Burden of celiac disease in the Mediterranean area

AIM: To estimate the burden of undiagnosed celiac disease (CD) in the Mediterranean area in terms of morbidity, mortality and health cost. METHODS: For statistics regarding the population of each country in the Mediterranean area, we accessed authoritative international sources (World Bank, World Health Organization and United Nations). The prevalence of CD was obtained for most countries from published reports. An overall prevalence rate of 1% cases/total population was finally estimated to represent the frequency of the disease in the area, since none of the available conf idence intervals of the reported rates significantly excluded this rate. The distribution of symptoms and complications was obtained from reliable reports in the same cohort. A standardized mortality rate of 1.8 was obtained from recent reports. Crude health cost was estimated for the years between symptoms and diagnosis for adults and children, and was standardized for purchasing power parity to account for the different economic prof iles amongst Mediterranean countries. RESULTS: In the next 10 years, the Mediterranean area will have about half a billion inhabitants, of which 120 million will be children. The projected number of CD diagnoses in 2020 is 5 million cases (1 million celiac children), with a relative increase of 11% compared to 2010. Based on the 2010 rate, there will be about 550 000 symptomatic adults and about 240 000 sick children: 85% of the symptomatic patients will suffer from gastrointestinal complaints, 40% are likely to have anemia, 30% will likely have osteopenia, 20% of children will have short stature, and 10% will have abnormal liver enzymes. The estimated standardized medical costs for symptomatic celiac patients during the delay between symptom onset and diagnosis (mean 6 years for adults, 2 years for children) will be about €4 billion (€387 million for children) over the next 10 years. A delay in diagnosis is expected to increase mortality: about 600 000 celiac patients will die in the next 10 years, with an excess of 44.4% vs age-and sexmatched controls. CONCLUSION: In the near future, the burden of CD will increase tremendously. Few Mediterranean countries are able to face this expanding epidemic alone.

Macrophage sequestration of HIV-1 enhances homeostatic-related systems in promoting viral spread and replication

Decisive modulatory systems of compromise and systems of dynamic turnover in lymphoid cells and macrophages are activated by repeated bursts of viremia and as promotional schemes of representation of subsequent spread and replication of HIV-1. In such operative systems of micro-environmental conditioning and reconditioning, a significant mechanism towards the turnover of specific cell-types occurs within context of sequestration within macrophages and circulating monocytes. Dendritic cells in germinal follicles and within specific organs such as the Langerhans cells of the skin are allied to dysfunctionality of such cellular subtypes as exemplified by the resident microglia of the central nervous system. Decisive perturbation in cell-type number and in dysfunctional activation indicate an exquisite modulatory role for HIV-1 in promoting homeostatic-related mechanisms within organs and tissues towards utilization in terms of viral dynamics and cytokine operability. In such manner, HIV-1 replication is itself a system of promotion in spread of viruses across cell-type and host cell specificities that tend to characterize and recharacterize systems of cytokine network operability in particular.

Distinctive parameters of action of stem cells and modulatory microenvironmental microcirculation in gliomagenesis

Definition of the malignant transformation event is central to a distinction between neural stem cells and cancer stem cells. In such manner, the descriptive analysis of various tumors such as gliomas would allow for the distinction of genetic injury and probably epigenetic events that transform gene transcription pathways. Hypoxia is a major conditioning influence acting on stem cell niche microenvironments that evolve in terms particularly of micro-vascular dynamics. The incremental involvement of entire fields of cancerization allows for the establishment of permissive conditions of repetitive nature and within the contextual involvement of multiple clones of injured cells that condition, in turn, the stem cell niche. In view of the establishment of progressive malignant change, it is significant to view the cancerization as an integral involvement of both sequential and concurrent events in defining the roles of stem cells and cancer stem cells in terms of a primal process of dedifferentiation beyond simple markers of morphologic transformation.

Elevated levels of the pollutant PM2.5 in crowded subways of cities with high COVID-19 related mortality-when COVID-19 went underground

Background:Recent literature indicates that the pollutant,particulate matter PM2.5,may have an impact on COVID-19 related infection and mortality.Genes coding for SARS-CoV-2 has been found adherent to PM2.5 and possibly the COVID-19/PM2.5 complex may be involved in the transmission and the exacerbation of COVID-19 infection.PM2.5 levels in deep underground subways have been found up to 90 times higher than roads closer to the surface.Method:The levels of PM2.5 were retrieved from literature assessing particulate matter PM2.5 measured on subway platforms in two groups of cities.These cities were differentiated by the COVID-19 population percentage mortality rate(0.007%vs 0.19%)(P<0.0004).Data regarding the number of stations,length of the networks(km)and the annual ridership were also obtained from literature related to underground commuting.Results:The population percentage mortality related to SARS-CoV-2 infection correlated significantly for both minimum(P<0.01)and maximum(P<0.00001)levels of PM2.5.The cities’subways with low COVID-19 mortality had minimum platform PM2.5 levels of 27.4(SD+/-17.2μg/m3)compared to 63.4μg/m3(SD+/-10.8μg/m3)in cities with high SARS-CoV-2 associated mortality(P<0.01).Subway maximum levels of PM2.5 in cities with low COVID-19 mortality was 53.4μg/m3(SD+/-21.8μg/m3)while that of underground networks with high COVID-19 mortality had maximum platform PM2.5 levels of 172.1μg/m3(SD+/-98μg/m3)(P<0.001).Conclusion:Underground networks may have inherent characteristics accelerating spread of SARSCoV-2 infection and consequent mortality.The highly elevated levels of PM2.5 in overcrowded subways with extensive reach,may have acted as a co-factor to disseminate the pandemic in a number of metropolises.

Operative sequentiality in tumor differentiation and progression as protein molecular structure and sequence context in modulating alternative splicing events

This review article discusses dimensional reconstruction of alternative splicing that not only affects primarily the distributional dimensions of isoforms of various protein species but especially influences the nature of interactivity events between various protein species and also the structure of the given protein molecules. In such terms, disorders of differentiation of individual tumors and of tumor types and subtypes would correlate with distinctive dimensions of expression of a limited number of genes in various modes of expressed selectivity programs. In particular, the differentiation programs of normal tissues would correlate with combinatorial systems of splicing factors and of auxiliary factors in the development of patterns of gene expression. The significance of mis-splicing events is consonant with the wide range of phenotypic expression of neoplastic lesions and in the great variety of differentiation patterns and also of the variable degrees of differentiation of various components of a given neoplasm. The structure of given protein isoforms resulting from alternative splicing correlate with the sequence context of exons in the enhancement or inhibition of splicing events and would also influence pathobiologic behavior patterns of given neoplastic lesions. The development of abnormal cell signalling pathways and of interactivity patterns in a combinatorial way would directly influence the stability and trafficking dynamics of given protein molecular species in inducing an abundance of protein isoform production. Series of multi-component systems ranging from receptivity to consequential pathways of development of differential phenotype would allow for a high degree of modulatory effect within systems implicating in particular the interactions of individual tumor cells with each other and with the matrix components. It is within the context of constitutive versus alternative splicing events that this review article proposes that proportional recreation of differentiation pathways promotes a self-progression of the pathobiologic processes of a given neoplastic lesion.

HIV-1 Primarily Targets the Innate Immune System and Only Secondarily Modulates Adaptive Immune Cell Depletion

Persistence of HIV-1 infection allows for permissive microenvironmental conditioning in terms of contextual innate immune participation. The progression of host cell injury constitutes an additional parametric formulation in self-amplifying modulation of the adaptive immune response in a manner that inclusively promotes the emergence of a final stage of AIDS that is both depletive and permissive for opportunistic infections and various forms of neoplasia. It is within contextual indices of promotion of depleted T-helper lymphocytes and of augmented viremic loads that manifestations of classic lesions emerge as the AIDS phenomenon. It is further to be realized that an apoptotic response of multiple cell subtypes including T-lymphocytes includes host-cell participation within formulated settings of further persistence of the retroviral infection. An all-inclusive phenomenon of dendritic cell-lymphocyte synapse formulation corresponds to the establishment of HIV-1 infection that specifically conditions all subsequent stages in depletion of the injured host cells regardless of the dynamics or kinetics of the retroviral replicative infectious process itself.

马耳他1993—2002年侵袭性恶性黑素瘤的概况

Background: The incidence of malignant melanoma of the skin has risen in every part of the world where reliable cancer registration data are found. Objective: Our study aims to describe the changing incidence of and survival from invasive cutaneous malignant melanoma inMalta, by analysing the data from the 211 cases that were registered at the Malta National Cancer Registry between 1993 and 2002. Results: The age standardized incidence rates for invasive cutaneous malignant melanoma rose from 3.7 per 100 000 population per year for males and 5.1 for females in the first 5-year period, to 8.0 per 100 000 population per year for males and 5.9 for females in the second 5-year period. In both sexes, numbers of thin (≤1.0 mm) invasive melanomas increased significantly between 1993 and 2002; males also registered a significant increase in intermediate-thickness (1.01-4.0 mm) melanomas. The increase in numbers of thin and intermediate-thickness melanomas between the two 5-year periods was greatest in patients aged 60 years and over. The overall absolute 5-year survival rate for the first period was 74%and for the second period 92%. Conclusion: Numbers of reported cases of invasive cutaneous malignant melanoma in Malta have more than doubled during the 10-year study period. This is mostly due to a marked rise in the diagnosis of thin melanomas in both sexes, occurring mainly in patients aged 60 years and over. As thin melanomas are of low metastasizing potential, this has resulted in an increase in survival between the two 5-year study periods.