Genomic characterization of small cell carcinomas of the uterine cervix

Small cell carcinoma (SCC) of the uterine cervix is a rare and aggressive form of neuroendocrine carcinoma, which resembles small cell lung cancer (SCLC) in its histology and poor survival rate. Here, we sought to define the genetic underpinning of SCCs of the uterine cervix and compare their mutational profiles with those of human papillomavirus (HPV)‐positive head and neck squamous cell carcinomas, HPV‐positive cervical carcinomas, and SCLCs using publicly available data. Using a combination of whole‐exome and targeted massively parallel sequencing, we found that the nine uterine cervix SCCs, which were HPV18‐positive (n = 8) or HPV16‐positive (n = 1), harbored a low mutation burden, few copy number alterations, and other than TP53 in two cases no recurrently mutated genes. The majority of mutations were likely passenger missense mutations, and only few affected previously described cancer‐related genes. Using RNA‐sequencing, we identified putative viral integration sites on 18q12.3 and on 8p22 in two SCCs of the uterine cervix. The overall nonsilent mutation rate of uterine cervix SCCs was significantly lower than that of SCLCs, HPV‐driven cervical adeno‐ and squamous cell carcinomas, or HPV‐positive head and neck squamous cell carcinomas. Unlike SCLCs, which are reported to harbor almost universal TP53 and RB1 mutations and a dominant tobacco smoke‐related signature 4, uterine cervix SCCs rarely harbored mutations affecting these genes (2/9, 22% TP53; 0% RB1) and displayed a dominant aging (67%) or APOBEC mutational signature (17%), akin to HPV‐driven cancers, including cervical adeno‐ and squamous cell carcinomas and head and neck squamous cell carcinomas. Taken together, in contrast to SCLCs, which are characterized by highly recurrent TP53 and RB1 alterations, uterine cervix SCCs were positive for HPV leading to inactivation of the suppressors p53 and RB, suggesting that these SCCs are convergent phenotypes.     

Protective and Risk Factors for Humerus Head Necrosis After Proximal Humerus Fracture Treated with Internal Locking Plate

BackgroundProximal humerus fractures (PHF) are common and lead to post-traumatic humerus head necrosis (HHN) in 3–35% after ORIF with an internal locking plate. Few studies focus on this condition and risk factors remain a discussion topic. Hertel’s criteria for initial head ischemia right after fracture (fracture complexity, medial hinge displacement and short metaphyseal head extension) have recently been correlated to HHN, but there is still a clear lack of evidence on the topic. Due to its anatomical similarities to the proximal femur, some authors argue that PHF may as well benefit from early surgery to avoid head necrosis.MethodsIn this 10-year retrospective study, we assessed 305 patients from a single center. All cases were treated with a PHILOS plate through a deltopectoral approach. The mean follow-up time was 467 days. The primary endpoint was HHN.ResultsHHN was diagnosed in 12 patients (4%), 10 of which were diagnosed within the first year and one case 4 years after surgery. A positive correlation (p < 0.04) was found between HHN and fracture type (both in AO and Neer’s classification), initial neck-shaft-angle (NSA) and metaphyseal head extension (MHE). Medial hinge displacement (MHD) occurred in all HHN cases. Achieving perfect reduction (< 2 mm dislocation) was relevant to avoiding HHN (p = 0.035). Although HHN developed in 32% of the high risk cases (four-part fractures with a short MHE), it was completely avoided (0%) when perfect reduction was achieved. Time until surgery after admission was neither a protective nor a risk factor for HHN.ConclusionWe conclude that fracture complexity (four-part and C-fractures) as well as disruption of the medial hinge with a metaphyseal head extension smaller than 8 mm are relevant risk factors for humerus head necrosis. A combination of these criteria generated an high risk pattern with a 32% rate of HHN. Though often difficult to achieve, perfect reduction was a clear protective factor and reduced HHN to 0%. Perfect reduction may be key to inosculation and, therefore, salvage of the humerus head, especially in high risk cases. Surgery timing did not correlate with HHN.Level of EvidenceLevel 3, retrospective cohort study.     

HDAC and MAPK/ERK Inhibitors Cooperate To Reduce Viability and Stemness in Medulloblastoma

Journal of Molecular Neuroscience - Medulloblastoma (MB), which originates from embryonic neural stem cells (NSCs) or neural precursors in the developing cerebellum, is the most common malignant...     

Detection of Zika virus in paired urine and amniotic fluid samples from symptomatic and asymptomatic women and their babies during a disease outbreak: association with neurological symptoms in newborns

Paired maternal and newborn urine and amniotic fluid from 138 subjects collected during a Zika virus (ZIKV) outbreak was analyzed for ZIKV by gene amplification (RT-qPCR), and the findings were correlated with clinical symptoms and neurological anomalies in the babies. ZIKV was detected in 1 of 9 symptomatic women (11.1%) and in 19 of 129 asymptomatic women (14.7%). Neurological manifestations were present in 19 babies (13.7%), 10 of 20 (50%) positive and 9 of 119 (7.6%) negative (p < 0.001) for ZIKV. Twelve (8.6%) urines collected during gestation were ZIKV-positive; only 2 remained positive for ZIKV postpartum. Six (4.1%) newborn urines collected within 1 day of delivery were ZIKV-positive cases. In 3 of these cases, ZIKV was detected in mother’s urine pre- and postpartum and in both mother’s urine and babies’ urine. Four of the amniotic fluid samples (2.9%) were ZIKV-positive. Among ZIKV-negative babies with neurological sequel, 87.5% were female; in contrast, 72.7% ZIKV-positive babies with neurological abnormalities were male (p = 0.019). We conclude that during a ZIKV outbreak, clinical symptoms and ZIKV detection in biological fluids are poor predictors of infection and adverse neurologic sequel in newborns.     

Burnt sugarcane harvesting is associated with rhinitis symptoms and inflammatory markers

IntroductionBurnt sugarcane harvesting requires intense physical exertion in an environment of high temperature and exposure to particulate matter.ObjectiveTo evaluate the effects of burnt sugarcane harvesting on rhinitis symptoms and inflammatory markers in sugarcane workers.MethodsA total of 32 male sugarcane workers were evaluated with questionnaire for rhinitis symptoms, and for inflammatory markers on peripheral blood and nasal lavage, in the non-harvesting, and 3 and 6 months into the sugarcane harvesting period. Weather data and particulate matter fine concentrations were measured in the same day.ResultsThe particulate matter concentrations in sugarcane harvesting were 27 (23–33 μg/m³), 112 (96–122 μg/m³), and 63 (17–263 μg/m³); 24 h temperatures were 32.6 (25.4–37.4 °C), 32.3 (26.7–36.7 °C) and 29.7 (24.1–34.0 °C) and relative humidities were 45.4 (35.0–59.7%), 47.9 (39.1–63.0%), and 59.9 (34.7–63.2%) in the non-harvesting period, three and 6 months of the harvesting period. The age was 37.4 ± 10.9 years. The prevalence of rhinitis symptoms was significantly higher at 3 months of the harvesting period (53.4%), compared to non-harvesting period (26.7%; p = 0.039) and at 6 months into the harvesting period (20%; p = 0.006). Concentrations of interleukin 6 (IL-6) in nasal lavage increased after 3 months of the harvesting period compared to the non-harvesting period (p = 0.012). The presence of rhinitis symptoms, after 3 months of the harvesting period, was directly associated with blood eosinophils and inversely associated with neutrophils.ConclusionsAfter 3 months of work in burnt sugarcane harvesting the prevalence of rhinitis symptoms and IL-6 in nasal lavage increased. Furthermore, eosinophil counts were directly associated with the rhinitis symptoms in the period of higher concentration of particulate matter.     

Absolute and Relative Agreement between the Current and Modified Brazilian Cardioprotective Nutritional Program Dietary Index (BALANCE DI) and the American Heart Association Healthy Diet Score (AHA-DS) in Post Myocardial Infarction Patients

The American Heart Association Diet Score (AHA-DS) defines the cardiovascular health, and the Brazilian Cardioprotective Nutritional Program Dietary Index (BALANCE DI) was designed to evaluate diet quality in secondary cardiovascular prevention settings. Our aim was to assess the absolute and relative agreement between both tools in Brazilian adults after a myocardial infarction (MI). In this cross-sectional study, 473 individuals were included and had their diet assessed by a 24 h food recall and a semi-quantitative Food Frequency Questionnaire. The weighted Kappa between BALANCE DI and primary AHA-DS was 0.66 (95% CI: 0.08–0.21), and between BALANCE DI and total AHA-DS was 0.70 (95% CI: 0.20–0.32). To improve the agreement between the tools, modifications were made to the BALANCE DI scoring system. The weighted Kappa between New BALANCE DI and primary AHA-DS was 0.77 (95% CI: 0.36–0.48), and between BALANCE DI and total AHA-DS was 0.76 (95% CI: 0.34–0.46). The mean bias observed between the New BALANCE DI as compared to the primary and total AHA-DS was −16% (−51 to 19) and −8% (−41 to 24), respectively. Our results suggest that the New BALANCE DI may be a useful tool to evaluate diet quality in post MI patients.     

Three-Dimensional Nanoscale Morphological Surface Analysis of Polymeric Particles Containing Allium sativum Essential Oil

Biodegradable particles were developed using poly-ε-caprolactone and gelatin carriers containing different concentrations of Allium sativum essential oil (EO) (360 µg/mL, 420 µg/mL, and 460 µg/mL). Atomic force microscopy was useful to evaluate the particles’ surface based on morphological parameters. The particles’ size varied from 150 nm to 300 nm. The diameter was related to the increase of the particles’ height as a function of the EO concentration, influencing the roughness of the surface core values (from 20 to 30 nm) and surface irregularity. The spatial parameters Str (texture aspect ratio) and Std (texture direction) revealed low spatial frequency components. The hybrid parameters Sdq (root mean square gradient) and Sdr (interfacial area ratio) also increased as a function of the EO concentration, revealing fewer flat particles. On the other hand, the functional parameters (inverse areal material ratio and peak extreme height) suggested differences in surface irregularities. Higher concentrations of EO resulted in greater microtexture asperity on the particles’ surface, as well as sharper peaks. The nanoscale morphological surface analysis allowed the determination of the most appropriate concentration of encapsulated EO, influencing statistical surface parameters.     

Effect of Aqueous Cinnamon Extract on the Postprandial Glycemia Levels in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial

Cinnamon is a spice used in traditional cuisine that has been investigated due to hypoglycemic properties. The objective of this study was to investigate the effect of aqueous cinnamon extract on postprandial glycemia levels in type 2 diabetes mellitus (DM2) adults. This clinical trial enrolled 36 adults with DM2, randomly allocated in two groups: the control group (n = 18) took only an oral glucose tolerance test (OGTT) and the intervention group (n = 18) took OGTT immediately followed by aqueous cinnamon extract (6 g/100 mL) ingestion. Blood glucose levels were measured on fasting and after 30, 60, 90 and 120 min in both groups. The chemical analysis of the aqueous cinnamon extract included total phenols content determination and antioxidant activity assessment through FRAP and DPPH methods. The data reveal that aqueous cinnamon extract ingestion did not show a significant difference in the incremental area under the curve (p = 0.834), maximum glucose concentration (p = 0.527) and glucose concentration variation (p = 0.873) compared with the control group. Cinnamon extract possess a total phenol content of 1554.9 mg/L gallic acid equivalent and a strong antioxidant capacity, revealed by the DPPH (5125.0 µmol Trolox/L) and FRAP (3658.8 µmol Trolox/L) tests. Aqueous cinnamon extract did not significantly influence postprandial glucose response in diabetic patients during an OGTT.     

Evaluation of Molecular Test for the Discrimination of “Naked” DNA from Infectious Parvovirus B19 Particles in Serum and Bone Marrow Samples

Low levels of parvovirus B19 (B19V) DNA can be detected in the circulation and in different tissue of immunocompetent individuals for months or years, which has been linked to inflammatory diseases such as cardiomyopathy, rheumatoid arthritis, hepatitis, and vasculitis. However, the detection of B19V DNA does not necessarily imply that infectious virions are present. This study aimed to evaluate the method based on the Benzonase^® treatment for differentiation between the infectious virions from “naked” DNA in serum and bone marrow (BM) samples to be useful for the B19V routine diagnosis. In addition, we estimated the period of viremia and DNAemia in the sera and bone marrow of nonhuman primates experimentally infected with B19V. Serum samples from ten patients and from four cynomolgus monkeys experimentally infected with B19V followed up for 60 days were used. Most of the human serum samples became negative after pretreatment; however, only decreased viral DNA loads were observed in four patients, indicating that these samples still contained the infectious virus. Reduced B19V DNA levels were observed in animals since 7th dpi. At approximately 45th dpi, B19V DNA levels were below 10⁵ IU/mL after Benzonase^® pretreatment, which was not a consequence of active B19V replication. The test based on Benzonase^® pretreatment enabled the discrimination of “naked DNA” from B19V DNA encapsidated in virions. Therefore, this test can be used to clarify the role of B19V as an etiological agent associated with atypical clinical manifestations.