Review of the Ubiquitin Role in DNA Repair and Tumorigenesis, with Emphasis in Breast Cancer Treatment; Current Data and Future Options

Breast carcinoma remains the commonest carcinoma among women worldwide. Despite the fact that impressive progression has been achieved so far regarding pathophysiology, histopathology and treatment of this cancer, there are still undiscovered fields on molecular and therapeutic levels. The need of resolving problems such as chemoresistance, recurrence and metastasis has led in revealing key molecules in the development and progression of malignancies, including breast tumors. In this review, we will briefly describe the functions of ubiquitin and post-translational modifications (PTMs) focusing specially in DNA repair and then discuss about the implication of ubiquitin and related molecules in tumorigenesis and specifically in breast carcinoma. So far there are only few drugs approved by FDA that target the ubiquitin system. There will be an analysis regarding the current and potential anti-cancer therapeutic strategies based on targeting specific ubiquitin-related molecules

Sex differences in the incidence and severity of respiratory tract infections

SummarySex is a significant epidemiological factor for several diseases. However, the role of sex in the development and outcome of various infections has not been extensively studied with the notable exception of urinary tract infections. We searched in the PubMed database to identify articles that could provide relevant data regarding sex differences in the incidence and severity of respiratory tract infections (RTIs). We extracted data from 84 relevant studies that provided information regarding sex differences in the incidence and severity of RTIs. Females are more commonly affected with infections of the upper respiratory tract, specifically sinusitis, tonsillitis, and otitis externa. On the other hand, males are more commonly affected with otitis media, croup, and most important, lower RTIs. It is also evident from the reviewed evidence that the course of most RTIs is more severe in males than in females, leading to higher mortality in males, especially in community-acquired pneumonia. In conclusion, the available data suggest that males are more susceptible than females to most types of RTIs in all age groups (adults and children). Overall, it seems that males develop RTIs more frequently than females, except for sinusitis, otitis externa, and probably tonsillitis. Anatomic, lifestyle, behavioural, and socioeconomic differences between males and females may explain the observed findings. The role of sex hormones in the regulation of the immune system may also contribute to the reported sex differences in the incidence and severity of the various types of RTIs, especially in adolescents and adults

Epidemiology of constipation in Europe and Oceania: a systematic review

<p>Abstract</p> <p>Background</p> <p>We aimed to review the literature regarding the epidemiology of constipation in Europe and Oceania and the associated prevalence/risk factors.</p> <p>Methods</p> <p>Two reviewers performed PubMed searches and a hand search of references. A study was considered eligible for inclusion if it reported data about the prevalence of constipation in any population, free of other gastrointestinal disorders, in Europe and Oceania. Studies were evaluated for quality. Data regarding the setting, type of study, definition of constipation, study population, prevalence of constipation, factors associated with increased odds for constipation, and the female to male ratio, were collected.</p> <p>Results</p> <p>The 21 reviewed studies depict prevalence rates in 34 different population groups ranging widely from a low 0.7% to a high 81%. In the general population of Europe the mean value of the reported constipation rates is 17,1 % and the median value 16.6%. Among the studies conducted in Oceania, the mean value of constipation prevalence was 15.3%. Female gender, age and socioeconomic and educational class seem to have major effect on constipation prevalence. A number of various other risk factors are, less clearly, associated with constipation.</p> <p>Conclusion</p> <p>This systematic review depicts the high prevalence and related risk factors of a disorder that decreases the health-related quality of life and has major economic consequences.</p

Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review

<p>Abstract</p> <p>Background</p> <p>The morbidity and mortality associated with cytomegalovirus (CMV) infection in immunocompromised patients (especially in HIV-infected patients and transplant recipients), as well as with congenital CMV infection are well known. In contrast, relatively little attention has been paid to the morbidity and mortality that CMV infection may cause in immunocompetent patients.</p> <p>Methods</p> <p>We reviewed the evidence associated with severe manifestations of CMV infection in apparently immunocompetent patients and the potential role of antiviral treatment for these infections. We searched in PubMed, Scopus, and the Cochrane Library for the period of 1950–2007 to identify relevant articles.</p> <p>Results</p> <p>We retrieved 89 articles reporting on severe CMV infection in 290 immunocompetent adults. Among these reports, the gastrointestinal tract (colitis) and the central nervous system (meningitis, encephalitis, transverse myelitis) were the most frequent sites of severe CMV infection. Manifestations from other organ-systems included haematological disorders (haemolytic anaemia, thrombocytopenia), thrombosis of the venous or arterial vascular system, ocular involvement (uveitis), and lung disease (pneumonitis). The clinical practice reported in the literature has been to prescribe antiviral treatment for the most severe manifestations of monophasic meningoencephalitis (seizures and coma), ocular involvement, and lung involvement due to CMV.</p> <p>Conclusion</p> <p>Severe life-threatening complications of CMV infection in immunocompetent patients may not be as rare as previously thought.</p

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals

Global Influenza Seasonality: Reconciling Patterns across Temperate and Tropical Regions

Bac k g r o u n d: Despite the significant disease burden of the influenza virus in humans, our understanding of the basis for its pronounced seasonality remains incomplete. Past observations that influenza epidemics occur in the winter across temperate climates, combined with insufficient knowledge about the epidemiology of influenza in the tropics, led to the perception that cool and dry conditions were a necessary, and possibly sufficient, driver of influenza epidemics. Recent reports of substantial levels of influenza virus activity and well-defined seasonality in tropical regions, where warm and humid conditions often persist year-round, have rendered previous hypotheses insufficient for explaining global patterns of influenza. Objectiv e: In this review, we examined the scientific evidence for the seasonal mechanisms that potentially explain the complex seasonal patterns of influenza disease activity observed globally. Me t h o d s: In this review we assessed the strength of a range of hypotheses that attempt to explain observations of influenza seasonality across different latitudes and how they relate to each other. We reviewed studies describing population-scale observations, mathematical models, and ecological, laboratory, and clinical experiments pertaining to influenza seasonality. The literature review includes studies that directly mention the topic of influenza seasonality, as well as other topics w

Antibody response to Haemophilus influenzae type-b conjugate vaccine in children and young adults with congenital asplenia or after undergoing splenectomy

Absence of the spleen constitutes a risk of infection caused by encapsulated bacteria. The aim of our study was to determine the immune response to Haemophilus influenzae type-b (Hib) conjugate vaccine (HibCV) in asplenic individuals, considering the cause of asplenia, the age when splenectomy was carried out, and previous Hib vaccinations. Twenty asplenic patients, aged five to 25 years, were immunized with a single dose of HibCV. The specific antibody concentrations against HibCV were measured by enzyme-linked immunosorbent assay. Before vaccinations, the geometric mean antibody concentration (GMC) had an average value of 3.21 μg/ml and was comparable for all of the patients, regardless of the causes of asplenia. After vaccinations, the GMC was significantly higher, with an average of 6.78 μg/ml. Further, 4.5 years after vaccinations, the GMC was comparable to that of previously unvaccinated children. Moreover, 17/20 patients had GMC ≥ 1.0 μg/ml, which included all of the children with congenital asplenia, children splenectomized before the age of six years, and only 57% of children splenectomized after that age. HibCV gives asplenic patients long-term protection. Hence, HibCV should be administered regardless of previous vaccinations and time from splenectomy, even if antibody evaluation is not available

Physicians Report Barriers to Deliver Best Practice Care for Asplenic Patients: A Cross-Sectional Survey

Background: Current management of asplenic patients is not in compliance with best practice standards, such as defined by the British Committee for Standards in Haematology. To improve quality of care, factors inhibiting best practice care delivery need to be identified first. With this study, we aimed to identify and quantify physicians' barriers to adhere to best practice management of asplenic patients in the Netherlands. Methods and Principal Findings: A cross-sectional survey, preceded by multiple focus group discussions, was performed among Dutch physicians responsible for prevention of infections in asplenic patients, including specialists ( of Internal medicine and Surgery) and general practitioners (GPs). Forty seven GPs and seventy three hospital specialists returned the questionnaire, yielding response rates of 47% and 36,5% respectively. Physicians reported several barriers to deliver best practice. For both GPs and specialists, the most frequently listed barriers were: poor patient knowledge (> 80% of hospital specialists and GPs) and lack of clarity about which physician is responsible for the management of asplenic patients (50% of Internists, 46% of Surgeons, 55% of GPs). Both GPs and hospital specialists expressed to experience a lack of mutual trust: specialists were uncertain whether the GP would follow their advice given on patient discharge (33-59%), whereas half of GPs was not convinced that specialists' discharge letters contained the correct recommendations. Almost all physicians (> 90%) indicated that availability of a national guideline would improve adherence to best practice, especially if accessible online. Conclusion: This study showed that, in accordance with reports on international performance, care delivery for asplenic patients in the Netherlands is suboptimal. We identified and quantified perceived barriers by physicians that prevent adherence to post-splenectomy guidelines for the first time. Better transmural collaboration and better informed patients are likely to improve the quality of care of the asplenic patient population. A national, online-available guideline is urgently require

Assessment of splenic function

Hyposplenic patients are at risk of overwhelming post-splenectomy infection (OPSI), which carries mortality of up to 70%. Therefore, preventive measures are warranted. However, patients with diminished splenic function are difficult to identify. In this review we discuss immunological, haematological and scintigraphic parameters that can be used to measure splenic function. IgM memory B cells are a potential parameter for assessing splenic function; however, more studies are necessary for its validation. Detection of Howell–Jolly bodies does not reflect splenic function accurately, whereas determining the percentage of pitted erythrocytes is a well-evaluated method and seems a good first-line investigation for assessing splenic function. When assessing spleen function, 99mTc-labelled, heat-altered, autologous erythrocyte scintigraphy with multimodality single photon emission computed tomography (SPECT)-CT technology is the best approach, as all facets of splenic function are evaluated. In conclusion, although scintigraphic methods are most reliable, they are not suitable for screening large populations. We therefore recommend using the percentage of pitted erythrocytes, albeit suboptimal, as a first-line investigation and subsequently confirming abnormal readings by means of scintigraphy. More studies evaluating the value of potentially new markers are needed