Neurological Sciences

Correction to: Effect of taping on scapular kinematics of patients with facioscapulohumeral muscular dystrophy The published version of this article unfortunately contained a mistake in Fig. 2. Only one graphic of different movement of scapula was published instead of three. The Figure is corrected here.

Incidence and prevalence of Parkinson's disease in the Italian region of Umbria: a population-based study using healthcare administrative databases Abstract Parkinson's disease is known to pose a significant burden on society in industrialized countries. However, few studies have been conducted in Italy using administrative healthcare databases for epidemiological purposes. We wanted to estimate the incidence and prevalence rates of Parkinson's disease in the Italian region of Umbria by means of linkage between several sources of administrative healthcare data: hospitalization episodes, exemptions from medical charges, drug prescriptions from general practitioners and physicians working in the public sector. Using a pre-defined algorithm, we estimated incident and prevalent cases of Parkinson's disease for the year 2016. The regional incidence rate, adjusted with Italian standard population data, was 0.40 new cases/1000 person-years (0.41 in females, 0.39 in males). We estimated that 5550 subjects were affected by Parkinson's disease, leading to an age-adjusted prevalence rate of 5.42/1000 inhabitants. Prevalence and incidence increased with age and male gender. However, due to the longer life expectancy of females, the absolute number of prevalent cases was greater among females. The heterogeneity of spatial distribution of disease was high. A considerable proportion of prevalent cases was hospitalized in 2016. The most recurrent reasons for hospitalization episodes were disorders related to the nervous system, respiratory system, cardiovascular system, and musculoskeletal and connective tissue apparatus. The study findings support the feasibility of future epidemiological studies of Parkinson's disease with administrative data as well as the need for an integrative care pathway for the patients with Parkinson's disease.

Sexual abuse and psychogenic nonepileptic seizures Abstract Objective We investigated the frequency of reported sexual abuse in patients with psychogenic nonepileptic seizures (PNES) in a Middle-Eastern culture (Iran) and tried to characterize the association between a history of sexual abuse and the clinical characteristics of PNES in these patients. Methods In this retrospective database study, patients with PNES, who were investigated at Shiraz Comprehensive Epilepsy Center at Shiraz University of Medical Sciences, from 2008 until 2018, were studied. Patients were categorized into two groups: (1) those with a history of sexual abuse and (2) those without such a history. Results A total of 314 patients were studied. Twenty-six patients (8.3%) had a history of sexual abuse, while 288 patients (91.7%) denied having such an experience. Sex ratio (OR: 3.53; 95% CI: 1.14–10.89; p = 0.02) and a history of child abuse (OR: 4.85; 95% CI: 1.82–12.96; p = 0.002) were significantly associated with a history of sexual abuse. Conclusion Some people with a history of sexual abuse are at risk of developing PNES later in their lives. While social, cultural, and even genetic predisposition may be interacting for such an association to come to play, there is no concrete direct evidence to clarify this link yet. This should be investigated in future international cross-cultural studies and also highlights the need for planning genetic studies in patients with PNES.

Neurosciences in the ninth art

Identification of a novel splice mutation in CTNNB1 gene in a Chinese family with both severe intellectual disability and serious visual defects Abstract The CTNNB1 gene encode the β-catenin protein which is a core unit of the cadherin/catenin multiprotein complex. The loss-of-function mutation of the CTNNB1 gene recently has been confirmed as a cause of intellectual disability. Previous studies have found that patients with CTNNB1 gene mutation may have other clinical manifestation such as microcephaly, abnormal facial features, motor and language delays, and mild visual defects. Here, we reported a 27-year-old Chinese pregnant woman with a severe intellectual disability and serious visual defects who was detected with a novel splice mutation (c.734+1G>A) in CTNNB1 gene by whole-exome sequencing and confirmed by Sanger sequencing. Further investigation showed that the variant was inherited from her mother with similar phenotypes. This report not only helps to expand the mutant spectrum of the CTNNB1 gene but also prompts a new insight into genetic diagnosis in patients with both serious intellectual disability and visual defects.

Highlights of the issue 8, 2019

Identification of a novel NOTCH3 mutation in an Italian family affected by a mild form of CADASIL

Carrier frequency of spinal muscular atrophy in Thailand Abstract Spinal muscular atrophy (SMA) is one of the leading causes of death in infants and young children from heritable diseases. Patients diagnosed with SMA develop symmetrical progressive muscle weakness and atrophy from degeneration of alpha motor neurons. Approximately 95% of patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene in exon 7 and inherited in autosomal recessive pattern. Considering the high prevalence of SMA carrier in many population, it is possible that SMA is one of the most common autosomal recessive disorders in Thailand and Southeast Asia. In this study, we analyzed DNA from peripheral blood of 505 healthy Thai adults using quantitative PCR-based for SMN1 gene exon 7 copy number analysis. Individual samples with heterozygous deletion of SMN1 gene were confirmed with MLPA. The result identified 9 samples (1.78%) with heterozygous deletion and 39 samples as more than 2 copies of SMN1. No homozygous deletion was detected in the samples. In conclusion, we established carrier frequency of SMA in selected Thai population at 1.8% from 505 participants. The prevalence coincides with prevalence in East Asia and Caucasian population. The result could be implemented for SMA carrier screening in couples at risk in the region.

Choosing Wisely: five recommendations related to tests, treatments, and procedures at risk of inappropriateness in the cure of Parkinson's disease (LIMPE-DISMOV Academy)

Complex multisystem phenotype associated with the mitochondrial DNA m.5522G>A mutation Abstract Mitochondrial tRNAs are responsible for more than half of pathogenic point mutations in the mitochondrial genome (mtDNA). Different mutations give rise to widely differing phenotypes, ranging from isolated organ-specific diseases to multisystem conditions. Herein, we report a 40-year-old woman presenting with a complex multisystem phenotype including sensorineural hearing loss, retinopathy, severe dilated cardiomyopathy, non-insulin dependent diabetes mellitus, and renal failure. Sequence analysis of mtDNA identified the m.5522G>A mutation in MT-TW, the gene encoding mitochondrial tRNA for tryptophan. The heteroplasmic variant, thus far described once, was almost exclusively confined to skeletal muscle tissue, as shown by massive parallel sequencing and corroborated by an ad hoc designed PCR-based strategy. This patient, presenting a severe, multisystem involvement apparently sparing the brain, contributes to the genetic heterogeneity of mitochondrial diseases caused by mutations in mitochondrial tRNAs.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Environmental Science and Pollution Research

Efficient microalgae removal from aqueous medium through auto-flocculation: investigating growth-dependent role of organic matter Abstract This study investigated the growth-dependent role of algal organic matters (AOMs) to achieve high removal efficiency (R.E) of microalgae. The results showed that the microalgae cells produced 96 ± 2% of total AOMs as loose bound AOMSS (LB-AOMs) and 4 ± 1% as cell-bound (CB-AOMs) in exponential phase. In stationary phase, LB-AOMs and CB-AOMs were 46 ± 0.7percentage and 54 ± 0.2 percentage, respectively. The R.Es in exponential and stationary phase were 83 ± 2.6% and 66 ± 1.2%, respectively. It is found that the difference of biomass concentration (between exponential and stationary phase) had no significant impact on the R.E (P > 0.01). Further investigations revealed that LB-AOMs inhibit flocculation in exponential and CB-AOMs in stationary phase; however, CB-AOMs showed stronger inhibition than the LB-AOMs (P < 0.01). The provision of calcium (17 ± 0.9 mg/L) to the culture reduced the AOMs inhibition and improved the R.E from 66 ± 1.2% (in control) to 90 ± 4.2%. An increase in R.E was attributed to the interaction of calcium with AOMs and subsequently acting as a flocculant. The findings of this study can be valuable to improve the performance of auto-flocculation technology, which is mainly limited by the presence of AOMs. Graphical Abstract

Fluorene-9-bisphenol inhibits epithelial-mesenchymal transition of human endometrial cancer Ishikawa cells by repressing TGF-β signaling pathway Abstract Fluorene-9-bisphenol (BHPF), a new derivative of bisphenol A (BPA), has been introduced for treatment with estrogen-related tumors, such as endometrial cancer. This study investigated the potential mechanism underlying the action of BHPF against endometrial cancer in vitro. We used the cell counting kit-8 (CCK8) method on Ishikawa cells to screen sub-lethal doses of BHPF and established the optimal concentration at which BHPF influenced the proliferation of Ishikawa cells. Effect of BHPF on cell migration and invasion was investigated by cell scratch assay and transwell assay, respectively. Expression levels of epithelial-mesenchymal transition (EMT)–related proteins were detected by Western blot analysis. BHPF was found to inhibit the proliferation of Ishikawa cells, whose migration and invasion abilities were also reduced. Western blot indicated that BHPF can significantly inhibit the EMT process of Ishikawa cells by blocking transforming growth factor-β (TGF-β) signaling pathway. This is the first report of the effect of BHPF on the biological behavior of endometrial cancer cells and its inhibition of endometrial cancer progression by repressing both endometrial cell proliferation and epithelial-mesenchymal transition, hence suggesting it as a novel anti-cancer drug. Graphical abstract Schematic representation of the molecular basis underlying BHPF treatment. BHPF repressed the EMT process by regulating EMT-related genes, such as E-cadherin, N-cadherin, and vimentin as well as the TGF-β signaling pathway–related genes, including p-Smad2/3 and slug, in a BHPF-dependent manner.

Application of a stable carbon isotope for identifying Broussonetia papyrifera pollen Abstract The objective of this study was to investigate whether δ13C values can be used to identify pollen specie in the atmosphere. A Burkard 7-day recording volumetric spore trap was used to collected pollens in the atmosphere in Tainan City, Taiwan, from January 2 to December 28, 2006, and a light microscope was used to identify the pollen species and concentrations. A Burkard cyclone sampler was used to collect particulate matter and an elemental analyzer with an isotope ratio mass spectrometer was used to analyze the δ13C values. Our data showed that the predominate pollen specie in the atmosphere was Broussonetia papyrifera pollen and that the annual average concentration was 27 grains/m3 (pollen season, 36; nonpollen season, 9 grains/m3). The average δ13C value was − 26.19‰ for particulate matter in the atmosphere (pollen season, − 26.00‰; nonpollen season, − 26.28‰). No significant association was observed between δ13C values and Broussonetia papyrifera pollen concentrations. However, the δ13C value in the atmosphere was associated with the levels of Broussonetia papyrifera pollen among the samples with a diameter of particulate matter smaller than 10 μm at a level lower than 40 μg/m3. In addition, the relative contribution of Broussonetia papyrifera pollen to the carbon in the atmosphere using a two end-member mixing models was found to be associated with the Broussonetia papyrifera pollen concentration. In summary, our study suggested that δ13C values can be applied in the assessment of Broussonetia papyrifera pollen specie under specific conditions in the atmosphere.

Performance and emission reduction characteristics of cerium oxide nanoparticle-water emulsion biofuel in diesel engine with modified coated piston Abstract In the present scenario, the utilization of petroleum fuel is expanding forcefully worldwide in the vitality store and plays a highly hazardous role in the ecological system. Biofuel stands out among the most tenable keys for this issue. The lemongrass oil is used as a biofuel because of low density and viscosity when compared with diesel. The lemongrass oil is extracted by steam distillation process. In the present investigation, partially stabilized zirconium, due to its higher thermal conductivity, is selected as coating material. The top surface of the piston and the inlet and exhaust valves are coated up to the preferred thickness of 500 μm by the plasma spray technique. The lemongrass emulsion fuel is prepared in the proportion of 94% of lemongrass oil, 5% of water, and 1% of surfactant span 80. The nanoparticles of cerium oxide were used with lemongrass oil (LGO) nano-emulsion in the measurement of 30 ppm. The four-stroke diesel engine execution, ignition, and the outflow extent were contrasted in the diesel and lemongrass oil (LGO) compared with the base diesel engine. The performance characteristic curves of lemongrass-cerium oxide nano-emulsion fuel show the increase in brake thermal efficiency of 17.21% when compared with the mineral diesel fuel. The emission characteristics of lemongrass-cerium oxide nano-emulsion fuel show a drop in hydrocarbon and carbon monoxide emission by 16.21% and 15.21%, respectively, when compared with base diesel fuel and also there is a decrease in oxides of nitrogen and smoke emission by 24.1% and 6.3%, respectively, when compared to mineral diesel fuel.

Green vehicle adoption behavior among low-income households: evidence from coastal Malaysia Abstract In an attempt to mitigate the effects of extreme natural events caused by greenhouse gases (GHGs), a significant number of researchers and environmentalists have repeatedly stressed the importance of implementing protective measures, including the promotion of green consumption. This study examined the elements that motivated the willingness and the practice of green behavior (GB) among low-income households in coastal Peninsular Malaysia. To meet the research objectives, this study adopted the survey questionnaire method to collect data from 380 low-income households. The findings revealed that self-efficacy (SE) and environmental concerns (EC) have statistically significant effects on the attitude toward green products (ATT), while subjective norms (SN) and perceived behavioral control (PBC) have influence on the intention of green vehicles. Eventually, the study discovered the effects of the intention to adopt green vehicle on green vehicle adoption behavior. Hence, the findings of this study provide new insights for policymakers in Malaysia to place more emphasis on improving consumer attitudes, social standards, and PBC, which will ultimately contribute to the adoption of environment-friendly vehicles. In addition, car manufacturers should support this program by designing products and options that would encourage those in the low-income group to replace their conventional vehicles with green alternatives in Malaysia.

Enhanced phytoremediation of PAHs-contaminated soil from an industrial relocation site by Ochrobactrum sp. Abstract Nowadays, the remediation of polycyclic aromatic hydrocarbons (PAHs)-contaminated soil has received wide attention. In this work, Ochrobactrum sp. (PW) was isolated through selective enrichment from PAHs-contaminated soil in coking plant of Beijing, and the effects of PW on phytoremediation of that soil by alfalfa (Medicago sativa L.) and ryegrass (Lolium multiflorum Lam.) were investigated through pot experiments. Plant biomass, peroxidase (POD) activity, malondialdehyde (MDA) contents, soil enzyme activity (polyphenol oxidase and dehydrogenase activity), and residual concentration of PAHs in soils were determined to illustrate the ability of PW for enhancing the degradation of PAHs by plants. The results showed that the fresh weight of ryegrass and alfalfa inoculated with PW was significantly (p < 0.05) increased while the activity of POD and MDA contents were notably (p < 0.05) reduced than that without inoculation. Additionally, PW enhanced the activity of polyphenol oxidase and dehydrogenase in soil significantly (p < 0.05), and further enhanced the degradability of the system to PAHs. Different treatment methods could be ranked by the following order according to the degradability: SP (alfalfa + PW) > RP (ryegrass + PW) > PW (PW) > S (alfalfa) > R (ryegrass). The combined action of PW and alfalfa/ryegrass could accelerate the degradability of PAHs from soil contaminated by coking plants. PW could be used as potential bacteria to promote phytoremediation of the soil contaminated by PAHs.

Hairdressers are exposed to high concentrations of formaldehyde during the hair straightening procedure Abstract The fact that hairdressers are exposed to toxic substances through the handling of creams and smoothing products prompted this study whose aim was to quantify the occupational exposure of hairdressers to formaldehyde by comparing the results of exposure for different types of beauty salon. The study population consisted of 23 beauty salons located in the city of Bauru, São Paulo state, Brazil. The samples were collected by inhaled air tests during the most critical 15-min period of the hair straightening procedure and during the 8-h work shift. The concentrations of formaldehyde contained in the formulations of these products were also evaluated and compared with exposure levels. The results were evaluated according to the exposure limits prescribed in Brazilian (NR15) and North American (US OSHA and US NIOSH) standards. The analysis of the smoothing products showed concentrations of formaldehyde of between 3 and 11% in their compositions, i.e., up to 54 times above the 0.2% limit allowed by the National Agency of Sanitary Surveillance (ANVISA). The present study showed that hairdressers are chronically exposed to high concentrations of formaldehyde in the workplace and these exposures are mainly associated with the work process, where many variables of this process influence the intensity of exposure.

Virulence, antimicrobial and heavy metal tolerance, and genetic diversity of Vibrio cholerae recovered from commonly consumed freshwater fish Abstract Vibrio cholerae is a leading waterborne pathogen worldwide. Continuous monitoring of V. cholerae contamination in aquatic products and identification of risk factors are crucial for assuring food safety. In this study, we determined the virulence, antimicrobial susceptibility, heavy metal tolerance, and genetic diversity of 400 V. cholerae isolates recovered from commonly consumed freshwater fish (Aristichthys nobilis, Carassius auratus, Ctenopharyngodon idellus, and Parabramis pekinensis) collected in July and August of 2017 in Shanghai, China. V. cholerae has not been previously detected in the half of these fish species. The results revealed an extremely low occurrence of pathogenic V. cholerae carrying the major virulence genes ctxAB (0.0%), tcpA (0.0%), ace (0.0%), and zot (0.0%). However, high incidence of virulence-associated genes was observed, including the RTX toxin gene cluster (rtxA-D) (83.0–97.0%), hlyA (87.8%), hapA (95.0%), and tlh (76.0%). Meanwhile, high percentages of resistance to antimicrobial agents streptomycin (65.3%), ampicillin (44.5%), and rifampicin (24.0%) were observed. Approximately 30.5% of the isolates displayed multidrug resistant (MDR) phenotypes with 42 resistance profiles, which were significantly different among the four fish species (MARI, P = 0.001). Additionally, tolerance of isolates to heavy metals Hg2+ (49.3%), Zn2+(30.3%), and Pb2+ (12.0%) was observed. The enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR)-based fingerprinting of the 400 V. cholerae isolates revealed 328 ERIC-genotypes, which demonstrated a large degree of genomic variation among the isolates. Overall, the results of this study support the need for food safety risk assessment of aquatic products.

Column and batch sorption investigations of nickel(II) on extractant-impregnated resin Abstract Macroporous resin-supported reagents have been identified as potential adsorbents for removal of toxic pollutants. This article presents an experimental designed to evaluate the sorption and desorption of nickel(II) with the help of column and batch procedure using simple extractant-impregnated resin (EIR). Isonitroso-4-methyl-2-pentanone (IMP) as an extractant was impregnated on a solid support like Amberlite XAD-4 to prepare the EIR sorbent. Column experimental conditions such as pH, sample flow rate and volume, eluting solution, and interfering ions were studied to optimize the nickel(II) sorption and recovery from aqueous media. The column results suggest that the quantitative nickel(II) sorption was observed at pH 5–6, and the quantitative recovery (≥ 95%) was achieved by using 1.0 M HNO3. The high concentrations of cations and anions (except EDTA) present in the spiked binary and multi-element mixture solution show no interferences in both quantitative sorption and recovery of nickel(II), whereas the batch experiments were performed to evaluate nickel(II) sorption behavior using the linearized and non-linearized kinetic and isotherm models. By error function analysis, the Freundlich isotherm and the pseudo-first-order kinetic model were found to describe best the experimental data obtained over the studied concentration range and sorption time, respectively. The maximum sorption capacity of nickel(II) onto the EIR sorbent was found to be ~ 81 mg/g. The mean free energy (E = 10.1 kJ/mol) determined using Dubinin-Radushkevich isotherm suggests chemical nature of nickel(II) sorption on EIR. The novelty of the EIR adsorbent lies in its potential for separation and recovery of nickel(II) at trace level in water samples of different origin.

Urinary metabolites of polycyclic aromatic hydrocarbons in pregnant women and their association with a biomarker of oxidative stress Abstract Exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy may pose adverse health risk to both the mothers and babies. In the present study, 188 pregnant women of different trimesters were recruited in Guangzhou, south China, and nine hydroxyl PAHs (OH-PAHs) and a biomarker of DNA oxidative damage, 8-hydroxy-2′-deoxyguanosine (8-OHdG), were determined in their urine samples. All OH-PAHs except for 4-hydroxyphenanthrene and 6-hydroxychrysene were found in > 90% samples, with total concentration in the range of 0.52 to 42.9 μg/g creatinine. In general, concentration levels of OH-PAHs in pregnant women were lower than those in general population in the same research area but with higher levels in working women than in housewives. The mean daily intakes of PAHs from dietary estimated by urinary OH-PAHs were 0.021, 0.004, 0.047, and 0.030 μg/kg_bw/day for naphthalene, fluorene, phenanthrene, and pyrene, respectively, which were much lower than the reference doses (20, 30, and 40 μg/kg_bw/day for naphthalene, pyrene, and fluorene, respectively) derived from chronic oral exposure data by the United States Environmental Protection Agency. The low exposure levels of PAHs may be attributed to the traditional dietary taboo of Chinese pregnant women, which is to minimize the consumption of "toxic" food. The concentrations of 8-OHdG (4.67–49.4 μg/g creatinine) were significantly positively correlated with concentrations of several OH-PAHs, such as metabolites of naphthalene, fluorene, and phenanthrene (r = 0.3–0.6). In addition, the concentrations of 8-OHdG were higher in working women than in housewives when exposed to the same levels of PAHs, partly indicating the possible relation between work-related pressure for working women and the oxidative stress.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Medical Microbiology and Immunology

Adverse immunological imprinting by cytomegalovirus sensitizing for allergic airway disease Abstract Cytomegalovirus (CMV) infection has a profound impact on the host's immune system. Immunological imprinting by CMV is not restricted to immunity against CMV itself, but can affect immunity against other viral or non-viral infectious agents and also immunopathological responses. One category is heterologous immunity based on molecular mimicry, where antigen recognition receptors specific for a CMV antigen with broad avidity distribution also bind with some avidity to unrelated antigens and exert effector functions against target structures other than those linked to CMV. Another category is induction of cytokines by CMV infection that inhibit or drive immune responses to bystander antigens unrelated to CMV, and a third category is the activation of antigen-presenting cells by CMV from which unrelated antigens profit as "stowaways". A striking example of the "stowaway" category, actually one that is of medical importance, has been published recently and will be discussed here for the more general reader. Specifically, in a murine model, CMV airway infection and inhaled environmental antigen of poor intrinsic allergenic potential were found to sensitize for allergic airway disease (AAD) only when combined. As to the mechanism, viral activation of CD11b+ conventional dendritic cells (CD11b+ cDC) that localize to airway mucosa facilitates uptake and processing of inhaled antigen. Thus, CMV serves as a "door opener" for otherwise harmless environmental antigens that have no intrinsic property to activate DC. Antigen-laden CD11b+ cDC migrate selectively to the airway draining lymph nodes, where they prime type-2 CD4+ T helper (Th-2) cells. Upon airway re-exposure to the inhaled antigen, Th-2 cells secrete interleukins (IL-4, IL-5, IL-9, and IL-25) known to induce goblet cell metaplasia, the lead histopathological manifestation of AAD that is characterized by thickening of airway epithelia and increased numbers of mucus-producing goblet cells, resulting in enhanced mucus secretion and airflow obstruction.

'Checks and balances' in cytomegalovirus-host cohabitation

Intertwined: SAMHD1 cellular functions, restriction, and viral evasion strategies Abstract SAMHD1 was initially described for its ability to efficiently restrict HIV-1 replication in myeloid cells and resting CD4+ T cells. However, a growing body of evidence suggests that SAMHD1-mediated restriction is by far not limited to lentiviruses, but seems to be a general concept that applies to most retroviruses and at least a number of DNA viruses. SAMHD1 anti-viral activity was long believed to be solely due to its ability to deplete cellular dNTPs by enzymatic degradation. However, since its discovery, several new functions have been attributed to SAMHD1. It has been demonstrated to bind nucleic acids, to modulate innate immunity, as well as to participate in the DNA damage response and resolution of stalled replication forks. Consequently, it is likely that SAMHD1-mediated anti-viral activity is not or not exclusively mediated through its dNTPase activity. Therefore, in this review, we summarize current knowledge on SAMHD1 cellular functions and systematically discuss how these functions could contribute to the restriction of a broad range of viruses besides retroviruses: herpesviruses, poxviruses and hepatitis B virus. Furthermore, we aim to highlight different ways how viruses counteract SAMHD1-mediated restriction to bypass the SAMHD1-mediated block to viral infection.

Role of antibodies in confining cytomegalovirus after reactivation from latency: three decades' résumé Abstract Cytomegaloviruses (CMVs) are highly prevalent herpesviruses, characterized by strict species specificity and the ability to establish non-productive latent infection from which reactivation can occur. Reactivation of latent human CMV (HCMV) represents one of the most important clinical challenges in transplant recipients secondary to the strong immunosuppression. In addition, HCMV is the major viral cause of congenital infection with severe sequelae including brain damage. The accumulated evidence clearly shows that cellular immunity plays a major role in the control of primary CMV infection as well as establishment and maintenance of latency. However, the efficiency of antiviral antibodies in virus control, particularly in prevention of congenital infection and virus reactivation from latency in immunosuppressed hosts, is much less understood. Because of a strict species specificity of HCMV, the role of antibodies in controlling CMV disease has been addressed using murine CMV (MCMV) as a model. Here, we review and discuss the role played by the antiviral antibody response during CMV infections with emphasis on latency and reactivation not only in the MCMV model, but also in relevant clinical settings. We provide evidence to conclude that antiviral antibodies do not prevent the initiating molecular event of virus reactivation from latency but operate by preventing intra-organ spread and inter-organ dissemination of recurrent virus.

Generation, maintenance and tissue distribution of T cell responses to human cytomegalovirus in lytic and latent infection Abstract Understanding how the T cell memory response directed towards human cytomegalovirus (HCMV) develops and changes over time while the virus persists is important. Whilst HCMV primary infection and periodic reactivation is well controlled by T cell responses in healthy people, when the immune system is compromised such as post-transplantation, during pregnancy, or underdeveloped such as in new-born infants and children, CMV disease can be a significant problem. In older people, HCMV infection is associated with increased risk of mortality and despite overt disease rarely being seen there are increases in HCMV-DNA in urine of older people suggesting that there is a change in the efficacy of the T cell response following lifelong infection. Therefore, understanding whether phenomenon such as "memory inflation" of the immune response is occurring in humans and if this is detrimental to the overall health of individuals would enable the development of appropriate treatment strategies for the future. In this review, we present the evidence available from human studies regarding the development and maintenance of memory CD8 + and CD4 + T cell responses to HCMV. We conclude that there is only limited evidence supportive of "memory inflation" occurring in humans and that future studies need to investigate immune cells from a broad range of human tissue sites to fully understand the nature of HCMV T cell memory responses to lytic and latent infection.

Impact of CMV upon immune aging: facts and fiction Abstract Aging is accompanied by significant defects in immunity and compromised responses to new, previously unencountered microbial pathogens. Most humans carry several persistent or latent viruses as they age, interacting with the host immune systems for years. In that context maybe the most studied persistent virus is Cytomegalovirus, infamous for its ability to recruit very large T cell responses which increase with age and to simultaneously evade elimination by the immune system. Here we will address how lifelong CMV infection and the immunological burden of its control might affect immune reactivity and health of the host over time.

'From immunosenescence to immune modulation': a re-appraisal of the role of cytomegalovirus as major regulator of human immune function Abstract In the year 2000, cytomegalovirus was identified as a risk factor for mortality in a seminal study of octogenarian residents in Sweden. This finding triggered a wave of additional epidemiological investigations, some of which supported this association whilst others observed no such effect. In addition, this increased risk of death in CMV-seropositive people was correlated with observed changes within the T-cell repertoire such that accelerated 'immunosenescence' became a de facto explanation, without strong evidence to this effect. Recent years have seen a re-appraisal of these findings. Interestingly, many studies show that cytomegalovirus acts to improve immune function, most clearly in younger donors. In addition, the excess mortality in older people that is observed in CMV-seropositive cohorts appears to be related primarily to an excess of vascular disease rather than impairment of immune function. CMV is an important member of the natural 'virome' of Homo sapiens and has an important, and generally positive, modulatory influence on human immune function throughout most of life. However, within certain populations, this influence can become negative and age, co-morbidity and environment all act as determinants of this effect. As such, it is important that new interventions are developed that can mitigate the damaging influence of CMV on human health in populations at risk.

Caspase-8 restricts natural killer cell accumulation during MCMV Infection Abstract Natural killer (NK) cells provide important host defense against herpesvirus infections and influence subsequent T cell control of replication and maintenance of latency. NK cells exhibit phases of expansion, contraction and memory formation in response to the natural mouse pathogen murine cytomegalovirus (MCMV). Innate and adaptive immune responses are tightly regulated in mammals to avoid excess tissue damage while preventing acute and chronic viral disease and assuring resistance to reinfection. Caspase (CASP)8 is an autoactivating aspartate-specific cysteine protease that initiates extrinsic apoptosis and prevents receptor interacting protein (RIP) kinase (RIPK)1–RIPK3-driven necroptosis. CASP8 also promotes death-independent signal transduction. All of these activities make contributions to inflammation. Here, we demonstrate that CASP8 restricts NK cell expansion during MCMV infection but does not influence NK memory. Casp8−/−Ripk3−/− mice mount higher NK response levels than Casp8+/−Ripk3−/− littermate controls or WT C57BL/6 J mice, indicating that RIPK3 deficiency alone does not contribute to NK response patterns. MCMV m157-responsive Ly49H+ NK cells support increased expansion of both Ly49H− NK cells and CD8 T cells in Casp8−/−Ripk3−/− mice. Surprisingly, hyperaccumulation of NK cells depends on the pronecrotic kinase RIPK1. Ripk1−/−Casp8−/−Ripk3−/− mice fail to show the enhanced expansion of lymphocytes observed in Casp8−/−Ripk3−/− mice even though development and homeostasis are preserved in uninfected Ripk1−/−Casp8−/−Ripk3−/− mice. Thus, CASP8 naturally regulates the magnitude of NK cell responses in response to infection where strong activation signals depend on another key regulator of death signaling, RIPK1. In addition, the strong NK cell response promotes survival of effector CD8 T cells during their expansion. Thus, hyperaccumulation of NK cells and crosstalk with T cells becomes amplified in the absence of extrinsic cell death machinery.

Persistent viral replication and the development of T-cell responses after intranasal infection by MCMV Abstract Natural transmission of cytomegalovirus (CMV) has been difficult to observe. However, recent work using the mouse model of murine (M)CMV demonstrated that MCMV initially infects the nasal mucosa after transmission from mothers to pups. We found that intranasal (i.n.) inoculation of C57BL/6J mice resulted in reliable recovery of replicating virus from the nasal mucosa as assessed by plaque assay. After i.n. inoculation, CD8+ T-cell priming occurred in the mandibular, deep-cervical, and mediastinal lymph nodes within 3 days of infection. Although i.n. infection induced "memory inflation" of T cells specific for the M38316–323 epitope, there were no detectable CD8+ T-cell responses against the late-appearing IE3416–423 epitope, which contrasts with intraperitoneal (i.p.) infection. MCMV-specific T cells migrated into the nasal mucosa where they developed a tissue-resident memory (TRM) phenotype and this could occur independently of local virus infection or antigen. Strikingly however, virus replication was poorly controlled in the nasal mucosa and MCMV was detectable by plaque assay for at least 4 months after primary infection, making the nasal mucosa a second site for MCMV persistence. Unlike in the salivary glands, the persistence of MCMV in the nasal mucosa was not modulated by IL-10. Taken together, our data characterize the development of local and systemic T-cell responses after intranasal infection by MCMV and define the nasal mucosa, a natural site of viral entry, as a novel site of viral persistence.

T-cell immunity against cytomegalovirus in HIV infection and aging: relationships with inflammation, immune activation, and frailty Abstract Both aging and treated human immunodeficiency virus (HIV) infection are characterized by low-level chronic inflammation and immune activation which contribute to the development of age-related diseases, frailty, and early mortality. Chronic cytomegalovirus (CMV) infection is highly prevalent in older adults and HIV-infected populations. A number of studies have shown that CMV induces broad and strong T-cell responses in CMV-seropositive older adults and HIV-infected individuals. CMV infection rarely develops into clinical disease in immunocompetent individuals. However, a large body of literature has shown adverse effects of chronic CMV infection on the health and longevity of these populations. It has been hypothesized that chronic CMV infection may be a driver of chronic inflammation and immune activation, and may further contribute to the development of frailty. Thus, there is a need to better understand the extent of the impact of chronic CMV infection on T-cell immunity and health in aging and HIV infection. In this review, we will address important considerations and challenges in the assessment of chronic CMV infection and CMV-specific T-cell responses. We will then review recent data on relationships between T-cell responses to CMV and levels of inflammatory markers and immune activation, as well as the onset of frailty.

The peculiar physiological responses of Rhizoctonia solani under the antagonistic interaction coupled by a novel antifungalmycin N2 from Streptomyces sp. N2 Abstract A novel antifungalmycin N2 (3-methyl-3,5-amino-4-vinyl-2-pyrone, C6H7O2N) was previously discovered from Streptomyces sp. N2, which exerted a broad-spectrum antagonistic activity against phytopathogenic fungi. To provide comprehensive insights into the antagonistic mechanisms and biocontrol efficacy of antifungalmycin N2, the present work investigated the physiological responses of Rhizoctonia solani under interaction with antifungalmycin N2. First, the mycelial growth of R. solani was significantly inhibited by antifungalmycin N2 during liquid shake-flask culture. Morphological observations showed that the morphogenesis of R. solani was influenced by antifungalmycin N2, in which the hyphae became severely shriveled and flattened, irregularly folded and branched. Additionally, an obvious accumulation of reactive oxygen species (ROS) was detected in R. solani hyphae, indicating oxidative stress induced by antifungalmycin N2. Further results showed that chitinase activity and its hydrolytic N-acetylglucosamine were significantly accelerated by antifungalmycin N2, demonstrating the cell wall of R. solani was damaged. Interestingly, the enzymatic antioxidant activities of R. solani were significantly induced in response to a relatively low concentration of antifungalmycin N2 (1.44–5.77 µg/mL). However, all antioxidant enzymes became highly inactive when the antifungalmycin N2 was increased to 11.53 µg/mL, suggesting that the enzymatic antioxidant system in R. solani was probably collapsed by the oxidative stress beyond its acceptance scope. In conclusion, antifungalmycin N2 exerted its antagonistic activity by inducing both cell wall degradation and oxidative stress in R. solani, thus leading to fungal morphogenesis and autolysis. Meanwhile, R. solani could induce and activate its antioxidant enzymes as a defence response to the oxidative stress caused by antifungalmycin N2.

Actively detached Pseudomonas aeruginosa biofilm cell susceptibility to benzalkonium chloride and associated resistance mechanism Abstract The present work aimed at studying physiological properties of Pseudomonas aeruginosa cells actively detached from biofilm formed on stainless steel and comparing them with their planktonic counterparts as a function of growth temperature (20 °C and 37 °C). The susceptibility of P. aeruginosa cells to benzalkonium chloride (BAC) was studied. Furthermore, the effect of BAC on the cell membrane integrity and the role of the cell membrane fluidity in the cell-scale-resistance mechanism were investigated. Our results showed that actively detached biofilm cells were more susceptible to BAC treatment than planktonic ones. A greater leakage of intracellular potassium after BAC addition was observed in actively detached biofilm cells, which reflects their membrane vulnerability. The rise of the growth temperature from 20 to 37 °C increased the membrane rigidity of planktonic cells comparatively to their actively detached biofilm ones. Under experimental conditions developed in this work, our data highlighted that actively biofilm-detached and planktonic P. aeruginosa cells have distinguishable phenotypes.

Bacterial communities of the microbial mats of Chokrak sulfide springs Abstract This is the comparative investigation of the composition of phototrophic microbial mats developing in sulfide-rich saline Chokrak springs with outflow at the shore of the hypersaline lake Chokrak by means of next-generation sequencing. The springs are characterized by low temperature (~ 15 °C), near-neutral pH (6.7–8.5), and high-sulfide content. In the species composition the benthic microbial communities of Chokrak springs are similar to microbial mats of marine supralittoral and lagoons. Our results showed that salinity limitation had a significant effect on the species composition of benthic microbial communities developing at the outflow of the Chokrak springs. Predominant oxygenic phototrophs belonged to the genera Phormidium, Lyngbya, Leptolyngbya, Geitlerinema, and Arthrospira. Anoxygenic phototrophic bacteria were represented by halophilic green sulfur bacteria Prosthecochloris spp., halotolerant Chlorobaculum sp., as well as marine and extremely halophilic purple bacteria Roseospira, Rhodovibrio, and Halochromatium. Monoculture of a new species of halotolerant anoxygenic filamentous phototrophic bacteria was isolated.

Heavy metal spill influences bacterial communities in freshwater sediments Abstract Bacteria are highly abundant in freshwater sediments and play a crucial role in biogeochemical cycling. Bacterial assemblage is known to be sensitive to heavy metal pollution. However, the shift in freshwater sediment bacterial community after a sudden exposure to heavy metal spill remains unknown. The present study explored the impact of metal (metalloid) spill on sediment bacterial community in a freshwater reservoir. Although sediment bacterial abundance was relatively insensitive to metal (metalloid) spill, bacterial richness, diversity and community structure displayed considerable temporal variations. In addition, the proportions of Proteobacteria Chloroflexi, Nitrospirae, Acidobacteria and Bacteroidetes drastically declined, while a significant enrichment of Firmicutes was observed.

Antibacterial activity against porcine respiratory bacterial pathogens and in vitro biocompatibility of essential oils Abstract Bacterial respiratory infections affecting pigs such as pneumonia, pleuropneumonia, and pleurisy, are a major health concern in the swine industry and are associated with important economic losses. This study aimed to investigate the antibacterial activities of essential oils against major swine respiratory pathogens with a view to developing a potential alternative to antibiotics. Their synergistic interactions with the bacteriocin nisin was also examined. Lastly, we assessed the in vitro biocompatibility of the most efficient essential oils using a pig tracheal epithelial cell line. Of the nine essential oils tested, those from cinnamon, thyme, and winter savory were the most active against Streptococcus suis, Actinobacillus pleuropneumoniae, Actinobacillus suis, Bordetella bronchiseptica, Haemophilus parasuis, and Pasteurella multocida, with minimum inhibitory concentrations and minimum bactericidal concentrations ranging from 0.01 to 0.156% (v/v). The main component found in cinnamon, thyme, and winter savory oils were cinnamaldehyde, thymol, and carvacrol, respectively. Treating pre-formed S. suis and A. pleuropneumoniae biofilms with thyme or winter savory oils significantly decreased biofilm viability. We also observed a synergistic growth inhibition of S. suis with mixtures of nisin and essential oils from thyme and winter savory. Concentrations of nisin and cinnamon, thyme and winter savory essential oils that were effective against bacterial pathogens had no effect on the viability of pig tracheal epithelial cells. The present study brought evidence that essential oils are potential antimicrobial agents against bacteria associated with porcine respiratory infections.

Isolation, characterization, and structural elucidation of 4-methoxyacetanilide from marine actinobacteria Streptomyces sp. SCA29 and evaluation of its enzyme inhibitory, antibacterial, and cytotoxic potential Abstract Marine actinobacteria are less explored than their terrestrial counterparts as potential source of natural products. The present study was aimed to elucidate the bioactive potential of metabolites produced by marine-derived actinobacterial strain Streptomyces sp.SCA29 isolated from Havelock Island, Andaman and Nicobar Islands, India. The potential isolate SCA29 was identified as Streptomyces sp. by phenotypic, genotypic (16S-rRNA) and phylogenetic analyses. The crude bioactive compound was extracted using organic solvents. The compounds were subjected to separation and purification by column chromatography which yielded six fractions. Each fraction was assayed for inhibition of α-glucosidase and α-amylase enzymes, antagonistic activity against bacterial pathogens, and cytotoxic activity against various cell lines. The fraction F3c was considered to be highly active owing to its significant inhibition potential against α-glucosidase and α-amylase enzymes with IC50 values as 44.26 and 53.19 µg/mL, respectively. The active fraction showed antibacterial activity against test bacterial pathogens with the MIC value ranged from 3.90 to 31.25 µg/mL. The compound also exhibited concentration-dependent cytotoxicity on various cell lines without significant effect against human normal cells. The bioassay-guided fractionation of extract led to the identification of 4-methoxyacetanilide, an acetamide derivative. The structure of the bioactive compound was confirmed by HR-MS, NMR (1H and 13C) and FT-IR spectra, and by comparison with literature data.

Biodiversity and antifouling activity of fungi associated with two soft corals from the South China Sea Abstract Bacteria in corals have been studied in detail in the past decades. However, the biodiversity and bioactivity of fungi in corals are still poorly understood. This study investigated the biodiversity and antifouling activity of fungi in soft corals Cladiella krempfi and Sarcophyton tortuosum from the South China Sea. A high diverse and abundant fungal community was found in the two soft corals. Furthermore, five isolates shared 83–95% similarity with their closest relatives, indicating that they might be novel species in genera Phaeoshaeria and Mucor. In addition, approximately 50% of the representative isolates exhibited distinct antifouling activity. In particular, isolates Fungal sp. SCAU132 and Fungal sp. SCAU133 displayed very strong antifouling activity against Bugula neritina, suggesting they can provide a potential resource for further investigation on isolation of novel antifouling metabolites. To our knowledge, this study is the first report to investigate the biodiversity and antifouling activity of fungi in C. krempfi and S. tortuosum.

Synergistic deletion of RGS1 and COS1 may reduce the pathogenicity of Magnaporthe oryzae Abstract Rice blast, caused by Magnaporthe oryzae, is a serious threat to global rice production. In recent years, many pathogenicity genes of M. oryzae have been identified, although most of their functions remain unknown. In this study, we report the synergistic deletion of RGS1 and COS1 that may reduce the pathogenicity of M. oryzae. The investigation involved comparing ΔMorgs1, ΔMocos1, and ΔMorgs1/ΔMocos1 mutants. The ΔMorgs1/ΔMocos1 mutant showed a weak reduction in vegetative growth, and the colonies displayed fewer and smoother aerial hyphae. The ΔMorgs1/ΔMocos1 mutant exhibited delayed appressorium-like structure formation and 'low pathogenicity' on detached rice seedling leaves when compared with ΔMocos1. Moreover, the melanin content of the single and double mutants was remarkably lower than that of the WT type. Thus, our results indicate that the synergy between RGS1 and COS1may be crucial in the pathogenicity of M. oryzae.

Arbuscular mycorrhiza: a viable strategy for soil nutrient loss reduction Abstract Arbuscular mycorrhiza fungi's (AMF) role in plant nutrition and stress management is well known, but very few researches and studies have been conducted so far on the fungal ability to reduce different nutrient losses (runoff, leaching and volatilization) from the soil system. This important ecosystem service of AMF had been neglected largely. From the recent findings, it has been confirmed that mycorrhizal symbiosis has potential to check the losses of applied nutrients. The role of soil biota in nutrient cycling is indispensable and determines the nutrient availability to plants. Among these biota, AMF's association with plants is the most prevalent, but the exact mechanisms followed by AMF in nutrient cycling, transformation and reducing nutrient loss ability are still inconclusive. In this review, we will try to unlock this particular aspect of AMF which is important to achieve global food demand in a sustainable way.

The stimulatory effects of plant growth promoting rhizobacteria and plant growth regulators on wheat physiology grown in sandy soil Abstract The present study was aimed to investigate the effects of plant growth promoting rhizobacteria (PGPR) and plant growth regulators (PGRs) on the physiology and yield of wheat grown in less fertile sandy soil. The isolated PGPR strains were identified by 16S-rRNA gene sequencing as Planomicrobium chinense (P1), Bacillus cereus (P2) and Pseudomonas fluorescens (P3). Wheat varieties (Galaxy-13 and Pak-2013) differing in sensitivity to drought were soaked in fresh cultures of bacterial isolates and the PGRs (salicylic acid and putrescine) were sprayed at 150 mg/L on seedlings at three leaf stage. PGPR and PGRs treated plants showed significant increase in the contents of chlorophyll, sugar and protein even under harsh environmental conditions. Drought stress enhanced the production of proline, antioxidant enzymes and lipid peroxidation but a decrease was noted in the biochemical content (i.e. chlorophyll, protein and sugar) of inoculated plants. PGPR inoculation also significantly enhanced the yield parameters (i.e. plant height, spike length, grain yield and weight) and improved the fertility status of sandy soil. The accumulation of macronutrient, total NO3-N and P concentration and soil moisture content of rhizosphere soil was also enhanced by PGPRs inoculation. It is concluded that the combined effects of PGPR and PGRs have profound effects on the biochemical responses and drought tolerance of wheat grown in sandy soils.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

A heavier weight at birth is associated with an elevated risk of total and follicular thyroid cancer, which underscores that prenatal exposures may be important in thyroid cancer aetiology.

https://sfakianakisorl.blogspot.com/2019/07/a-heavier-weight-at-birth-is-associated.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Cancer Epidemiology

Clinicopathologic and epidemiological characteristics of prognostic factors in post-surgical survival of colorectal cancer patients in Jiangsu Province, China Publication date: October 2019 Source: Cancer Epidemiology, Volume 62 Author(s): Said Abasse Kassim, Weiyan Tang, Muhammad Abbas, Shenzhen Wu, Qingdao Meng, Chengcheng Zhang, Xiaobo Li, Rui Chen Abstract Poor survival among colorectal cancer (CRC) patients has been widely associated with clinico-epidemiological features and treatment regimen. In Jiangsu (China), however, it is not known which one of the prognostic factors explains the survival disparities among patients with CRC. This prospective study using 1078 patients (stages I-IV) that underwent surgery at Jiangsu Hospital, explored the relevant factors affecting the prognoses of right-side colon cancer (RCC), left-side colon cancer (LCC) and rectal cancer (ReC) patients. Of these cases, 234 (21.7%), 241 (22.4%) and 603 (55.9%) were found to have RCC, LCC and ReC respectively. Compared to LCC, RCC exhibited a greater proportion of older patients, poorly differentiated carcinomas, higher T-stage and higher TNM-stage. The overall survival (OS) for RCC was 60 vs.78 or 77 months for LCC or ReC respectively (P = 0.030). There were no significant differences in OS between LCC and ReC across the subgroups (P = 0.633). In multivariate analysis, RCC patients had age (>60 vs. ≤60 years, HR = 1.529, P = 0.019), N-stage (N1 vs. N0, HR = 4.056, P = 0.012) and M-stage (M1 vs. M0, HR = 3.442, P < 0.0001) as independent prognostic factors, whereas smoking status was found to be a predictor of mortality (smoker vs. nonsmoker, HR = 2.343, P = 0.017) for LCC. In addition, age (>60 vs. ≤60 years, HR = 2.199, P < 0.0001), alcohol consumption (drinker vs. nondrinker, HR = 0.510, P = 0.034), tumor grade (Poor vs. well/moderate, HR = 2.759, P = 0.031) and T-stage (T3-4 vs. T1-2, HR = 1.742, P < 0.0001) were found to be predictors of mortality for ReC. There were significant pairwise interactions across subgroups. Furthermore, significant differences were observed for LCC vs. RCC (OS, HR = 0.783, P = 0.039), but no statistically significant differences for ReC vs. RCC (P = 0.149) and LCC vs. ReC (P = 0.355). Nevertheless, significant differences remained between ReC vs. RCC for male (HR = 0.591, P = 0.009), drinker (HR = 0.396, P = 0.005), rural resident (HR = 0.437,P = 0.022), tumor grade (well/moderate, HR = 0.475, P = 0.022), T-stage (T1-2, HR = 0.362, P = 0.001), N-stage (N0, HR = 0.604, P = 0.011), M-stage(M0, HR = 0.401, P = 0.006) and TNM-stage (I-II, HR = 0.567, P = 0.005). Statistically significant differences were observed for LCC vs. RCC for gender (female, HR = 0.495, P = 0.003) and T-stage (T1-2, HR = 0.417, P = 0.010) as well as for LCC vs. ReC in patients with smoking habits (HR = 1.951, P = 0.002) and M-stage (M0, HR = 2.291, P = 0.003). These findings suggest that the variations in CRC post-surgical survival in China may be primarily explained with the clinicopathologic features and epidemiological characteristic of the patients. Patients with RCC had significantly worse OS compared to both LCC and ReC in several subgroups.

Incidence, mortality and outcome of meningiomas: A population-based study from Germany Publication date: October 2019 Source: Cancer Epidemiology, Volume 62 Author(s): Bernd Holleczek, Daniel Zampella, Steffi Urbschat, Felix Sahm, Andreas von Deimling, Joachim Oertel, Ralf Ketter Abstract Background Meningiomas are mostly benign tumors that originate from the coverings of the brain and spinal cord. Compared to malignant glial tumors, meningiomas are relatively understudied with regard to their risk factors and epidemiology. In particular, population-based data on cancer burden and patient outcomes are scant. Methods Population-based data from Saarland, a federal state in South-Western Germany, were used; the data included 992 patients diagnosed with a first meningioma between 2000 and 2015. Incidence and mortality rates—as well as estimates of observed and relative survival and cumulative incidence of tumor recurrence up to 10 years after diagnosis—were derived by sex, age, WHO grade, and whether or not the patient had undergone surgery. Results This population-based study not only included patients treated in the regional university hospital but also those treated elsewhere or patients without any surgical treatment. The mean age of the patients at diagnosis was 63 years, and 70%, 28% and 3% had WHO grade I, II and III meningiomas, respectively. Ten-year observed and relative survival of all patients combined was 72% and 91% respectively. Tumor-related mortality varied by sex and increased with age at diagnosis and the WHO grade of the tumor. The overall 10-year cumulative incidence of meningioma recurrence was 9%. Conclusion This analysis represents the first modern population-based analysis of meningioma incidence and mortality and outcomes of patients with such neoplasms in Germany. Derived from an unselected sample of patients, this study may fill a hitherto existing gap in the literature on meningiomas.

Birthweight and risk of thyroid cancer and its histological types: A large cohort study Publication date: October 2019 Source: Cancer Epidemiology, Volume 62 Author(s): Julie Aarestrup, Cari M. Kitahara, Jennifer L. Baker Abstract Background The aetiology of thyroid cancer is poorly understood, but it is possible that this malignancy has origins early in life. It is, however, currently unknown if birthweight, as an indicator of prenatal growth, is related to thyroid cancer risk. Objective To investigate if birthweight is associated with the later risk of thyroid cancer and its histological types. Methods 246,141 children (120,505 girls, 125,636 boys) from the Copenhagen School Health Records Register, born 1936–1989, were prospectively followed in the Danish Cancer Registry. Cox regressions were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). Results During follow up, 241 individuals (172 women, 69 men) were diagnosed with thyroid cancer (162 papillary, 53 follicular). Birthweight was significantly and positively associated with risk of thyroid cancer overall (HR = 1.30 [95% CI: 1.03–1.64] per kilogram). There were no sex differences in the associations. Birthweight was positively and significantly associated with follicular thyroid cancer (HR = 1.74 [95% CI: 1.07–2.82] per kilogram), and although there was an indication of a positive association, it did not reach statistical significance for the more common papillary type (HR = 1.20 [95% CI: 0.90–1.59] per kilogram). Conclusion A heavier weight at birth is associated with an elevated risk of total and follicular thyroid cancer, which underscores that prenatal exposures may be important in thyroid cancer aetiology.

Increasing incidence and survival of corpus uteri cancer in Estonia over the past two decades Publication date: October 2019 Source: Cancer Epidemiology, Volume 62 Author(s): Kristiina Ojamaa, Piret Veerus, Aleksei Baburin, Hele Everaus, Kaire Innos Abstract Background Corpus uteri cancer has become the fourth most common female cancer in Europe. In Estonia, the prevalence of obesity is increasing, and corpus uteri cancer survival has been relatively low. The aim of the study was to evaluate incidence, mortality and survival trends of corpus uteri cancer in Estonia by age, stage and histological subtypes with an emphasis on surgical treatment. Methods Estonian Cancer Registry data on incident cases of corpus uteri cancer were used to examine incidence trends (1995–2016) and calculate relative survival ratios (RSR) (1996–2016). Cases were classified by morphology and FIGO stage. Causes of Death Registry data were used to analyse corrected mortality (1995–2017). Results A total of 4281 cases were diagnosed in 1996–2016. A significant increase was seen in age-standardized incidence from 2009, while mortality remained stable throughout the study period. Significant increases were observed for type I cancers and age groups ≥65 years. Overall age-standardized 5-year RSR improved from 70% in 1996–2002 to 78% in 2010–2016. Survival increased for type I cancers, all age groups and all stages (significantly for stage IV). The proportion of surgically treated cases increased significantly from 85% to 89%, with the largest increases seen in older age groups and later stages. Discussion The rising corpus uteri cancer incidence in Estonia is driven by the type I cancer trend. Survival gain for later stages and older age groups likely reflected more frequent surgical treatment. To reduce mortality, further efforts are necessary to ensure appropriate care for all patients.

Screening baseline characteristics of early lung cancer on low-dose computed tomography with computer-aided detection in a Chinese population Publication date: October 2019 Source: Cancer Epidemiology, Volume 62 Author(s): Yuanyuan Liu, Hongbin Luo, Haomiao Qing, Xiaodong Wang, Jing Ren, Guohui Xu, Shibei Hu, Changjiu He, Peng Zhou Abstract Objectives This study investigated appropriate baseline characteristics for screening a Chinese population at high risk of early lung cancer, assisted by low-dose computed tomography (LDCT) with computer-aided detection (CAD). Included is a discussion of the viability of using LDCT in the screening guideline and optimizing the guideline. Methods In 2014, 1016 individuals from Sichuan Province were enrolled who satisfied the criteria for high risk according to the 2013 National Comprehensive Cancer Network (NCCN) Guidelines for Non-Small Cell Lung Cancer. From 2014 to 2018, each subject was followed using LDCT with CAD, and pathologically confirmed lung cancers and baseline nodule characteristics (size and density) were recorded. Positive risk was considered a non-calcified solid or part-solid nodule on LDCT with diameter ≥5 mm and ground-glass nodule ≥8 mm, as newly recommended by the China National Lung Cancer Screening Guideline. Results From 2014–2018, 13 cases of lung cancer were detected; 5 of these were early stage (38.5%). According to the NCCN criteria, 54 women were included and one of these (1.8%) developed lung cancer. The prevalence of lung cancer was 0.7% at baseline. For the entire population (excluding subjects with a tumor mass at baseline, n = 4), the rate of positivity was 20.4% at baseline; applying the Chinese criteria, the false positive rate was 19.5% (197/1012). Conclusions Further studies are warranted to establish appropriate eligible criteria and management strategies for Chinese populations.

Establishing population-based surveillance of diagnostic timeliness using linked cancer registry and administrative data for patients with colorectal and lung cancer Publication date: August 2019 Source: Cancer Epidemiology, Volume 61 Author(s): Clare Pearson, Jess Fraser, Michael Peake, Roland Valori, Veronique Poirier, Victoria H. Coupland, Sara Hiom, Sean McPhail, Jodie Moffat, Georgios Lyratzopoulos, Jon Shelton Abstract Background Diagnostic timeliness in cancer patients is important for clinical outcomes and patient satisfaction but, to-date, continuous monitoring of diagnostic intervals in nationwide incident cohorts has been impossible in England. Methods We developed a new methodology for measuring the secondary care diagnostic interval (SCDI - first relevant secondary care contact to diagnosis) using linked cancer registration and healthcare utilisation data. Using this method, we subsequently examined diagnostic timeliness in colorectal and lung cancer patients (2014–15) by socio-demographic characteristics, diagnostic route and stage at diagnosis. Results The approach assigned SCDIs to 94.4% of all incident colorectal cancer cases [median length (90th centile) of 25 (104) days] and 95.3% of lung cancer cases [36 (144) days]. Advanced stage patients had shorter intervals (median, colorectal: stage 1 vs 4 - 34 vs 19 days; lung stage 1&2 vs 3B&4 - 70 vs 27 days). Routinely referred patients had the longest (colorectal: 61, lung: 69 days) and emergency presenters the shortest intervals (colorectal: 3, lung: 14 days). Comorbidities and additional diagnostic tests were also associated with longer intervals. Conclusion This new method can enable repeatable nationwide measurement of cancer diagnostic timeliness in England and identifies actionable variation to inform early diagnosis interventions and target future research.

Development of predictive models to identify advanced-stage cancer patients in a US healthcare claims database Publication date: August 2019 Source: Cancer Epidemiology, Volume 61 Author(s): Daina B. Esposito, Leo Russo, Dina Oksen, Ruihua Yin, Vibha C.A. Desai, Jennifer G. Lyons, Patrice Verpillat, Jose L. Peñalvo, Francois-Xavier Lamy, Stephan Lanes Abstract Background Although healthcare databases are a valuable source for real-world oncology data, cancer stage is often lacking. We developed predictive models using claims data to identify metastatic/advanced-stage patients with ovarian cancer, urothelial carcinoma, gastric adenocarcinoma, Merkel cell carcinoma (MCC), and non-small cell lung cancer (NSCLC). Methods Patients with ≥1 diagnosis of a cancer of interest were identified in the HealthCore Integrated Research Database (HIRD), a United States (US) healthcare database (2010–2016). Data were linked to three US state cancer registries and the HealthCore Integrated Research Environment Oncology database to identify cancer stage. Predictive models were constructed to estimate the probability of metastatic/advanced stage. Predictors available in the HIRD were identified and coefficients estimated by Least Absolute Shrinkage and Selection Operator (LASSO) regression with cross-validation to control overfitting. Classification error rates and receiver operating characteristic curves were used to select probability thresholds for classifying patients as cases of metastatic/advanced cancer. Results We used 2723 ovarian cancer, 6522 urothelial carcinoma, 1441 gastric adenocarcinoma, 109 MCC, and 12,373 NSCLC cases of early and metastatic/advanced cancer to develop predictive models. All models had high discrimination (C > 0.85). At thresholds selected for each model, PPVs were all >0.75: ovarian cancer = 0.95 (95% confidence interval [95% CI]: 0.94–0.96), urothelial carcinoma = 0.78 (95% CI: 0.70–0.86), gastric adenocarcinoma = 0.86 (95% CI: 0.83–0.88), MCC = 0.77 (95% CI 0.68–0.89), and NSCLC = 0.91 (95% CI 0.90 – 0.92). Conclusion Predictive modeling was used to identify five types of metastatic/advanced cancer in a healthcare claims database with greater accuracy than previous methods.

Net survival in recurrence-free colon cancer patients Publication date: August 2019 Source: Cancer Epidemiology, Volume 61 Author(s): Antoine Drouillard, Anne-Marie Bouvier, Olayidé Boussari, Gaëlle Romain, Sylvain Manfredi, Come Lepage, Jean Faivre, Valérie Jooste Abstract Purpose Conditional net survival in recurrence-free patients (CNS-RF) provides relevant clinical information and has never been assessed yet in a non-selected colon cancer population. We aimed to estimate conditional 5-year net survival in recurrence-free patients with colon cancer in the population-based Digestive Cancer Registry of Burgundy (France). Methods CNS-RF was estimated in the 3736 patients resected for cure for primary colon cancer between 1976 and 2006, using a flexible parametric model of net survival for every additional year survived at diagnosis and from 1 to 5 years thereafter. Results The net probability of surviving 5 more years increased from 72% at diagnosis to 92% for recurrence-free patients who survived 5 years after diagnosis. CNS-RF was over 90% 3 years after diagnosis in patients aged 75 and below. CNS-RF was over 95% in patients diagnosed after 2000 who were recurrence-free 3, 4 or 5 years after diagnosis. CNS-RF was similar between patients with stage I and II disease from 2 years after diagnosis and patients with stage III disease from 5 years after diagnosis. The initial differences in net survival related to gross features, clinical presentation, number of harvested nodes in stage II, and number of involved nodes in stage III disappeared after 2 years. Conclusions CNS-RF is a relevant measure of prognosis in patients who have already achieved a period of remission. Providing an updated estimation of prognosis in the years following diagnosis may improve the survivors' quality of life and access to credit or insurance.

Defining a mutational signature for endometrial cancer screening and early detection Publication date: August 2019 Source: Cancer Epidemiology, Volume 61 Author(s): Laura Costas, Luis Palomero, Yolanda Benavente, Magdalena Guardiola, Jon Frias-Gomez, Miquel Ángel Pavón, Maite Climent, José Manuel Martinez, Marc Barahona, Mónica Salinas, Marta Pineda, Ilaria Bianchi, Jaume Reventós, Gabriel Capellà, Mireia Diaz, August Vidal, Josep Maria Piulats, Jordi Ponce, Joan Brunet, Francesc Xavier Bosch Abstract Introduction The current availability of genomic information represents an opportunity to develop new strategies for early detection of cancer. New molecular tests for endometrial cancer may improve performance and failure rates of histological aspirate-based diagnosis, and provide promising perspectives for a potential screening scenario. However, the selection of relevant biomarkers to develop efficient strategies can be a challenge. Materials and methods We developed an algorithm to identify the largest number of patients with endometrial cancer using the minimum number of somatic mutations based on The Cancer Genome Atlas (TCGA) dataset. Results The algorithm provided the number of subjects with mutations (sensitivity) for a given number of biomarkers included in the signature. For instance, by evaluating the 50 most representative point mutations, up to 81.9% of endometrial cancers can be identified in the TCGA dataset. At gene level, a 92.9% sensitivity can be obtained by interrogating five genes. Discussion We developed a computational method to aid in the selection of relevant genomic biomarkers in endometrial cancer that can be adapted to other cancer types or diseases.

Neuroblastoma in relation to joint effects of vitamin A and maternal and offspring variants in vitamin A-related genes: A report of the Children's Oncology Group Publication date: August 2019 Source: Cancer Epidemiology, Volume 61 Author(s): Angela L. Mazul, Clarice R. Weinberg, Stephanie M. Engel, Anna Maria Siega-Riz, Fei Zou, Kathryn S. Carrier, Patricia V. Basta, Zalman Vaksman, John M. Maris, Sharon J. Diskin, Charlene Maxen, Arlene Naranjo, Andrew F. Olshan Abstract Background There is evidence vitamin A plays a role in neuroblastoma. Not only is 13-cis-retinoic acid used as maintenance therapy for high-risk cases, but prenatal vitamin intake use may decrease neuroblastoma risk. We hypothesized that single nucleotide polymorphisms (SNPs) in vitamin A-related genes are may be associated with neuroblastoma risk and potentially be modified by vitamin A intake. Methods The Neuroblastoma Epidemiology in North America (NENA) study recruited 563 case-parent sets through the Children's Oncology Group's Childhood Cancer Research Network. We ascertained dietary nutrient intake through questionnaires and genotyped 463 SNPs in vitamin A-related genes from saliva DNA. Offspring and maternal log-additive risk ratios (RR) and stratum-specific RR for gene-environment interaction were estimated with a log-linear model. We avoided false positives due to multiple testing by using the false discovery rate (FDR). Results When all neuroblastoma cases were considered together, no offspring variants met the significance criteria (FDR Q-value < 0.2). One maternal SNP (rs12442054) was associated with decreased risk of neuroblastoma (RR: 0.61; 95% Confidence Interval (CI): 0.47–0.79, Q = 0.076). When the cases were categorized according to prognostic risk category and age at onset, nine offspring SNPs were significantly associated with intermediate-risk neuroblastoma. Maternal rs6776706 was associated with (RR: 0.49; 95% CI: 0.33–0.72, Q = 0.161) high-risk neuroblastoma and maternal rs11103603 (RR: 0.60; 95% CI: 0.45–0.79, Q = 0.127) was associated with neuroblastoma aged <1 year. For gene-environment interaction, maternal rs729147 was associated with decreased risk of neuroblastoma among mothers with vitamin A consumption above the recommendation. Conclusions Although there is biologic plausibility for the role of vitamin A in neuroblastoma, we found weak evidence of a relationship between vitamin A related genes and neuroblastoma.

Alexandros Sfakianakis
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alsfakia@gmail.com