The Theory of Disappearing Microbiota and the Epidemics of Chronic Diseases.

In the present era, medical scientists have been confounded by the increasing incidence of multiple diseases across the world, beginning first in developed countries, and gradually spreading to other areas as they develop. These include the rises in cases of obesity, asthma, hay fever, food allergies, inflammatory bowel disease, juvenile (type 1) diabetes and autism, among many others. Are these diseases, which affect different body systems, unrelated or can a unified theory explain the increased incidence of all of these?

I believe that the latter possibility is true, and that the central theory to explain why these diseases have arisen and by what mechanism is based on modern changes in early life events that are related to the human microbiome. According to this theory, the microbiome of humans and of other animals is not accidental, but has been selected over long time periods to optimize host reproductive success through interactions between the microbiota and host physiology. Early life is the crucial period during which the adult microbiome becomes established, and development of the host and of the microbiota occur together in a conjoined manner through a dynamic equilibrium that follows a well-choreographed path. In early life, the context is set for the important developmental decisions that are required for the immune system to distinguish between what is self and what is not self, for metabolic organs to partition how much energy to expend or to save, and for the brain to determine how to respond socially to a person who might be either a friend or a foe.

Read more: The theory of disappearing microbiota and the epidemics of chronic diseases

Figure 1: A model for the interaction of the inherited microbiota with
early life immunological development in past and present children.

Source: NATURE REVIEWS IMMUNOLOGY

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Heterogeneity in Tuberculosis.

Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), results in a range of clinical presentations in humans. Most infections manifest as a clinically asymptomatic, contained state that is termed latent TB infection (LTBI); a smaller subset of infected individuals present with symptomatic, active TB. Within these two seemingly binary states, there is a spectrum of host outcomes that have varying symptoms, microbiologies, immune responses and pathologies. Recently, it has become apparent that there is diversity of infection even within a single individual. A good understanding of the heterogeneity that is intrinsic to TB — at both the population level and the individual level — is crucial to inform the development of intervention strategies that account for and target the unique, complex and independent nature of the local host–pathogen interactions that occur in this infection. In this Review, we draw on model systems and human data to discuss multiple facets of TB biology and their relationship to the overall heterogeneity observed in the human disease.

Read more: Heterogeneity in Tuberculosis.

Figure 1: A classical tuberculosis granuloma. The hallmark tuberculosis
granuloma is a highly organized collection of immune cells that aggregate
around a central necrotic core.

Source: NATURE REVIEWS IMMUNOLOGY

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Association Between Genetic Variation And Influenza Severity.

It is estimated that in the USA influenza -related deaths in recent years have ranged from 12,000 to 56,000. Factors like age, obesity, pregnancy and such chronic health conditions as asthma, chronic lung disease and heart disease are associated with an elevated risk of complications and death.

However, there are no proven genetic markers of influenza risk with an established mechanism of action. Interferon Induced Transmembrane Protein 3 (IFITM3) is an anti-viral protein that helps to block influenza infection of lung cells and to promote survival of the killer T cells that help clear the infection in the airways.

Image: A scanning electron micrograph of a CD8+ T cell engaging a virus.

(Photo courtesy of Dennis Kunkel).

A group of scientists collaborating with those at St. Jude Children's Research Hospital (Memphis, TN, USA) searched for other possible IFITM3 variants that correlated with gene expression, levels of the IFITM3 proteins and were common in influenza patients in the USA. The search led to an IFITM3 variant known as rs34481144. They checked 86 children and adults in Memphis with confirmed influenza infections and found two-thirds of patients with the most severe symptoms carried at least one copy of the newly identified high-risk IFITM3 variant. The high-risk variant was found in just 32% of patients with milder symptoms.

The team also found an association between the newly identified high-risk variant and severe and fatal influenza infections in 265 critically ill pediatric patients hospitalized in one of 31 intensive care units nationwide. The patients did not have health problems that put them at high risk for severe influenza. Of the 17 patients in this group who died from the infection, 14 carried at least one copy of the newly identified high-risk variant. Further study revealed how binding differed between the high-risk and protective variants. Those differences led to lower levels of the IFITM3 protein in individuals with two copies of the high-risk gene variant compared to other patients. The Memphis influenza patients also had fewer of the killer T cells in their upper airways. The study identifies a new regulator of IFITM3 expression that associates with CD8+ T cell levels in the airways and a spectrum of clinical outcomes.

Paul Thomas, PhD, an immunologist and corresponding author of the study, said, “A genetic marker of influenza risk could make a life-saving difference, particularly during severe influenza outbreaks, by helping prioritize high-risk patients for vaccination, drug therapy and other interventions. These results raise hopes that this newly identified IFITM3 variant might provide such a marker.” The study was published on July 17, 2017, in the journal Nature Medicine.

Source: labmedica

Screen Your Blood Cholesterol Levels For Your Heart Disease Risk!

Researchers have developed a first-of-its-kind rapid assay for measuring effectiveness of a patient’s high-density lipoprotein cholesterol (HDL-C) in cleaning up arterial cholesterol. This HDL-C function test could improve risk assessment and diagnosis, and help provide and monitor more personalized treatments for cardiovascular disease (CVD) patients.

Image: Research suggests a HDL-C function test could improve risk assessment and diagnosis,
and help provide and monitor more personalized treatments for CVD patients
(Photo courtesy of iStock).

While scientists have yet to fully elucidate how HDL-C helps protects against heart disease, one of its chief functions is thought to be mediating the removal of cholesterol from blood vessel walls. Recent studies have indicated that the ability of a patient’s HDL-C to do this – known as its cholesterol efflux capacity (CEC) – is a better gauge of CVD development than HDL-C levels on their own. This means, for example, that a patient with low levels of HDL-C but optimal CEC could be protected against heart disease to a greater degree than a patient with high levels of HDL-C but low CEC. However, the current standard research procedures for measuring CEC involve radioisotope-labeled cholesterol and cultured macrophages, making these methods too complex and time-consuming for clinical testing.

In this study, a team of researchers led by Amane Harada, PhD, of Sysmex Corporation (Kobe, Japan) and Ryuji Toh, MD, PhD, of Kobe University Graduate School of Medicine (Kobe, Japan) has developed a test for HDL-C function that is simple enough for clinical use. With a turnaround time of less than 6 hours, the test determines cholesterol uptake capacity (CUC) – the ability of HDL-C to accept additional cholesterol – which the researchers found correlates with CEC but is easier to measure. 

They evaluated their CUC test in 156 patients who had undergone revascularization (such as a stent or bypass) due to coronary artery disease and who had subsequently decreased their low-density lipoprotein cholesterol to a healthier level of less than 100 mg/dL. The study found that low CUC in these patients after treatment was significantly associated with the recurrence of coronary lesions. The researchers also determined that combining CUC with established CVD risk factors significantly improved the power of established factors to forecast which patients would redevelop heart disease.

If further trials validate this test, it could enable healthcare providers to use CUC in conjunction with HDL-C levels to better predict who is at risk for CVD onset or recurrence. This test could also be used to develop new treatments that increase CEC and to monitor their efficacy in patients.

“A more efficient enhancement of the atheroprotective functions of HDL may decrease the risk of atherosclerosis and [cardiovascular disease], although it has been difficult to develop therapeutic drugs with the expected effects,” wrote Harada and Toh in this paper, “We consider that this can be explained in part by the lack of a convenient assay system to evaluate HDL functionality without complicated or time-consuming procedures. In this respect, our cholesterol uptake assay provides a concise, accurate, and robust system for high-throughput analysis at low cost.”

The study, by Harada A et al, was published in the May 2017 issue of the Journal of Applied Laboratory Medicine.

Source: labmedica

Cardiac Biomarkers and Clinical Decision Making

New video discusses the importance of cardiac biomarkers

Click to watch video

In this video, hear from a former operating engineer at the White House who, despite an active lifestyle and basic good health, experienced sudden heart failure. In the context of his healthcare journey, the video highlights the role of cardiac biomarkers in clinical decision making and the diagnosis of a heart attack.

Diagnosed with advanced coronary artery disease, the patient underwent cardiac bypass surgery and was enrolled in a biomarker study during his postoperative course of treatment. “There’s no doubt that biomarkers have completely transformed how we care for our patients in cardiovascular medicine,” says the patient’s cardiologist.

एक बर्षे अमेरिका अनुभव : जन्मभूमि त छाड्यौं, कर्मभूमिप्रति गनगन किन ?

म अमेरिका आएको लगभग एक बर्ष पुग्न लाग्यो, म अमेरिकाको बारेमा जानकार व्यक्ति होइन तर विभिन्न अनलाइन पोर्टलमा समय समयमा अमेरिका र अरु देशमा बसोबास गरेका नेपालीहरुले आफू बसोबास गरेको देशको नकारात्मक कुरा मात्र लेखेको देखेर केही पंक्ति कोर्ने दुस्साहस गरेको हुँ । बिश्वको एउटा अति गरिव देशबाट बिश्व कै सबैभन्दा बिकसित देशमा आउन पाउनुलाई मैले व्यक्तिगत रुपमा सुवर्ण मौका ठानेको छु । यहाँ आएर कसैलाई बेकारमा आइएछ जस्तो लाग्छ भने खुरुक्क नेपाल फर्किन सल्लाह दिन्छु । यदी कसैले इच्छा त थिएन । तर, बाध्यताले बसिएको छ भनेर भन्छ भने देश छाडेर परदेशमा बस्नु हाम्रो बाध्यता हो न कि अमेरिकी सरकारको, यसरी आफ्नो फाइदाको लागि अरुको देशमा बसेर निरर्थक गनगन गर्नु बुद्धिमानी होइन । यँहा बस्ने मान्छेहरुले भित्र भित्रै खुशी भएपनि आफुलाई इच्छा बिपरित बस्नु परेको जस्तो देखाउन अरुको अगाडी केहि कारणहरु दिने गर्छन्, जसलाई तल उल्लेख गरेको छु । सबैभन्दा पहिलो, अमेरिकामा दुख छ भन्ने भनाइलाई लिऔं । यदि कामलाई दुखको रुपमा लिने होभने यो संसारमा कतै पनि सुख छैन । हाम्रो देश नेपालमा श्रम गर्नेलाई अपमान र बाबुबाजेले कमाएर छाडेको सम्पत्तिमा मोज गर्ने कामचोरहरु र दिनभरी सडक नापेर हल्लिरहने हरुलाई सम्मान गर्ने अनौठो र उल्टो चलन छ । तर, अमेरिकामा त्यस्तो रहेन छ, श्रम गर्नेलाई सम्मान गरिंदो रहेछ, चाहे त्यो जस्तोसुकै काम गरोस् । अमेरिकामा एउटा श्रमजीविले काम गरेर आफ्नो जीवन यापन राम्रोसँग गर्न सक्छ । तर, नेपालमा दिनभरी घोटिँदा पनि पेटभरि खान नपुग्ने अवस्था छ ।

दोश्रो, फुर्सत नै हुँदैन र सामाजिक जीवन छैन भन्ने कुरामा । संसारमा कर्मयोगी मान्छेहरुलाई फुर्सत हुदैन नै, आफ्नो काममा व्यस्त रहेको मान्छेलाई अर्काको नानाथरि कुरा गर्ने न त फुर्सद हुन्छ न त त्यस्ता तल्लो स्तरको कुरामा कुनै रुचि नै हुन्छ । यो कुरा नेपालमै रहेका मान्छेहरुमा पनि लागु हुन्छ । तर, त्यो मान्छे कर्मयोगी हुनुपर्छ, फुर्सद भनेको काम नभएको मान्छेहरुसंग मात्र हुन्छ चाहे त्यो अमेरिका होस् वा नेपालमा । जहाँसम्म सामाजिक जीवनको कुरा छ, बरु यहाँ होला नेपालमा धनीहरुको मात्र सामाजिक जीवन छ । गरिबहरुलाई कसैले वास्ता गर्दैनन् । नेपालमा गरिबको कुनै इज्जत छैन र गरिबी एउटा अभिशाप हो । 

तेश्रो, सोचेको जस्तो भएन भन्ने कुरामा । एउटा मान्छेले के सोच्छ र सोचेको जस्तो पाउछ वा पाउदैन भन्ने कुरा त्यो सम्योग मात्र हो । साधारणतया कुनैपनि मान्छेले पाउने काम र उसले कमाउने धन भनेको उसको व्यक्तिगत योग्यता र क्षमतामा भर पर्छ । अमेरिकामा मात्र होइन कि संसारको जुनसुकै कुनामा पनि । कहिलेकही योग्य व्यक्तिले सानो पद र अयोग्य व्यक्तिले ठुलो पद पाउने भनेको अपवाद मात्र हो र यस्तो अमेरिकामा भन्दा नेपालमै बढी हुन्छ । अब कसैले आफ्नो क्षमता भन्दा ठुलो कुरा सोचेर बस्छ र उसले त्यो कुरा पाउदैन भने उसले अमेरिकालाई भन्दा आफ्नो बुद्धि लाइ गाली गर्नु लाभदायक हुन्छ । 

करिब एक बर्ष अगाडी नेपाली काँग्रेसका नेता रामचन्द्र पौडेलले अमेरिकामा सबै नेपाली भाँडा माझ्दा रहेछन्, भनेका थिए । मलाई लाग्छ, उनले यो भाँडा माझ्नु भनेको सानोतिनो कामलाई भनेको हुन सक्छ । मेरो बिचारमा यदि कुनै मान्छेले इमान्दारीपूर्वक भाँडा नै माझ्छ भनेपनि त्यो आदर गर्न लायक कुरा हो । तर, पौडेलले सायद देखेनन् होला, अमेरिकामा नेपालमा जस्तो परालको मस्कोले खरानी चोप्दै भाडा माझ्नु पर्दैन । कि त मेसिनले माझ्छ कि त चौबिसै घण्टा धाराबाट आउने तातो पानीले साबुन लगाएर माझ्न सकिन्छ । कांग्रेस नेता पौडेललाई बिनम्रतापूर्वक मेरो एउटा प्रश्न छ, अमेरिकामा रहेका तपाईंको छोरा वा छोरीले भाँडा माझ्छन् कि माझ्दैनन् ? किनकि अमेरिकामा नेपालमा जस्तो सबैले जुठो पारेको भाडा एउटा मान्छेले माझ्ने चलन हुँदैन, प्रत्येक व्यक्तिले आफुले प्रयोग गरेको जुठो भाँडा आफैले माझ्ने चलन छ । घरेलु कामदार राख्न कानुनले प्रतिबन्ध लगाएको छ र यदी कसैको सहयोग लिउँ भन्यो भने पनि त्यो सम्भवत कुनै नेपालीले मुल्य तिर्न सक्दैन । 

यसको साथै प्राय सबै नेपाली हरुमा एउटा ठुलो भ्रम भनेको यहाका महिलाहरुले बाटो मै अँगालो हाल्छन् भन्ने छ । कसैले व्यक्त गरुन् कि नगरुन्, हुन त अंग्रेजी सिनेमामा नायिकाले नायकसँग गरेको प्रेमालाप देखेर मलाई पनि यस्तै हुन्छ कि भन्ने धारणा बनेको थियो । तर, सत्य कुरा के हो भने हामी नेपाली यो देशमा अहिले पनि नेपालमा जंगलमै जीवन बिताइरहेका राउटे जस्तै देखिन्छौं । अब अपवादको रुपमा कुनै अमेरिकी महिलाको नेपालीसँग प्रेम हुन् सक्ला तर यो घटनाले पूर्ण रुपमा प्रतितिधत्व गर्दैन । 

अत विभिन्न कारण र प्रक्रियाले अमेरिका आएका सज्जनहरुले आफुले काम गरेर जीवन चलाएको र आर्थिक रुपमा सबल भएको देशको बारेमा केवल नकारात्मक कुरा गरेर आफ्नो कर्म देशप्रति बेइमानी नगरौं, उसै पनि आफ्नो जन्मभूमि छोडेर हामीले आफ्नो देशप्रति त अन्याय गरिसकेका छौं । यद्यपी म व्यक्तिगत रुपमा यो कुरा स्वीकार गर्दिन । 'कुण्ड कुण्ड पानी र मुण्डमुण्ड बुद्धि' भनेको जस्तो झिंगालाई फोहर नै र मौरी लाई फूल नै मन पर्छ भनेको जस्तो म भने अमेरिकाबाट पूर्ण रुपमा सन्तुष्ट छु, यदी कुनै दिन कुनै पनि कारणले सन्तुष्ट हुन सकिन भने खुरुक्क नेपाल फर्किन्छु । यहाँ बेकारको गनगन गरेर बस्दिन । 

अन्तमा, जसलाई देसको माया लाग्छ उनीहरु आफ्नै देशमा बसुन् र जसलाई बिदेशमा गएर बस्ने इच्छा छ, त्यो मौका पनि पाएका छन् । उनीहरु बिदेश जान्छन । अरुको व्यक्तिगत जीवनमा यो गर्नु र यो नगर्नु भनेर उपदेश दिनु कुनै सभ्यता होइन र त्यस्तो कसैलाई अधिकार पनि छैन । मेरो भन्नु यति मात्र हो कि अनेकौ प्रयास र तिकडम गरेर पनि यहाँ आउन नसकेर पिल्सिएपछि 'अमिलो अंगुर' भने जस्तो बिरोध नगरौं । यसको मतलव अमेरिकामा बस्ने सबै महान र नेपालमा बस्ने सबै तल्लोस्तरका भन्ने अर्थ नलागोस् । 

प्रकाशित: चैत्र ३१, २०७३

कान्तिपुर

Source: kantipur

Key Regulator of Intestinal Homeostasis Identified

SP140, an epigenetic reader protein mutated in a number of autoimmune disorders, is essential for macrophage function and preventing intestinal inflammation, scientists show. 

Read more: Key Regulator of Intestinal Homeostasis Identified

Artist's rendition of a macrophage in the gut and epigenome (green balls are the basic units of chromatin,
with nucleosomes wrapped twice around an octamer of a histone)

Researchers are only beginning to understand the roles of the hundreds of proteins involved in reading, writing, and erasing the epigenome. One of the epigenetic regulators, SP140, which is mutated in a number autoimmune disorders, including Crohn’s disease and multiple sclerosis, is also essential to macrophage function and intestinal homeostasis in both humans and mice, scientists reported today (March 3) in Science Immunology.

“Many immune-mediated disorders are driven by a combination of genetic susceptibility as well as environmental influences [so] epigenetics is a suitable critical juncture between those two aspects of the disease,” said coauthor Kate Jeffrey, a researcher investigating the epigenetic control of innate immunity at Massachusetts General Hospital.

Source: the-scientist

What It Means When You Dream About Being Naked In Public

You’re at the office and everything is normal... Until you get up during a meeting to give a presentation and you realize you are totally naked. 

It’s a dream many people have had in some iteration. But experts still aren’t entirely sure what it means.

Most psychologists agree it probably doesn’t represent a literal desire to be naked in public, but more likely is related to being embarrassed about something about yourself that other people don’t know about you.

Other psychologists have suggested this type of dream comes from harboring feels of guilt or inferiority ― or may be triggered by feeling neglected or deprived of attention in the past.

Of course some people think it means nothing at all. But neuroscientists and psychologists are convinced that, apart from meaning, dreams serve an important role in maintaining our mental and emotional health.

Decades of research suggest that dreams help us make memories, solve the problems we struggle with in our waking hours and process emotions ― even unpleasant ones where you accidentally expose yourself to everyone at work.

Read more: What It Means When You Dream About Being Naked In Public

Biomedical Video: What it means when you dream of being naked in public

Source: msn.com/en-us/health

The Mucosal Immune System: Master Regulator of Bidirectional Gut–Brain Communications

Communication between the brain and gut is not one-way, but a bidirectional highway whereby reciprocal signals between the two organ systems are exchanged to coordinate function. The messengers of this complex dialogue include neural, metabolic, endocrine and immune mediators responsive to diverse environmental cues, including nutrients and components of the intestinal microbiota (microbiota–gut–brain axis). We are now starting to understand how perturbation of these systems affects transition between health and disease. The pathological repercussions of disordered gut–brain dialogue are probably especially pertinent in functional gastrointestinal diseases, including IBS and functional dyspepsia. New insights into these pathways might lead to novel treatment strategies in these common gastrointestinal diseases. In this Review, we consider the role of the immune system as the gatekeeper and master regulator of brain–gut and gut–brain communications. Although adaptive immunity (T cells in particular) participates in this process, there is an emerging role for cells of the innate immune compartment (including innate lymphoid cells and cells of the mononuclear phagocyte system). We will also consider how these key immune cells interact with the specific components of the enteric and central nervous systems, and rapidly respond to environmental variables, including the microbiota, to alter gut homeostasis.

Key points

• Common gastrointestinal diseases, such as IBS, functional dyspepsia and IBD, are closely linked to psychological morbidity
• This link is driven in part through bidirectional signaling between the brain and gut, which reciprocally regulate each other
• Growing evidence implicates the importance of immune activation, which might be overt (IBD) or more subtle (IBS, functional dyspepsia) in pathological gut–brain interactions
• The composition of the intestinal microbiota affects behaviour and mood, which could in part rely on selective activation of distinct host cytokine responses
• Therapeutic targeting of gut microorganisms, host immunity or psychological symptoms could hold the key to uncoupling pathological interactions between the gut and brain

Read more: The Mucosal Immune System: Master Regulator of Bidirectional Gut–Brain Communications

Key brain–immune–gut interactions

Source: Nature Reviews: Gastroenterology & Hepatology

Before Automating The Blood Bank, Evaluate Compatibility With Existing Systems

Automation in the blood bank can be a turnaround time saver and staffing force multiplier. However, optimizing the testing workflow on the existing platforms should be the first order of business when considering new automation. There are companies that can be hired to do this, and they may present ways to optimize current analyzers with minor adjustments in the workflow process. Beginning with the end in mind, mapping the current workflow processes will provide a baseline for improving operations in any blood bank and laboratory.

Consider the laboratory structure. Is there a core laboratory concept with blood bank and microbiology located in the same workspace? Is it necessary to consider changes to the power, IT connections, and physical space in the planning process for new automation? Many laboratory structures limit the ability to share technologies and products, which creates operational gaps and challenges staffing models. Workflow process mapping will ensure that a lab leader has defined the many interconnected operations that impact the overall efficiency of a laboratory and point out key areas where automation may help make great strides in productivity. Placement of automation can allow for integration and cross training of the technical staff. A well-trained, cross-functional staff can be a great tool in generating efficiencies as well as reducing laboratorian burnout.

Read more: Before Automating The Blood Bank, Evaluate Compatibility With Existing Systems

Source: MedicalLaboratoryObserver