Advances in ME/CFS: Past, Present, and Future

The forerunner of what is today termed myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) was described by the U.S. Public Health Service in 1934. At the present time, we still do not know its cause and/or how to detect it by routine clinical laboratory tests. In consequence, the pathological nature of ME/CFS has been overlooked and the disease has been stigmatized by being mislabeled as psychosomatic or somatoform illness. Such misperceptions of the disease have led to insufficient research exploration of the disease and minimal to absent patient care. A 2015 Institute of Medicine report on the illness declared ME/CFS a disease affecting up to 2.5 million Americans and chastised the U.S. government for doing little to research the disease and to support its patients. Clinicians who currently treat this disease declare it to be more devastating than HIV/AIDS. A comparison of the histories of the two diseases, an examination of the current status of the two diseases, and a listing of the accomplishments that would be needed for ME/CFS to achieve the same level of treatment and care as currently experienced by patients with HIV/AIDS is provided

Our Evolving Understanding of ME/CFS

Funding Information: The IOM report of 2015 also declared ME/CFS a disease, as opposed to its classification of being a syndrome [14], based upon the severity of the illness and its unique set of symptoms [5]. Nevertheless, and important for the hypothesis put forward here, ME/CFS remains technically a syndrome: a collection of symptoms of unknown etiology. Much work directed towards identifying the underlying pathology has been undertaken across the world, in many locations including North America and Europe, where the European ME/CFS Research Network (EUROMENE), established in 2006, has, with funding from the European Union’s COST (Cooperation in Science and Technology) program, helped to address this issue (COST project CA15111) [15]. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.The potential benefits of the scientific insights gleaned from years of treating ME/CFS for the emerging symptoms of COVID-19, and in particular Longhaul-or Longhauler-COVID-19 are discussed in this opinion article. Longhaul COVID-19 is the current name being given to the long-term sequelae (symptoms lasting beyond 6 weeks) of SARS-CoV-2 infection. Multiple case definitions for ME/CFS exist, but post-exertional malaise (PEM) is currently emerging as the ‘hallmark’ symptom. The inability to identify a unique trigger of ME/CFS, as well as the inability to identify a specific, diagnostic laboratory test, led many physicians to conclude that the illness was psychosomatic or non-existent. However, recent research in the US and the UK, championed by patient organizations and their use of the internet and social media, suggest underlying pathophysiologies, e.g., oxidative stress and mitochondrial dysfunction. The similarity and overlap of ME/CFS and Longhaul COVID-19 symptoms suggest to us similar pathological processes. We put forward a unifying hypothesis that explains the precipitating events such as viral triggers and other documented exposures: For their overlap in symptoms, ME/CFS and Longhaul COVID-19 should be described as Post Active Phase of Infection Syndromes (PAPIS). We further propose that the underlying biochemical pathways and pathophysiological processes of similar symptoms are similar regardless of the initiating trigger. Exploration of the biochemical pathways and pathophysiological processes should yield effective therapies for these conditions and others that may exhibit these symptoms. ME/CFS patients have suffered far too long. Longhaul COVD-19 patients should not be subject to a similar fate. We caution that failure to meet the now combined challenges of ME/CFS and Longhaul COVID-19 will impose serious socioeconomic as well as clinical consequences for patients, the families of patients, and society as a whole.Peer reviewe

Turning a corner in me/cfs research

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.This collection of research papers addresses fundamental questions concerning the nature of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS), the problem of disbelief and lack of knowledge and understanding of the condition among many doctors and the origins of this problem, and its impact on patients and their families. We report briefly the growing knowledge of the underlying pathological processes in ME/CFS, and the development of new organizations, including Doctors with ME, the US ME/CFS Clinical Coalition and EUROMENE, to address aspects of the challenges posed by the illness. We discuss the implications of COVID-19, which has much in common with ME/CFS, with much overlap of symptoms, and propose a new taxonomic category, which we are terming post-active phase of infection syndromes (PAPIS) to include both. This collection of papers includes a number of papers reporting similar serious impacts on the quality of life of patients and their families in various European countries. The advice of EUROMENE experts on diagnosis and management is included in the collection. We report this in light of guidance from other parts of the world, including the USA and Australia, and in the context of current difficulties in the UK over the promulgation of a revised guideline from the National Institute for Health and Care Excellence (NICE). We also consider evidence on the cost-effectiveness of interventions for ME/CFS, and on the difficulties of determining the costs of care when a high proportion of people with ME/CFS are never diagnosed as such. The Special Issue includes a paper which is a reminder of the importance of a person-centred approach to care by reviewing mind–body interventions. Finally, another paper reviews the scope for prevention in minimizing the population burden of ME/CFS, and concludes that secondary prevention, through early detection and diagnosis, could be of value.publishersversionPeer reviewe

Vitamin A Status of Women and Children in Yaoundé and Douala, Cameroon, is Unchanged One Year after Initiation of a National Vitamin A Oil Fortification Program.

Vitamin A (VA) fortification of cooking oil is considered a cost-effective strategy for increasing VA status, but few large-scale programs have been evaluated. We conducted representative surveys in Yaoundé and Douala, Cameroon, 2 years before and 1 year after the introduction of a mandatory national program to fortify cooking oil with VA. In each survey, 10 different households were selected within each of the same 30 clusters (n = ~300). Malaria infection and plasma indicators of inflammation and VA (retinol-binding protein, pRBP) status were assessed among women aged 15-49 years and children aged 12-59 months, and casual breast milk samples were collected for VA and fat measurements. Refined oil intake was measured by a food frequency questionnaire, and VA was measured in household oil samples post-fortification. Pre-fortification, low inflammation-adjusted pRBP was common among children (33% <0.83 µmol/L), but not women (2% <0.78 µmol/L). Refined cooking oil was consumed by >80% of participants in the past week. Post-fortification, only 44% of oil samples were fortified, but fortified samples contained VA concentrations close to the target values. Controlling for age, inflammation, and other covariates, there was no difference in the mean pRBP, mean breast milk VA, prevalence of low pRBP, or prevalence of low milk VA between the pre- and post-fortification surveys. The frequency of refined oil intake was not associated with VA status indicators post-fortification. In sum, after a year of cooking oil fortification with VA, we did not detect evidence of increased plasma RBP or milk VA among urban women and preschool children, possibly because less than half of the refined oil was fortified. The enforcement of norms should be strengthened, and the program should be evaluated in other regions where the prevalence of VA deficiency was greater pre-fortification

Discrete Particle Swarm Optimization for the minimum labelling Steiner tree problem

Particle Swarm Optimization is an evolutionary method inspired by the social behaviour of individuals inside swarms in nature. Solutions of the problem are modelled as members of the swarm which fly in the solution space. The evolution is obtained from the continuous movement of the particles that constitute the swarm submitted to the effect of the inertia and the attraction of the members who lead the swarm. This work focuses on a recent Discrete Particle Swarm Optimization for combinatorial optimization, called Jumping Particle Swarm Optimization. Its effectiveness is illustrated on the minimum labelling Steiner tree problem: given an undirected labelled connected graph, the aim is to find a spanning tree covering a given subset of nodes, whose edges have the smallest number of distinct labels

A Path Algorithm for Constrained Estimation

Many least squares problems involve affine equality and inequality constraints. Although there are variety of methods for solving such problems, most statisticians find constrained estimation challenging. The current paper proposes a new path following algorithm for quadratic programming based on exact penalization. Similar penalties arise in $l_1$ regularization in model selection. Classical penalty methods solve a sequence of unconstrained problems that put greater and greater stress on meeting the constraints. In the limit as the penalty constant tends to $\infty$, one recovers the constrained solution. In the exact penalty method, squared penalties are replaced by absolute value penalties, and the solution is recovered for a finite value of the penalty constant. The exact path following method starts at the unconstrained solution and follows the solution path as the penalty constant increases. In the process, the solution path hits, slides along, and exits from the various constraints. Path following in lasso penalized regression, in contrast, starts with a large value of the penalty constant and works its way downward. In both settings, inspection of the entire solution path is revealing. Just as with the lasso and generalized lasso, it is possible to plot the effective degrees of freedom along the solution path. For a strictly convex quadratic program, the exact penalty algorithm can be framed entirely in terms of the sweep operator of regression analysis. A few well chosen examples illustrate the mechanics and potential of path following.Comment: 26 pages, 5 figure

The Hispanic Paradox: Race/Ethnicity and Nativity, Immigrant Enclave Residence and Cognitive Impairment Among Older US Adults

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137472/1/jgs14806.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137472/2/jgs14806_am.pd

Posttraumatic stress disorder and type 2 diabetes outcomes in veterans

IMPORTANCE: Posttraumatic stress disorder (PTSD) symptom reduction is linked with lower risk of incident type 2 diabetes (T2D), but little is known about the association between PTSD and comorbid T2D outcomes. Whether PTSD is a modifiable risk factor for adverse T2D outcomes is unknown. OBJECTIVE: To determine whether patients with PTSD who improved and no longer met diagnostic criteria for PTSD had a lower risk of adverse T2D outcomes compared with patients with persistent PTSD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used deidentified data from US Veterans Health Administration (VHA) historical medical records (from October 1, 2011, to September 30, 2022) to create a cohort of patients aged 18 to 80 years with comorbid PTSD and T2D. Data analysis was performed from March 1 to June 1, 2024. EXPOSURES: Diagnoses of PTSD and T2D. MAIN OUTCOMES AND MEASURES: The main outcomes were insulin initiation, poor glycemic control, any microvascular complication, and all-cause mortality. Improvement of PTSD was defined as no longer meeting PTSD diagnostic criteria, per a PTSD Checklist score of less than 33. Entropy balancing controlled for confounding. Survival and competing risk models estimated the association between meeting PTSD criteria and T2D outcomes. Subgroup analyses examined variation by age, sex, race, PTSD severity, and comorbid depression status. RESULTS: The study cohort included 10 002 veterans. More than half of patients (65.3%) were aged older than 50 years and most (87.2%) were men. Patients identified as Black (31.6%), White (62.7%), or other race (5.7%). Before controlling for confounding with entropy balancing, patients who no longer met PTSD diagnostic criteria had similar incidence rates for starting insulin (22.4 vs 24.4 per 1000 person-years), poor glycemic control (137.1 vs 133.7 per 1000 person-years), any microvascular complication (108.4 vs 104.8 per 1000 person-years), and all-cause mortality (11.2 vs 11.0 per 1000 person-years) compared with patients with persistent PTSD. After controlling for confounding, no longer meeting PTSD criteria was associated with a lower risk of microvascular complications (hazard ratio [HR], 0.92 [95% CI, 0.85-0.99]). Among veterans aged 18 to 49 years, no longer meeting PTSD criteria was associated with a lower risk of insulin initiation (HR, 0.69 [95% CI, 0.53-0.88]) and all-cause mortality (HR, 0.39 [95% CI, 0.19-0.83]). Among patients without depression, no longer meeting PTSD criteria was associated with a lower risk of insulin initiation (HR, 0.73 [95% CI, 0.55-0.97]). CONCLUSIONS AND RELEVANCE: The findings of this cohort study of patients with comorbid PTSD and T2D suggest that PTSD is a modifiable risk factor associated with a modest reduction in microvascular complications. Further research is needed to determine whether findings are similar in non-VHA health care settings

SN~2012cg: Evidence for Interaction Between a Normal Type Ia Supernova and a Non-Degenerate Binary Companion

We report evidence for excess blue light from the Type Ia supernova SN 2012cg at fifteen and sixteen days before maximum B-band brightness. The emission is consistent with predictions for the impact of the supernova on a non-degenerate binary companion. This is the first evidence for emission from a companion to a SN Ia. Sixteen days before maximum light, the B-V color of SN 2012cg is 0.2 mag bluer than for other normal SN~Ia. At later times, this supernova has a typical SN Ia light curve, with extinction-corrected M_B = -19.62 +/- 0.02 mag and Delta m_{15}(B) = 0.86 +/- 0.02. Our data set is extensive, with photometry in 7 filters from 5 independent sources. Early spectra also show the effects of blue light, and high-velocity features are observed at early times. Near maximum, the spectra are normal with a silicon velocity v_{Si} = -10,500$ km s^{-1}. Comparing the early data with models by Kasen (2010) favors a main-sequence companion of about 6 solar masses. It is possible that many other SN Ia have main-sequence companions that have eluded detection because the emission from the impact is fleeting and faint.Comment: accepted to Ap