Neurotoxicity with high dose disulfiram and vorinostat used for HIV latency reversal

OBJECTIVE: To examine whether administering both vorinostat and disulfiram to people with HIV (PWH) on antiretroviral therapy (ART) is safe and can enhance HIV latency reversal. DESIGN: Vorinostat and disulfiram, can increase HIV transcription in people with HIV (PWH) on antiretroviral therapy (ART). Together these agents may lead to significant HIV latency reversal. METHODS: Virologically suppressed PWH on ART received disulfiram 2000 mg daily for 28 days and vorinostat 400 mg daily on days 8-10 and 22-24. The primary endpoint was plasma HIV RNA on day 11 relative to baseline using a single copy assay. Assessments included cell-associated (CA) unspliced (US) RNA as a marker of latency reversal, HIV DNA in CD4+ T-cells, plasma HIV RNA and plasma concentrations of ART, vorinostat and disulfiram. RESULTS: The first two participants (P1 and P2) experienced grade 3 neurotoxicity leading to trial suspension. After 24 days, P1 presented with confusion, lethargy, and ataxia having stopped disulfiram and ART. Symptoms resolved by day 29. After 11 days, P2 presented with paranoia, emotional lability, lethargy, ataxia and study drugs were ceased. Symptoms resolved by day 23. CA-US RNA increased by 1.4- and 1.3-fold for P1 and P2 respectively. Plasma HIV RNA was detectable from day 8-37 (peak 81 copies/mL) for P2 but was not increased in P1 Antiretroviral levels were therapeutic and neuronal injury markers were elevated in P1. CONCLUSIONS: The combination of prolonged high dose disulfiram and vorinostat was not safe in PWH on ART and should not be pursued despite evidence of latency reversal

Rubber Hands Feel Touch, but Not in Blind Individuals

Psychology and neuroscience have a long-standing tradition of studying blind individuals to investigate how visual experience shapes perception of the external world. Here, we study how blind people experience their own body by exposing them to a multisensory body illusion: the somatic rubber hand illusion. In this illusion, healthy blindfolded participants experience that they are touching their own right hand with their left index finger, when in fact they are touching a rubber hand with their left index finger while the experimenter touches their right hand in a synchronized manner (Ehrsson et al. 2005). We compared the strength of this illusion in a group of blind individuals (n = 10), all of whom had experienced severe visual impairment or complete blindness from birth, and a group of age-matched blindfolded sighted participants (n = 12). The illusion was quantified subjectively using questionnaires and behaviorally by asking participants to point to the felt location of the right hand. The results showed that the sighted participants experienced a strong illusion, whereas the blind participants experienced no illusion at all, a difference that was evident in both tests employed. A further experiment testing the participants' basic ability to localize the right hand in space without vision (proprioception) revealed no difference between the two groups. Taken together, these results suggest that blind individuals with impaired visual development have a more veridical percept of self-touch and a less flexible and dynamic representation of their own body in space compared to sighted individuals. We speculate that the multisensory brain systems that re-map somatosensory signals onto external reference frames are less developed in blind individuals and therefore do not allow efficient fusion of tactile and proprioceptive signals from the two upper limbs into a single illusory experience of self-touch as in sighted individuals

Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross‐PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations

Risk factors for the onset and persistence of neck pain in undergraduate students: 1-year prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Although neck pain is common in young adulthood, studies on predictive factors for its onset and persistence are scarce. It is therefore important to identify possible risk factors among young adults so as to prevent the development of neck pain later in life.</p> <p>Methods</p> <p>A prospective study was carried out in healthy undergraduate students. At baseline, a self-administered questionnaire and standardized physical examination were used to collect data on biopsychosocial factors. At 3, 6, 9, and 12 months thereafter, follow-up data were collected on the incidence of neck pain. Those who reported neck pain on ≥ 2 consecutive follow-ups were categorized as having persistent neck pain. Two regression models were built to analyze risk factors for the onset and persistence of neck pain.</p> <p>Results</p> <p>Among the recruited sample of 684 students, 46% reported the onset of neck pain between baseline and 1-year follow-up, of whom 33% reported persistent neck pain. The onset of neck pain was associated with computer screen position not being level with the eyes and mouse position being self-rated as suitable. Factors that predicted persistence of neck pain were position of the keyboard being too high, use of computer for entertainment < 70% of total computer usage time, and students being in the second year of their studies.</p> <p>Conclusion</p> <p>Neck pain is quite common among undergraduate students. This study found very few proposed risk factors that predicted onset and persistence of neck pain. The future health of undergraduate students deserves consideration. However, there is still much uncertainty about factors leading to neck pain and more research is needed on this topic.</p

sj-docx-1-msj-10.1177_13524585241237388 – Supplemental material for Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study

Supplemental material, sj-docx-1-msj-10.1177_13524585241237388 for Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study by M Johnsson, YT Stenberg, HH Farman, K Blennow, H Zetterberg, C Malmeström, S Sandgren, I Rosenstein, J Lycke, M Axelsson and L Novakova in Multiple Sclerosis Journal</p

sj-docx-4-msj-10.1177_13524585241237388 – Supplemental material for Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study

Supplemental material, sj-docx-4-msj-10.1177_13524585241237388 for Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study by M Johnsson, YT Stenberg, HH Farman, K Blennow, H Zetterberg, C Malmeström, S Sandgren, I Rosenstein, J Lycke, M Axelsson and L Novakova in Multiple Sclerosis Journal</p

sj-docx-3-msj-10.1177_13524585241237388 – Supplemental material for Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study

Supplemental material, sj-docx-3-msj-10.1177_13524585241237388 for Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study by M Johnsson, YT Stenberg, HH Farman, K Blennow, H Zetterberg, C Malmeström, S Sandgren, I Rosenstein, J Lycke, M Axelsson and L Novakova in Multiple Sclerosis Journal</p

sj-docx-2-msj-10.1177_13524585241237388 – Supplemental material for Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study

Supplemental material, sj-docx-2-msj-10.1177_13524585241237388 for Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study by M Johnsson, YT Stenberg, HH Farman, K Blennow, H Zetterberg, C Malmeström, S Sandgren, I Rosenstein, J Lycke, M Axelsson and L Novakova in Multiple Sclerosis Journal</p

Fennoscandian summers from AD 500: Temperature changes on short and long timescales

Quantitative estimates of 1480 years of summer temperatures in northern Fennoscandia have previously been derived from continuous treering records from northern Sweden. Here we show the results of spectral analyses of these data. Only a few peaks in the spectra are consistently significant when the data are analyzed over a number of sub-periods. Relatively timestable peaks are apparent at periods of 2.1, 2.5, 3.1, 3.6, 4.8, ~ 32-33 and for a range between ~ 55-100 years. These results offer no strong evidence for solar-related forcing of summer temperatures in these regions. Our previously published reconstruction was limited in its ability to represent long-timescale temperature change because of the method used to standardize the original tree-ring data. Here we employ an alternative standardization technique which enables us to capture temperature change on longer timescales. Considerable variance is now reconstructed on timescales of several centuries. In comparison with modern normals (1951-70) generally extended periods when cool conditions prevailed, prior to the start of the instrumental record, include 500-700, 790-870, 1110-1150, 1190-1360, 1570-1750 (A.D.) with the most significant cold troughs centred on about 660, 800, 1140, 1580-1620 and 1640. Predominantly warm conditions occurred in 720-790, 870-1110 and 1360-1570 with peaks of warmth around 750, 930, 990, 1060, 1090, 1160, 1410, 1430, 1760 and 1820