GENETIC POLYMORPHISM OF REVERSE TRANSCRIPTASE AND PROTEASE ASSOCIATED WITH THE ANTIRETROVIRAL (ARV) INEFFICIENCY IN PEOPLE LIVING WITH HUMAN IMMUNODEFICIENCY VIRUS TYPE-2 (HIV-2) IN ABIDJAN, CÔTE D’IVOIRE

Objectives: To analyse the genetic polymorphism of reverse transcriptase and protease genes in patients living with HIV-2, to search for possible mutations preventing the effectiveness of antiretroviral drugs (ARVs). Methods: RNA Viral was extracted after lysis of the virus particles and purified on filter columns (Qiagen). After their extraction, DNA fragments were amplified by the method of reverse transcription/polymerase chain reaction (RT/PCR) on one hand and by the PCR method enchase on the other hand. The study of genetic polymorphisms in reverse transcriptase and protease was performed after sequencing of amplicons. Results: A significant polymorphism was observed in positions involved in resistance to antiretrovirals. The most frequent was mutations M 46 I, M 36 I/V, V82I, L 89 I on protease and Y 181 I, Y 188 L, G 190A on reverse transcriptase. Conclusion: Polymorphic mutations were observed in the genes of the protease and reverse transcriptase and could be involved in the HIV-2 resistance to antiretrovirals (ARVs). It would be desirable to do the quantification of DNA provirus of HIV-2 in the other for a durable therapeutic monitoring of patients having HIV-2

Methodological issues in estimating survival in patients with multiple primary cancers: an application to women with breast cancer as a first tumour

<p>Abstract</p> <p>Background</p> <p>Comparing survival of patients with a single tumour and patients with multiple primaries poses different methodological problems. In population based studies, where we cannot rely on detailed clinical information, the issue is disentangling the share of survival probability from the first and second cancer, and their compounded effect. We examined three hypotheses: A) the survival probability since the first tumour does not change with the occurrence of a second tumour; B) the probability of surviving a tumour does not change with the presence of a previous primary; C) the probabilities of surviving two subsequent primary tumours are independent (additivity hypothesis on mortality rates).</p> <p>Methods</p> <p>We studied the survival probabilities modelling mortality rates according to hypotheses A), B) and C). Mortality rates were calculated using Aalen-Johansen estimators which allowed to discount for the lag-time survival before developing a second tumour. We applied this approach to a cohort of 436 women with breast cancer (BC) and a subsequent tumour in the resident population of Turin, Italy, between 1985 and 2002.</p> <p>Results</p> <p>We presented our results in term of a Standardised Mortality Ratio calculated (<it>SMR</it>_<it>AJ</it>) after 10 years of follow-up. For hypothesis A we observed a significant excess mortality of 2.21 (95% C.I. 1.94 – 2.45). Concerning hypothesis B we found a not significant <it>SMR</it>_{<it>AJ </it>}of 0.98 (95% C.I. 0.87 – 1.10). The additivity hypothesis (C) was not confirmed as it overestimated the risk of death, in fact <it>SMRs</it>_{<it>AJ </it>}were all below 1: 0.75 (95% C.I. 0.66 – 0.84) for BC and all subsequent cancers, 0.72 (95% C.I. 0.55 – 0.94) for BC and colon-rectum cancer, 0.76 (95% C.I. 0.48 – 1.14) for BC and corpus uteri cancer (not significant).</p> <p>Conclusion</p> <p>This method proved to be useful in disentangling the effect of different subsequent cancers on mortality. In our application it shows a worse long-term mortality for women with two cancers than that with BC only. However, the increase in mortality was lower than expected under the additivity assumption.</p

Frontostriatal salience network expansion in individuals in depression

Published on 4 september 2024Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset1. Furthermore, whereas depression is episodic, few longitudinal neuroimaging studies exist, limiting understanding of mechanisms that drive mood-state transitions. The emerging field of precision functional mapping has used densely sampled longitudinal neuroimaging data to show behaviourally meaningful differences in brain network topography and connectivity between and in healthy individuals2–4, but this approach has not been applied in depression. Here, using precision functional mapping and several samples of deeply sampled individuals, we found that the frontostriatal salience network is expanded nearly twofold in the cortex of most individuals with depression. This effect was replicable in several samples and caused primarily by network border shifts, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was stable over time, unaffected by mood state and detectable in children before the onset of depression later in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in frontostriatal circuits that tracked fluctuations in specific symptoms and predicted future anhedonia symptoms. Together, these findings identify a trait-like brain network topology that may confer risk for depression and mood-state-dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time.We thank the staff at the Citigroup Biomedical Imaging Center for assistance with data collection. We thank all study participants and especially the SIMD study participants for their time and dedication to science. R. Kong and T. Yeo helped with implementing the multi-session hierarchical Bayesian modelling42 method. This work was supported by grants to C.L. from the National Institute of Mental Health, the National Institute on Drug Addiction, the Hope for Depression Research Foundation and the Foundation for OCD Research. C.J.L. was supported by an NIMH F32 National Research Service Award (F32MH120989). N.S. was supported by K23 MH123864. Work on ‘Personalized therapeutic neuromodulation for anhedonic depression’ is supported by Wellcome Leap as part of the Multi-Channel Psych Program. M.L. was supported by Deutsche Forschungsgemeinschaft (DFG grant CRC 1193, subproject B01)