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
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Journal of Voice

Reply to Functional Dysphonia: A Clear Need for Differential Diagnosis Publication date: Available online 18 July 2019 Source: Journal of Voice Author(s): Tamonud Modak

Factor Analysis of the Persian Version of the Voice Disability Coping Questionnaire Publication date: Available online 16 July 2019 Source: Journal of Voice Author(s): Farzaneh Salehimanesh, Majid Soltani, Maryam Dastoorpoor, Negin Moradi Abstract Introduction Voice disorders can affect the quality of life and coping mechanisms and also coping mechanisms can affect the way in which patients deal with their voice problems. People with voice disorders need to use coping strategies to deal with the problems caused by their voice disorder. The purpose of this study was to examine the psychometric properties and cultural adaptation of the Voice Disability Coping Questionnaire in the Iranian population. Methods The translation and cross-cultural adaptation procedures were performed according to the basic rules and instructions set by the International Quality of Life Assessment Project. Two hundred and forty-eight adults (218 patients with voice disorder and 30 healthy controls) were participated in the study. Face and content validity, clinical validity, and construct validity of the questionnaire were investigated by modern psychometric methods. Results Quantitative methods were used to measure content validity and all items were detected applicable. This means that the final version was clear and easy to answer. Clinical validity shows that the Persian version of VDCQ can distinguish between patients and healthy controls (P < 0.001). The construct validity of the VDCQ was tested in a cross-sectional study. The questionnaire was analyzed by exploratory and confirmatory factor analyses. Investigation of initial communality and after extraction of factors by Varimax rotation method showed that the share of items for all items in the questionnaire except item 12, is higher than 0.5. Therefore, item 12 should be removed from the questionnaire (Table 3). Based on the confirmatory factor analysis model, items 2 and 10, whose factor load were less than 0.4, were excluded from the questionnaire (Fig. 1). For reliability the Cronbach's alpha coefficient and ICC were obtained as 0.82 and 0.99, respectively. The results of studying the role of items in the reliability of the VDCQ showed that all items increase internal consistency. Conclusion Based on modern statistical analysis conducted in this study, the original 15 item questionnaire was reduced to 12 item. The 12 item questionnaire is a valid and reliable tool for quantifying coping strategies in people with voice disorder.

Vocal Fold "Paralysis": An Early Sign in Multiple System Atrophy Publication date: Available online 16 July 2019 Source: Journal of Voice Author(s): Philip W. Tipton, Dale C. Ekbom, Amy L. Rutt, Jay A. van Gerpen Summary Multiple system atrophy (MSA) is a neurodegenerative disease characterized by a cerebellar syndrome, autonomic dysfunction, and extrapyramidal signs. Extrapyramidal signs may manifest as parkinsonism as well as dystonia, which is the involuntary contraction of a muscle(s) resulting in an abnormal posture. MSA belongs to a family of diseases known as α-synucleinopathies which are associated with dream enactment reflecting REM sleep behavior disorder (RBD). In patients with MSA, dystonia or paresis may involve the laryngeal muscles resulting in vocal fold hypomobility. We identified four individuals presenting with vocal complaints and subsequently diagnosed with vocal fold "paralysis." Within one year, each patient developed neurologic symptoms and upon evaluation by a movement disorders specialist was diagnosed with probable MSA. Our findings highlight the importance of screening by otolaryngologists when patients are diagnosed with vocal fold hypomobility. Specifically, patients should be assessed for RBD by questioning others if he/she acts out their dreams. The presence of RBD raises clinical suspicion for a synucleinopathy such as MSA. Untreated patients with MSA experiencing nocturnal stridor and breathing disorders have an increased risk for sudden death. Therefore, early evaluation by a movement disorders specialist to promptly diagnose MSA may have a substantial effect on morbidity and mortality in this high-risk patient population.

Book Review of Janet Baker's book, "Psychosocial Perspectives on the Management of Voice Disorders: Implications for Client, Options and Strategies for Clinicians." Publication date: Available online 15 July 2019 Source: Journal of Voice Author(s): Miriam van Mersbergen

Long-Term Effects of a Voice Training Program to Prevent Voice Disorders in Teachers Publication date: Available online 13 July 2019 Source: Journal of Voice Author(s): Birte Meier, Ulla Beushausen Abstract Objectives Research findings about long-term effectiveness of voice training programs for teachers are limited. This study shows long-term evaluation results of a statewide voice training program for teachers in Lower Saxony/Germany. Method Twenty-seven voice training sessions with 286 participating teachers were evaluated with different questionnaire surveys on three different occasions (prior and after seminar, follow-up 3 months later). Prior the training and 3 months after completion of the training the validated self-assessment tool Voice Profile for Professional Voice users (VPPV) was used to measure subjective impact of voice problems on the participating teachers. In addition, questionnaires to evaluate benefits of the seminars for everyday working life, possible voice changes and satisfaction with the program were used. Results Prior the training 64.9% of the participating teachers were above the cut-off point of the VPPV that indicates a high subjective impact of voice problems. Three month after the training this number decreased by −14.9% down to 50% (P= 0.001, T = 3.437, df = 314). Ninety-three percent of the respondents implemented aspects of the voice training seminar in their occupational everyday life. Furthermore, teachers showed a slight or considerable improvement of their vocal resilience (72.2%) 3 months after the training. This included rarer clearing of the throat (80.6%) and/or a reduction of vocal tract discomfort symptoms (66%). Conclusion The results indicate that a vast majority of teachers implement contents of the voice training program in their occupational everyday life and that these changes in behavior lead to a better vocal capacity and vocal performance. Nevertheless, the number of teachers that have a mean value in the VPPV that can be regarded as very high self-perceived voice impact which indicates a risk for a voice disorder is still high after the voice training. Voice training sessions held so far proofed to be an important aspect to reduce self-perceived voice impact in teachers in Lower Saxony/Germany.

Intraglottal Pressure: A Comparison Between Male and Female Larynxes Publication date: Available online 13 July 2019 Source: Journal of Voice Author(s): Sheng Li, Ronald C. Scherer, MingXi Wan, SuPin Wang, Bo Song Summary Acoustic differences in the phonated sounds made by men and women are related to laryngeal and vocal tract structural differences. This model-based study explored how typical vocal fold differences between males and females affect intraglottal pressure distributions under conditions of different glottal angles and transglottal pressures, and thus how they may affect phonation. The computational code ANSYS Fluent 6.3 was used to obtain the pressure distributions and other aerodynamic parameters for laminar, incompressible flow. Typical values of the vocal fold length, the vertical glottal duct length, and the lateral vocal fold tissue depth were selected both for males and females under conditions of nine typical convergent/divergent glottal angles and three transglottal pressures. There was no coupling of the upstream or downstream vocal tracts, and also no vocal fold contact in these two-dimensional static glottal geometries. Results suggest that males tend to have greater intraglottal pressures for the convergent glottal shape that occurs during glottal opening, and the male glottis offers less flow resistance than the female glottis. These results suggest that the male vocal folds may vibrate more easily (ie, with lower transglottal pressure) but the tissue differences may nullify such an hypothesis. Also, the peak velocities in the glottis were dependent on the transglottal pressure driving the flow and the minimal glottal diameter, which were the same for both the male and female larynxes, rather than on the inferior-superior length of the glottis or the anterior-posterior glottal length. In addition, the tangential forces for larger glottal convergent angles was significantly greater in the female larynx. The entrance loss coefficients, however, were similar between the male and female larynxes, except for the uniform glottis for which the values were larger for the male larynx. The results suggest that the structural differences between male and female vocal folds should be well specified when building computational and physical models of the larynx.

Dehydration and Estrous Staging in the Rat Larynx: an in vivo Prospective Investigation Publication date: Available online 13 July 2019 Source: Journal of Voice Author(s): Abigail Cox, Naila Cannes do Nascimento, Andrea Pires dos Santos, M. Preeti Sivasankar Abstract Objective This novel study sought to untangle the association between hydration state and the estrous cycle in the vocal folds, since the voice is reported to negatively change in speakers during the estrous cycle and with dehydration. We hypothesized that there would be alterations in vocal fold tissue morphology depending on hydration state and that these changes would vary with the estrous cycle. Study Design Prospective, in vivo study design. Methods Female Sprague Dawley rats (n = 30) were used in this study. Sixteen rats were systemically dehydrated to an average of 10% reduction in body weight by withholding water (range of body weight loss: 8%–13%). Fourteen rats were assigned to euhydrated, control condition. Estrous stage of female Sprague Dawley rats (n = 30) was determined via cytological evaluation of vaginal smears. Following euthanization, larynges were prepared for histological staining with hematoxylin and eosin, Masson's trichrome and alcian blue (pH 2.5). To quantify hyaluronan, alcian blue staining was completed pre- and posthyaluronidase incubation. The change in staining percent was quantified with image analysis algorithms and reported as the hyaluronan quantity. Relative collagen distribution (index of dehydration), hyaluronan quantity, and tissue morphology were the outcome measures. Results Systemic dehydration was associated with changes in hyaluronan quantity in the rat vocal fold lamina propria. Dehydration did not significantly affect the collagen distribution nor the tissue morphology. Estrous stage alone does not impact the quantity of vocal fold hyaluronan, alter tissue morphology, or change collagen distribution. Conclusion Decreases in hyaluronan quantity in the lamina propria of the rat vocal fold may play a role in tissue fluid balance during systemic dehydration. Future studies will expand this work to investigate additional components of the vocal fold extracellular matrix to fully elucidate the impact of hydration state on the vocal fold.

Translation and Cross-Cultural Adaptation of the Newcastle Laryngeal Hypersensitivity Questionnaire to Brazilian Portuguese Publication date: Available online 13 July 2019 Source: Journal of Voice Author(s): Vanessa Veis Ribeiro, Anne Vertigan, Mara Behlau Abstract Objective To translate and cross-culturally adapt the Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) to the Brazilian Portuguese language. Material and methods The translation and cross-cultural adaptation procedures were performed in five stages: translation, synthesis, back-translation, committee review, and pretest performance. Results At the end of the first four stages, a questionnaire was produced in Brazilian Portuguese, known as the Questionário Newcastle de Hipersensibilidade Laríngea (LHQ-Br). This version was given as a pretest to 31 participants with laryngeal hypersensitivity: 14 were in the muscle tension dysphonia clinical group, 10 in the refractory chronic cough group, and seven in the globus pharyngeus group. There was a difference in the frequency of occurrence choices in question five ("my throat is blocked"; P = 0.007) and question eight ("I have a sensation of something pushing on my chest"; P = 0.026), but in both questions, the frequency choice of "never" was significantly higher than the other options in all three clinical groups. The relative frequency of participants picking the 'nonapplicable' option in all clinical groups for all questions was zero. Conclusion This study showed satisfactory results for the translation and cross-cultural adaptation of the LHQ to Brazilian Portuguese (LHQ-Br).

Monitoring Breathing Muscle Performance During Singing Noninvasively Using Mechanomyography and Electromyography Publication date: Available online 9 July 2019 Source: Journal of Voice Author(s): Muhammad Imran Ramli, Nur Azah Hamzaid, Julia Patrick Engkasan Abstract Objectives The aim of this study was to investigate the performance of mechanomyography (MMG) and electromyography (EMG) in monitoring the sternocleidomastoid (SCM) as accessory respiratory muscles when breathing during singing. Methods MMG and EMG were used to record the activity of the SCM in 32 untrained singers reciting a monotonous text and a standard folk song. Their voices were recorded and their pitch, or fundamental frequency (FF), and intensity were derived using Praat software. Instants of inhale and exhales were identified during singing from their voice recordings and the corresponding SCM MMG and EMG activities were analysed. Results The SCM MMG, and EMG signals during breathing while singing were significantly different than breathing at rest (p < 0.001). On the other hand, MMG was relatively better correlated to voice intensity in both reading and singing than EMG. EMG was better, but not significantly, correlated with FF in both reading and singing as compared to MMG. Conclusions This study established MMG and EMG as the quantitative measurement tool to monitor breathing activities during singing. This is useful for applications related to singing therapy performance measure including potentially pathologically effected population. While the MMG and EMG could not distinguish FF and intensity significantly, it is useful to serve as a proxy of inhalation and exhalation levels throughout a particular singing session. Further studies are required to determine its efficacy in a therapeutic setting.

Laboratory Evaluation of Spasmodic Dysphonia Publication date: Available online 6 July 2019 Source: Journal of Voice Author(s): Sammy Othman, Srihari Daggumati, Rohan Patel, Justin Ross, Robert T. Sataloff Summary Objectives To evaluate the utility of comprehensive laboratory evaluation in patients with spasmodic dysphonia (SD). Study Design Retrospective chart review. Methods A review of the medical records of 40 patients diagnosed with spasmodic dysphonia from 2009-2018 was preformed to evaluate abnormal test results that were significant when compared with abnormal results of the general population and for any other clinically relevant pathology. Results Erythrocyte sedimentation rate, ceruloplasmin levels, and anti-AChR were found to be elevated at levels considered statistically significant (p <0.05). Furthermore, we found levels of cholesterol, thyroid-stimulating hormone (TSH), T3, fasting blood glucose, creatine kinase, immunoglobulin, antinuclear antibody (ANA), and alpha-fetoprotein (AFP) levels to be abnormal at a greater rate in our population, but these were not statistically significant. Workup revealed several underlying conditions including thyroid neoplasms, hypothyroidism, and laryngopharyngeal reflux. Additionally, brain MRI revealed age-related ischemic pathology in an elevated number of patients, but with no obvious clinical sequalae. Conclusion There is an association between serological values and spasmodic dysphonia that can aid in diagnosing pathology, as well as establishing a directed workup. Additionally, our study shows the utility of comprehensive evaluation in identifying undetected disease.

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

6948891480

alsfakia@gmail.com

Medicine - Vol. 98, No. 29, July 2019 Lippincott Journals eTOC

Therapeutic effect of lutein supplement on non-proliferative diabetic retinopathy: A retrospective study This study retrospectively evaluated the effect of lutein supplement (LS) on patients with non-proliferative diabetic retinopathy (NPDR). A total of 72 patients with NPDR were included in this study. All patients received Zeaxanthin during the study period. In addition, 36 patients also received LS and were assigned to the treatment group, while the other 36 patients did not receive LS and were assigned to the control group. All patients were treated for a total of 4 months. The endpoints included visual acuity (VA), contrast sensitivity (CS), and glare sensitivity (GS). In addition, any adverse events were also assessed. All endpoints were measured before and after 4-month treatment. Before treatment, there were no significant differences in VA (P = .75), CS (P = .71), and GS (P = .73) between two groups. After 4-month treatment, there were still no significant differences in all endpoints of VA (P = .66), CS (P = .58), and GS (P = .61) between two groups. No adverse events were recorded in either group. The results of this retrospective study showed that LS may not benefit for patients with NPDR after 4-month treatment. More high quality randomized controlled trials should still be needed to warrant the results of this study.

Diagnostic value of polymerase chain reaction/acid-fast bacilli in conjunction with computed tomography–guided pleural biopsy in tuberculous pleurisy: A diagnostic accuracy study Patients with tuberculous pleurisy often remain undiagnosed even after blind thoracentesis and closed pleural biopsy (PB). In this study, we assessed the value of computed tomography (CT)-guided core needle biopsy of pleural lesion and evaluated the diagnostic accuracy of polymerase chain reaction (PCR)/staining for acid-fast bacilli (AFB) in suspicious tuberculous pleurisy undiagnosed in blind thoracentesis. Patients with exudative pleural effusion (PE) without specific etiology after blind thoracentesis and closed PB were enrolled in this study. PB specimens were obtained through CT-guided core needle biopsy of pleural lesion, then underwent PCR, AFB, histopathological examination, and some routine tests. Diagnostic values were evaluated through sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. A total of 261 participants (TB group: 241, non-TB group: 20) were recruited. In this cohort, the sensitivity, specificity, and accuracy were 56.0%, 95.0%, and 59.0%, respectively for PCR, whereas 57.3%, 95.0%, and 60.2%, respectively for AFB. Their parallel test achieved an improved sensitivity (76.8%) and accuracy (77.8%), with a slight decrease in specificity (90.0%). In histopathological examination, granuloma was the most common finding in TB group (88.4%, 213/241), but also observed in non-TB group (10.0%, 2/20). In addition, pleural lymphocyte percentage in TB group was significantly higher than that of non-TB group (92% vs 61%, respectively; P = .003). However, no significant differences were found for other biomarkers. CT-guided core needle PB is essential for patients with exudative PE but undiagnosed after blind thoracentesis. Combining with PCR and AFB, it strongly improves the diagnosis of tuberculous pleurisy.

Prognostic role of C-reactive protein to albumin ratio in colorectal cancer: A meta analysis Objective: This meta-analysis evaluates the prognosis value of C-reactive protein to albumin ratio (CAR) in colorectal cancer. Methods: Embase, PubMed, and Web of Science were searched. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used as effective values. Results: A total of 6 studies with 1942 patients were included in this study. Pooled results revealed that elevated pretreatment CAR was related with poorer overall survival (OS) (HR: 2.09, 95%CI: 1.78–2.45, P < .001) in colorectal cancer. Conclusion: Elevated CAR was associated with poor prognosis in colorectal cancer. Thus CAR might be used as a prognostic system and classification of colorectal patients in clinical potential.

Efficacy of prison-based cognitive behavioral rehabilitation intervention on violent sexual behaviors among sex offenders in Nigerian prisons Background/Objective: Evidence showed that reoffending habits are increasing among offenders with violent sexual behaviors. Given the recidivism rates, a psychotherapeutic intervention becomes imperative. This study examined the efficacy of prison-based cognitive behavioral rehabilitation intervention (PCBRI) on violent sexual behaviors among sex offenders in Nigerian prisons. Method: A total of45 participants were the sample size. Compulsive Sexual Behavior Inventory and Hypersexual Behavior Inventory were employed in assessing the participants at 3 points. Using a simple random allocation sequence, 23 participants were exposed to PCBRI programme and 22 participants allocated to control condition. The data obtained were analyzed using repeated measures 2-way analysis of variance. Results: Results indicated a significant effect of the treatment on violent sexual behaviors among sex offenders in Nigerian prisons exposed to the PCBRI programme when compared to the no-intervention group. Result also showed a significant interaction effect of time and group on sex offenders with violent sexual behaviors. Follow-up tests showed significant decrease in violent sexual behaviors after 6 months for the PCBRI group in comparison to the control group. Conclusion: This study concluded that PCBRI approach is a type of psychotherapy that reduces violent sexual behaviors among sex offenders in Southeast Nigeria.

Correction of labial tubercle defect in repaired bilateral cleft lips using bilateral vermilion musculomucosal sliding flaps: Case series Rationale: Insignifificant, asymmetrical or lack of labial tubercle often occurs after cleft lip surgery due to improper treatment of vermilion tissue. Especially in the cases of bilateral cleft lip, because of short front lip and insuffificient vermilion tissue, the median vermilion depression often occurs after surgery, forming a "whistling" deformity. The object of this study is to verify the outcomes of patients with median labial tubercle detects after treatment with bilateral vermilion musculomucosal sliding flflaps (VMSF). Patient concerns: Six patients with median labial tubercle defect after bilateral cleft lip repair from March 2015 to May 2017 were enrolled in our department and subjected to bilateral lip deformity correction under general anesthesia. Diagnoses: Secondary deformity of bilateral cleft lip forming a "whistling" deformity were diagnosed in all the patients. Interventions: Bilateral VMSF were designed and used to reconstruct the median labial tubercles by sliding downward so as to eliminate the whistling deformity. Outcomes: During the 10 to 37 months of follow-up, the reconstructed vermilion tubercles had stable morphology showing no whistling deformity and the overall lip shapes were satisfactory. Lessons: Reconstructing MVTD and eliminating whistling deformity using the scar tissues that need to be removed previously on the vermilion musculomucosa has achieved stable and satisfactory results and is worthy of clinical application.

Upregulation of microRNA-191 can serve as an independent prognostic marker for poor survival in prostate cancer MicroRNA-191 (miR-191) has been identified as being upregulated in several types of cancers, and plays the role of oncogene. The expression of miR-191 has been found to be upregulated in prostate cancer tissues as well as cell lines. In this study, we analyzed the correlation of miR-191 expression with clinicopathologic factors and prognosis in prostate cancer. Prostate cancer tissue samples and adjacent normal prostate tissue samples were collected from 146 patients who underwent laparoscopic radical prostatectomy between April 2013 and March 2018. Student two-tailed t-test was used for comparisons of 2 independent groups. The relationships between miR-191 expression and different clinicopathological characteristics were evaluated using the Chi-squared test. Kaplan–Meier survival plots and log-rank tests were used to assess the differences in overall survival of the different subgroups of prostate cancer patients. miR-191 expression was significantly higher in prostate cancer tissues compared with normal adjacent prostate tissues (P < .001). miR-191 expression was observed to be significantly correlated with Gleason score (P < .001), pelvic lymph node metastasis (P = .006), bone metastases (P < .001), and T stage (P = .005). Kaplan–Meier analysis showed that patients with higher levels of miR-191 had significantly poorer survival than those with lower expression of this miRNA in prostate cancer patients (log rank test, P = .011). Multivariate analysis revealed that miR-191 expression (hazard ratio [HR] = 2.311, 95% confidence interval, [CI]: 1.666–9.006; P = .027) was independently associated with the overall survival of prostate cancer patients. Our results demonstrated that miR-191 might serve as an independent prognostic indicator for prostate cancer patients.

Autologous hematopoietic stem cell transplantation for human immunodeficiency virus associated gastric Burkitt lymphoma: A case report Rationale: HIV-related lymphoma, especially non-Hodgkin lymphoma, is one of the most common malignant tumors in HIV/acquired immune deficiency syndrome (AIDS) patients. Autologous hematopoietic stem cell transplantation (AHSCT) for the patients with Burkitt lymphoma (BL) is needed to be further explored. Patient concerns: A 57-year-old man was hospitalized with intermittent pain on upper abdomen and melena for >1 month. Diagnosis: HIV antibody testing was positive. The upper gastrointestinal endoscopy was performed and histopathology and immunohistochemistry revealed BL. Interventions: Highly effective antiretroviral therapy and sixth cycles of chemotherapy were administered, followed by autologous hematopoietic stem cell transplantation. Outcomes: The patient has had tumor-free survival for >6 years with normal CD4+ T cell counts and HIV viral load below the lowest detection Lessons: The patient was treated with AHSCT followed complete remission after chemotherapy and achieved long-term disease-free survival. AHSCT may be a promising way for clinical cure of HIV-related BL.

Diagnostic accuracy of different computer-aided diagnostic systems for malignant and benign thyroid nodules classification in ultrasound images: A systematic review and meta-analysis protocol Objective: The aim of this study was to determine the diagnostic accuracy of different computer-aided diagnostic (CAD) systems for thyroid nodules classification. Methods: A systematic search of the literature was conducted from inception until March, 2019 using the PubMed, EMBASE, Web of science, and Cochrane library. Literature selection and data extraction were conducted by 2 independent reviewers. Numerical values for sensitivity and specificity were obtained from false negative (FN), false positive (FP), true negative (TN), and true positive (TP) rates, presented alongside graphical representations with boxes marking the values and horizontal lines showing the confidence intervals (CIs). Summary receiver operating characteristic (SROC) curves were applied to assess the performance of diagnostic tests. Data were processed using Review Manager 5.3 and Stata 15. The methodological quality of included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Trial registration number: PROSPERO CRD42019132540

The erector spinae plane block for effective analgesia after lung lobectomy: Three cases report Rationale: The thoracic epidural block and thoracic paravertebral block are widely used techniques for multimodal analgesia after thoracic surgery. However, they have several adverse effects, and are not technically easy. Recently, the erector spinae plane block (ESPB), an injected local anesthetic deep to the erector spinae muscle, is a relatively simple and safe technique. Patient concerns: Three patients were scheduled for video assisted thoracoscopic lobectomy with mediastinal lymph node dissection. All the patients denied any past medical history to be noted. Diagnoses: They were diagnosed with primary adenocarcinoma requiring lobectomy of lung. Interventions: The continuous ESPB was performed at the level of the T5 transverse process. The patient was received the multimodal analgesia consisted of oral celecoxib 200 mg twice daily, intravenous patient-controlled analgesia (Fentanyl 700 mcg, ketorolac 180 mg, total volume 100 ml), and local anesthetic (0.375% ropivacaine 30 ml with epinephrine 1:200000) injection via indwelling catheter every 12 hours for 5 days. Additionally, we injected a mixture of ropivacaine and contrast through the indwelling catheter for verifying effect of ESPB and performed Computed tomography 30 minutes later. Outcomes: The pain score was maintained below 3 points for postoperative 5 days, and no additional rescue analgesics were administered during this period. In the computed tomography, the contrast spread laterally from T2-T12 deep to the erector spinae muscle. On coronal view, the contrast spread to the costotransverse ligament connecting the rib and the transverse process. In the 3D reconstruction, the contrast spread from T6-T10 to the costotransverse foramen. Lessons: Our contrast imaging data provides valuable information about mechanism of ESPB from a living patient, and our report shows that ESPB can be a good option as a multimodal analgesia after lung lobectomy.

Association of CTLA-4 tagging polymorphisms and haplotypes with hepatocellular carcinoma risk: A case-control study It has been proposed that cytotoxic T-lymphocyte antigen 4 (CTLA-4) may attenuate the T-cell activation threshold, thereby decreasing the antitumor response and conferring susceptibility to hepatocellular carcinoma (HCC). In the present study, we selected CTLA-4 tagging single nucleotide polymorphisms (SNPs) and explored the relationship between these polymorphisms and susceptibility to HCC. A hospital-based case-control study, comprising 584 cases with HCC and 923 controls, was performed in an eastern Chinese Han population. CTLA-4 SNPs were genotyped using a custom-by-design 48-Plex SNPscan Kit. We found that the CTLA-4 rs3087243 G>A polymorphism might be associated with increased risk of HCC (GA vs GG: adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.04–1.85; P = .028 and AA/GA vs GG: adjusted OR, 1.43; 95% CI, 1.08–1.89; P = .012). After using Bonferroni correction, this association remained (P = .012 for the AA/GA vs GG genetic model). In addition, the power value was 0.904 in the AA/GA versus GG genetic model. Haplotype analysis showed that CTLA4 Crs16840252Ars231775Ars3087243Trs733618, Crs16840252Grs231775Ars3087243Trs733618, and other haplotypes might increase the risk of HCC risk (P = .018, <.001, and .017, respectively). However, we found that CTLA4 Trs16840252A rs231775Grs3087243Trs733618 decreased the risk of HCC (P = .020). Our results suggest that the CTLA-4 rs3087243 G>A polymorphism increases susceptibility to HCC in an eastern Chinese Han population. CTLA-4 haplotypes may influence the development of HCC. In the future, a population-based fine-mapping study with functional assessment should be performed to further determine these potential correlations.

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

6948891480

alsfakia@gmail.com