Tremor in motor neuron disease may be central rather than peripheral in origin

BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. METHODS: A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. RESULTS: Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition

The canopy interception–landslide initiation conundrum: insight from a tropical secondary forest in northern Thailand

The interception and smoothing effect of forest canopies on pulses of incident rainfall and its delivery to the soil has been suggested as a factor in moderating peak pore water pressure in soil mantles, thus reducing the risk of shallow landslides. Here we provide 3 years of rainfall and throughfall data in a tropical secondary dipterocarp forest characterized by few large trees in northern Thailand, along with selected soil moisture dynamics, to address this issue. Throughfall was an estimated 88 % of rainfall, varying from 86 to 90 % in individual years. Data from 167 events demonstrate that canopy interception was only weakly associated (via a nonlinear relationship) with total event rainfall, but not significantly correlated with duration, mean intensity, or antecedent 2-day precipitation (API2). Mean interception during small events (≤  35 mm) was 17 % (n  =  135 events) compared with only 7 % for large events (&gt; 35 mm; n  =  32). Examining small temporal intervals within the largest and highest intensity events that would potentially trigger landslides revealed complex patterns of interception. The tropical forest canopy had little smoothing effect on incident rainfall during the largest events. During events with high peak intensities, high wind speeds, and/or moderate-to-high pre-event wetting, measured throughfall was occasionally higher than rainfall during large event peaks, demonstrating limited buffering. However, in events with little wetting and low-to-moderate wind speed, early event rainfall peaks were buffered by the canopy. As rainfall continued during most large events, there was little difference between rainfall and throughfall depths. A comparison of both rainfall and throughfall depths to conservative mean intensity–duration thresholds for landslide initiation revealed that throughfall exceeded the threshold in 75 % of the events in which rainfall exceeded the threshold for both wet and dry conditions. Throughfall intensity for the 11 largest events (rainfall  =  65–116 mm) plotted near or above the intensity–duration threshold for landslide initiation during wet conditions; 5 of the events were near or above the threshold for dry conditions. Soil moisture responses during large events were heavily and progressively buffered at depths of 1 to 2 m, indicating that the timescale of any short-term smoothing of peak rainfall inputs (i.e.,  ≤  1 h) has little influence on peak pore water pressure at depths where landslides would initiate in this area. Given these findings, we conclude that canopy interception would have little effect on mitigating shallow landslide initiation during the types of monsoon rainfall conditions in this and similar tropical secondary forest sites.</p

Assessment of productivity of spring and winter wheat sorts from China and Pakistan in high mountain Tajikistan

Wheat is a staple crop and critical for food security in the high mountains of Tajikistan. Despite the local and introduced varieties of wheat, overall yields remain low and crops are vulnerable to diseases and climatic shocks. To improve production, new adapted and disease-resistant crops are crucial. We tested ten spring wheat sorts from Pakistan and seven from China with higher yields, disease resistance, and shorter stems compared to local varieties. Local varieties performed better than foreign varieties in stem length (77% longer), 25% more grains in the main spike, 45% longer main spike, 4% more spikelets in the main spike, and more productive tillers. Foreign cultivars had shorter morphogenic events, 16% higher grain weight in the main spike, 23% higher weight of 1000 grain, and 11% more grains per spikelet. Yield components and morpho-physiological traits for Chinese cultivars were weakly correlated. The main phenotypic traits affecting crop yield components were general and productive tillering. In contrast to Chinese cultivars, the main crop yield component values of local cultivars negatively interacted with most genotypic and phenotypic traits. Foreign cultivars were less susceptible to lodging and diseases; however, their shorter stems made them less attractive to local farmers

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies

Lipodystrophy in HIV infected patients on long term Antiretroviral therapy in western Kenya

Changes in fat distribution has been observed in patients on highly active antiretroviral therapy. The frequently reported drugs that cause fat redistribution are stavudine and protease inhibitors. Stavudine also causes a high incidence of metabolic complications and peripheral neuropathy

An integrated approach to neuroscience care: An innovative model to support the new integrated care system

Integrated care systems join up health and care services, so that people have the support they need, in the right place, at the right time. The aims include improving outcomes in healthcare, tackling inequalities in access and enhancing productivity and value for money. This is needed for neuroscience care as the traditional delivery of neuroscience care is inefficient, outdated and expensive, and can involve complex referral pathways and long waiting times. In preparation for the formation of the integrated care system (ICS), a novel innovative collaboration across multiple NHS trusts developed across North Central London in 2021. We developed a model where neuroscience specialists engage in collaborative care with clinicians outside the specialist hospital setting. Pivotal to the pathway is a multidisciplinary meeting, and collaborative working enables joint clinical reviews, diagnostics and medication initiation. This innovative collaboration has already significantly improved access, addressed inequalities due to borough variation and enhanced the delivery and quality of neuroscience care in our ICS. It is a translatable model that can be adapted to suit other regions in the UK. It fulfils many of the objectives of the integrated care system and these benefits are seen without the need for significantly more resource

Skeletal muscle MRI differentiates SBMA and ALS and correlates with disease severity

OBJECTIVE: To investigate the use of muscle MRI for the differential diagnosis and as a disease progression biomarker for 2 major forms of motor neuron disorders: spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS). // METHODS: We applied quantitative 3-point Dixon and semiquantitative T1-weighted and short tau inversion recovery (STIR) imaging to bulbar and lower limb muscles and performed clinical and functional assessments in ALS (n = 21) and SBMA (n = 21), alongside healthy controls (n = 16). Acquired images were analyzed for the presence of fat infiltration or edema as well as specific patterns of muscle involvement. Quantitative MRI measurements were correlated with clinical measures of disease severity in ALS and SBMA. // RESULTS: Quantitative imaging revealed significant fat infiltration in bulbar (p < 0.001) and limb muscles in SBMA compared to controls (thigh: p < 0.001; calf: p = 0.001), identifying a characteristic pattern of muscle involvement. In ALS, semiquantitative STIR imaging detected marked hyperintensities in lower limb muscles, distinguishing ALS from SBMA and controls. Finally, MRI measurements correlated significantly with clinical scales of disease severity in both ALS and SBMA. // CONCLUSIONS: Our findings show that muscle MRI differentiates between SBMA and ALS and correlates with disease severity, supporting its use as a diagnostic tool and biomarker for disease progression. This highlights the clinical utility of muscle MRI in motor neuron disorders and contributes to establish objective outcome measures, which is crucial for the development of new drugs

Interaction of the Retinoblastoma Protein with Orc1 and Its Recruitment to Human Origins of DNA Replication

Background: The retinoblastoma protein (Rb) is a crucial regulator of cell cycle progression by binding with E2F transcription factor and repressing the expression of a variety of genes required for the G1-S phase transition. Methodology/Principal Findings: Here we show that Rb and E2F1 directly participate in the control of initiation of DNA replication in human HeLa, U2OS and T98G cells by specifically binding to origins of DNA replication in a cell cycle regulated manner. We show that, both in vitro and inside the cells, the largest subunit of the origin recognition complex (Orc1) specifically binds hypo-phosphorylated Rb and that this interaction is competitive with the binding of Rb to E2F1. The displacement of Rb-bound Orc1 by E2F1 at origins of DNA replication marks the progression of the G1 phase of the cell cycle toward the G1-S border. Conclusions/Significance: The participation of Rb and E2F1 in the formation of the multiprotein complex that binds origins of DNA replication in mammalian cells appears to represent an effective mechanism to couple the expression of gene

Correcting Mortality for Loss to Follow-Up: A Nomogram Applied to Antiretroviral Treatment Programmes in Sub-Saharan Africa

Matthias Egger and colleagues present a nomogram and a web-based calculator to correct estimates of program-level mortality for loss to follow-up, for use in antiretroviral treatment programs