced clastogenic, aneugenic cytotoxic, and potential mutagenic effects. The possible relationships between the classes of compounds found in the extracts and effects on cells and DNA were determined.

Neonatal upper limb fractures - a narrative overview of the literature.

The aim of this paper is to review the topic of neonatal fractures of the upper limb, describing the different types of fractures focusing on the etiology, epidemiology, risk factors, clinical approach, diagnosis, treatment and prognosis of these injuries. We included all types of research studies, both experimental and observational, published in English, French, Portuguese and Spanish. The information was obtained using the keywords neonatal upper limb fracture, clavicle fracture or humerus fracture from the following resources: MEDLINE database, Embase® database and LILACS database. Other resources such as hand searches of the references of retrieved literature and authoritative texts, personal and hospital libraries searching for texts on upper limb neonatal fractures, discussions with experts in the field of upper limb neonatal fractures and personal experience, were also considered for the completion of the article.Neonatal fractures of the upper limb are consensually considered to have a good prognosis and no long-term sequelae. Conservative treatment is the option in the vast majority of the fractures and is associated with excellent results, with good healing, full range of motion, adequate remodeling without obvious deformity, neurologic impairment or functional implications.

Chromosome diversity in Buthidae and Chactidae scorpions from Brazilian fauna: Diploid number and distribution of repetitive DNA sequences.

In this work, we analyzed cytogenetically eight Chactidae and Buthidae, including the localization of repetitive DNA sequences. The chactids possess monocentric chromosomes and the highest diploid numbers (2n=50 in Brotheas amazonicus, 2n=36 in Chactopsis amazonica, 2n=30 in Neochactas sp.) when compared with buthids (2n=10 in Tityus bahiensis, 2n=14 in Tityus apiacas and Tityus metuendus, 2n=18 in Tityus aba, 2n=26 in Ischnotelson peruassu). The localization of rDNA genes and (TTAGG)n sequences exhibited a conserved pattern of two terminal/subterminal ribosomal cistrons and terminal telomere signals. However, the comparison between the data of C-banding, DAPI after FISH and Cot-DNA fraction indicated a variable quantity and distribution of these regions, as follow: (i) positive heterochromatin and Cot-DNA signals (B. amazonicus and I. peruassu), (ii) small blocks of heterochromatin with large Cot-DNA signals (T. metuendus), (iii) positive heterochromatic regions and absence of Cot-DNA signals (T. aba and T. apiacas), and (iv) negative heterochromatin and Cot-DNA signals (T. bahiensis). Therefore, our results revealed that there still is not a clear relation between quantity of heterochromatin and presence of monocentric or holocentric chromosomes and occurrence of chromosomal rearrangements, indicating that repetitive regions in scorpions must be analyzed using different cytogenetic approaches.

Th22 cytokines and yellow fever: Possible implications for the immunopathogenesis of human liver infection.

Yellow fever (YF) is an infectious disease considered a public health problem in tropical and subtropical areas. YF has many pathophysiological events that are correlated with the host immune response. In this study, the in situ Th22 cytokine profile was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died of the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical (IHC) analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of interleukin (IL)-22, IL-13, tumour necrosis factor-alpha, and FGF basic (FGF b) in YFV-positive cases than that in flavivirus-negative controls. These results indicate that the response of Th22 cytokines emerges as an alternative for a better understanding of adaptive immunity in the hepatic parenchyma, highlighting the role of cytokines in the repair and suppressive responses in the immunopathogenesis of YFV infection.

Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett's esophagus.

PURPOSE: The incidence of esophageal adenocarcinoma (EAC) has been increasing for decades without significant improvements in treatment. Barrett's esophagus (BE) is best established risk factor for EAC, but current surveillance with random biopsies cannot predict progression to cancer in most BE patients due to the low sensitivity and specificity of high-definition white light endoscopy. METHODS: Here, we evaluated the membrane-bound highly specific Hsp70-specific contrast agent Tumor-Penetrating Peptide (Hsp70-TPP) in guided fluorescence molecular endoscopy biopsy. RESULTS: Hsp70 was significantly overexpressed as determined by IHC in dysplasia and EAC compared with non-dysplastic BE in patient samples (n = 12) and in high-grade dysplastic lesions in a transgenic (L2-IL1b) mouse model of BE. In time-lapse microscopy, Hsp70-TPP was rapidly taken up and internalized  by human BE dysplastic patient-derived organoids. Flexible fluorescence endoscopy of the BE mouse model allowed a specific detection of Hsp70-TPP-Cy5.5 that corresponded closely with the degree of dysplasia but not BE. Ex vivo application of Hsp70-TPP-Cy5.5 to freshly resected whole human EAC specimens revealed a high (> 4) tumor-to-background ratio and a specific detection of previously undetected tumor infiltrations. CONCLUSION: In summary, these findings suggest that Hsp70-targeted imaging using fluorescently labeled TPP peptide may improve tumor surveillance in BE patients.

Effects of Obesity and Diabetes on Sperm Cell Proteomics in Rats.

Infertility caused by male factors is potentially associated with metabolic disorders such as obesity and/or diabetes. This experimental study was conducted in a male rodent model to assess the effects of different diseases on semen quality and sperm proteomics. Ten Wistar rats were used for each treatment. Rats were fed commercial food provided controllably to the control group and the diabetic group, and a hypercaloric diet supplemented with 5% sucrose in water was provided ad libitum to the obese group for 38 weeks. Diabetes was induced with 35 mg/kg streptozotocin. After euthanasia, testicles, spermatozoa, fat, and blood (serum) samples were collected. Spermatozoa were evaluated for quality and subjected to proteomics analyses. Histology and cytology of the testis, and serum leptin, adiponectin, interleukin 8 (IL-8), blood glucose, and testosterone levels, were also assessed. Body weight, retroperitoneal and testicular fat, and the Lee index were also measured. Obesity and diabetes were induced. The diabetic group showed noticeable changes in spermatogenesis and sperm quality. The mass spectrometry proteomics data have been deposited in Mendeley Data (doi: 10.17632/rfp7kfjcsd.5). Fifteen proteins varied in abundance between groups, especially proteins related to energy production and structural function of the spermatozoa, suggesting disturbances in energy production with a subsequent alteration in sperm motility in both groups, but with a compensatory response in the obese group.

Evaluation of radiological instability signs in the distal radioulnar joint in children and adolescents with arthroscopically-verified TFCC tears.

INTRODUCTION: Recent reports in the adult literature reported the use of standardized radiographic measurement techniques to determine distal radioulnar joint (DRUJ) instability. The aim of this study was to evaluate the efficacy and accuracy of (1) the MRI-based modified radioulnar ratio technique and (2) the pisoscaphoid (PiSca) and radioulnar (RaUl) distances in true lateral radiographs in children and adolescents with arthroscopically-verified TFCC tears. MATERIALS AND METHODS: We retrospectively assessed lateral wrist radiographs and axial MRI sequences of 18 adolescent patients (22 wrists) who had arthroscopically-confirmed TFCC tears and compared them to similar imaging of a control group of 28 healthy patients (28 wrists). Three raters assessed the images twice in a 2-week interval. Intraclass correlation coefficients (ICCs), unifactorial ANOVA, and ROC analysis were performed with regards to the different radiographic variables. RESULTS: The interrater ICCs were almost perfect for all measurements except RaUl1, which showed a substantial agreement (0.751) among the three observers. The intrarater ICCs were almost perfect when measuring PiSca and MRI, and substantial to almost perfect for RaUl. Pearson's correlation showed a moderate, positive correlation between PiSca and RaUl distances (r = 0.608; p < 0.001), and a moderate, negative correlation between RaUl distance and MRI shift (r = - 0.486; p = 0.010). When the three core groups (peripheral, central tear, controls) were compared to each other regarding the radiographic instability parameters, only the MRI shift revealed a statistically significant difference (p = 0.003). Comparisons revealed significant differences between patients and controls (p = 0.004) and peripheral tears vs. controls (p = 0.001 and p = 0.010). The ROC analysis revealed a significant AUC only for the MRI (AuC 0.787 and p = 0.002). CONCLUSIONS: Children and adolescents with peripheral TFCC tears showed significantly increased instability parameters in MRI compared to controls. These measurement techniques are no replacement for a thorough clinical examination but may be helpful for indicating diagnostic wrist arthroscopy in ambiguous cases. LEVEL OF EVIDENCE: Level III; Diagnostic.

Physiological responses and thermal equilibrium of Jersey dairy cows in tropical environment.

Long-term assessments of thermal responses of housed Jersey cows raised in tropical conditions were performed to investigate the effect of climate environment on their physiological performance and thermal equilibrium. Twelve Jersey dairy cows with 326.28 ± 30 kg of body weight, 17.66 ± 1.8 of milk yield, and 165.5 ± 6.8 of days in milking were assigned in two 12 × 12 Latin square designs. Air temperature, relative humidity, partial vapor pressure, direct and diffuse short-wave solar radiation and black globe temperature under the shade, and direct sunlight were recorded. Physiological responses as respiratory rate (RR, breaths min-1), ventilation (VE, L s-1), proportion (%) of oxygen (O2) and carbon dioxide (CO2), saturation pressure (PS{TEXH}), and air temperature (TEXH, °C) of the exhaled air were assessed protected from solar radiation and rain. Rectal temperature (TR, °C), skin temperature (TEP, °C), and hair coat surface temperature (TS, °C) were also recorded. The thermal equilibrium was determined from biophysical equations according to the principles of the energy conservation law in a control volume. Exploratory and confirmatory analyses were performed from principal components and by the least square method, respectively. The cows were evaluated under range of ambient air temperature from 26 to 35 °C, relative humidity from 27 to 89%, and short-wave radiation from 0 to 729 W m-2. Exploratory and confirmatory analyses demonstrated that a similar level of nocturnal and diurnal air temperatures evoked distinct (P < 0.05) responses for rectal (TR, °C) and skin (TEP, °C) temperatures, ventilation (VE, L s-1), tidal volume (TV, L breaths-1), and oxygen consumption (∆O2, %) and carbon dioxide output (∆CO2, %), clearly revealing an endogenous rhythm dependence. In conclusion, these findings clarify how the circadian rhythmicity of the thermal environment and animal's biological clock dictate dynamics of heat generated by metabolism, dissipated to the environment and physiological parameters of the housed Jersey cows raised in tropical condition; therefore, it is fundamental to help us to understand how the Jersey dairy cows under tropics are affected by the climatic conditions, leading to better ways of the environmental management.

Short-term aging and the dentin bond strength of adhesive systems.

The aim of this study was to compare the effects of 2 aging methods on the dentin bond strength of different adhesive systems, including a universal adhesive. Seventy-two third molars were sectioned to create flat midcoronal dentin surfaces, which were randomly assigned to 12 groups (n = 6 each) according to the aging method (conventional aging, defined as 6 months of water storage; accelerated aging by means of a pH-cycling method; or negative control [immediate bond strength]) and adhesive system (Adper Single Bond 2, Clearfil SE Bond, Prime & Bond 2.1, or Scotchbond Universal). Composite resin blocks were constructed on the flattened dentin surfaces after application of the appropriate adhesive, and the specimens were stored in water for 24 hours. Specimens from the control group were immediately sectioned into resin-dentin sticks (0.8 mm2) and subjected to a microtensile bond strength test. Specimens from the experimental groups were sectioned and tested after undergoing the assigned aging method. Data were analyzed with 2-way analysis of variance and a Tukey test (α = 0.05). The study findings showed that neither aging method significantly affected the dentin bond strength (P = 0.917). Of the 4 adhesives, Adper Single Bond 2 had the highest bond strength value after aging (P < 0.001). Scotchbond Universal adhesive demonstrated statistically significantly higher bond strength values than Clearfil SE Bond and Prime & Bond 2.1, which had statistically similar values. Adhesive failures at the resin-dentin interface or adhesive failures mixed with cohesive failure of the adjacent substrate predominated in all groups. The 2 aging processes did not result in degradation of the adhesive interface or jeopardize the dentin bond strength of any of the adhesives tested.

Endodontic Irrigation Protocols: Effects on Bonding of Adhesive Systems to Coronal Enamel and Dentin.

OBJECTIVE:  To evaluate the influence of endodontic irrigation protocols on bond strength of total-etch and self-etch adhesive systems to coronal enamel and dentin. MATERIALS AND METHODS:  A total of 66 coronal slices from 11 permanent molars were assigned to six groups (n = 11): endodontic irrigation protocols (5% sodium hypochlorite + 17% EDTA; 2% chlorhexidine gel + saline solution + 17% EDTA or no solution - control) and adhesive systems (Adper Single Bond 2 or Clearfil SE Bond). Dental slices were exposed to endodontic irrigation protocols for 30-minute prior to the application of the adhesive systems. Starch tubes were placed over the enamel and the dentin surfaces of each slice (2-4 tubes in each substrate) and filled with Filtek Z350 XT (3M ESPE) to build the microshear bond strength (µSBS) specimens (0.72 mm2 sectional area). After 24 hours of water storage (37°C), µSBS test was performed. Bond strength data (MPa) were analyzed by two-way ANOVA, separately for enamel and dentin (α = 0.05). RESULTS:  µSBS means were not influenced by endodontic irrigation protocols in enamel (p = 0.12) nor dentin (p = 0.49). Clearfil SE Bond system presented higher µSBS values than Adper Single Bond 2 both on enamel (p = 0.024) and dentin (p = 0.005). CONCLUSION:  Endodontic irrigation protocols (5% sodium hypochlorite or 2% chlorhexidine gel + saline solution combined with 17% EDTA) do not jeopardize the bond strength of adhesive systems to coronal enamel and dentin. CLINICAL SIGNIFICANCE: The results of this in vitro study suggest that endodontic irrigation protocols do not impair on bonding effectiveness of adhesive systems to coronal enamel and dentin. (J Esthet Restor Dent 29:222-228, 2017).

The genome of Anopheles darlingi, the main neotropical malaria vector.

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vector-human and vector-parasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles-darlingi.

Seasonal variation in the populations of Polyphagotarsonemus latus and Tetranychus bastosi in physic nut (Jatropha curcas) plantations.

Studies on the seasonal variation of agricultural pest species are important for the establishment of integrated pest control programs. The seasonality of pest attacks on crops is affected by biotic and abiotic factors, for example, climate and natural enemies. Besides that, characteristics of the host plant, crop management, location and the pests' bioecology also affect this seasonality. The mites Polyphagotarsonemus latus (Prostigmata: Tarsonemidae) and Tetranychus bastosi (Prostigmata: Tetranychidae) are the most important pests in the cultivation of physic nut, Jatropha curcas (Euphorbiaceae). All parts of J. curcas can be used for a wide range of purposes. In addition many researchers have studied its potential for use as neat oil, as transesterified oil (biodiesel), or as a blend with diesel. However studies about physic nut pests have been little known. The objective of this study was to assess the seasonal variation of P. latus and T. bastosi in physic nut. This study was conducted at three sites in the state of Tocantins, Brazil. We monitored climatic elements and the densities of the two mite species and of their natural enemies for a period of 2 years. Attack by P. latus occurred during rainy seasons, when the photoperiod was short and the physic nut had new leaves. In contrast, attack by T. bastosi occurred during warmer seasons with longer photoperiods and stronger winds. Populations of both mites and their natural enemies were greater in sites with greater plant diversity adjacent to the plantations. The predators found in association with P. latus and T. bastosi were Euseius concordis (Acari: Phytoseiidae), spiders, Stethorus sp. (Coleoptera: Coccinellidae) and Chrysoperla sp. (Neuroptera: Chrysopidae).

Human papillomavirus (HPV) 16 and the prognosis of head and neck cancer in a geographical region with a low prevalence of HPV infection.

BACKGROUND: The role of human papillomavirus (HPV) on head and neck squamous cell carcinoma (HNSCC) survival in regions with low HPV prevalence is not yet clear. We evaluated the HPV16 infection on survival of HNSCC Brazilian patient series. METHODS: This cohort comprised 1,093 HNSCC cases recruited from 1998 to 2008 in four Brazilian cities and followed up until June 2009. HPV16 antibodies were analyzed by multiplex Luminex assay. In a subset of 398 fresh frozen or paraffin blocks of HNSCC specimens, we analyzed for HPV16 DNA by L1 generic primer polymerase chain reaction. HNSCC survival according to HPV16 antibodies was evaluated through Kaplan-Meier method and Cox regression. RESULTS: Prevalence of HPV16 E6 and E6/E7 antibodies was higher in oropharyngeal cancer than in other head and neck tumor sites. HPV16 DNA positive in tumor tissue was also higher in the oropharynx. Seropositivity for HPV16 E6 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer. The presence of HPV16 E6/E7 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer survival. The death risk of oropharyngeal squamous cell carcinoma patients HPV16 E6/E7 antibodies positive was 78 % lower than to those who test negative. CONCLUSION: Oropharyngeal squamous cell carcinoma is less aggressive in the HPV16 E6/E7 positive serology patients. HPV16 E6/E7 antibody is a clinically sensible surrogate prognostic marker of oropharyngeal squamous cell carcinoma.

Trigger Thumb, Trigger Finger and Clasped Thumb.

Finger deformities are a common reason for medical observation in children. Subtle clinical differences can have a significant impact on the diagnosis and treatment of these patients. Identification of the basic diagnostic and treatment principles of trigger thumb, trigger finger, and clasped thumb is of paramount importance to all general practitioners, pediatricians, and orthopedic surgeons who are involved in the care of children. The purpose of this article is to review the most important concepts regarding these important topics, focusing on etiology, epidemiology, clinical presentation, diagnosis, treatment and prognosis.

Trigger thumb treatment approach: Results of a survey of EPOS members.

Purpose: The aim of this study is to analyze the clinical reality of pediatric trigger thumb among members of the European Paediatric Orthopaedic Society. Methods: A 35-question survey was sent to all European Paediatric Orthopaedic Society members, focusing on surgeon's profile and experience, trigger thumb diagnostic and trigger thumb treatment approach. Descriptive statistics were performed. Results: A total of 99 responses were analyzed. Most important factor considered in the therapeutic approach was the presence of a locked interphalangeal joint (52%). Regarding treatment, 41.4% opt for conservative approach as the first line of treatment, while 30.3% consider surgery and 28.3% just observe. Nevertheless, 76% mention to treat conservatively their patients and 99% to consider surgery at some stage. Regarding surgical technique, 96% do it open and 56% consider 2 years as the minimum age for procedure. Most surgeons perform this procedure in out-patient care (87%), don't administer prophylactic antibiotherapy (80%), use a tourniquet (75%), don't use any postoperative immobilization (64%), and report complications related to surgery (64%), mainly recurrence/incomplete division (59%) and superficial wound infection (30%). Conclusion: Our study shows a significant variability in the initial management of pediatric trigger thumb with a predominance of conservative management, followed by surgery and observation without treatment. The disparity in treatment options and timing, or waiting times before moving on to different therapeutic options, shows us that this is a controversial issue and that the development of prospective randomized controlled studies is needed to analyze the different treatment methods and determine which ones give the best outcomes.

Ray resection in pediatric population after trauma injuries.

The aim of this study is to assess the functional, emotional, and social adaptation of pediatric patients submitted to a hand ray resection to treat a traumatic hand injury. Retrospective study of pediatric patients undergoing hand ray resection, in the period 2013-2022, performed in two hospital institutions. Inclusion criteria: age less than 18 years, primary/secondary resection due to traumatic etiology and follow-up time of more than 1 year. Data concerning demographic information, lesion location, traumatic mechanism and surgical description were collected. Functional outcomes (QuickDASH Score), social and emotional integration (PEDSQL) and satisfaction were evaluated. Seven patients were included, with male predominance (n = 4) and the right side was the most affected (n = 5). Median age at the time of surgery was 10 years (2-15). Primary ray resection, without previous revascularization, was performed in three patients. Secondary ray resection was performed in four patients. Three patients with an unsuccessful revascularization procedure attempt another patient with a sequela with severe deformity. All patients presented a good adaptation to daily living activities, with good pinch and grip function. The median follow-up was 4 years (min:1; max:9). The scores were collected on six out of seven patients. Median QuickDASH score of 14 (min:11; max:22), and PEDSQL[physical] of 95.31 (min:78.13; max:100) and PEDSQL[social] of 93.47 (min:66.3; max:100). Hand ray resection is a rare procedure in pediatric age and usually difficult for patients and parents to accept. However, it is a useful and safe technique that allows for an improvement in overall hand function and psychosocial readaptation in specific and selected cases. Level of evidence: Level of evidence IV - case series.

PARP1-targeted fluorescence molecular endoscopy as novel tool for early detection of esophageal dysplasia and adenocarcinoma.

BACKGROUND: Esophageal cancer is one of the 10 most common cancers worldwide and its incidence is dramatically increasing. Despite some improvements, the current surveillance protocol with white light endoscopy and random untargeted biopsies collection (Seattle protocol) fails to diagnose dysplastic and cancerous lesions in up to 50% of patients. Therefore, new endoscopic imaging technologies in combination with tumor-specific molecular probes are needed to improve early detection. Herein, we investigated the use of the fluorescent Poly (ADP-ribose) Polymerase 1 (PARP1)-inhibitor PARPi-FL for early detection of dysplastic lesions in patient-derived organoids and transgenic mouse models, which closely mimic the transformation from non-malignant Barrett's Esophagus (BE) to invasive esophageal adenocarcinoma (EAC). METHODS: We determined PARP1 expression via immunohistochemistry (IHC) in human biospecimens and mouse tissues. We also assessed PARPi-FL uptake in patient- and mouse-derived organoids. Following intravenous injection of 75 nmol PARPi-FL/mouse in L2-IL1B (n = 4) and L2-IL1B/IL8Tg mice (n = 12), we conducted fluorescence molecular endoscopy (FME) and/or imaged whole excised stomachs to assess PARPi-FL accumulation in dysplastic lesions. L2-IL1B/IL8Tg mice (n = 3) and wild-type (WT) mice (n = 2) without PARPi-FL injection served as controls. The imaging results were validated by confocal microscopy and IHC of excised tissues. RESULTS: IHC on patient and murine tissue revealed similar patterns of increasing PARP1 expression in presence of dysplasia and cancer. In human and murine organoids, PARPi-FL localized to PARP1-expressing epithelial cell nuclei after 10 min of incubation. Injection of PARPi-FL in transgenic mouse models of BE resulted in the successful detection of lesions via FME, with a mean target-to-background ratio > 2 independently from the disease stage. The localization of PARPi-FL in the lesions was confirmed by imaging of the excised stomachs and confocal microscopy. Without PARPi-FL injection, identification of lesions via FME in transgenic mice was not possible. CONCLUSION: PARPi-FL imaging is a promising approach for clinically needed improved detection of dysplastic and malignant EAC lesions in patients with BE. Since PARPi-FL is currently evaluated in a phase 2 clinical trial for oral cancer detection after topical application, clinical translation for early detection of dysplasia and EAC in BE patients via FME screening appears feasible.

Poor oral health influences head and neck cancer patient survival: an International Head and Neck Cancer Epidemiology Consortium pooled analysis.

BACKGROUND: Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. METHODS: Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations between measures of oral health and overall survival. RESULTS: Remaining natural teeth (10-19 teeth: RR = 0.81, 95% confidence interval [CI] = 0.69 to 0.95; ≥20 teeth: RR = 0.88, 95% CI = 0.78 to 0.99) and frequent dental visits (>5 visits: RR = 0.77, 95% CI = 0.66 to 0.91) were associated with better overall survival. The inverse association with natural teeth was most pronounced among patients with hypopharyngeal and/or laryngeal, and not otherwise specified head and neck squamous cell carcinoma. The association with dental visits was most pronounced among patients with oropharyngeal head and neck squamous cell carcinoma. Patient-reported gingival bleeding, tooth brushing, and report of ever use of mouthwash were not associated with overall survival. CONCLUSIONS: Good oral health as defined by maintenance of the natural dentition and frequent dental visits appears to be associated with improved overall survival among head and neck squamous cell carcinoma patients.