Today, heterosexuals in Europe are at particular risk of carrying HIV for so long that they remain undiagnosed until their immune system starts to fail and they become ill.
An international study under the leadership of the HIV in Europe initiative has now revealed that a number of diseases, including herpes zoster and certain forms of cancer, should be on the list of indicators for having HIV – and thus serve to prompt health care professionals to suggest an HIV-test to their patients.
The new results and guidelines are to be debated at a major international HIV conference in Copenhagen on 19th-20th March.
‘At the HIV in Europe conference we will be discussing how to disseminate knowledge of the new HIV indicator diseases to non-HIV doctors and health care professionals across Europe,’ says Jens Lundgren, Co-chair of the HIV in Europe initiative.
He’s also a Professor of Viral Diseases at Rigshospitalet and the Faculty of Health and Medical Sciences at the University of Copenhagen, where he heads the Copenhagen HIV Programme, one of the leading HIV/AIDS centres in the world.
Half of all people living with HIV are diagnosed very late in the course of their chronic HIV infection. People infected through heterosexual transmission now comprise 42 per cent of these late presenters, as a study of 90,000 Europeans tested HIV positive since 2.000 shows.
UNAIDS has estimated that 2,5 million Europeans carry an HIV infection, and as many as 900 000 of these, are still unaware of this. Inside EU the numbers are 800.000 infected with 250.000 undiagnosed.
Ton Coenen, co-chair of the HIV in Europe initiative, Director of Aids Funds and Soa AIDS Nederland suggests that since the HIV/AIDS issue is no longer high on the agenda in many European countries, and since people have to actively choose to be HIV-tested, many perhaps no longer consider going for a test if they have had unsafe sex.
However, the sooner HIV-infected individuals receive a diagnosis and start therapy, the greater are their chances of survival and their quality of life. And new research also shows therapy lowers the risk of passing the infection on to someone else.
‘The currently situation shows that we need more effective testing strategies and guidelines,’ Ton Coenen continues. ‘More than 300 doctors, health care professionals, NGOs and health politicians from 40 European countries will be discussing this need at the conference on 19th and 20th of March, so we have the ideal forum for it.’
‘We already have a list of Aids defining diseases, the vast majority of which indicate a weak immune system. This is a symptom of HIV and should lead to an immediate HIV test,’ Professor Lundgren explains. ‘We nned to find people living with HIV sooner than is currently the case, but to do so requires that doctors and other health care professionals offer tests to people presenting with diseases indicative of a hidden and undiagnosed HIV infection earlier in the course of the disease.’
The HIV in Europe initiative took up this challenge in 2009 and started the HIDES study (HIV Indicator Diseases Across Europe), which investigated eight new diseases and how often they proved to be signs of an undiagnosed HIV infection among the 3588 patients in the study.
‘We could see that if an adult had a sexually transmitted infection, malignant lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B or C, ongoing mononucleosis-like illness, inexplicable, persistent decline in the number of circulating white blood cells, or seborrheic dermatitis/exanthema, the risk of HIV infection was so high that it would be cost-effectiveness for society to routinely offer them a test,’ Professor Lundgren says. He also emphasises that the new indicator diseases do not necessarily mean that the patient has HIV.
‘But the incidence of HIV is greater for these eight indicator diseases and they should encourage health care professionals to offer the patient an HIV test. Draft guidelines on how to ensure this throughout Europe are one of the topics we need to debate and decide on, before they can be implemented.’ University of Copenhagen

A malignancy-risk gene signature developed for breast cancer has been found to have predictive and prognostic value for patients with early stage non-small cell lung cancer. The advancement was made by researchers at Moffitt Cancer Center in Tampa.
According to corresponding author Dung-Tsa Chen, Ph.D., associate member with the Moffitt Biostatistics program, non-small cell lung cancer (NSCLC) accounts for 80-90 percent of all lung cancers. Patients with NSCLC have a 30-50 percent relapse rate after surgery and a 40-70 percent five-year survival rate. Although adjuvant chemotherapy (ACT) has increased survival rates and has become standard treatment for NSCLC, a proportion of patients do not derive any benefit from it.
‘Better prognostic tools have been needed to identify both patients with a high probability of relapse and those who would benefit from adjuvant chemotherapy,’ said Chen.
He added that the Moffitt researchers are confident that their newly tested malignancy-risk gene signature for NSCLC will provide that tool because their malignancy-risk gene signature is a proliferative gene signature, one associated with both cancer risk and progression.
According to the researchers, their findings suggest a ‘transferability’ of the malignancy-risk gene signature between breast cancer and NSCLC, a ‘unique feature not seen in other gene signatures derived for various tumor types.’
‘To the best of our knowledge, our study is the first to show a high consistency of the gene signature on both breast cancer and NSCLC,’ said Chen. ‘The gene signature demonstrated a statistically significant association with overall survival and other clinical predictors in NSCLC.’
Originally, the malignancy-risk signature gene was designed to distinguish between normal breast tissues and breast cancer tissues by identifying abnormal molecular structure. The Moffitt research team further applied the signature to tissue samples from 442 NSCLC patients in the Director’s Challenge Consortium for the Molecular Classification of Lung Adenocarcinoma.
‘Additionally, the malignancy-risk gene signature has demonstrated the potential to identify early-stage NSCLC patients who would be likely to benefit from adjuvant chemotherapy,’ explained Chen. ‘This malignancy-risk gene signature may provide an additional tool to help identify a subset of patients at high-risk for low overall survival and who may benefit from ACT.’
Study results revealed a predictive feature of the malignancy-risk gene signature with an ability to predict overall survival in NSCLC patients. Further, the malignancy-risk gene signature was able to consistently distinguish between low and high malignancy risk groups and correlate the groups by good to poor overall survival rates. Moffitt Cancer Center

‘The overactive bladder syndrome has become an accepted way to simplify a complex array of symptoms and leads people to believe that an overactive bladder is an independent disease in itself. However, the truth is not as simple as this, as there are usually several factors at work explaining the symptoms. This is also one of the reasons why so called overactive bladder medications often do not bring the hoped result,’ says Kari Tikkinen, MD, PhD, from the HUCS Department of Urology.
The article on overactive bladder syndrome, which was co-written by Tikkinen, who currently holds a senior researcher post at the McMaster University in Canada, and Anssi Auvinen, Professor of Epidemiology from the University of Tampere, was recently published. For the article, the researchers systematically reviewed the studies on overactive bladder and the channels through which these studies have been funded.
The authors argue that the symptoms of an ‘overactive bladder’ ought to be studied individually and not as an ambiguous constellation of symptoms. This way the underlying causes of the symptoms can be better understood and more effective treatments can be developed.
The expression ‘overactive bladder’ was coined at an industry-sponsored symposium held in 1997. The following year, the FDA approved the first drug for the treatment of ‘symptoms of overactive bladder’, after which the pharmaceutical industry launched high-profile, worldwide promotional campaigns for drugs aimed at treatment of the syndrome.
According to the current definition, overactive bladder (OAB) syndrome is defined as the presence of urinary urgency with or without urgency incontinence, usually with increased daytime frequency and nocturia in the absence of infection or other obvious pathology.
‘The definition is vague and ambiguous because it includes unspecific terms, such as ‘usually’ and ‘with or without’, and the unclear expression ‘other obvious pathology’,’ Tikkinen says and continues, ‘For the pharmaceutical industry this definition is probably quite useful, as it is partly the reason why one medicine can be prescribed to a large number of patients.’
Research into overactive bladder has increased significantly over the past ten years and the pharmaceutical industry has invested heavily in it. ‘It has previously been shown that research funded by commercial actors often ends up unpublished if the results don’t serve the interests of the company,’ Tikkinen points out.
Tikkinen and Auvinen also bring to the fore that in many studies on prevalence of overactive bladder, very mild symptoms have been classified as abnormal.
‘More independent, non-commercially funded research on the subject is needed. There are, in the end, a huge number of people who suffer from urinary urgency and increased urinary frequency, and current treatments are not bringing sufficient relief,’ Tikkinen says. EurekAlert

Mammalian spermatogenesis is maintained by spermatogonial stem cells (SSCs). However, since evidentiary assays and unequivocal markers are still missing in non-human primates and man, the identity of primate SSCs is unknown. In contrast, in the mouse, germ cell transplantation studies functionally demonstrated the presence of SSCs. LIN28 is an RNA-binding pluripotent stem cell factor, which is also strongly expressed in undifferentiated mouse spermatogonia. By contrast, two recent reports indicated that LIN28 is completely absent from adult human testes. Here, we analysed LIN28 expression in marmoset monkey (Callithrix jacchus) and human testes during development and adulthood and compared it with the mouse. In the marmoset, LIN28 was strongly expressed in migratory PGCs and gonocytes. Strikingly, we found a rare LIN28-positive subpopulation of spermatogonia also in the adult marmoset testis. This was corroborated by western blotting and quantitative RT-PCR. Importantly, in contrast to previous publications, we found LIN28-positive spermatogonia also in normal adult human and additional adult non-human primate testes. Some seasonal breeders exhibit a degenerated (involuted) germinal epithelium during their non-breeding season consisting only of Sertoli cells and SSCs. The latter re-initiate spermatogenesis prior to the next breeding-season. Fully involuted testes from a seasonal hamster and NHP (Lemur catta) exhibited numerous LIN28-positive spermatogonia, indicating a SSC-identity of the labeled cells. We conclude that LIN28 is differentially expressed in mouse and non-human primate spermatogonia and might be a marker for a rare SSC population in non-human primates and man. Further characterization of the LIN28-positive population is required. European Society of Human Reproduction and Embryology

Researchers at the Hospital de Mar Research Institute (IMIM) have discovered that the protein LOXL2 has a function within the cell nucleus thus far unknown. They have also described a new chemical reaction of this protein on histone H3 that would be involved in gene silencing, one of which would be involved in the progression of breast, larynx, lung and skin tumours.
Led by Dr Sandra Peiró, the study is a significant advance in describing the evolution of tumours and opens the door to researching new treatments that block their activity. ‘LOXL2’s action on the intra-cellular level and its interaction with histone H3 stimulates tumour growth. The fact that the protein LOXL2 is an enzyme and is overly expressed in many types of cancer makes it a very good therapeutic target. Now that we know how it acts, we need to keep working to develop chemical inhibitors that counteract its activity’, the researcher explained.
Previous studies had identified the extra-cellular function of the protein LOXL2, and it was being studied as a possible therapeutic target for avoiding metastasis in certain kinds of tumours. However, this study has described the presence of this protein at the level of the cell nucleus for the first time.
The process of gene expression in cells consists of transforming the information of the DNA into the proteins necessary to carry out different functions. The DNA molecule has been found to form a certain structure due to its interaction with some proteins called histones. When these histones are modified, the structure of the DNA is also modified and the final result is the expression or non-expression of a certain group of genes.
In the case of tumour cells, the protein LOXL2 acts upon one of these histones (histone H3) and modifies it, eliminating the lysine 4 amino group, a change never described before. As a result of its action, the genes modulated by histone H3, modified by LOXL2, stop expression, preventing the cells from behaving normally and favouring tumour development.
The work of Sandra Peiró’s team is the conclusion of three years of effort focused on the biochemical characterisation of the protein LOXL2 and the study of its role in the modification of histone H3. Since this modification had never been described before, the data obtained open many lines of research. The location on the genomic level of the protein LOXL2 and histone H3, modified by LOXL2, and the possible existence of some enzyme that might neutralise its function, are two of the questions that the group aims to tackle in the years to come. IMIM (Hospital del Mar Research Institute)