Τετάρτη, 7 Δεκεμβρίου 2016

Radical Scavenging Potential: Antioxidant Vitamins and Total Phenolics Contents of Raw and Hydrothermal Processed Herbs In Vitro

2016-12-07T17-58-25Z
Source: Journal of Experimental and Integrative Medicine
Okey Alphonsus Ojiako, Paul Chidoka Chikezie, Doris I. Ukairo, Chiedozie Onyejiaka Ibegbulem, Reginald N. Nwaoguikpe.
Aim/Background: The present study evaluated the antioxidant vitamins and total phenolics contents from Monodora myristica, Chromolaena odorata, Buccholzia coriacea and Sphenostylis stenocarpa in connection with their comparative radical scavenging potential between the raw and hydrothermal processed herbs using in vitro models. Methods: Antioxidant vitamins and total phenolics contents as well as radical scavenging capacities and ferric reducing antioxidant power of the herbs were measured using standard spectrophotometric methods. Results: The hydrothermal processed herbs exhibited relatively lower antioxidant vitamins and total phenolics contents compared with the raw herbs. Total phenolics contents of the raw and hydrothermal processed herbs varied within relatively narrow range: 0.26 ± 0.04 7.97 ± 0.20 mg GAE/g dry sample. The SCI50 of raw herbal extracts against O2− was within the range of 201.61 ± 4.09 305.21 ± 5.11 µg/mL, whereas those of corresponding hydrothermal processed herbs gave 211.02 ± 4.15 531.66 ± 8.14 µg/mL. For the most part, SCI50 of the raw herbs against NO− were significantly lower (p

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Parturient recall of neuraxial analgesia risks: Impact of labor pain vs no labor pain

Information exchange between anesthesia providers and parturients about neuraxial analgesia risks often occurs in the presence of labor pain. This study examined whether the presence of pain impacted the level of recall of information provided to parturients regarding risks of neuraxial techniques.

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Vasoplegic syndrome during Whipple procedure

Vasoplegic syndrome is an unusual cause of refractory hypotension under general anesthesia. It is commonly described in the setting of cardiac surgery, but rarely seen in noncardiac setting. We describe successful management of vasoplegic syndrome during Whipple procedure with vasopressin infusion. A high index of suspicion and prompt treatment with vasopressin can be lifesaving in patients with risk factors for vasoplegic syndrome who present with severe refractory hypotension and who respond poorly to fluid administration and routine vasopressor infusion.

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Audit of postoperative pain management after open thoracotomy and the incidence of chronic postthoracotomy pain in more than 500 patients at a tertiary center

To evaluate the quality of postoperative pain relief during the first 3 days after surgery and to evaluate with the incidence of persistent pain at 6 months after surgery.

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Anesthesia and Brugada syndrome: a 12-year case series

The aim of this 12-year case series was to review the drugs used during anesthetic management of patients with diagnosis of or risk criteria for Brugada syndrome (BrS), and to document any possible association between these drugs and arrhythmogenic activity or unexplained hemodynamic instability.

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The Perspective of Celiac Disease Patients on Emerging Treatment Options and Non-Celiac Gluten Sensitivity

Non-celiac gluten sensitivity (NCGS) and emerging treatment options are hot topics in the celiac disease (CeD) scientific literature. However, very little is known about the perspective on these issues of CeD patients.

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Individual difference in β-band corticomuscular coherence and its relation to force steadiness during isometric voluntary ankle dorsiflexion in healthy humans

Stabilizing muscle force is an important ability for mobility of daily activities. This function is often referred as "force steadiness", and is quantified by calculating the magnitude of fluctuations in isometric muscle force around the averaged value. Indeed, this measure has been often calculated in the field of exercise and/or clinical neurophysiology, primarily to examine changes in motor function caused by several factors such as aging (Galganski et al., 1993; Tracy and Enoka, 2002; Vaillancourt and Newell, 2003), lack of muscle use (Shinohara et al., 2003; Clark et al., 2007), and neural disorders such as stroke (Chow and Stokic, 2014).

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The Perspective of Celiac Disease Patients on Emerging Treatment Options and Non-Celiac Gluten Sensitivity

Non-celiac gluten sensitivity (NCGS) and emerging treatment options are hot topics in the celiac disease (CeD) scientific literature. However, very little is known about the perspective on these issues of CeD patients.

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Cadaver lab training for paramedic students

Paramedic students use cadavers to practice various airway and vascular access procedures at United Tissue Network's Phoenix facility.

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Wake County EMS documentary

The documentary captures four decades of service from Wake County EMS told through each of the department's directors.

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Cadaver lab training for paramedic students

Paramedic students use cadavers to practice various airway and vascular access procedures at United Tissue Network's Phoenix facility.

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Wake County EMS documentary

The documentary captures four decades of service from Wake County EMS told through each of the department's directors.

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Cadaver lab training for paramedic students

Paramedic students use cadavers to practice various airway and vascular access procedures at United Tissue Network's Phoenix facility.

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Wake County EMS documentary

The documentary captures four decades of service from Wake County EMS told through each of the department's directors.

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Cadaver lab training for paramedic students

Paramedic students use cadavers to practice various airway and vascular access procedures at United Tissue Network's Phoenix facility.

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Wake County EMS documentary

The documentary captures four decades of service from Wake County EMS told through each of the department's directors.

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Ethics in EMS: 10 things you need to know to save lives

Principles for the ethical EMS provider

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Why quality of care and patient satisfaction should matter to your agency

As patient satisfaction surveys begin to affect Medicare reimbursement for physicians and hospitals, EMS agencies should consider ways to improve care and reduce costs

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Alaska paramedic program sweeps state competition

By EMS1 Staff

ANCHORAGE, Alaska — Paramedics from Fairbanks swept every category at a statewide EMS skills Olympic competition last month. 

Faculty, students and staff from the Paramedic Academy at University of Alaska Fairbanks Community and Technical College showed their skills in the Alaska EMS Symposium. Students who graduated from the program last summer scored a 100 percent first-time pass rate on the NREMT exam, reported News Miner

Graduates and current academy students took first place in six categories: overall state paramedic, overall state EMT 2/3, overall state EMT 1, splinting broken bones, oxygen administrator and bleeding control. 

The competition brought EMS professionals from across the state to demonstrate their skills, from administering oxygen to splinting broken bones. Trainings, exhibits and discussions were also held at the symposium. 

"For the first time, we not only had to be capable of doing the skills well, we also had to do them the fastest," Kinzea Jones, a recent Fairbanks paramedic graduate, said. She said the program's high standards and simulation scenarios are what fully prepared her for the competition. 

Myles Jellison, a 2012 graduate of the program, won first place in the overall state paramedic category. "I had never competed in any EMS competition before and the experience was great. The EMS field is constantly changing."



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EMS chiefs: Listen for theories

In improvement science, we define "theory" as an idea or concept that's testable. Theories are different than facts or laws that imply that something is fixed and unchangeable. A theory invites inquiry and experimentation.

One powerful leadership tool is to listen for theories when people say things as if they were facts. Here are a few that I've heard recently:

  • Response times are a lousy measure of EMS system performance.
  • Too much focus on pain management by EMS providers is contributing to the opiate overdose epidemic.
  • There has to be a consequence for poor EMS provider patient care.
  • Patients die every day in our system who could be saved with rapid sequence induction facilitated intubation.

Those of us who are deeply immersed in the science of improvement have a few annoying habits. One of these is responding to pronouncements of fact with something like, "That's an interesting theory, tell me more about that. Where did it originate" I'd love to see the evidence behind it."

Several years ago, I worked with a Chief Financial Officer (long since retired) that would call those of us running EMS ambulance operations whenever one of our key performance numbers went down for the second month in a row.

The first time I got one of these phone calls he said, "Your transport volume is down for the second month in a row. What's going on and what are you going to do about it""

There was a long and dreadful silence after I told him, "Volume is down because less people called 911."

I could not believe it when he responded, "Well what are you going to do about that""

It took all of my resistance not to say something career-endingly sarcastic.

Testing the CFO's theory
A month or so after this phone call, I had the opportunity to ask him why he made these phone calls. He said, "A one month drop in performance can happen to anyone. If it happens a second time, then that means there is a trend and a real problem. When I call, things get better. And, quite frankly, a little fear is necessary to lead effectively."

The way he said it indicated that this was factual, the way it is. He left no room for question or debate. Of course I said, "That's an interesting theory."

Let's break his declaration into testable chunks:

"When I call things get better."
Since our organization (long since amalgamated) had several 911 operations in various locations, this theory would be easy to test. We could do a prospective controlled experiment. Half of the operations would be on the call list and the other half would be left alone. We could track their respective performance over time and compare the two groups. This method would not get us published in the New England Journal of Medicine, but we are doing improvement not peer reviewed research. The methodology does not have to be perfect, just good enough to reliably answer a performance question for our organization.

"A little fear is necessary to lead effectively."
Just like spanking a toddler, this topic tends to produce hot-blooded opinions for and against. W. Edwards Deming, Ph.D., one of the originators of improvement science, is solidly in the "drive fear out of the workplace" camp. Fans of Machiavelli tend to believe that fear of punishment is helpful.

This is a good spot for reader participation. How would you test the impact of a fear-based leadership style" It would also be great to hear your stories about leading or being led with or without fear. Please respond in the comments or send me an e-mail . We will gather your perspectives and share them in a future article.

"A one month drop in performance can happen to anyone. If it happens a second time, then that means there is a trend and a real problem."
This is a theory that's been extensively tested by expert statisticians again and again since the 1930s. It highlights one of the cornerstones of improvement science, understanding variation.

All processes have variation. The process that produces response time performance, your blood pressure and your team's happiness level all yield different results at different times. Your blood pressure at this moment is not exactly the same as it was when you fell asleep last night.

These normal up and down alterations are known as "common cause variation." So the first part of our CFO's theory, "a one month drop in performance can happen to anyone" is supported by decades of statistical evidence. With common cause variation, a smart leader will not ask about specific data points, but will ask if the overall performance is good enough or not. That's because with common cause variation, the individual ups and downs don't mean anything.

If you're allergic to bees and get stung on the inside of your mouth by a bee that's landed in your soda can, chances are your blood pressure will drop so low that a limbo dancer would not be able to get under it. This level of change in performance is known as "special cause variation" or as Walter Shewhart, the father of improvement statistics, called it "assignable variation."

When you have special cause variation, smart leaders will ask, "What happened here"" That's because special cause variation signals that something has changed for better or worse.

In a future article, we will teach you several ways to differentiate common cause variation from special cause variation. For now, let's just focus on one. If you have six or more data points in a row that are going up or down, it's a sign of a special cause. Five or fewer data points — going up or down — is common cause variation.

So our CFO was asking a special cause question based on only two data points, common cause variation. When someone higher on the pecking order asks special cause questions of common cause variation, people will come up with answers that are logical, compelling, rational and completely fabricated.

Acting on those fabricated answers often makes things worse. Of course that's just my theory.



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Wash. ambulance crashes with patient onboard

Officials said the ambulance veered off the road into a water-filled ditch and struck some trees

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Mutations in DYNC2H1, the cytoplasmic dynein 2, heavy chain 1 motor protein gene, cause short-rib polydactyly type I, Saldino-Noonan type

Abstract

The short-rib polydactyly syndromes (SRPS) are autosomal recessively inherited, genetically heterogeneous skeletal ciliopathies. SRPS phenotypes were historically categorized as types I–IV, with type I first delineated by Saldino and Noonan in 1972. Characteristic findings among all forms of SRP include short horizontal ribs, short limbs and polydactyly. The SRP type I phenotype is characterized by a very small thorax, extreme micromelia, very short, poorly mineralized long bones, and multiple organ system anomalies. To date, the molecular basis of this most severe type of SRP, also known as Saldino-Noonan syndrome, has not been determined. We identified three SRP cases that fit the original phenotypic description of SRP type I. In all three cases, exome sequence analysis revealed compound heterozygosity for mutations in DYNC2H1, which encodes the main component of the retrograde IFT A motor, cytoplasmic dynein 2 heavy chain 1. Thus SRP type I, II, III and asphyxiating thoracic dystrophy (ATD), which also result from DYNC2H1 mutations. Herein we describe the phenotypic features, radiographic findings, and molecular basis of SRP type I.

Thumbnail image of graphical abstract

Graphical Abstract



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Why EMS leaders should listen for theories

In improvement science, we define "theory" as an idea or concept that's testable. Theories are different than facts or laws that imply that something is fixed and unchangeable. A theory invites inquiry and experimentation.

One powerful leadership tool is to listen for theories when people say things as if they were facts. Here are a few that I've heard recently:

  • Response times are a lousy measure of EMS system performance.
  • Too much focus on pain management by EMS providers is contributing to the opiate overdose epidemic.
  • There has to be a consequence for poor EMS provider patient care.
  • Patients die every day in our system who could be saved with rapid sequence induction facilitated intubation.

Those of us who are deeply immersed in the science of improvement have a few annoying habits. One of these is responding to pronouncements of fact with something like, "That's an interesting theory, tell me more about that. Where did it originate" I'd love to see the evidence behind it."

Several years ago, I worked with a Chief Financial Officer (long since retired) that would call those of us running EMS ambulance operations whenever one of our key performance numbers went down for the second month in a row.

The first time I got one of these phone calls he said, "Your transport volume is down for the second month in a row. What's going on and what are you going to do about it""

There was a long and dreadful silence after I told him, "Volume is down because less people called 911."

I could not believe it when he responded, "Well what are you going to do about that""

It took all of my resistance not to say something career-endingly sarcastic.

Testing the CFO's theory
A month or so after this phone call, I had the opportunity to ask him why he made these phone calls. He said, "A one month drop in performance can happen to anyone. If it happens a second time, then that means there is a trend and a real problem. When I call, things get better. And, quite frankly, a little fear is necessary to lead effectively."

The way he said it indicated that this was factual, the way it is. He left no room for question or debate. Of course I said, "That's an interesting theory."

Let's break his declaration into testable chunks:

"When I call things get better."
Since our organization (long since amalgamated) had several 911 operations in various locations, this theory would be easy to test. We could do a prospective controlled experiment. Half of the operations would be on the call list and the other half would be left alone. We could track their respective performance over time and compare the two groups. This method would not get us published in the New England Journal of Medicine, but we are doing improvement not peer reviewed research. The methodology does not have to be perfect, just good enough to reliably answer a performance question for our organization.

"A little fear is necessary to lead effectively."
Just like spanking a toddler, this topic tends to produce hot-blooded opinions for and against. W. Edwards Deming, Ph.D., one of the originators of improvement science, is solidly in the "drive fear out of the workplace" camp. Fans of Machiavelli tend to believe that fear of punishment is helpful.

This is a good spot for reader participation. How would you test the impact of a fear-based leadership style" It would also be great to hear your stories about leading or being led with or without fear. Please respond in the comments or send me an e-mail . We will gather your perspectives and share them in a future article.

"A one month drop in performance can happen to anyone. If it happens a second time, then that means there is a trend and a real problem."
This is a theory that's been extensively tested by expert statisticians again and again since the 1930s. It highlights one of the cornerstones of improvement science, understanding variation.

All processes have variation. The process that produces response time performance, your blood pressure and your team's happiness level all yield different results at different times. Your blood pressure at this moment is not exactly the same as it was when you fell asleep last night.

These normal up and down alterations are known as "common cause variation." So the first part of our CFO's theory, "a one month drop in performance can happen to anyone" is supported by decades of statistical evidence. With common cause variation, a smart leader will not ask about specific data points, but will ask if the overall performance is good enough or not. That's because with common cause variation, the individual ups and downs don't mean anything.

If you're allergic to bees and get stung on the inside of your mouth by a bee that's landed in your soda can, chances are your blood pressure will drop so low that a limbo dancer would not be able to get under it. This level of change in performance is known as "special cause variation" or as Walter Shewhart, the father of improvement statistics, called it "assignable variation."

When you have special cause variation, smart leaders will ask, "What happened here"" That's because special cause variation signals that something has changed for better or worse.

In a future article, we will teach you several ways to differentiate common cause variation from special cause variation. For now, let's just focus on one. If you have six or more data points in a row that are going up or down, it's a sign of a special cause. Five or fewer data points — going up or down — is common cause variation.

So our CFO was asking a special cause question based on only two data points, common cause variation. When someone higher on the pecking order asks special cause questions of common cause variation, people will come up with answers that are logical, compelling, rational and completely fabricated.

Acting on those fabricated answers often makes things worse. Of course that's just my theory.



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What EMS leaders need to know about public health

By Sean Caffrey, NEMSMA

It has been said that EMS is at the intersection of public safety, health care and public health.

The public safety component of EMS is the most clear. EMS systems are prepared to respond to medical emergencies and traumatic injuries in their communities 24/7 with staff, vehicles and equipment. Much like police departments, fire departments and emergency management, this availability to the community constitutes an essential safety net that can respond immediately. It is this availability to respond that often justifies the public funding of EMS through tax collections or other assessments on the community as a whole.

The health care role for EMS is also pretty clear and begins as soon as we encounter a patient in the field. From that point forward, we are providing individual health care services much like any other part of the health care system. This aspect of EMS requires medical knowledge, care protocols, physician oversight and a level of integration with other health care components. It is the provision of these individual health care services that is the justification for EMS to bill patients directly, a practice uncommon to other public safety functions.

What is the public health connection to EMS"
Public health is an amazingly broad discipline which includes injury prevention, disease surveillance, meeting the needs of underserved populations, and much more. The American Public Health Association has no less than 31 interest areas and or sections for its members, spanning from HIV/AIDs to school-based health to health information systems to behavioral health. There is even an emergency health services section concerned with EMS and emergency care systems.

As a general rule, public health is a catch-all discipline that is concerned with the health of communities in general. As a result, it is essentially anything health-related that is not an individual health care service. Despite its broad mission, public health is only a fraction of the health care system, especially in the U.S. where we have a substantial focus on acute care services.

The history of public health is extensive, and includes many great successes regarding environmental health, the control of infectious diseases, occupational health and reductions in smoking amongst the general public. Public health is often a governmental responsibility and is accomplished to varying degrees at all levels of local, state and federal government. At the federal level, multiple agencies, including the U.S. Public Health Service and the Centers for Disease Control and Prevention, have public health responsibilities. Every state has a health department, as do almost all counties and many larger municipalities.

Many public health professionals are very concerned with vulnerable populations and health equity issues. Individuals at the lower end of the socio-economic spectrum are more likely to suffer from many diseases, particularly those linked to the environment like asthma or lead paint exposure. Many of these populations also suffer from a lack of access to medical care. The poor and vulnerable, however, often benefit the most from public health accomplishments over time including advances key areas such as clean air and clean water.

Why does public health matter to EMS"
Perhaps the most visible area where public health crosses over into EMS are regarding access to care and regulatory oversight issues, a key role of state health departments. Odds are good that your state EMS office is part of the state health department.

State EMS offices are concerned with ensuring that ambulance and EMS systems meet minimum standards and are accessible to all citizens. Many of these offices also investigate complaints to ensure the public is protected from substandard care.

You may also note that there is somewhat of an inherent contradiction in that state EMS offices are often charged with both regulating and building EMS capacity simultaneously in their enabling state legislation. This relates to the public health aspects of EMS where both access to care and effective regulation are essential.

What are the types of public health prevention"
Public health practitioners view their work through three types of prevention.

  • Primary prevention that involves eliminating disease before it occurs.
  • Secondary prevention that involves identifying disease early through screening and other methods and limiting its progression.
  • Tertiary prevention that occurs in concert with acute treatment and involves minimizing the impact of disease on individuals and populations.

What are the types of diseases"
Public health views disease as infectious or non-infectious. Infectious diseases are exactly as they sound and are the historic bread and butter of public health work. Diseases such as cholera, malaria, measles, Ebola and Zika virus qualify in this category.

Non-infectious diseases, however, represent what EMS is most involved with including such diseases as asthma, diabetes, heart disease and trauma. Due to the success of previous efforts to eradicate infectious diseases, non-infectious diseases have become the population health challenge of our time, and EMS is on the front lines of combating them. Health departments also spend a large amount of time developing and deploying programs to prevent and mitigate these non-infectious diseases.

How is public health engaged in emergency preparedness and response"
Another important aspect of public health activities is emergency preparedness and response to public health emergencies. This begins with surveillance activity for a variety of reportable diseases and also involves epidemiology, the investigative aspect of health.

As emerging diseases are identified, public health officials are charged with monitoring outbreaks and mitigating the consequences. This also involves multi-disciplinary planning activities, such as those to address SARS, pandemic influenza and Ebola that likely involved your EMS service at some level in the past. If you are in an area prone to large scale natural disasters, such as hurricanes or floods, you have also likely participated in public health emergency planning activities.

What is a public health assessment"
A final aspect, particularly of local public health agencies, is community health assessments. These assessments are usually taken on as part of the routine planning activities of local health agencies and are updated on a regular basis. These assessments identify the key health risks in the community and programs in place to address them. In many cases, they have become the basis for community paramedicine and similar programs in the community. If you haven't seen one for your community, you can probably find it on your local agency's website. You may be surprised at how much it could inform the activities of your EMS system.

What is the future of EMS and public health collaboration"
EMS will continue to be regulated and influenced by public health at multiple levels. We are fortunate, however, that public health professionals will also remain very interested in the availability and viability of our EMS systems. State rural health offices, the National EMS Information System and the federal EMS for Children program are examples of this type of involvement.

EMS systems should also be willing to partner with their local public health agencies as they often face many of the same population health concerns as EMS. They receive funding from a variety of sources that may help your service provide injury prevention and other programs. At the very least, knowing your local health officials can come in very handy if you find yourself in the middle of a disease outbreak or similar emergency.

Make sure to befriend and connect with public health practitioners in your state and community. Many of them hold a Masters in Public Health or a similar advanced degree. As EMS leaders, we can both benefit from, and provide benefits to, the overall health of our community through public health partnerships.



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Researchers show off medical drones for disasters, shootings

The drones would ferry medical supplies to places that are remote or temporarily cut off

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Regulation of Secondary Metabolism by the Velvet Complex Is Temperature-Responsive in Aspergillus

Sensing and responding to environmental cues is critical to the lifestyle of filamentous fungi. How environmental variation influences fungi to produce a wide diversity of ecologically important secondary metabolites (SMs) is not well understood. To address this question, we first examined changes in global gene expression of the opportunistic human pathogen, Aspergillus fumigatus, after exposure to different temperature conditions. We found that 11 of the 37 SM gene clusters in A. fumigatus were expressed at higher levels at 30° than at 37°. We next investigated the role of the light-responsive Velvet complex in environment-dependent gene expression by examining temperature-dependent transcription profiles in the absence of two key members of the Velvet protein complex, VeA and LaeA. We found that the 11 temperature-regulated SM gene clusters required VeA at 37° and LaeA at both 30 and 37° for wild-type levels of expression. Interestingly, four SM gene clusters were regulated by VeA at 37° but not at 30°, and two additional ones were regulated by VeA at both temperatures but were substantially less so at 30°, indicating that the role of VeA and, more generally of the Velvet complex, in the regulation of certain SM gene clusters is temperature-dependent. Our findings support the hypothesis that fungal secondary metabolism is regulated by an intertwined network of transcriptional regulators responsive to multiple environmental factors.



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Epigenetic Control of Phenotypic Plasticity in the Filamentous Fungus Neurospora crassa

Phenotypic plasticity is the ability of a genotype to produce different phenotypes under different environmental or developmental conditions. Phenotypic plasticity is a ubiquitous feature of living organisms, and is typically based on variable patterns of gene expression. However, the mechanisms by which gene expression is influenced and regulated during plastic responses are poorly understood in most organisms. While modifications to DNA and histone proteins have been implicated as likely candidates for generating and regulating phenotypic plasticity, specific details of each modification and its mode of operation have remained largely unknown. In this study, we investigated how epigenetic mechanisms affect phenotypic plasticity in the filamentous fungus Neurospora crassa. By measuring reaction norms of strains that are deficient in one of several key physiological processes, we show that epigenetic mechanisms play a role in homeostasis and phenotypic plasticity of the fungus across a range of controlled environments. In general, effects on plasticity are specific to an environment and mechanism, indicating that epigenetic regulation is context dependent and is not governed by general plasticity genes. Specifically, we found that, in Neurospora, histone methylation at H3K36 affected plastic response to high temperatures, H3K4 methylation affected plastic response to pH, but H3K27 methylation had no effect. Similarly, DNA methylation had only a small effect in response to sucrose. Histone deacetylation mainly decreased reaction norm elevation, as did genes involved in histone demethylation and acetylation. In contrast, the RNA interference pathway was involved in plastic responses to multiple environments.



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G3 Reviewer Index 2016



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Corrigendum



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An RNAi Screen To Identify Protein Phosphatases That Function Within the Drosophila Circadian Clock

Circadian clocks in eukaryotes keep time via cell-autonomous transcriptional feedback loops. A well-characterized example of such a transcriptional feedback loop is in Drosophila, where CLOCK-CYCLE (CLK-CYC) complexes activate transcription of period (per) and timeless (tim) genes, rising levels of PER-TIM complexes feed-back to repress CLK-CYC activity, and degradation of PER and TIM permits the next cycle of CLK-CYC transcription. The timing of CLK-CYC activation and PER-TIM repression is regulated posttranslationally, in part through rhythmic phosphorylation of CLK, PER, and TIM. Previous behavioral screens identified several kinases that control CLK, PER, and TIM levels, subcellular localization, and/or activity, but two phosphatases that function within the clock were identified through the analysis of candidate genes from other pathways or model systems. To identify phosphatases that play a role in the clock, we screened clock cell-specific RNA interference (RNAi) knockdowns of all annotated protein phosphatases and protein phosphatase regulators in Drosophila for altered activity rhythms. This screen identified 19 protein phosphatases that lengthened or shortened the circadian period by ≥1 hr (p ≤ 0.05 compared to controls) or were arrhythmic. Additional RNAi lines, transposon inserts, overexpression, and loss-of-function mutants were tested to independently confirm these RNAi phenotypes. Based on genetic validation and molecular analysis, 15 viable protein phosphatases remain for future studies. These candidates are expected to reveal novel features of the circadian timekeeping mechanism in Drosophila that are likely to be conserved in all animals including humans.



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A Genetic Screen To Assess Dopamine Receptor (DopR1) Dependent Sleep Regulation in Drosophila

Sleep is an essential behavioral state of rest that is regulated by homeostatic drives to ensure a balance of sleep and activity, as well as independent arousal mechanisms in the central brain. Dopamine has been identified as a critical regulator of both sleep behavior and arousal. Here, we present results of a genetic screen that selectively restored the Dopamine Receptor (DopR/DopR1/dumb) to specific neuroanatomical regions of the adult Drosophila brain to assess requirements for DopR in sleep behavior. We have identified subsets of the mushroom body that utilizes DopR in daytime sleep regulation. These data are supported by multiple examples of spatially restricted genetic rescue data in discrete circuits of the mushroom body, as well as immunohistochemistry that corroborates the localization of DopR protein within mushroom body circuits. Independent loss of function data using an inducible RNAi construct in the same specific circuits also supports a requirement for DopR in daytime sleep. Additional circuit activation of discrete DopR+ mushroom body neurons also suggests roles for these subpopulations in sleep behavior. These conclusions support a new separable function for DopR in daytime sleep regulation within the mushroom body. This daytime regulation is independent of the known role of DopR in nighttime sleep, which is regulated within the Fan-Shaped Body (FSB). This study provides new neuroanatomical loci for exploration of dopaminergic sleep functions in Drosophila, and expands our understanding of sleep regulation during the day vs. night.



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Whole Genome Sequence of Two Wild-Derived Mus musculus domesticus Inbred Strains, LEWES/EiJ and ZALENDE/EiJ, with Different Diploid Numbers

Wild-derived mouse inbred strains are becoming increasingly popular for complex traits analysis, evolutionary studies, and systems genetics. Here, we report the whole-genome sequencing of two wild-derived mouse inbred strains, LEWES/EiJ and ZALENDE/EiJ, of Mus musculus domesticus origin. These two inbred strains were selected based on their geographic origin, karyotype, and use in ongoing research. We generated 14x and 18x coverage sequence, respectively, and discovered over 1.1 million novel variants, most of which are private to one of these strains. This report expands the number of wild-derived inbred genomes in the Mus genus from six to eight. The sequence variation can be accessed via an online query tool; variant calls (VCF format) and alignments (BAM format) are available for download from a dedicated ftp site. Finally, the sequencing data have also been stored in a lossless, compressed, and indexed format using the multi-string Burrows-Wheeler transform. All data can be used without restriction.



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Microenvironmental Gene Expression Plasticity Among Individual Drosophila melanogaster

Differences in phenotype among genetically identical individuals exposed to the same environmental condition are often noted in genetic studies. Despite this commonplace observation, little is known about the causes of this variability, which has been termed microenvironmental plasticity. One possibility is that stochastic or technical sources of variance produce these differences. A second possibility is that this variation has a genetic component. We have explored gene expression robustness in the transcriptomes of 730 individual Drosophila melanogaster of 16 fixed genotypes, nine of which are infected with Wolbachia. Three replicates of flies were grown, controlling for food, day/night cycles, humidity, temperature, sex, mating status, social exposure, and circadian timing of RNA extraction. Despite the use of inbred genotypes, and carefully controlled experimental conditions, thousands of genes were differentially expressed, revealing a unique and dynamic transcriptional signature for each individual fly. We found that 23% of the transcriptome was differentially expressed among individuals, and that the variability in gene expression among individuals is influenced by genotype. This transcriptional variation originated from specific gene pathways, suggesting a plastic response to the microenvironment; but there was also evidence of gene expression differences due to stochastic fluctuations. These observations reveal previously unappreciated genetic sources of variability in gene expression among individuals, which has implications for complex trait genetics and precision medicine.



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Evolutionary Insights into Taste Perception of the Invasive Pest Drosophila suzukii

Chemosensory perception allows insects to interact with the environment by perceiving odorant or tastant molecules; genes encoding chemoreceptors are the molecular interface between the environment and the insect, and play a central role in mediating its chemosensory behavior. Here, we explore how the evolution of these genes in the emerging pest Drosophila suzukii correlates with the peculiar ecology of this species. We annotated approximately 130 genes coding for gustatory receptors (GRs) and divergent ionotropic receptors (dIRs) in D. suzukii and in its close relative D. biarmipes. We then analyzed the evolution, in terms of size, of each gene family as well of the molecular evolution of the genes in a 14 Drosophila species phylogenetic framework. We show that the overall evolution of GRs parallels that of dIRs not only in D. suzukii, but also in all other analyzed Drosophila. Our results reveal an unprecedented burst of gene family size in the lineage leading to the suzukii subgroup, as well as genomic changes that characterize D. suzukii, particularly duplications and strong signs of positive selection in the putative bitter-taste receptor GR59d. Expression studies of duplicate genes in D. suzukii support a spatio-temporal subfunctionalization of the duplicate isoforms. Our results suggest that D. suzukii is not characterized by gene loss, as observed in other specialist Drosophila species, but rather by a dramatic acceleration of gene gains, compatible with a highly generalist feeding behavior. Overall, our analyses provide candidate taste receptors specific for D. suzukii that may correlate with its specific behavior, and which may be tested in functional studies to ultimately enhance its control in the field.



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The Interaction of Genotype and Environment Determines Variation in the Maize Kernel Ionome

Plants obtain soil-resident elements that support growth and metabolism from the water-flow facilitated by transpiration and active transport processes. The availability of elements in the environment interacts with the genetic capacity of organisms to modulate element uptake through plastic adaptive responses, such as homeostasis. These interactions should cause the elemental contents of plants to vary such that the effects of genetic polymorphisms will be dramatically dependent on the environment in which the plant is grown. To investigate genotype by environment interactions underlying elemental accumulation, we analyzed levels of elements in maize kernels of the Intermated B73 Mo17 (IBM) recombinant inbred population grown in 10 different environments, spanning a total of six locations and five different years. In analyses conducted separately for each environment, we identified a total of 79 quantitative trait loci (QTL) controlling seed elemental accumulation. While a set of these QTL was found in multiple environments, the majority were specific to a single environment, suggesting the presence of genetic by environment interactions. To specifically identify and quantify QTL by environment interactions (QEIs), we implemented two methods: linear modeling with environmental covariates, and QTL analysis on trait differences between growouts. With these approaches, we found several instances of QEI, indicating that elemental profiles are highly heritable, interrelated, and responsive to the environment.



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Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes

Enhancers physically interact with transcriptional promoters, looping over distances that can span multiple regulatory elements. Given that enhancer–promoter (EP) interactions generally occur via common protein complexes, it is unclear whether EP pairing is predominantly deterministic or proximity guided. Here, we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions. By reanalyzing transcriptome datasets, we find that the transcription of gene neighbors is correlated over distances that scale with genome size. We experimentally show that nonspecific EP interactions can explain such correlation, and that EP distance acts as a scaling factor for the transcriptional influence of an enhancer. We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation.



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Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

Outcomes of traumatic brain injury (TBI) vary because of differences in primary and secondary injuries. Primary injuries occur at the time of a traumatic event, whereas secondary injuries occur later as a result of cellular and molecular events activated in the brain and other tissues by primary injuries. We used a Drosophila melanogaster TBI model to investigate secondary injuries that cause acute mortality. By analyzing mortality percentage within 24 hr of primary injuries, we previously found that age at the time of primary injuries and diet afterward affect the severity of secondary injuries. Here, we show that secondary injuries peaked in activity 1–8 hr after primary injuries. Additionally, we demonstrate that age and diet activated distinct secondary injuries in a genotype-specific manner, and that concurrent activation of age- and diet-regulated secondary injuries synergistically increased mortality. To identify genes involved in secondary injuries that cause mortality, we compared genome-wide mRNA expression profiles of uninjured and injured flies under age and diet conditions that had different mortalities. During the peak period of secondary injuries, innate immune response genes were the predominant class of genes that changed expression. Furthermore, age and diet affected the magnitude of the change in expression of some innate immune response genes, suggesting roles for these genes in inhibiting secondary injuries that cause mortality. Our results indicate that the complexity of TBI outcomes is due in part to distinct, genetically controlled, age- and diet-regulated mechanisms that promote secondary injuries and that involve a subset of innate immune response genes.



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New Insights into the Roles of Host Gene-Necrotrophic Effector Interactions in Governing Susceptibility of Durum Wheat to Tan Spot and Septoria nodorum Blotch

Tan spot and Septoria nodorum blotch (SNB) are important diseases of wheat caused by the necrotrophic fungi Pyrenophora tritici-repentis and Parastagonospora nodorum, respectively. The P. tritici-repentis necrotrophic effector (NE) Ptr ToxB causes tan spot when recognized by the Tsc2 gene. The NE ToxA is produced by both pathogens and has been associated with the development of both tan spot and SNB when recognized by the wheat Tsn1 gene. Most work to study these interactions has been conducted in common wheat, but little has been done in durum wheat. Here, quantitative trait loci (QTL) analysis of a segregating biparental population indicated that the Tsc2-Ptr ToxB interaction plays a prominent role in the development of tan spot in durum. However, analysis of two biparental populations indicated that the Tsn1-ToxA interaction was not associated with the development of tan spot, but was strongly associated with the development of SNB. Pa. nodorum expressed ToxA at high levels in infected Tsn1 plants, whereas ToxA expression in P. tritici-repentis was barely detectable, suggesting that the differences in disease levels associated with the Tsn1-ToxA interaction were due to differences in pathogen expression of ToxA. These and previous results together indicate that: (1) the effects of Tsn1-ToxA on tan spot in common wheat can range from nonsignificant to highly significant depending on the host genetic background; (2) Tsn1-ToxA is not a significant factor for tan spot development in durum wheat; and (3) Tsn1-ToxA plays a major role in SNB development in both common and durum wheat. Durum and common wheat breeders alike should strive to remove both Tsc2 and Tsn1 from their materials to achieve disease resistance.



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cdc-25.4, a Caenorhabditis elegans Ortholog of cdc25, Is Required for Male Mating Behavior

Cell division cycle 25 (cdc25) is an evolutionarily conserved phosphatase that promotes cell cycle progression. Among the four cdc25 orthologs in Caenorhabditis elegans, we found that cdc-25.4 mutant males failed to produce outcrossed progeny. This was not caused by defects in sperm development, but by defects in male mating behavior. The cdc-25.4 mutant males showed various defects during male mating, including contact response, backing, turning, and vulva location. Aberrant turning behavior was the most prominent defect in the cdc-25.4 mutant males. We also found that cdc-25.4 is expressed in many neuronal cells throughout development. The turning defect in cdc-25.4 mutant males was recovered by cdc-25.4 transgenic expression in neuronal cells, suggesting that cdc-25.4 functions in neurons for male mating. However, the neuronal morphology of cdc-25.4 mutant males appeared to be normal, as examined with several neuronal markers. Also, RNAi depletion of wee-1.3, a C. elegans ortholog of Wee1/Myt1 kinase, failed to suppress the mating defects of cdc-25.4 mutant males. These findings suggest that, for successful male mating, cdc-25.4 does not target cell cycles that are required for neuronal differentiation and development. Rather, cdc-25.4 likely regulates noncanonical substrates in neuronal cells.



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Robust Transgene Expression from Bicistronic mRNA in the Green Alga Chlamydomonas reinhardtii

The unicellular green alga Chlamydomonas reinhardtii is a model organism that provides an opportunity to understand the evolution and functional biology of the lineage that includes the land plants, as well as aspects of the fundamental core biology conserved throughout the eukaryotic phylogeny. Although many tools are available to facilitate genetic, molecular biological, biochemical, and cell biological studies in Chlamydomonas, expression of unselected transgenes of interest (GOIs) has been challenging. In most methods used previously, the GOI and a selectable marker are expressed from two separate mRNAs, so that their concomitant expression is not guaranteed. In this study, we developed constructs that allow expression of an upstream GOI and downstream selectable marker from a single bicistronic mRNA. Although this approach in other systems has typically required a translation-enhancing element such as an internal ribosome entry site for the downstream marker, we found that a short stretch of unstructured junction sequence was sufficient to obtain adequate expression of the downstream gene, presumably through post-termination reinitiation. With this system, we obtained robust expression of both endogenous and heterologous GOIs, including fluorescent proteins and tagged fusion proteins, in the vast majority of transformants, thus eliminating the need for tedious secondary screening for GOI-expressing transformants. This improved efficiency should greatly facilitate a variety of genetic and cell-biological studies in Chlamydomonas and also enable new applications such as expression-based screens and large-scale production of foreign proteins.



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Little White Lies: Pericarp Color Provides Insights into the Origins and Evolution of Southeast Asian Weedy Rice

Weedy rice is a conspecific form of cultivated rice (Oryza sativa L.) that infests rice fields and results in severe crop losses. Weed strains in different world regions appear to have originated multiple times from different domesticated and/or wild rice progenitors. In the case of Malaysian weedy rice, a multiple-origin model has been proposed based on neutral markers and analyses of domestication genes for hull color and seed shattering. Here, we examined variation in pericarp (bran) color and its molecular basis to address how this trait evolved in Malaysian weeds and its possible role in weed adaptation. Functional alleles of the Rc gene confer proanthocyanidin pigmentation of the pericarp, a trait found in most wild and weedy Oryzas and associated with seed dormancy; nonfunctional rc alleles were strongly favored during rice domestication, and most cultivated varieties have nonpigmented pericarps. Phenotypic characterizations of 52 Malaysian weeds revealed that most strains are characterized by the pigmented pericarp; however, some weeds have white pericarps, suggesting close relationships to cultivated rice. Phylogenetic analyses indicate that the Rc haplotypes present in Malaysian weeds likely have at least three distinct origins: wild O. rufipogon, white-pericarp cultivated rice, and red-pericarp cultivated rice. These diverse origins contribute to high Rc nucleotide diversity in the Malaysian weeds. Comparison of Rc allelic distributions with other rice domestication genes suggests that functional Rc alleles may confer particular fitness benefits in weedy rice populations, for example, by conferring seed dormancy. This may promote functional Rc introgression from local wild Oryza populations.



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Comprehensive Cross-Population Analysis of High-Grade Serous Ovarian Cancer Supports No More Than Three Subtypes

Four gene expression subtypes of high-grade serous ovarian cancer (HGSC) have been previously described. In these early studies, a fraction of samples that did not fit well into the four subtype classifications were excluded. Therefore, we sought to systematically determine the concordance of transcriptomic HGSC subtypes across populations without removing any samples. We created a bioinformatics pipeline to independently cluster the five largest mRNA expression datasets using k-means and nonnegative matrix factorization (NMF). We summarized differential expression patterns to compare clusters across studies. While previous studies reported four subtypes, our cross-population comparison does not support four. Because these results contrast with previous reports, we attempted to reproduce analyses performed in those studies. Our results suggest that early results favoring four subtypes may have been driven by the inclusion of serous borderline tumors. In summary, our analysis suggests that either two or three, but not four, gene expression subtypes are most consistent across datasets.



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snpGeneSets: An R Package for Genome-Wide Study Annotation

Genome-wide studies (GWS) of SNP associations and differential gene expressions have generated abundant results; next-generation sequencing technology has further boosted the number of variants and genes identified. Effective interpretation requires massive annotation and downstream analysis of these genome-wide results, a computationally challenging task. We developed the snpGeneSets package to simplify annotation and analysis of GWS results. Our package integrates local copies of knowledge bases for SNPs, genes, and gene sets, and implements wrapper functions in the R language to enable transparent access to low-level databases for efficient annotation of large genomic data. The package contains functions that execute three types of annotations: (1) genomic mapping annotation for SNPs and genes and functional annotation for gene sets; (2) bidirectional mapping between SNPs and genes, and genes and gene sets; and (3) calculation of gene effect measures from SNP associations and performance of gene set enrichment analyses to identify functional pathways. We applied snpGeneSets to type 2 diabetes (T2D) results from the NHGRI genome-wide association study (GWAS) catalog, a Finnish GWAS, and a genome-wide expression study (GWES). These studies demonstrate the usefulness of snpGeneSets for annotating and performing enrichment analysis of GWS results. The package is open-source, free, and can be downloaded at: http://ift.tt/2fxy3R0.



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Multiple Genes Cause Postmating Prezygotic Reproductive Isolation in the Drosophila virilis Group

Understanding the genetic basis of speciation is a central problem in evolutionary biology. Studies of reproductive isolation have provided several insights into the genetic causes of speciation, especially in taxa that lend themselves to detailed genetic scrutiny. Reproductive barriers have usually been divided into those that occur before zygote formation (prezygotic) and after (postzygotic), with the latter receiving a great deal of attention over several decades. Reproductive barriers that occur after mating but before zygote formation [postmating prezygotic (PMPZ)] are especially understudied at the genetic level. Here, I present a phenotypic and genetic analysis of a PMPZ reproductive barrier between two species of the Drosophila virilis group: D. americana and D. virilis. This species pair shows strong PMPZ isolation, especially when D. americana males mate with D. virilis females: ~99% of eggs laid after these heterospecific copulations are not fertilized. Previous work has shown that the paternal loci contributing to this incompatibility reside on two chromosomes, one of which (chromosome 5) likely carries multiple factors. The other (chromosome 2) is fixed for a paracentric inversion that encompasses nearly half the chromosome. Here, I present two results. First, I show that PMPZ in this species cross is largely due to defective sperm storage in heterospecific copulations. Second, using advanced intercross and backcross mapping approaches, I identify genomic regions that carry genes capable of rescuing heterospecific fertilization. I conclude that paternal incompatibility between D. americana males and D. virilis females is underlain by four or more genes on chromosomes 2 and 5.



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Genome-Wide Association Study of Meiotic Recombination Phenotypes

Meiotic recombination is an essential step in gametogenesis, and is one that also generates genetic diversity. Genome-wide association studies (GWAS) and molecular studies have identified genes that influence of human meiotic recombination. RNF212 is associated with total or average number of recombination events, and PRDM9 is associated with the locations of hotspots, or sequences where crossing over appears to cluster. In addition, a common inversion on chromosome 17 is strongly associated with recombination. Other genes have been identified by GWAS, but those results have not been replicated. In this study, using new datasets, we characterized additional recombination phenotypes to uncover novel candidates and further dissect the role of already known loci. We used three datasets totaling 1562 two-generation families, including 3108 parents with 4304 children. We estimated five different recombination phenotypes including two novel phenotypes (average recombination counts within recombination hotspots and outside of hotspots) using dense SNP array genotype data. We then performed gender-specific and combined-sex genome-wide association studies (GWAS) meta-analyses. We replicated associations for several previously reported recombination genes, including RNF212 and PRDM9. By looking specifically at recombination events outside of hotspots, we showed for the first time that PRDM9 has different effects in males and females. We identified several new candidate loci, particularly for recombination events outside of hotspots. These include regions near the genes SPINK6, EVC2, ARHGAP25, and DLGAP2. This study expands our understanding of human meiotic recombination by characterizing additional features that vary across individuals, and identifying regulatory variants influencing the numbers and locations of recombination events.



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Fluoroscopy improves femoral stem placement in cementless total hip arthroplasty

2016-12-07T07-25-15Z
Source: Medicine Science | International Medical Journal
Haluk Cabuk, Cem Dincay Buyukkurt, Suleyman Semih Dedeoglu, Yunus Imren, Ali Cagrı Tekin, Hakan Gurbuz.
Fluoroscopy is routinely used in trauma cases to evaluate alignment and reduction quality. Because conventional templating has a high mismatch rate, we sought to explore whether we could use intraoperative fluoroscopy while implanting the femoral stem. Sixty patients with Croft 3-4 coxarthrosis were included in this study. No preoperative templating was performed in either of the two groups. The final conformations of the stem sizes and positions were achieved freehand intraoperatively using anatomic landmarks. In the second group, after surgeons intraoperatively agreed on the final stem size, C-arm fluoroscopy images are obtained with the last rasp size before the stem implantation. The alignment of femoral stem according to the femoral canal, the lower leg discrepancy (LLD) and the lateral offsets were evaluated with X ray. The stem/endosteal areas at 2 cm above the trochanter minor (T+2) and 2 cm below the trochanter minor (T-2) and the deviation of the stem tip from the center of the femoral canal were evaluated in CT images. The stems that were implanted under fluoroscopic control filled the medullary cavity better at both the T+2 and T-2 levels. On fluoroscopy, in the control group, the malpositioning of the femoral stems were less, the centralizations were better, and the restorations of the lateral offset and LLD were more accurate. The use of fluoroscopy while rasping the femoral canal leads to proper alignment and press fitting of the stem and provides the opportunity to intraoperatively correct malpositionings of the stem.


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Bootstrapping the P300 in diagnostic psychophysiology: How many iterations are needed?

Abstract

In psychophysiological research, bootstrapping procedures are often used to classify individual participants. How many iterations are required for a reliable bootstrap test is not universally agreed upon. To investigate the number of iterations needed for a stable bootstrap estimate, we reanalyzed P300 data collected in concealed information test paradigms. We also distinguished between the bootstrap and permutations approaches. We compared results in several studies using 100 versus 1,000 versus 10,000 iterations in the bootstrap, and we concluded that 100 iterations were adequate as results from all three iteration numbers correlated highly.



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Taking time to feel our body: Steady increases in heartbeat perception accuracy and decreases in alexithymia over 9 months of contemplative mental training

Abstract

The ability to accurately perceive signals from the body has been shown to be important for physical and psychological health as well as understanding one's emotions. Despite the importance of this skill, often indexed by heartbeat perception accuracy (HBPa), little is known about its malleability. Here, we investigated whether contemplative mental practice can increase HBPa. In the context of a 9-month mental training study, the ReSource Project, two matched cohorts (n = 77 and n = 79) underwent three training modules of 3 months' duration that targeted attentional and interoceptive abilities (Presence module), socio-affective (Affect module), and socio-cognitive (Perspective module) abilities. A third cohort (n = 78) underwent 3 months of practice (Affect module) and a retest control group (n = 84) did not undergo any training. HBPa was measured with a heartbeat tracking task before and after each training module. Emotional awareness was measured by the Toronto Alexithymia Scale (TAS). Participants with TAS scores > 60 at screening were excluded. HBPa was found to increase steadily over the training, with significant and small- to medium-sized effects emerging after 6 months (Cohen's d = .173) and 9 months (d = .273) of mental training. Changes in HBPa were concomitant with and predictive of changes in emotional awareness. Our results suggest that HBPa can indeed be trained through intensive contemplative practice. The effect takes longer than the 8 weeks of typical mindfulness courses to reach meaningful magnitude. These increments in interoceptive accuracy and the related improvements in emotional awareness point to opportunities for improving physical and psychological health through contemplative mental training.



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Inclusion of a rest period in diaphragmatic breathing increases high frequency heart rate variability: Implications for behavioral therapy

Abstract

Heart rate variability (HRV) is associated with positive physiological and psychological effects. HRV is affected by breathing parameters, yet debate remains regarding the best breathing interventions for strengthening HRV. The objective of the current study was to test whether the inclusion of a postexhalation rest period was effective at increasing HRV, while controlling for breathing rate. A within-subject crossover design was used with 40 participants who were assigned randomly to a breathing pattern including a postexhalation rest period or a breathing pattern that omitted the postexhalation rest period. Participants completed training on each breathing pattern, practiced for 6 min, and sat quietly during a 5-min washout period between practices. Participants were given instructions for diaphragmatic breathing at a pace of six breaths/minute with or without a postexhalation rest period. Recordings of heart rate, breathing rate, HF-HRV, RMSSD, LF-HRV, and SDNN were collected before and during each of the breathing trials. HRV indices were derived from Lead 1 ECG recordings. Pairwise contrasts showed that inclusion of a postexhalation rest period significantly decreased heart rate (p < .001) and increased HF-HRV (p < .05). No differences were found for breathing rates (p > .05), RMSSD (p > .05), and SDNN (p > .05). Results indicated that omission of the postexhalation rest period resulted in higher LF-HRV (p < .05). A postexhalation rest period improves HF-HRV, commonly associated with self-regulatory control, yet the importance of a postexhalation rest period requires further exploration.



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A pupil size response model to assess fear learning

Abstract

During fear conditioning, pupil size responses dissociate between conditioned stimuli that are contingently paired (CS+) with an aversive unconditioned stimulus, and those that are unpaired (CS-). Current approaches to assess fear learning from pupil responses rely on ad hoc specifications. Here, we sought to develop a psychophysiological model (PsPM) in which pupil responses are characterized by response functions within the framework of a linear time-invariant system. This PsPM can be written as a general linear model, which is inverted to yield amplitude estimates of the eliciting process in the central nervous system. We first characterized fear-conditioned pupil size responses based on an experiment with auditory CS. PsPM-based parameter estimates distinguished CS+/CS- better than, or on par with, two commonly used methods (peak scoring, area under the curve). We validated this PsPM in four independent experiments with auditory, visual, and somatosensory CS, as well as short (3.5 s) and medium (6 s) CS/US intervals. Overall, the new PsPM provided equal or decisively better differentiation of CS+/CS- than the two alternative methods and was never decisively worse. We further compared pupil responses with concurrently measured skin conductance and heart period responses. Finally, we used our previously developed luminance-related pupil responses to infer the timing of the likely neural input into the pupillary system. Overall, we establish a new PsPM to assess fear conditioning based on pupil responses. The model has a potential to provide higher statistical sensitivity, can be applied to other conditioning paradigms in humans, and may be easily extended to nonhuman mammals.



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