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Abstract Background Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. Methods We will carry out this trial with our team’s established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. Discussion Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).

Abstract Background The COVID-19 pandemic caused societal disruption in the United States and most of the world, affecting many aspects of life, including healthcare and health-related behaviors such as diet, food security, and physical activity. Communities with economic and health disparities may have been particularly affected. This study was undertaken to determine how conditions in the early pandemic (January, 2021–February, 2022) affected Latino patients of Mexican Ancestry at high risk of type 2 diabetes mellitus who participated in El Banco por Salud biobank project in Tucson, Arizona. Methods Baseline, prepandemic measurements were available in 17, 21, and 60 patients with normal hemoglobin A1c (HbA1c), prediabetes, and type 2 diabetes, respectively. Results People with healthy HbA1c were significantly younger, less obese, and had higher HDL cholesterol. HbA1c was unaffected by the pandemic in any group. Triglycerides, total and HDL cholesterol levels fell in all groups during the pandemic. Physical activity levels in all groups were remarkably low, with most reporting no engagement in any voluntary physical activity. Engagement in physical activity or its enjoyment was lower in patients with diabetes and prediabetes than in younger, less obese patients. Major diet differences were between men and women and were present before the pandemic. Women consumed significantly more vegetables, fruit, and salad than men. The only pandemic-related change in diet was a drop in egg consumption, possibly explaining the fall in total cholesterol. Conclusion Societal disruption during the COVID-19 pandemic had minimal effects on adverse health-related behaviors, cardiometabolic risk, or changes in glycemic control in a Latino community with diabetes and healthcare disparities in the Southwest US.

Abstract Background The clinical significance of single cell invasion and large nuclear diameter is not well documented in early-stage oral tongue squamous cell carcinoma (OTSCC). Methods We used hematoxylin and eosin-stained sections to evaluate the presence of single cell invasion and large nuclei in a multicenter cohort of 311 cases treated for early-stage OTSCC. Results Single cell invasion was associated in multivariable analysis with poor disease-specific survival (DSS) with a hazard ratio (HR) of 2.089 (95% CI 1.224–3.566, P = 0.007), as well as with disease-free survival (DFS) with a HR of 1.666 (95% CI 1.080–2.571, P = 0.021). Furthermore, large nuclei were associated with worse DSS (HR 2.070, 95% CI 1.216–3.523, P = 0.007) and with DFS in multivariable analysis (HR 1.645, 95% CI 1.067–2.538, P = 0.024). Conclusion Single cell invasion and large nuclei can be utilized for classifying early OTSCC into risk groups.

Abstract Background This study evaluated if genetic variations in the WNT family members and RUNX2 are associated with craniofacial maturation, investigating dental and skeletal maturity in children and teenagers. Methods Radiographs from pre-orthodontic treatment of Brazilian patients (7 to 17 years-old) were used to assess dental (panoramic radiographs) and skeletal maturity (cephalometric radiographs). The chronological age (CA) was calculated based on the date of birth and the time the radiographs were performed. For the dental maturity analysis, the Demirjian (1973) method was used and a delta [dental age - chronological age (DA-CA)] was calculated. For the skeletal maturity analysis, the Baccetti et al. (2005) method was used and the patients were classified as “delayed skeletal maturation”, “advanced skeletal maturation” or “normal skeletal maturation”. DNA isolated from buccal cells was used for genotyping of two genetic variations in WNT family genes: rs708111 (G > A) in WNT3A and rs1533767 (G > A) in WNT11; and two genetic variations in RUNX2: rs1200425 (G > A) and rs59983488 (G > T). A statistical analysis was performed and values of p 0.05). In the skeletal maturity analysis, the allele A in the rs708111 (WNT3A) was statistically more frequent in patients with delayed skeletal maturation (Prevalence Ratio = 1.6; 95% Confidence Interval = 1.00 to 2.54; p-value = 0.042). Conclusions The rs708111 in the WNT3A gene impacts on skeletal maturation.

Abstract The CIAO Study (“Complicated Intra-Abdominal infection Observational” Study) is a multicenter investigation performed in 68 medical institutions throughout Europe over the course of a 6-month observational period (January-June 2012). Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 2,152 patients with a mean age of 53.8 years (range: 4–98 years) were enrolled in the study. 46.3% of the patients were women and 53.7% were men. Intraperitoneal specimens were collected from 62.2% of the enrolled patients, and from these samples, a variety of microorganisms were collectively identified. The overall mortality rate was 7.5% (163/2.152). According to multivariate analysis of the compiled data, several criteria were found to be independent variables predictive of patient mortality, including patient age, the presence of an intestinal non-appendicular source of infection (colonic non-diverticular perforation, complicated diverticulitis, small bowel perforation), a delayed initial intervention (a delay exceeding 24 hours), sepsis and septic shock in the immediate post-operative period, and ICU admission. Given the sweeping geographical distribution of the participating medical centers, the CIAO Study gives an accurate description of the epidemiological, clinical, microbiological, and treatment profiles of complicated intra-abdominal infections (IAIs) throughout Europe.

Abstract The CIAO Study is a multicenter observational study currently underway in 66 European medical institutions over the course of a six-month study period (January-June 2012). This preliminary report overviews the findings of the first half of the study, which includes all data from the first three months of the six-month study period. Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 912 patients with a mean age of 54.4 years (range 4–98) were enrolled in the study during the first three-month period. 47.7% of the patients were women and 52.3% were men. Among these patients, 83.3% were affected by community-acquired IAIs while the remaining 16.7% presented with healthcare-associated infections. Intraperitoneal specimens were collected from 64.2% of the enrolled patients, and from these samples, 825 microorganisms were collectively identified. The overall mortality rate was 6.4% (58/912). According to univariate statistical analysis of the data, critical clinical condition of the patient upon hospital admission (defined by severe sepsis and septic shock) as well as healthcare-associated infections, non-appendicular origin, generalized peritonitis, and serious comorbidities such as malignancy and severe cardiovascular disease were all significant risk factors for patient mortality. White Blood Cell counts (WBCs) greater than 12,000 or less than 4,000 and core body temperatures exceeding 38°C or less than 36°C by the third post-operative day were statistically significant indicators of patient mortality.

Abstract Obesity and insulin resistance (IR), the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation. Bariatric surgery leads to a considerable reduction in the adipose tissue mass and systemic inflammation along with a reduction of IR, with a whole-body metabolic improvement. However, a sizable portion of people experience an IR relapse within few years of remission. Numerous studies have attempted to explore the best clinical predictors of the improvement of insulin sensitivity and the maintenance of glucose homeostasis after bariatric surgery, but no simple fasting blood test has been found to be effective in predicting the short and long-term beneficial effects on glycaemia. With the present study, we investigated T-cell and antibody responses against CD300e, an antigen highly expressed in the adipose tissue of patients with obesity before the bariatric surgery-induced weight loss. We found both in fat tissue and in peripheral blood anti-CD300e-specific T helper 1 responses. Moreover, we evidenced in the sera of individuals with obesity an antibody response towards CD300e and revealed the existence of a significant correlation between the level of antibodies before surgery and the maintenance of glucose control after the intervention.

Abstract Background Physical activity and a healthy diet are important in helping to maintain mobility with aging. This umbrella review aims to identify group-based physical activity and/or nutrition interventions for community-dwelling older adults that improve mobility-related outcomes. Methods Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, Sociological Abstracts) were searched from inception to December 2021. Eligibility criteria included systematic reviews exploring the effectiveness of physical activity or structured exercise, alone or combined with nutrition interventions on mobility-related outcomes (aerobic capacity, physical function, balance, falls/safety, muscle strength, health-related quality of life/wellbeing). Interventions must have been delivered in a group setting to community-dwelling older adults aged 55+. Two reviewers independently performed eligibility screening, critical appraisal (using AMSTAR 2) and data extraction. The GRADE approach was used to reflect the certainty of evidence based on the size of the effect within each mobility-related outcome category. Older adult/provider research partners informed data synthesis and results presentation. Results In total, 62 systematic reviews (1 high, 21 moderate, 40 low/critically low quality) were identified; 53 included physical activity only, and nine included both physical activity and nutritional supplements. No reviews included nutrition interventions alone. Combined aerobic/resistance, general physical activity, and mind-body exercise all improved physical function and balance (moderate-high certainty). Aerobic/resistance training improved aerobic capacity (high certainty). Resistance training and general physical activity improved muscle strength (moderate certainty). Aerobic/resistance training and general physical activity are likely to reduce falls among older adults (moderate certainty). There was no evidence of benefit for nutritional supplementation with physical activity. Conclusions Group-based physical activity interventions that combine aerobic and resistance, general PA and mind-body exercise can improve measures of mobility in community-dwelling older adults. We found no reviews focused on nutrition only, highlighting a gap in the literature.

Abstract Background Acute appendicitis is one of the most frequent abdominal surgical emergencies. Intra-abdominal abscess is a frequent post-operative complication. The aim of this meta-analysis was to compare peritoneal irrigation and suction versus suction only when performing appendectomy for complicated appendicitis. Methods According to PRISMA guidelines, a systematic review was conducted and registered into the Prospero register (CRD42020186848). The risk of bias was defined to be from low to moderate. Results Seventeen studies (9 RCTs and 8 CCTs) were selected, including 5315 patients. There was no statistical significance in post-operative intra-abdominal abscess in open (RR 1.27, 95% CI 0.75–2.15; I 2 = 74%) and laparoscopic group (RR 1.51, 95% CI 0.73–3.13; I 2 = 83%). No statistical significance in reoperation rate in open (RR 1.27, 95% CI 0.04–2.49; I 2 = 18%) and laparoscopic group (RR 1.42, 95% CI 0.64–2.49; I 2 = 18%). In both open and laparoscopic groups, operative time was lower in the suction group (RR 7.13, 95% CI 3.14–11.12); no statistical significance was found for hospital stay (MD − 0.39, 95% CI − 1.07 to 0.30; I 2 = 91%) and the rate of wound infection (MD 1.16, 95% CI 0.56–2.38; I 2 = 71%). Conclusions This systematic review has failed to demonstrate the statistical superiority of employing intra-operative peritoneal irrigation and suction over suction-only to reduce the rate of post-operative complications after appendectomy, but all the articles report clinical superiority in terms of post-operative abscess, wound infection and operative times in suction-only group.

Abstract Background The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck cancer. Methods Four databases (Scopus, Medline, PubMed and Web of Science) were searched using the term tumo(u)r-stroma ratio. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed. Results TSR was studied in nine studies of different subsites (including cohorts of nasopharyngeal, oral, laryngeal and pharyngeal carcinomas). In all studies, TSR was evaluated using hematoxylin and eosin staining. Classifying tumors based on TSR seems to allow for identification of high-risk cases. In oral cancer, specifically, our meta-analysis showed that TSR is significantly associated with both cancer-related mortality (HR 2.10, 95%CI 1.56–2.84) and disease-free survival (HR 1.84, 95%CI 1.38–2.46). Conclusions The assessment of TSR has a promising prognostic value and can be implemented with minimum efforts in routine head and neck pathology.

Abstract Crop genomics has seen dramatic advances in recent years due to improvements in sequencing technology, assembly methods, and computational resources. These advances have led to the development of new tools to facilitate crop improvement. The study of structural variation within species and the characterization of the pan-genome has revealed extensive genome content variation among individuals within a species that is paradigm shifting to crop genomics and improvement. Here, we review advances in crop genomics and how utilization of these tools is shifting in light of pan-genomes that are becoming available for many crop species.

Abstract Background Epidemiological studies have indicated a higher incidence of breast and gastric cancer in patients with nonsyndromic cleft lip with or without cleft palate (NSCL ± P) and their relatives, which can be based on similar genetic triggers segregated within family with NSCL ± P. Methods This multicenter study evaluated the association of 9 single nucleotide polymorphisms (SNP) in AXIN2 and CDH1, representing genes consistently altered in breast and gastric tumors, with NSCL ± P in 223 trios (father, mother and patient with NSCL ± P) by transmission disequilibrium test (TDT). Results Our results showed that the minor A allele of rs7210356 (p = 0.01) and the T-G-G-A-G haplotype formed by rs7591, rs7210356, rs4791171, rs11079571 and rs3923087 SNPs (p = 0.03) in AXIN2 were significantly under-transmitted to patients with NSCL ± P. In CDH1 gene, the C-G-A-A and A-G-A-G haplotypes composed by rs16260, rs9929218, rs7186053 and rs4783573 polymorphisms were respectively over-transmitted (p = 0.01) and under-transmitted (p = 0.008) from parents to the children with NSCL ± P. Conclusions The results suggest that polymorphic variants in AXIN2 and CDH1 may be associated with NSCL ± P susceptibility, and reinforce the putative link between cancer and oral clefts.

Abstract Cystatin 9 (CST9) is a member of the type 2 cysteine protease inhibitor family, which has been shown to have immunomodulatory effects that restrain inflammation, but its functions against bacterial infections are unknown. Here, we report that purified human recombinant (r)CST9 protects against the deadly bacterium Francisella tularensis (Ft) in vitro and in vivo. Macrophages infected with the Ft human pathogen Schu 4 (S4), then given 50 pg of rCST9 exhibited significantly decreased intracellular bacterial replication and increased killing via preventing the escape of S4 from the phagosome. Further, rCST9 induced autophagy in macrophages via the regulation of the mammalian target of rapamycin (mTOR) signaling pathways. rCST9 promoted the upregulation of macrophage proteins involved in antiinflammation and antiapoptosis, while restraining proinflammatory-associated proteins. Interestingly, the viability and virulence of S4 also was decreased directly by rCST9. In a mouse model of Ft inhalation, rCST9 significantly decreased organ bacterial burden and improved survival, which was not accompanied by excessive cytokine secretion or subsequent immune cell migration. The current report is the first to show the immunomodulatory and antimicrobial functions of rCST9 against Ft. We hypothesize that the attenuation of inflammation by rCST9 may be exploited for therapeutic purposes during infection.

Abstract Background The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC). Methods A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area. Results The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan–Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09–3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11–2.48; P = 0.014). Conclusion Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system.

Abstract Background Multiple acyl-CoA dehydrogenase deficiency (MADD) or glutaric aciduria type II is an extremely rare autosomal recessive inborn error of fatty acid beta oxidation and branched-chain amino acids, secondary to mutations in the genes encoding the electron transfer flavoproteins A and B (ETFs; ETFA or ETFB) or ETF dehydrogenase (ETFDH). The clinical manifestation of MADD are heterogeneous, from severe neonatal forms to mild late-onset forms. Case presentation We report the case of a preterm newborn who died a few days after birth for a severe picture of untreatable metabolic acidosis. The diagnosis of neonatal onset MADD was suggested on the basis of clinical features displaying congenital abnormalities and confirmed by the results of expanded newborn screening, which arrived the day the newborn died. Molecular genetic test revealed a homozygous indel variant c.606 + 1 _606 + 2insT in the ETFDH gene, localized in a canonical splite site. This variant, segregated from the two heterozygous parents, is not present in the general population frequency database and has never been reported in the literature. Discussion and conclusion Recently introduced Expanded Newborn Screening is very important for a timely diagnosis of Inherited Metabolic Disorders like MADD. In some cases which are the most severe, diagnosis may arrive after symptoms are already present or may be the neonate already died. This stress the importance of collecting all possible samples to give parents a proper diagnosis and a genetic counselling for future pregnacies.

Key Points High glucose quickly induces an atypical NF-kB pro-inflammatory program. CamKII phosphorylation of Rpt6 subunit of the proteasome stimulates IkBα turnover and p65-p50 release. Inhibition of either CamkII or proteasome blocks this pathway.

Abstract Background Immunosenescence is described as age-associated changes within the immune system that are responsible for decreased immunity and increased cancer risk. Physically active individuals have fewer ‘senescent’ and more naïve T-cells compared to their sedentary counterparts, but it is not known if exercise training can rejuvenate ‘older looking’ T-cell profiles. We determined the effects of 12-weeks supervised exercise training on the frequency of T-cell subtypes in peripheral blood and their relationships with circulating levels of the muscle-derived cytokines (i.e. ‘myokines’) IL-6, IL-7, IL-15 and osteonectin in older women at high risk of breast cancer. The intervention involved 3 sessions/week of either high intensity interval exercise (HIIT) or moderate intensity continuous exercise (MICT) and were compared to an untrained control (UC) group. Results HIIT decreased total granulocytes, CD4+ T-cells, CD4+ naïve T-cells, CD4+ recent thymic emigrants (RTE) and the CD4:CD8 ratio after training, whereas MICT increased total lymphocytes and CD8 effector memory (EM) T-cells. The change in total T-cells, CD4+ naïve T-cells, CD4+ central memory (CM) T-cells and CD4+ RTE was elevated after MICT compared to HIIT. Changes in V ̇ O 2 max $$ \dot{\mathrm{V}}{\mathrm{O}}_{2\max } $$ after training, regardless of exercise prescription, was inversely related to the change in highly differentiated CD8+ EMRA T-cells and positively related to changes in β2-adrenergic receptor (β2-AR) expression on CM CD4+ and CM CD8+ T-cells. Plasma myokine levels did not change significantly among the groups after training, but individual changes in IL-7 were positively related to changes in the number of β2-AR expressing CD4 naïve T cells in both exercise groups but not controls. Further, CD4 T-cells and CD4 naive T-cells were negatively related to changes in IL-6 and osteonectin after HIIT but not MICT, whereas CD8 EMRA T-cells were inversely related to changes in IL-15 after MICT but not HIIT. Conclusions Aerobic exercise training alters the frequency of peripheral T-cells associated with immunosenescence in middle aged/older women at high risk of breast cancer, with HIIT (pro-senescent) and MICT (anti-senescent) evoking divergent effects. Identifying the underlying mechanisms and establishing whether exercise-induced changes in peripheral T-cell numbers can alter the risk of developing breast cancer warrants investigation.

Abstract Background Usual interstitial pneumonia can present with a probable pattern on high-resolution computed tomography (HRCT), but the probability of identifying usual interstitial pneumonia by surgical lung biopsy in such cases remains controversial. We aimed to determine the final clinical diagnosis in patients with a probable usual interstitial pneumonia pattern on HRCT who were subjected to surgical lung biopsy. Methods HRCT images were assessed and categorized by three radiologists, and tissue slides were evaluated by two pathologists, all of whom were blinded to the clinical findings. The final clinical diagnosis was accomplished via a multidisciplinary discussion. Patients with a single layer of honeycombing located outside of the lower lobes on HRCT were not excluded. Results A total of 50 patients were evaluated. The most common final clinical diagnosis was fibrotic hypersensitivity pneumonitis (38.0%) followed by idiopathic pulmonary fibrosis (24.0%), interstitial lung disease ascribed to gastroesophageal reflux disease (12.0%) and familial interstitial lung disease (10.0%). In the group without environmental exposure (n = 22), 10 patients had a final clinical diagnosis of idiopathic pulmonary fibrosis (45.5%). Irrespective of the final clinical diagnosis, by multivariate Cox analysis, patients with honeycombing, dyspnoea and fibroblastic foci on surgical lung biopsy had a high risk of death. Conclusions The most common disease associated with a probable usual interstitial pneumonia pattern on HRCT is fibrotic hypersensitivity pneumonitis followed by idiopathic pulmonary fibrosis and interstitial lung disease ascribed to gastroesophageal reflux disease. In patients without environmental exposure, the frequencies of usual interstitial pneumonia and a final clinical diagnosis of idiopathic pulmonary fibrosis are not sufficiently high to obviate the indications for surgical lung biopsy.

Abstract Background Cell-in-cell structures (caused by cell cannibalistic activity) have been related to prognosis of many cancers. This is the first multi-institutional study to assess the prognostic impact of cell-in-cell structures in a large cohort of early oral tongue squamous cell carcinomas (OTSCC). Methods A total of 308 cases from five Finnish University Hospitals and from the A.C. Camargo Cancer Center, São Paulo, Brazil, were included in this study. Cell-in-cell structures were evaluated on surgical postoperative sections that stained with hematoxylin and eosin staining. Results We found that cell-in-cell structures associated with cancer-related mortality in univariable analysis with a hazard ratio (HR) of 2.99 (95%CI 1.52–5.88; P = 0.001). This association was confirmed in multivariable analysis (HR 2.22, 95%CI 1.12–4.44; P = 0.024). In addition, statistically significant associations were observed between the cell-in-cell structures and other adverse histopathologic characteristics including deep invasion (P

Abstract Background In recent years, the flow of patients to the Emergency Departments (ED) of Western countries has steadily increased, thus generating overcrowding and extended waiting times. Scholars have identified four main causes for this phenomenon, related to: continuity of primary care services; availability of specific clinical pathways for chronic patients; ED’s personnel endowment; organization of the ED. This study aims at providing a logical diagnostic framework to support managers in investigating specific solutions to be applied to their EDs to cope with high ED waiting times. The framework is based on the ED waiting times and ED admission rate matrix. It was applied to the Tuscan EDs as illustrative example. Methods To provide the factors to be analyzed once the EDs are positioned into the matrix, a list of issues has been identified. The matrix was applied to Tuscan EDs. Data were collected from the Tuscan performance evaluation system, integrated with specific data on Tuscan EDs’ personnel. The Tuscan EDs matrix, the descriptive statistics for each quadrant and the Spearman’s rank correlation analysis among waiting times, admission rates and a set of performance indicators were conducted to help managers to read the phenomena that they need to investigate. Results The combined reading of the correlations and waiting times-admission rates matrix shows that there are no optimal rules for all the EDs in managing admission rates and waiting times, but solutions have to be found considering mixed and personalized strategies. Conclusions The waiting times-admission rates matrix provides a tool able to support managers in detecting the problems related to the management of ED services. In particular, using this matrix, healthcare managers could be facilitated in the identification of possible solutions for their specific situation.

Abstract Background Pathogens with a global distribution face diverse biotic and abiotic conditions across populations. Moreover, the ecological and evolutionary history of each population is unique. Xylella fastidiosa is a xylem-dwelling bacterium infecting multiple plant hosts, often with detrimental effects. As a group, X. fastidiosa is divided into distinct subspecies with allopatric historical distributions and patterns of multiple introductions from numerous source populations. The capacity of X. fastidiosa to successfully colonize and cause disease in naïve plant hosts varies among subspecies, and potentially, among populations. Within Central America (i.e. Costa Rica) two X. fastidiosa subspecies coexist: the native subsp. fastidiosa and the introduced subsp. pauca. Using whole genome sequences, the patterns of gene gain/loss, genomic introgression, and genetic diversity were characterized within Costa Rica and contrasted to other X. fastidiosa populations. Results Within Costa Rica, accessory and core genome analyses showed a highly malleable genome with numerous intra- and inter-subspecific gain/loss events. Likewise, variable levels of inter-subspecific introgression were found within and between both coexisting subspecies; nonetheless, the direction of donor/recipient subspecies to the recombinant segments varied. Some strains appeared to recombine more frequently than others; however, no group of genes or gene functions were overrepresented within recombinant segments. Finally, the patterns of genetic diversity of subsp. fastidiosa in Costa Rica were consistent with those of other native populations (i.e. subsp. pauca in Brazil). Conclusions Overall, this study shows the importance of characterizing local evolutionary and ecological history in the context of world-wide pathogen distribution.

Abstract Background Gastrinoma is a rare form of neuroendocrine neoplasm. The presence of a primary lymph node localization of gastrinoma is a much debated and controversial topic in the literature, as regards whether these cases represent metastatic disease from an as yet unidentified primary tumor, or the de novo occurrence of a gastrinoma in a lymph node. Case presentation We report the case of a 24-year-old male with intense epigastric pain treated at the beginning with high dose proton pump inhibitors. Further workup with CT and subsequent laparotomy revealed a single peripancreatic lymph node. Histological examination highlighted a well-differentiated neuroendocrine tumor. Conclusion This case underlines that the primitive lymph node gastrinoma is a distinct nosological entity with a precise location in the context of rare neuroendocrine tumors that should be considered when specific symptoms are associated with the identification of isolated lymph nodes, after excluding any possible primitive locations of neoplastic localization.

Abstract Introduction Women with pathogenic germline gene variants in BRCA1 and/or BRCA2 are at increased risk of developing ovarian and breast cancer. While surgical and pharmacological approaches are effective for risk-reduction, it is unknown whether lifestyle approaches such as healthful dietary habits, weight management, and physical activity may also contribute to risk-reduction. We conducted a systematic review of evidence related to dietary habits, weight status/change, and physical activity on ovarian and breast cancer risk among women with BRCA1/2 pathogenic variants. Methods We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to October 3, 2019. We identified 2775 records and included 21. Results There is limited evidence related to these factors and ovarian cancer risk. For breast cancer risk, evidence suggests higher diet quality, adulthood weight-loss of ≥10 pounds, and activity during adolescence and young-adulthood may be linked with decreased risk. Higher meat intake and higher daily energy intake may be linked with increased risk. Conclusions There is not enough evidence to suggest tailored recommendations for dietary habits or weight management among women with BRCA1/2 pathogenic variants compared to the general population for ovarian and breast cancer risk-reduction, and physical activity recommendations should remain the same.

Abstract Background Aim of the study was to evaluate the gelatinolytic activity in the saliva and gingival crevicular fluid from a sample group of subjects with Marfan syndrome. Methods Two groups were analyzed in this case-control study. A group of 28 subjects with Marfan syndrome (MG) was recruited from the Centre for Rare Disease, Marfan Clinic of Tor Vergata University Hospital. The second sample, 23 subjects, with the same characteristics and without any syndrome, was the control group (CG). Saliva and gingival crevicular fluid were collected and transferred to a sterile test tube and stored frozen at − 20 °C until analysis at the Medical Chemistry Laboratory. Gelatin substrate zymography was used for the evaluation and characterization of saliva and crevicular fluid proteinases. Correlation test and Student’s t-test have been used to analyze data. Results In all samples different gelatin-degrading activities were observed. Two bands, which are related to the molecular weights of pro-MMP-9 and active MMP-9, respectively, were detectable in 100% of Marfan and control samples. MMP-2 activity was higher in Marfan group. Additional bands (55/48 kDa), corresponding to the activated forms of collagenase (MMP-13), were observed in saliva samples of both groups. Conclusions The association of an enhanced activity by MMP-13 with an increased amount of active MMP-9 might be an important biomarker for the diagnosis of Marfan syndrome.

Abstract Background Respiratory failure requiring mechanical ventilation is a common manifestation of end-organ damage among patients with sepsis and has a high morbidity and mortality rate, as well as substantial associated treatment costs. Considering the burden of this condition, there is great need to identify novel, pragmatic therapies to improve outcomes in this population. Hypercapnia has shown benefits in several different ex vivo and in vivo models of lung injury. However, it is currently unclear if hypercapnia can confer clinical benefit among patients with sepsis. The objective of this systematic review is to collate the biomedical literature of preclinical and clinical studies testing the effects of higher PaCO2 levels in the setting of sepsis. Methods We will perform a qualitative systematic review of preclinical and clinical studies evaluating the effects of hypercapnia in sepsis. We will search CENTRAL, PubMed, CINAHL, and EMBASE using a comprehensive strategy. We will screen the reference lists of the articles we select for inclusion to identify additional studies for potential inclusion. Two independent reviewers will review all search results. Upon inclusion of articles, we will extract data using a standardized form. We will use tables to describe the study type, population included, exposure and control groups, outcome measures, and effects of exposure on outcome measures compared to controls. Discussion This systematic review aims to synthesize the world’s literature on the effects of hypercapnia in the setting of sepsis. We expect this systematic review will find that majority of the studies will demonstrate a potential benefit of higher PaCO2 levels in sepsis. The results of this systematic review will contribute to the understanding of the effects of hypercapnia in the setting of sepsis and promote future research of PaCO2 management in mechanically ventilated patients with sepsis. Systematic review registration The systematic review is registered in the PROSPERO international prospective register of systematic review (PROSPERO # CRD42018086703).

Abstract Microglia, unique myeloid cells residing in the brain parenchyma, represent the first line of immune defense within the central nervous system. In addition to their immune functions, microglial cells play an important role in other cerebral processes, including the regulation of synaptic architecture and neurogenesis. Chronic microglial activation is regarded as detrimental, and it is considered a pathogenic mechanism common to several neurological disorders. Microglial activation and function have been extensively studied in rodent experimental models, whereas the characterization of human cells has been limited due to the restricted availability of primary sources of human microglia. To overcome this problem, human immortalized microglial cell lines have been developed. The human microglial clone 3 cell line, HMC3, was established in 1995, through SV40-dependent immortalization of human embryonic microglial cells. It has been recently authenticated by the American Type Culture Collection (ATCC®) and distributed under the name of HMC3 (ATCC®CRL-3304). The HMC3 cells have been used in six research studies, two of which also indicated by ATCC® as reference articles. However, a more accurate literature revision suggests that clone 3 was initially distributed under the name of CHME3. In this regard, several studies have been published, thus contributing to a more extensive characterization of this cell line. Remarkably, the same cell line has been used in different laboratories with other denominations, i.e., CHME-5 cells and C13-NJ cells. In view of the fact that “being now authenticated by ATCC®” may imply a wider distribution of the cells, we aimed at reviewing data obtained with the human microglia cell line clone 3, making the readers aware of this complicated nomenclature. In addition, we also included original data, generated in our laboratory with the HMC3 (ATCC®CRL-3304) cells, providing information on the current state of the culture together with supplementary details on the culturing procedures to obtain and maintain viable cells.

Abstract Background Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy. Results To define alterations in epigenetic landscapes in breast cancers, we profiled the distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO-seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines that represent 5 molecular subtypes of breast cancer and immortalized human mammary epithelial cells. Discussion Using combinatorial patterns of distinct histone modification signals, we defined subtype-specific chromatin signatures to nominate potential biomarkers. This approach identified AFAP1-AS1 as a triple negative breast cancer-specific gene associated with cell proliferation and epithelial-mesenchymal-transition. In addition, our chromatin mapping data in basal TNBC cell lines are consistent with gene expression patterns in TCGA that indicate decreased activity of the androgen receptor pathway but increased activity of the vitamin D biosynthesis pathway. Conclusions Together, these datasets provide a comprehensive resource for histone modification profiles that define epigenetic landscapes and reveal key chromatin signatures in breast cancer cell line subtypes with potential to identify novel and actionable targets for treatment.

Abstract Background Obesity is a disease that is caused by genetic and environmental factors. However, epigenetic mechanisms of obesity are less well known. DNA methylation provides a mechanism whereby environmental factors can influence gene transcription. The aim of our study was to investigate skeletal muscle DNA methylation of sorbin and SH3 domain containing 3 (SORBS3) with weight loss induced by Roux-en-Y gastric bypass (RYGB). Results Previously, we had shown increased methylation (5.0 to 24.4%) and decreased gene expression (fold change − 1.9) of SORBS3 with obesity (BMI > 30 kg/m2) compared to lean controls. In the present study, basal muscle biopsies were obtained from seven morbidly obese (BMI > 40 kg/m2) female subjects pre- and 3 months post-RYGB surgery, in combination with euglycemic-hyperinsulinemic clamps to assess insulin sensitivity. We identified 30 significantly altered promoter and untranslated region methylation sites in SORBS3 using reduced representation bisulfite sequencing (RRBS). Twenty-nine of these sites were decreased (− 5.6 to − 24.2%) post-RYGB compared to pre-RYGB. We confirmed the methylation in 2 (Chr.8:22,423,690 and Chr.8:22,423,702) of the 29 decreased SORBS3 sites using pyrosequencing. This decreased methylation was associated with an increase in SORBS3 gene expression (fold change + 1.7) post-surgery. In addition, we demonstrated that SORBS3 promoter methylation in vitro significantly alters reporter gene expression (P

Abstract Colon cancer cells contain high levels of cystathlonlne-β-synthase (CBS). Its product, hydrogen sulfide (H2S), promotes the growth and proliferation of colorectal tumor cells. To improve the antitumor efficacy of the prototypical CBS inhibitor aminooxyacetic acid (AOAA), we have designed and synthesized YD0171, a methyl ester derivative of AOAA. The antiproliferative effect of YD0171 exceeded the antiproliferative potency of AOAA in HCT116 human colon cancer cells. The esterase inhibitor paraoxon prevented the cellular inhibition of CBS activity by YD0171. YD0171 suppressed mitochondrial respiration and glycolytic function and induced G0/G1 arrest, but did not induce tumor cell apoptosis or necrosis. Metabolomic analysis in HCT116 cells showed that YD0171 affects multiple pathways of cell metabolism. The efficacy of YD0171 as an inhibitor of tumor growth was also tested in nude mice bearing subcutaneous HCT116 cancer cell xenografts. Animals were treated via subcutaneous injection of vehicle or AOAA (0.1, 0.5 or 1 mg/kg/d) for 3 wks. Tumor growth was significantly reduced by 9 mg/kg/d AOAA, but not at the lower doses. YD0171 was more potent: tumor volume was significantly inhibited at 0.5 and 1 mg/kg/d. Thus, the in vivo efficacy of YD0171 is nine times higher than that of AOAA. YD0171 (1 mg/kg/d) attenuated tumor growth and metastasis formation in the intracecal HCT116 tumor model. YD0171 (3 mg/kg/d) also reduced tumor growth in patient-derived tumor xenograft bearing athymic mice. YD0171 (3 mg/kg/d) induced the regression of established HCT116 tumors in vivo. A 5-d safety study in mice demonstrated that YD0171 at 20 mg/kg/d (given in two divided doses) does not increase plasma markers of organ injury, nor does it induce histological alterations in the liver or kidney. YD0171 caused a slight elevation in plasma homocysteine levels. In conclusion, the prodrug approach improves the pharmacological profile of AOAA; YD0171 represents a prototype for CBS inhibitory anticancer prodrugs. By targeting colorectal cancer bioenergetics, an emerging important hallmark of cancer, the approach exemplified herein may offer direct translational opportunities.

Abstract Background Melanoacanthoma (MA) has been described in the oral mucosa as a solitary lesion or, occasionally, as multiple lesions. MA mainly affects dark skinned patients and grows rapidly, showing a plane or slightly raised appearance and a brown to black color. The differential diagnosis includes oral nevi, amalgam tattoos, and melanomas. We report here the case of a 58-year-old black woman who presented multiple pigmented lesions on the hard palate. Case presentation Based on the differential diagnosis of melanoma, a punch biopsy (4 mm in diameter) was performed. The material was fixed in 10% formalin, embedded in paraffin, and stained with hematoxylin-eosin or submitted to immunohistochemical analysis. Immunohistochemistry using antibodies against protein S-100, melan-A, HMB-45, MCM-2, MCM-5, Ki-67 and geminin was performed. Immunohistochemical analysis revealed strong cytoplasmic immunoreactivity of dendritic melanocytes for proteinS-100, HMB-45 and melan-A.Positive staining for proliferative markers (MCM-2, MCM-5, Ki-67) was only observed in basal and suprabasal epithelial cells, confirming the reactive etiology of the lesion. The diagnosis was oral Melanoacanthoma (MA). Conclusion The patient has been followed up for 30 months and shows no clinical alterations. MA should be included in the differential diagnosis of pigmented lesions of the oral cavity.

Abstract Background With an abundant amount of microarray gene expression data sets available through public repositories, new possibilities lie in combining multiple existing data sets. In this new context, analysis itself is no longer the problem, but retrieving and consistently integrating all this data before delivering it to the wide variety of existing analysis tools becomes the new bottleneck. Results We present the newly released inSilicoMerging R/Bioconductor package which, together with the earlier released inSilicoDb R/Bioconductor package, allows consistent retrieval, integration and analysis of publicly available microarray gene expression data sets. Inside the inSilicoMerging package a set of five visual and six quantitative validation measures are available as well. Conclusions By providing (i) access to uniformly curated and preprocessed data, (ii) a collection of techniques to remove the batch effects between data sets from different sources, and (iii) several validation tools enabling the inspection of the integration process, these packages enable researchers to fully explore the potential of combining gene expression data for downstream analysis. The power of using both packages is demonstrated by programmatically retrieving and integrating gene expression studies from the InSilico DB repository [https://insilicodb.org/app/].

Abstract Background HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer. Methods In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT) and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA) containing 127 oral squamous cell carcinomas (OSCC) was performed to determine the prognostic role of HOXA1 expression. Results We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells) decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026). Conclusion Our findings indicate that HOXA1 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and suggest that HOXA1 expression might be helpful as a prognostic marker for patients with OSCC.

Abstract Background Huanglongbing (HLB) is one of the most destructive citrus diseases in the world. The disease is associated with the presence of a fastidious, phloem-limited α- proteobacterium, 'Candidatus Liberibacter asiaticus', 'Ca. Liberibacter africanus' or 'Ca. Liberibacter americanus'. HLB-associated Liberibacters have spread to North America and South America in recent years. While the causal agents of HLB have been putatively identified, information regarding the worldwide population structure and epidemiological relationships for 'Ca. L. asiaticus' is limited. The availability of the 'Ca. L. asiaticus' genome sequence has facilitated development of molecular markers from this bacterium. The objectives of this study were to develop microsatellite markers and conduct genetic analyses of 'Ca. L. asiaticus' from a worldwide collection. Two hundred eighty seven isolates from USA (Florida), Brazil, China, India, Cambodia, Vietnam, Taiwan, Thailand, and Japan were analyzed. Results A panel of seven polymorphic microsatellite markers was developed for 'Ca. L. asiaticus'. Microsatellite analyses across the samples showed that the genetic diversity of 'Ca. L. asiaticus' is higher in Asia than Americas. UPGMA and STRUCTURE analyses identified three major genetic groups worldwide. Isolates from India were genetically distinct. East-southeast Asian and Brazilian isolates were generally included in the same group; a few members of this group were found in Florida, but the majority of the isolates from Florida were clustered separately. eBURST analysis predicted three founder haplotypes, which may have given rise to three groups worldwide. Conclusions Our results identified three major genetic groups of 'Ca. L. asiaticus' worldwide. Isolates from Brazil showed similar genetic makeup with east-southeast Asian dominant group, suggesting the possibility of a common origin. However, most of the isolates recovered from Florida were clustered in a separate group. While the sources of the dominant 'Ca. L. asiaticus' in Florida were not clearly understood, the less-pervasive groups may have been introduced directly from Asia or via Brazil. Notably, the recent outbreak of HLB in Florida probably occurred through multiple introductions. Microsatellite markers developed in this study provide adequate discriminatory power for the identification and differentiation of closely-related isolates, as well as for genetic studies of 'Ca. L. asiaticus'.

Abstract Background Meconium abnormalities are characterized by a wide spectrum of severity, from the meconium plug syndrome to the complicated meconium ileus associated with cystic fibrosis. Meconium Related Ileus in absence of Cystic Fibrosis includes a combination of highly viscid meconium and poor intestinal motility, low grade obstruction, benign systemic and abdominal examination, distended loops without air fluid levels. Associated risk factors are severe prematurity and low birth weight, Caesarean delivery, Maternal MgSO4 therapy, maternal diabetes. In the last 20 yrs a new specific type of these meconium related obstructions has been described in premature neonates with low birth weight. Its incidence has shown to increase while its management continues to be challenging and controversial for the risk of complicated obstruction and perforation. Materials and methods Among 55 newborns admitted between 1992-2008 with Meconium Related Ileus as final diagnosis, data about Low Birth Weight infants (LBW < 1500 g) were extracted and compared to those of patients ≥ 1500 g. Hischsprung's Diseases and Cystic Fibrosis were excluded by rectal biopsy and genetic probe before discharge. A softening enema with Gastrografin was the first option whenever overt perforation was not present. Temporary stoma or trans appendiceal bowel irrigation were elected after unsuccessful enema while prompt surgical exploration was performed in perforated cases. NEC was excluded in all operated cases. Data collected were perinatal history and neonatal clinical data, radiological signs, clinical course and complications, management and outcome. Results 30 cases with BW ≥ 1500 g had an M/F ratio16/14, Mean B.W. 3052 g, Mean G.A. 37 w Caesarean section rate 40%. There were 10 meconium plug syndrome, 4 small left colon syndromes, and 16 meconium ileus without Cystic Fibrosis. Five cases were born at our institution (inborn) versus 25 referred after a mean of 2, 4 Days (1-7) after birth in another Hospital (outborn). They were managed, after a Gastrografin enema with 90% success rate, by 1 temporary Ileostomy and 2 trans appendiceal irrigation. 25 cases with BW< 1500 g (LBW) had M/F ratio 11/14, Mean B.W. 818 g, Mean G.A. 27 w, Caesarean section rate 70%, assisted ventilation 16/25. There were 8 inborn and 17 outborn. Gastrografin enema was successful in 6 out 8 inborn infants only, all referred within one week from birth. There were 12 perforations mainly among late referred LBW outborn. Conclusions Meconium Related Ileus without Cystic Fibrosis responds to conservative management and softening enema in most of mature infants. In LBW clinical course is initially benign but as any long standing bowel obstruction management may present particular challenges. Clinical and plain radiographic criteria are reliable for making diagnosis and testing for Cystic Fibrosis may not be indicated. Enema may be resolutive when performed in a proper environment. Perforated cases may be confused with NEC which is excluded by clinical history, no signs of sepsis, lab signs missing, abdominal signs missing, typical radiological signs missing. The higher complication rate is recorded among cases delivered and initially managed in Neonatal Units without co-located Surgical Facilities. Early diagnosis and aggressive medical therapy may lead to higher success rate and help avoiding surgical interventions. Surgical therapy in uncomplicated cases, unresponsive to medical management, should be minimally aggressive.

Abstract Background Respiratory syncytial virus is the most important pathogen in lower respiratory tract infection in infants and young children. In high-risk populations it may develop severe, sometimes fatal, lower respiratory tract infections. A proportion of these infants require admission to intensive care units due to the severity of the condition and the level of care needed. Furthermore, we must consider the possible increased risk of asthma following RSV infection in infancy. Methods The aim of this work is to show how we strictly coordinated, during the 2008-2009 RSV season, the delivery of prophylaxis while minimising drug cost through vial sharing and cohorting infants with a software performed through Visual Basic programming system. Results By using this method we have been able to obtain a saving of the 29.2% compared to the theoretical amount. No infant requested hospitalisation for a RSV infection. Conclusions Such a model ensures all patients to receive appropriate immunization and thus positively influencing the cost-benefit of palivizumab prophylaxis. We hope that our model of care delivery will be of use to other hospitals.

Abstract Background Huanglongbing (HLB, previously known as citrus greening), is associated with Candidatus Liberibacter species and is a serious threat to citrus production world-wide. The pathogen is a Gram negative, unculturable, phloem-limited bacterium with limited known genomic information. Expanding the genetic knowledge of this organism may provide better understanding of the pathogen and possibly develop effective strategies for control and management of HLB. Results Here, we report cloning and characterization of an additional 14.7 Kb of new genomic sequences from three different genomic regions of the Candidatus Liberibacter asiaticus (Las). Sequence variation analyses among the available Ca. Liberibacter species sequences as well as the newly cloned 1.5 Kb of rpoB gene from different Ca. Liberibacter strains have identified INDELs and SNPs. Phylogenetic analysis of the deduced protein sequences from the cloned regions characterizes the HLB-associated Candidatus Liberibacter as a new clade in the sub-division of the α-proteobacteria. Conclusion Comparative analyses of the cloned gene regions of Candidatus Liberibacter with members of the order Rhizobiales suggest overall gene structure and order conservation, albeit with minor variations including gene decay due to the identified pseudogenes. The newly cloned gene regions contribute to our understanding of the molecular aspects of genomic evolution of Ca. Liberibacter.

Abstract Background The xylem-inhabiting bacterium Xylella fastidiosa (Xf) is the causal agent of Pierce's disease (PD) in vineyards and citrus variegated chlorosis (CVC) in orange trees. Both of these economically-devastating diseases are caused by distinct strains of this complex group of microorganisms, which has motivated researchers to conduct extensive genomic sequencing projects with Xf strains. This sequence information, along with other molecular tools, have been used to estimate the evolutionary history of the group and provide clues to understand the capacity of Xf to infect different hosts, causing a variety of symptoms. Nonetheless, although significant amounts of information have been generated from Xf strains, a large proportion of these efforts has concentrated on the study of North American strains, limiting our understanding about the genomic composition of South American strains – which is particularly important for CVC-associated strains. Results This paper describes the first genome-wide comparison among South American Xf strains, involving 6 distinct citrus-associated bacteria. Comparative analyses performed through a microarray-based approach allowed identification and characterization of large mobile genetic elements that seem to be exclusive to South American strains. Moreover, a large-scale sequencing effort, based on Suppressive Subtraction Hybridization (SSH), identified 290 new ORFs, distributed in 135 Groups of Orthologous Elements, throughout the genomes of these bacteria. Conclusion Results from microarray-based comparisons provide further evidence concerning activity of horizontally transferred elements, reinforcing their importance as major mediators in the evolution of Xf. Moreover, the microarray-based genomic profiles showed similarity between Xf strains 9a5c and Fb7, which is unexpected, given the geographical and chronological differences associated with the isolation of these microorganisms. The newly identified ORFs, obtained by SSH, represent an approximately 10% increase in our current knowledge of the South American Xf gene pool and include new putative virulence factors, as well as novel potential markers for strain identification. Surprisingly, this list of novel elements include sequences previously believed to be unique to North American strains, pointing to the necessity of revising the list of specific markers that may be used for identification of distinct Xf strains.

Abstract Background Thyroid gland derives from one median anlage at the base of the tongue, and from the two fourth branchial pouches. A number of anomalies may occur during their migration. These can be in form of ectopic tissues, which are frequently found along the course of thyroglossal duct and rarely in other sites, many of these may develop same diseases as the thyroid gland. Case presentation A 36-years-old female presented with a 3 month history of left side neck mass. The mass disappeared following aspiration of brown colored fluid, which on cytological examination showed cells with nuclear irregularities that warranted the resection of the lesion. The histology demonstrated a thyroid papillary carcinoma arising within the branchial cyst. Thereafter, the patient underwent a total thyroidectomy with central lymph nodes dissection. Histology showed a multifocal papillary carcinoma with central lymph nodes metastases. Only four cases of primary thyroid carcinomas in neck branchial cyst have been described so far. Conclusion In a lateral cystic neck mass, although rare, occurrence of ectopic thyroid tissue and presence of a papillary thyroid carcinoma should be kept in mind.