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Amyotrophic Lateral Sclerosis (ALS) Linked to Intestinal Microbiota Dysbiosis & Systemic Microbial Infection in Human Patients: A Cross-Sectional Clinical Study

  • Steenblock Research Institute
  • Indonesian Medical Council

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Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's disease is a neurodegenerative and neuromuscular disorder characterized by a progressive death of motor neurons & motor paralysis that culminates in death, usually within 3-5 years of diagnosis from respiratory failure due to paralysis. Currently approved ALS therapies are not curative and fail to increase healthy lifespan. The worldwide prevalence of ALS is expected to increase by 69% over the next 25 years, yet its etiology remains scientifically unverified, complicating the discovery and development of effective therapies. Through this cross-sectional clinical study employing microbiological and cellular analyses of fecal and blood samples isolated from human patients with and without ALS, we achieved to confirm recently emerging pre-clinical and clinical evidence linking ALS with intestinal dysbiosis & systemic microbial infection, and thus provide rationale for future scientific investigations of intestinal dysbiosis as a potential therapeutic target for improving and extending the healthy lifespan of human patients diagnosed with ALS.
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Steenblock et al. Int J Neurodegener Dis 2018, 1:003
Volume 1 | Issue 1
Open Access
International Journal of
Neurodegenerative Disorders
Page 1 of 4
Citaon: Steenblock DA, Ikrar T, Antonio ASS, Wardaningsih E, Azizi MJ (2018) Amyotrophic Lateral
Sclerosis (ALS) Linked to Intesnal Microbiota Dysbiosis & Systemic Microbial Infecon in Human
Paents: A Cross-Seconal Clinical Study. Int J Neurodegener Dis 1:003.
Accepted: September 10, 2018; Published: September 12, 2018
Copyright: © 2018 Steenblock DA, et al. This is an open-access arcle distributed under the terms
of the Creave Commons Aribuon License, which permits unrestricted use, distribuon, and
reproducon in any medium, provided the original author and source are credited.
Steenblock et al. Int J Neurodegener Dis 2018, 1:003
Amyotrophic Lateral Sclerosis (ALS) Linked to Intesnal Microbi-
ota Dysbiosis & Systemic Microbial Infecon in Human Paents:
A Cross-Seconal Clinical Study
David A Steenblock1#, Taruna Ikrar2,3,4*#, Andrew S San Antonio2,4, El Wardaningsih4 and Masoud J
1Steenblock Research Instute, USA
2Internaonal School of Biomedical Sciences, Pacic Health Sciences University, USA
3Cellcure Center, The Indonesia Army and Presidenal Central Hospital, Indonesia
4Neurodegenerave Disease Research Program, Pacic Health Sciences University, USA
#These authors (T.I. & D.A.S.) contributed equally to this work.
*Corresponding author: Prof. Dr. Taruna Ikrar, MD, M. Pharm, PhD, Cellcure Center, The Indonesia Army and Presidenal
Central Hospital, (RSPAD Gatot Subroto), Jln. Abdul Rahman Saleh No. 24, Jakarta 10410, Indonesia; Internaonal School
of Biomedical Sciences and Neurodegenerave Disease Research (NDR) Program, Pacic Health Sciences University
(PHSU), 5401 Business Park South, Suite 107, Bakerseld, California, 93309, USA; Tel: +62-21-3441008; +62-21-3840702,
+1 661-200-7210 , Ext 5005, Fax: +62-21-350619, +1-661-200-7216
by progressive degeneraon of both upper and lower
motor neurons, and manifests as progressive physical
paralysis that culminates in death (most oen due to
respiratory failure) within an average of 3-5 years from
disease onset [1-3]. ALS is the most common adult-onset
motor neuron disease (MND), with a worldwide annu-
al incidence of about 2 per 100,000 [4]. The worldwide
prevalence of this fatal disease is expected to increase
by up to 69% over the next 25 years [5]. ALS aects in-
dividuals of all races and ethnicies (both male and fe-
male); however, whites, males, non-Hispanics, individu-
als aged > 50 years, and those with a family history of
ALS are more likely to develop this disease [6-8]. There
is currently no cure for ALS, and its eology remains elu-
sive. The only 2 drugs approved by the FDA to treat this
disease are riluzole (a glutamate inhibitor) and edara-
vone (an an-oxidant), both of which fail to halt the pro-
gression of this disease and fail to consistently prolong
healthy lifespan (healthspan) of ALS paents beyond
several months. Thus, there is an urgent need for the
ethical scienc discovery, development, and delivery of
therapeucs that consistently extends the healthy lifes-
Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s dis-
ease is a neurodegenerative and neuromuscular disorder
characterized by a progressive death of motor neurons &
motor paralysis that culminates in death, usually within 3-5
years of diagnosis from respiratory failure due to paralysis.
Currently approved ALS therapies are not curative and fail
to increase healthy lifespan. The worldwide prevalence of
ALS is expected to increase by 69% over the next 25 years,
yet its etiology remains scientically unveried, complicat-
ing the discovery and development of effective therapies.
Through this cross-sectional clinical study employing micro-
biological and cellular analyses of fecal and blood samples
isolated from human patients with and without ALS, we
achieved to conrm recently emerging pre-clinical and clini-
cal evidence linking ALS with intestinal dysbiosis & system-
ic microbial infection, and thus provide rationale for future
scientic investigations of intestinal dysbiosis as a potential
therapeutic target for improving and extending the healthy
lifespan of human patients diagnosed with ALS.
Check for
Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s
disease is a neurodegenerave disorder characterized
Steenblock et al. Int J Neurodegener Dis 2018, 1:003 Page 2 of 4
82 human paents included in this study, 54 (26 male
& 28 female) were diagnosed with ALS per the revised
El Escorial criteria, and 28 (14 male & 14 female) did
not have ALS or ALS-related symptoms and served as
a control group in this study. At the me of biological
(blood and feces) sample collecon & analyses, the
mean age of human paents with ALS (ALS Paents)
was 63.5 ± 12.3 years, and those without ALS (Non-ALS
Paents) was 59.4 ± 13.4 years.
Fecal & blood sample analyses
Concentraon of fecal secretory-IgA was determined
by an enzyme-linked immunosorbent assay (ELISA). Se-
rum white blood cell dierenal was determined by au-
tomated cell counng. Screening for a panel of 5 intes-
nal pathogenic bacteria was conducted per culture-based
microbiological methodology. LabCorp, Doctor’s Data,
and Great Palms Laboratory completed all afore men-
oned fecal & blood samples analyses per contemporary
best pracces in clinical laboratory science.
pan (healthspan) of ALS paents beyond what is current-
ly possible. The eology of ALS has not been fully elu-
cidated in the peer-reviewed scienc literature; how-
ever, evidence is emerging to indicate that disturbances
in the intesnal microbiota are involved in the cause &
progression of ALS and other neurodegenerave diseas-
es [9]. Here, we provide clinical evidence linking intes-
nal dysbiosis & systemic microbial infecon with ALS
and discuss raonale for further scienc invesgaon
of this link and it’s potenal as a therapeuc target.
Materials and Methods
Human subjects
Data from the blood and fecal analyses of 82 human
paents were used in this retrospecve cross-seconal
study. The Steenblock Research Instute (SRI) & its Eth-
ics Commiee approved of this retrospecve cross-sec-
onal clinical study. All human paents were > 18 years
of age & were able to provide informed consent. Of the
Concentraon (mg/dl)
F I G U RE 1 : FE C A L S E C R ET O R Y
A L S VS . N O N- A L S H U M A N P A T I EN T S
( C O N T R O L )
Figure 1: Mean concentration of fecal secretory-IgA is consistently & signicantly higher in ALS relative to Non-ALS Patients
(323.96 ± 30.73 mg/dL vs. 106.71 ± 5.56 mg/dL; P < 0.001).
regeri: 16.67%
group: 16.67%
Salmonella spp:
Prevalence (%)
Figure 2: Fecal carriage of one or more bacterial species was detected in 100% of the 54 Human ALS Patients in this study.
Steenblock et al. Int J Neurodegener Dis 2018, 1:003 Page 3 of 4
alence of pseudomonas aeruginosa and salmonella spp
is found to be 83.3% and 66.7%, respecvely (Figure 2),
thereby indicang an increased suscepbility in the ALS
Paents’ intesne to harbor pathogenic bacterial spe-
cies relave to that of healthy non-clinical populaons.
This study’s nding of intesnal dysbiosis as a feature in
ALS is in agreement with smaller cross-seconal clinical
studies conducted in 2016 [14] and 2017 [15], both of
which evaluated the intesnal microbiome of ALS Pa-
ents through dierent methodologies to confer status
of intesnal dysbiosis.
This study’s analysis of serum white blood cell con-
centraon indicates that human ALS Paents have a
signicantly elevated neutrophil-to-lymphocyte rao
(Figure 3), which is an indicaon of systemic inamma-
on in response to systemic microbial infecon [16,17].
Intesnal dysbiosis has been shown to cause intesnal
barrier dysfuncon or intesnal epithelial hyperper-
meability in a mouse model of ALS [18,19], thereby
providing an anatomical pathway for the migraon of
pathogenic intesnal microbes and/or their metabol-
ic byproducts into the systemic circulaon via the gut
circulatory system to elicit systemic microbial infecon.
Given the co-occurrence of intesnal dysbiosis and sys-
temic microbial infecon in 100% of the ALS Paents
enrolled in this study, it is plausible that a similar physio-
logical phenomenon is occurring in human ALS Paents.
This study’s nding of systemic microbial infecon as a
feature of ALS Paents is consistent with that of a pre-
vious smaller study reporng the presence of serum
pathogenic microbial byproducts & systemic inamma-
on in human ALS Paents [20].
In a recent pre-clinical study ulizing a mouse mod-
el of ALS, it was demonstrated that intesnal dysbio-
sis precedes the development and progression of ALS
Data expression & analysis
Dierences between groups (ALS Paents vs. Non-
ALS Paents) were determined by ANOVA with Stu-
dent’s t-test. Data are expressed as mean ± standard
error of the mean (SEM). A P < 0.05 was considered as
stascal signicance.
Figure 1, Figure 2 and Figure 3.
Intesnal dysbiosis is widely dened as an abnormal
elevaon in the concentraon of pathogenic microbial
species that reside within the intesnal lumen and has
recently been associated with the eology and progres-
sion of many neurodegenerave diseases [9]. Secretory
immunoglobulin A (SIgA), an endogenous anmicrobial
factor measurable in feces, is naturally found in the ex-
ternal secreons bathing mucosal surfaces of the intes-
ne at a concentraon that is posively proporonal to
the concentraon of pathogenic microbial species that
reside within the intesnal lumen [10]. This cross-sec-
onal clinical study found that the mean concentraon
of fecal secretory immunoglobulin A (SIgA) is signicant-
ly higher (> 300%) in ALS Paents relave to Non-ALS
Paents (Figure 1), thereby indicang that ALS Paents
harbor a signicantly higher concentraon of patho-
genic microbial species in their intesnal lumen and are
thus in a state of intesnal dysbiosis. Furthermore, fecal
carriage prevalence of one or more pathogenic bacterial
species was conrmed in 100% of ALS Paents enrolled
in this study (Figure 2). Among healthy human popula-
ons, fecal carriage prevalence of the pathogenic bac-
teria pseudomonas aeruginosa and salmonella spp is
8.2% and 2-3%, respecvely [11-13]. However, in this
study’s populaon of ALS Paents, fecal carriage prev-
Concentraon (1x10^9 Cells Per uL)
Figure 3: Mean serum concentration of Neutrophils (10.09 × 109 Cells vs. 2.78 × 109 Cells, P = 0.036), Lymphocytes (4.63 ×
109 Cells vs. 2.19 × 109 Cells, P = 0.015), and Eosinophils (1.95 × 109 Cells vs. 0.14 × 109 Cells, P = 0.023) are signicantly
higher in ALS relative to Non-ALS Human Patients.
Steenblock et al. Int J Neurodegener Dis 2018, 1:003 Page 4 of 4
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symptoms, and that reversal of intesnal dysbiosis with
a dietary probioc intervenon alleviates ALS symptoms
and progression, reverses intesnal barrier dysfuncon,
and prolongs healthy lifespan [19]. This strongly indi-
cates that intesnal dysbiosis may be a modiable cause
of ALS. Through this cross-seconal clinical study, we
achieved to conrm recently emerging pre-clinical and
clinical evidence linking ALS with intesnal dysbiosis &
systemic microbial infecon, and thus provide raonale
for future scienc invesgaon of intesnal dysbiosis as
a potenal therapeuc target for extending the healthy
lifespan of human paents diagnosed with ALS.
Author Contribuons
T.I. and D.A.S. performed data collecon & paent
examinaons. T.I. performed data analysis, prepared
the gures, & wrote the manuscript. M.J.A composed &
revised the manuscript per reviewer feedback. A.S.S.A.
& E.W. revised the manuscript.
Conflict of Interest Statement
The authors declare that the research was conduct-
ed in the absence of any commercial or nancial rela-
onships that could be construed as a potenal conict
of interest. Authors claim no conicts of interest related
to the research described in the manuscript.
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... For example, P. aeruginosa rhamnolipids, secreted surfactants, were shown to enhance the aggregation of human α-synuclein [37], and its functional amyloid, FapC, was involved in heterologous cross-seeding with amyloid-beta [25]. Combined with our data, these results may explain why P. aeruginosa abundance is overrepresented in patients with PCDs [38,39]. Additionally, P. aeruginosa can adhere to the intestinal epithelial barrier and secrete virulence factors that damage the intestinal epithelium [40]. ...
... With an estimated 8% of the population being asymptomatically colonized by P. aeruginosa, this bacterium may be one of the primary silent microbial contributors to neurodegenerative diseases [47]. data, these results may explain why P. aeruginosa abundance is overrepresented in patients with PCDs [38,39]. Additionally, P. aeruginosa can adhere to the intestinal epithelial barrier and secrete virulence factors that damage the intestinal epithelium [40]. ...
Neurodegenerative protein conformational diseases are characterized by the misfolding and aggregation of metastable proteins encoded within the host genome. The host is also home to thousands of proteins encoded within exogenous genomes harbored by bacteria, fungi, and viruses. Yet, their contributions to host protein-folding homeostasis, or proteostasis, remain elusive. Recent studies, including our previous work, suggest that bacterial products contribute to the toxic aggregation of endogenous host proteins. We refer to these products as bacteria-derived protein aggregates (BDPAs). Furthermore, antibiotics were recently associated with an increased risk for neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis-possibly by virtue of altering the composition of the human gut microbiota. Other studies have shown a negative correlation between disease progression and antibiotic administration, supporting their protective effect against neurodegenerative diseases. These contradicting studies emphasize the complexity of the human gut microbiota, the gut-brain axis, and the effect of antibiotics. Here, we further our understanding of bacteria's effect on host protein folding using the model Caenorhabditis elegans. We employed genetic and chemical methods to demonstrate that the proteotoxic effect of bacteria on host protein folding correlates with the presence of BDPAs. Furthermore, the abundance and proteotoxicity of BDPAs are influenced by gentamicin, an aminoglycoside antibiotic that induces protein misfolding, and by butyrate, a short-chain fatty acid that we previously found to affect host protein aggregation and the associated toxicity. Collectively, these results increase our understanding of host-bacteria interactions in the context of protein conformational diseases.
... Similar findings have been reported for certain food-borne gram-negative pathogens. (Steenblock et al. 2018) Occupations such as cleaning services or jobs related to health and research are often associated with higher use of disinfectants and greater familiarity with protocols that prevent contamination and infection, thus providing a potential explanation for the protective associations we observed. Similarly, the positive association with employment in the preserved food industry may be explained by the potential use of chemicals involved in the preservation process. ...
Investigating the joint exposure to several risk factors is becoming a key component of epidemiologic studies. Individuals are exposed to multiple factors, often simultaneously, and evaluating patterns of exposures and high-dimension interactions may allow for a better understanding of health risks at the individual level. When jointly evaluating high-dimensional exposures, common statistical methods should be integrated with machine learning techniques that may better account for complex settings. Among these, Logic regression was developed to investigate a large number of binary exposures as they relate to a given outcome. This method may be of interest in several public health settings, yet has never been presented to an epidemiologic audience. In this paper, we review and discuss Logic regression as a potential tool for epidemiological studies, using an example of occupation history (68 binary exposures of primary occupations) and amyotrophic lateral sclerosis in a population-based Danish cohort. Logic regression identifies predictors that are Boolean combinations of the original (binary) exposures, fully operating within the regression framework of interest (e. g. linear, logistic). Combinations of exposures are graphically presented as Logic trees, and techniques for selecting the best Logic model are available and of high importance. While highlighting several advantages of the method, we also discuss specific drawbacks and practical issues that should be considered when using Logic regression in population-based studies. With this paper, we encourage researchers to explore the use of machine learning techniques when evaluating large-dimensional epidemiologic data, as well as advocate the need of further methodological work in the area.
... While the pathophysiology of sporadic ALS remains unclear, some environmental factors including heavy metals has been considered as an etiologic player in the disease [6,[10][11][12]. ...
Maintaining commensal diversity is essential to host homeostasis, because microbial species provide a range of metabolic products and continuously educate the host immune system. The mucosal immune system must actively gather information about the composition of the microbiota, while offering an appropriate response. In mammals, bacterial sensing leads to the production of specific immunoglobulins (Ig), which reach the intestinal lumen as secretory Ig (SIg). Recent work has shed more light on the mechanisms by which SIg can shape bacterial repertoires and contribute to regulating host metabolism. In parallel, bacterial metabolites modulate Ig production and secretion. Here, we present an overview of the current knowledge of the relationship between bacterial metabolites and host SIg, correlating the disruption of this balance with chronic inflammation in humans.
Full-text available
Protein conformational diseases are characterized by misfolding and toxic aggregation of metastable proteins, often culminating in neurodegeneration. Enteric bacteria influence the pathogenesis of neurodegenerative diseases; however, the complexity of the human microbiome hinders our understanding of how individual microbes influence these diseases. Disruption of host protein homeostasis, or proteostasis, affects the onset and progression of these diseases. To investigate the effect of bacteria on host proteostasis, we used Caenorhabditis elegans expressing tissue-specific polyglutamine reporters that detect changes in the protein folding environment. We found that colonization of the C . elegans gut with enteric bacterial pathogens disrupted proteostasis in the intestine, muscle, neurons, and the gonad, while the presence of bacteria that conditionally synthesize butyrate, a molecule previously shown to be beneficial in neurodegenerative disease models, suppressed aggregation and the associated proteotoxicity. Co-colonization with this butyrogenic strain suppressed bacteria-induced protein aggregation, emphasizing the importance of microbial interaction and its impact on host proteostasis. Further experiments demonstrated that the beneficial effect of butyrate depended on the bacteria that colonized the gut and that this protective effect required SKN-1/Nrf2 and DAF-16/FOXO transcription factors. We also found that bacteria-derived protein aggregates contribute to the observed disruption of host proteostasis. Together, these results reveal the significance of enteric infection and gut dysbiosis on the pathogenesis of protein conformational diseases and demonstrate the potential of using butyrate-producing microbes as a preventative and treatment strategy for neurodegenerative disease.
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Amyotrophic lateral sclerosis (ALS) is a systemic disorder that involves dysfunction of multiple organs. Growing evidence has shown that neurodegenerative disorders with gut dysbiosis affect the central nervous system via pro‐inflammatory mediators thus impacting gut‐brain communications. We have demonstrated dysbiosis and increased intestinal permeability in the SOD1G93AALS mouse model. In this study, we comprehensively examined the human gut microbiome in stool samples and evaluated infection and markers of intestinal inflammation in five patients with ALS and motor neuron disorders. Five patients we studied all had alteration in their gut microbiome characterized by a low diversity of the microbiome, compared to healthy cohorts with relatively intact abundance. Firmicutes and Bacteroidetes are the two major members of bacteria at the phylum level. Low Ruminococcus spp. occurred in three patients with low Firmicutes/Bacteroidetes (F/B) ratio. A majority of patients had signs of intestinal inflammation. This is the first comprehensive examination of inflammatory markers in the stool of ALS patients. Studies in gut health and microbiome related to the onset and progression of ALS may reveal novel therapeutic targets for disease modulation.
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PurposeTo study the role of the neutrophil:lymphocyte ratio (NLR) and monocyte:lymphocyte ratio (MLR) in discriminating between different patient groups hospitalized for fever due to infection and those without infection. Methods For 299 patients admitted to hospital for fever with unknown cause, a number of characteristics including NLR and MLR were recorded. These characteristics were used in a multiple multinomial regression analysis to estimate the probability of a final diagnostic group of bacterial, viral, clinically confirmed, or no infection. ResultsBoth NLR and MLR significantly predicted final diagnostic group. Being highly correlated, however, both variables could not be retained in the same model. Both variables also interacted significantly with duration of fever. Generally, higher values of NLR and MLR indicated larger probabilities for bacterial infection and low probabilities for viral infection. Patients with septicemia had significantly higher NLR compared to patients with other bacterial infections with fever for less than one week. White blood cell counts, neutrophil counts, and C-reactive proteins did not differ significantly between septicemia and the other bacterial infection groups. ConclusionsNLR is a more useful diagnostic tool to identify patients with septicemia than other more commonly used diagnostic blood tests. NLR and MLR may be useful in the diagnosis of bacterial infection among patients hospitalized for fever.
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Although amyotrophic lateral sclerosis (ALS) is relatively rare, the socioeconomic significance of the disease is extensive. It is therefore vital to project the epidemiologic trend of ALS. To date, there have been few published studies attempting to estimate the number and distribution of ALS cases in the upcoming years. Here we show that the number of ALS cases across the globe will increase from 222,801 in 2015 to 376,674 in 2040, representing an increase of 69%. This increase is predominantly due to ageing of the population, particularly among developing nations. This projection is likely an underestimate due to improving healthcare and economic conditions. The results should be used to inform healthcare policy to more efficiently allocate healthcare resources.
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Problem/condition: Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease for which no cure or viable treatment has been identified. ALS, like most noncommunicable diseases, is not a nationally notifiable disease in the United States. The prevalence of ALS in the United States during 2010-2011 was estimated to be 3.9 cases per 100,000 persons in the general population. Updated prevalence estimates are needed to help monitor disease status, better understand etiology, and identify risk factors for ALS. Period covered: 2012-2013. Description of system: The National ALS Registry, established in 2009, collects data on ALS patients in the United States to better describe the incidence and prevalence of ALS, examine risk factors such as environmental and occupational exposures, and characterize the demographics of those living with ALS. To identify prevalent cases of ALS, data are compiled from four national administrative databases (maintained by the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration). To identify cases not included in these databases and to better understand risk-factors associated with ALS and disease progression, the Registry also includes data that are collected from patients who voluntarily enroll and complete online surveys. Results: During 2012 and 2013, the Registry identified 14,713 and 15,908 persons, respectively, who met the surveillance case definition of ALS. The estimated ALS prevalence rate was 4.7 cases per 100,000 U.S. population for 2012 and 5.0 per 100,000 for 2013. Due to revisions to the algorithm and use of death data from the National Death Index, an updated prevalence estimate has been calculated retrospectively for October 19, 2010-December 31, 2011. This updated estimate showed a prevalence rate of 4.3 per 100,000 population and a total of 13,282 cases. Since the inception of the Registry, the pattern of characteristics (e.g., age, sex, and race/ethnicity) among persons with ALS have remained unchanged. Overall, ALS was more common among whites, males, and persons aged 60-69 years. The age groups with the lowest number of ALS cases were persons aged 18-39 years and those aged ≥80 years. Males had a higher prevalence rate of ALS than females overall and across all data sources. These findings remained consistent during October 2010-December 2013. Interpretation: The Registry is the only available data source that can be used to estimate the national prevalence for ALS in the United States. Use of both administrative national databases and self-report from patients enables a comprehensive approach to estimate ALS prevalence. The overall increase in the prevalence rate from 4.3 per 100,000 persons (revised) during 2010-2011 to 4.7 and 5.0 per 100,000 persons, respectively, during 2012-2013 likely is not an actual increase in the number of ALS cases. Rather, this increase might be attributed to improved case ascertainment due to the refinement of the algorithm used to identify definite ALS cases, along with an increased public awareness of the Registry. Registry estimates of ALS prevalence are consistent with findings from long-established ALS registries in Europe and from smaller-scale epidemiologic studies previously conducted in the United States. Public health actions: Data collected by the National ALS Registry are being used to better describe the epidemiology of ALS in the United States and to help facilitate research. The combined approach of using national administrative databases and a self-enrollment web portal to collect data is novel and potentially could be used for other non-notifiable diseases such as Parkinson's disease or multiple sclerosis. Increased public awareness of the Registry might lead to more ALS cases being identified from the secure web portal (, which can ascertain cases apart from the national administrative databases. For example, in 2014, the ALS Ice Bucket Challenge, a social media-centered campaign, received extensive public visibility and created increased awareness of ALS. The Agency for Toxic Substances and Disease Registry (ATSDR) works closely with ALS advocacy and support groups, researchers, health care professionals, and others to promote the National ALS Registry and to identify all cases of ALS in the United States. In addition to estimating the prevalence of ALS, the Registry is being used to collect specimens from patient enrollees through a new biorepository, connect patient enrollees with new clinical trials and epidemiologic studies, and fund studies to help learn more about the etiology of ALS. Additional information about the National ALS Registry is available at or by calling toll-free at 1-877-442-9719.
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Introduction: Food handlers play a major role in the transmission of Salmonella serotype Typhi (S. Typhi), Shigella, and intestinal parasites. This study was conducted to determine the prevalence of S. Typhi, Shigella, and intestinal parasites among food handlers at Bahir Dar University, Ethiopia. Methodology: A cross-sectional study was conducted in June 2014. Stool samples from 410 food handlers were examined for bacterial pathogens and parasites. Pearson's Chi-square test, Fisher's exact test, and bivariate and multivariate logistic regression analyses were used where appropriate. Results: The prevalence of S. Typhi, Shigella, and intestinal parasites among food handlers was 11 (2.7%), 5 (1.2%), and 53 (12.9%), respectively. Among eight intestinal parasites identified, the two most prevalent intestinal parasites were hookworm 26 (6.3%) and G. lamblia 13 (3.1%). Male food handlers were more likely to be positive than were female food handlers for S. Typhi and intestinal parasites. Furthermore, food handlers who had a history of regular medical checkups were less infected with intestinal parasites. Being male (AOR: 2.1, 95% CI: 1.2, 4.4) and not attending medical checkups (AOR: 2.9, 95% CI: 1.4, 6.1) were independent predictors of intestinal parasitic infection in food handlers. Male food handlers were reluctant to have regular parasitological examinations. Conclusions: There was a high proportion of food handlers with S. Typhi, Shigella, and intestinal parasites in their faces. Special emphasis should be placed on S. Typhicarriers and male food handlers. Education and periodical medical checkups for intestinal parasites and S. Typhi should be considered as intervention measures.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that specifically affects motor neurons and leads to a progressive and ultimately fatal loss of functions, resulting in death typically within 3 to 5 years of diagnosis. The disease starts with a focal center of weakness, such as one limb, and usually spreads to other extremities, the brain, and often kills by affecting the respiratory muscles. Recent studies reveal a trend towards an increase in the ALS mortality rate, but the significance of this trend remains unclear. Recent ALS incidence studies have given new insight into ALS epidemiology. ALS seems to be distributed uniformly in different countries, with age-specific incidence rates showing a progressive increase up to the 60-79 age group [1]. The pathophysiological mechanisms underlying the development of familial ALS seem multifactorial with emerging evidence of a complex interaction between genetic and molecular pathways [2]. This review provides new insights into the two different form of ALS which primarily highlights epidemiology, clinical manifestations, pathophysiological, current state of ALS therapy and what the best directions are regarding future ALS research. Future directions to treat and manage ALS via stem cell therapy, possibly new drug discoveries, and diet are given.
Purpose of review: Despite the extensive research carried out in the past decades, the current pathophysiological notions of neurodegenerative disease as well as effective treatments to reduce their progression are largely unknown. Alterations of the human microbiota, the plethora of different microscopic organisms that our body hosts, have been linked to neurodegenerative disease risk, onset and progression. This review summarizes the current knowledge on the possible role of microbiota in neurodegenerative disorders and briefly discusses strategies to restore microbiota homeostasis. Recent findings: Preclinical evidences and human cross-sectional studies posit the gut microbiota as a key actor in the Parkinson's disease onset and progression, reporting the presence of a specific gut microbiota profile in association with the modulation of disease and symptoms. Gut microbiota alterations have been correlated with brain disease and peripheral inflammation also in Alzheimer's patients. Summary: The interaction between the microbiota and the host is promising to answer clinical questions that have so far escaped clarification with the current pathophysiological notions of health and disease. However, human longitudinal studies starting in the earlier disease phases are needed to understand the causative relation between microbiota and the hallmarks of these neurodegenerative disorders and to develop innovative treatments aimed at preventing or slowing brain damages.
Objectives Early identification of patients with blood stream infection (BSI), especially bacteraemia, is important as prompt treatment improves outcome. The initial stages of severe infection may be characterised by increased numbers of neutrophils in the peripheral blood and depression of the lymphocyte count (LC). The neutrophil to LC ratio (NLCR) has previously been compared with conventional tests, such as C-reactive protein (CRP) and white cell count (WCC), and has been proposed as a useful marker in the timely diagnosis of bacteraemia. Methods Data on consecutive adult patients presenting to the emergency department with pyrexial illness during the study period, November 2009 to October 2010, were analysed. The main outcome measure was positive blood cultures (bacteraemia). Sensitivity, specificity, positive and negative predictive values and likelihood ratios were determined for NLCR, CRP, WCC, neutrophil count and LC. Results 1954 patients met the inclusion criteria. Blood cultures were positive in 270 patients, hence the prevalence of bacteraemia was 13.8%. With the exception of WCC, there were significant differences in the mean value for each marker between bacteraemic and non-bacteraemic patients (p<0.001). The area under the receiver operating characteristic curve was highest for NLCR (0.72; 95% CI 0.69 to 0.75) and LC (0.71; 0.68 to 0.74) and lowest for WCC (0.54; 0.40 to 0.57). The sensitivity and specificity of NLCR for predicting bacteraemia were 70% (64% to 75%) and 57% (55% to 60%), respectively. Positive and negative predictive values for NLCR were 0.20 (0.18 to 0.23) and 0.92 (0.91 to 0.94), respectively. The positive likelihood ratio was 1.63 (1.48 to 1.79) and the negative likelihood ratio was 0.53 (0.44 to 0.64). Conclusions Although NLCR outperforms conventional markers of infection, it is insufficient in itself to guide clinical management of patients with suspected BSI, and it offers no advantage over LC. However, it may offer some diagnostic utility when taken into account as part of the overall assessment.