Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases.

High school graduation is a landmark event for students. It also plays an important role in the state accountability systems designed to ensure that schools provide all students a high-quality education. Yet relying on a school's four-year graduation rate for federal accountability purposes can have unintended consequences for English Learners, who may need extra time to graduate.

Large outflows of educated young people escaping high levels of unemployment, in tandem with inflows of unauthorized migrants, pose a fresh set of challenges for Greek policymakers. This Transatlantic Council on Migration report examines Greek emigration, and its economic implications, before exploring policy directions to minimize the costs and maximize the benefits of this mobility.

Bangladeshis in 2017 suddenly emerged as one of the top migrant groups entering Europe illegally. While Europe is a new destination, Bangladeshi labor migration has been an important part of the country's development since the 1970s, with growing numbers heading abroad, largely to the Gulf Cooperation Council countries. This article explores and contextualizes the new phenomenon of Bangladeshi migration to Europe.

The recent rise in xenophobia in Hungary stands in marked contrast with the country's rich migration history. After 390,000 migrants and asylum seekers arrived in 2015, the government of Viktor Orbán issued policies to significantly limit migration and enacted a law criminalizing humanitarian assistance to migrants. This country profile examines Hungary’s migration past and present, tracing the country’s multicultural heritage to the current wave of anti-immigrant sentiment.

This policy brief explores the relationship between environmental change and migration to Europe in light of recent scholarship challenging the notion that environmental change triggers mass migration. It presents an overview of European policy response in this area and summarizes the spectrum of proposed solutions.

Amid aging populations and the growth of chronic diseases, the demand for skilled health-care professionals is on the rise in the United States, Canada, and Mexico. This report explores the policy implications, benefits, and challenges of harmonizing nursing qualifications in the region, suggesting that a more collaborative approach could result in greater supply and quality of nurses.

Authors of a year-long study of reception and reintegration services in Mexico and the Northern Triangle discuss the findings of their fieldwork, including the differing reintegration needs of individual migrant groups, promising reception and reintegration programs, ongoing challenges for origin communities, and policy recommendations to improve reintegration strategies. 

Apr 1, 2012; 30:86-86
Patient Information

Hannele Yki-Järvinen
Dec 1, 2014; 37:3235-3243
Emerging Technologies and Therapeutics

Roy W. Beck
Aug 1, 2017; 40:994-999
Perspectives in Care

Enzo Bonora
May 1, 2011; 34:S184-S190
Diabetes

Matthew C. Riddle
Oct 1, 2014; 37:2755-2762
Emerging Technologies and Therapeutics

Dorothee Deiss
Dec 1, 2006; 29:2730-2732
BR Emerging Treatments and Technologies

Enzo Bonora
May 1, 2011; 34:S184-S190
Diabetes

This MPI webinar focuses on reception and reintegration services for returning migrants, along with the heightened pressure policymakers in Mexico and Central America are facing to design systems and programs that support both returnees and the communities in which they settle. Authors of a year-long study of reception and reintegration services in Mexico and the Northern Triangle discuss the findings of their fieldwork.

It’s a conviction that was published in the November issue of The Journal of the American Dental Association and the basis for the October 2019 forum that Dr. Francisco Ramos-Gomez fostered, where dentists, physicians, nurses and public health and public policy experts proposed, discussed and recommended solutions for preventing early childhood caries through the lens of social justice, health equity and human rights.

The ADA is partnering with the Organization for Safety, Asepsis and Prevention in providing a free on-demand webinar on Friday, March 20, with content for the program based on questions the ADA has received from members looking for guidance while navigating the novel coronavirus pandemic.

ADA Member Advantage announced April 1 it ended its endorsement relationship with Chase for credit card processing.

Washington — The Office for Civil Rights released a statement April 3 warning of an individual posing as an OCR investigator. The imposter has been calling entities covered by the Health Insurance Portability and Accountability Act of 1996 in an attempt to get patient information.

The U.S. Department of Homeland Security issued an alert April 8 warning that cybercriminals are increasingly exploiting the COVID-19 pandemic to target individuals, small and medium businesses and large organizations.

ADA Member Advantage announced May 1 that it has selected Best Card as its exclusively endorsed credit card processing solution for Association members.

Oil prices fell early Thursday despite an OPEC report confirming a sizable cut due to bearishness related to rising United States production and inventories.

Oil prices fell Monday as the number of rigs in the United States saw a weekly rise, analysts said

Nearly 5,000 workers in 115 meat processing workers across 19 states have been diagnosed with COVID-19, according to figures released Friday by the U.S. Centers for Disease Control and Prevention.

OBJECTIVE

To determine if temporal glucose profiles differed between 1) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG), 2) women who used insulin pumps or multiple daily insulin injections (MDIs), and 3) women whose infants were born large for gestational age (LGA) or not, by assessing CGM data obtained from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT).

RESEARCH DESIGN AND METHODS

Standard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM, n = 100; SMBG, n = 100) taken at baseline and at 24- and 34-weeks gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups.

RESULTS

FDA revealed that women using RT-CGM had significantly lower glucose (0.4–0.8 mmol/L [7–14 mg/dL]) for 7 h/day (0800 h–1200 h and 1600 h–1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4–0.9 mmol/L [7–16 mg/dL]) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4–0.7 mmol/L (7–13 mg/dL) for 4.5 h/day at baseline; by 0.4–0.9 mmol/L (7–16 mg/dL) for 16 h/day at 24 weeks; and by 0.4–0.7 mmol/L (7–13 mg/dL) for 14 h/day at 34 weeks.

CONCLUSIONS

FDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose.

OBJECTIVE

This study evaluated the ability of the Building, Relating, Assessing, and Validating Outcomes (BRAVO) risk engine to accurately project cardiovascular outcomes in three major clinical trials—BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME), Canagliflozin Cardiovascular Assessment Study (CANVAS), and Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction (DECLARE-TIMI 58) trial—on sodium–glucose cotransporter 2 inhibitors (SGLT2is) to treat patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Baseline data from the publications of the three trials were obtained and entered into the BRAVO model to predict cardiovascular outcomes. Projected benefits of reducing risk factors of interest (A1C, systolic blood pressure [SBP], LDL, or BMI) on cardiovascular events were evaluated, and simulated outcomes were compared with those observed in each trial.

RESULTS

BRAVO achieved the best prediction accuracy when simulating outcomes of the CANVAS and DECLARE-TIMI 58 trials. For the EMPA-REG OUTCOME trial, a mild bias was observed (~20%) in the prediction of mortality and angina. The effect of risk reduction on outcomes in treatment versus placebo groups predicted by the BRAVO model strongly correlated with the observed effect of risk reduction on the trial outcomes as published. Finally, the BRAVO engine revealed that most of the clinical benefits associated with SGLT2i treatment are through A1C control, although reductions in SBP and BMI explain a proportion of the observed decline in cardiovascular events.

CONCLUSIONS

The BRAVO risk engine was effective in predicting the benefits of SGLT2is on cardiovascular health through improvements in commonly measured risk factors, including A1C, SBP, and BMI. Since these benefits are individually small, the use of the complex, dynamic BRAVO model is ideal to explain the cardiovascular outcome trial results.

OBJECTIVE

We analyzed data from inpatients with diabetes admitted to a large university hospital to predict the risk of hypoglycemia through the use of machine learning algorithms.

RESEARCH DESIGN AND METHODS

Four years of data were extracted from a hospital electronic health record system. This included laboratory and point-of-care blood glucose (BG) values to identify biochemical and clinically significant hypoglycemic episodes (BG ≤3.9 and ≤2.9 mmol/L, respectively). We used patient demographics, administered medications, vital signs, laboratory results, and procedures performed during the hospital stays to inform the model. Two iterations of the data set included the doses of insulin administered and the past history of inpatient hypoglycemia. Eighteen different prediction models were compared using the area under the receiver operating characteristic curve (AUROC) through a 10-fold cross validation.

RESULTS

We analyzed data obtained from 17,658 inpatients with diabetes who underwent 32,758 admissions between July 2014 and August 2018. The predictive factors from the logistic regression model included people undergoing procedures, weight, type of diabetes, oxygen saturation level, use of medications (insulin, sulfonylurea, and metformin), and albumin levels. The machine learning model with the best performance was the XGBoost model (AUROC 0.96). This outperformed the logistic regression model, which had an AUROC of 0.75 for the estimation of the risk of clinically significant hypoglycemia.

CONCLUSIONS

Advanced machine learning models are superior to logistic regression models in predicting the risk of hypoglycemia in inpatients with diabetes. Trials of such models should be conducted in real time to evaluate their utility to reduce inpatient hypoglycemia.

OBJECTIVE

Preanalytical processing of blood samples can affect plasma glucose measurement because on-going glycolysis by cells prior to centrifugation can lower its concentration. In June 2017, ACT Pathology changed the processing of oral glucose tolerance test (OGTT) blood samples for pregnant women from a delayed to an early centrifugation protocol. The effect of this change on the rate of gestational diabetes mellitus (GDM) diagnosis was determined.

RESEARCH DESIGN AND METHODS

All pregnant women in the Australian Capital Territory (ACT) are recommended for GDM testing with a 75-g OGTT using the World Health Organization diagnostic criteria. From January 2015 to May 2017, OGTT samples were collected into sodium fluoride (NaF) tubes and kept at room temperature until completion of the test (delayed centrifugation). From June 2017 to October 2018, OGTT samples in NaF tubes were centrifuged within 10 min (early centrifugation).

RESULTS

A total of 7,509 women were tested with the delayed centrifugation protocol and 4,808 with the early centrifugation protocol. The mean glucose concentrations for the fasting, 1-h and 2-h OGTT samples were, respectively, 0.24 mmol/L (5.4%), 0.34 mmol/L (4.9%), and 0.16 mmol/L (2.3%) higher using the early centrifugation protocol (P < 0.0001 for all), increasing the GDM diagnosis rate from 11.6% (n = 869/7,509) to 20.6% (n = 1,007/4,887).

CONCLUSIONS

The findings of this study highlight the critical importance of the preanalytical processing protocol of OGTT blood samples used for diagnosing GDM. Delay in centrifuging of blood collected into NaF tubes will result in substantially lower rates of diagnosis than if blood is centrifuged early.

CNN reports that a study confirms that early autism intervention in toddlers is effective. A study was completed with a program called the Early Start Denver Model (ESDM). This program involves about twenty hours a week in the child's own home. It involves play and parents can easily learn some of the skills that can be applied in other settings. The study compared a group of toddlers that were given ESDM intervention to a group of toddlers receiving typical community interventions. Both groups showed improvement, but the ESDM group improved IQ by 18 points compared to 8 points with traditional interventions. The study is reporting that some of the children "virtually caught up to the typical kids their age." However, they are not claiming it is a cure for autism. According to the article they are working on a replication study to determine if there are similar results. Personally, I'm looking forward to the results of the replication study and want to find out more about this method. From what I understand it is less of a time constraint than ABA therapy.

This study also demonstrated the need for early intervention, which also includes early identification. When children are diagnosed early, they can begin receiving interventions that are proven effective. The study showed that current methods are working, but there may be a new program that can be even more effective on the horizon.

I'd love to hear more from my readers if you have any experience with ESDM or more information about it.

Two years into my position in a culturally diverse school system has taught me many things that I never would have learned in my previous position in a school system with much less diversity. I had hoped to be bilingual by now, but I’m not even close to that goal. However, I do have the training to conduct assessments with bilingual students. Thanks to Samuel Ortiz, Ph.D. for his workshops, research, and books that we use so much in our system. Thanks to the other Psychologists in my system for mentoring me and helping me learn this process. It has helped us to better identify which students have a disability and which students only look like they have a disability because of their performance on tests that are not standardized on children with different cultural and linguistic backgrounds. Learning a second language is not a disability. Just because a student is struggling academically, does not mean he should qualify for special education.

What everyone involved in school needs to know:
It takes many years for a person learning a language to develop academic use of language to the same level as monolingual individuals. It does not always seem that way when a person has excellent conversational skills in English. However, social use of language is not as sophisticated as academic use of language. Students can appear to be fluent, when in actuality the language and vocabulary is not on grade level. If a student’s comprehension and expression of language is below grade level, academics will naturally be below grade level as well. This is not the same as having a disabling condition.

A child with good social use of language, but developing academic use of language often looks to teachers like a student with a disability, when in reality the student may be a typically developing second language learner. Special education is not the answer for this student; the answer comes through hard work, patience, and instruction through a high quality English as a Second Language Program. In the past (and currently in many systems) this child would be misidentified as a student with a disability and inappropriately put into special education programs.

What Parents need to know:
Traditional assessments are not standardized for use with culturally and linguistically diverse students, so typical interpretation of scores on these assessments are inappropriate. When school systems try to use these assessments in the traditional way and then apply the unreliable scores into eligibility criteria, it’s frankly scary.

If you are a parent of an English Language learner, insist that a bilingual assessment be administered. I recognize that the irony of this statement is that many parents of bilingual students are not reading this blog as it is in English only. I don’t really have a good answer for that at this time.

What Teachers need to know:
If you are a teacher, recognize that academic language competency takes time and it requires additional assessment tools to tease out if the difficulties are primarily the result of language and cultural differences or if it is the result of a disability.

What School Psychologists need to know:
If you are a School Psychologist and not using the Cattell-Horn-Carroll Cross-Battery Assessment, I strongly encourage you to take a look. Here is an article from the National Association of School Psychologists Website by Samuel Ortiz, Ph.D. on resources for cultural competency. http://www.nasponline.org/resources/culturalcompetence/ortiz.pdf Advocate that all School Psychologists in your system be trained to administer bilingual assessments or at least have someone competent on hand for these assessments. You can’t hire a School Psychologist in every possible language you might need, so it only makes sense for all School Psychologists to be trained to assess all students. It takes more time to do the assessment, interpret data, and write a report and it requires the use of hiring an interpreter for portions of the assessment, but it is well worth the time and money to properly identify these students. If your school system does not see it this way, bring it up as a solution to disproportionality.

Our senses help us understand and navigate our world. They help us feel, see, taste, etc. When one or more of those processes is more or less sensitive to world, life feels different to that person. It is hard to understand what it feels like to have sensory differences unless you have sensory differences. It’s easy to tell someone to ignore a noise that doesn’t seem excessively annoying to you. It’s hard to understand when someone has an intense need for pressure unless you have a similar need. Having these sensory differences can be anxiety producing and stressful. In a classroom, it can make that person less attentive or have a more difficult time sitting still. Kids don’t always have the words or understanding to express what they are feeling. As a result, children who have sensory processing issues are often misunderstood. Sensory issues are often associated with children who have an Autism Spectrum Disorder. There is also an association between Attention Deficit Hyperactivity Disorder and sensory issues. Many times a child will have sensory issues and not have any other disability. Those children may have Sensory Processing disorder, which is a neurological disorder that makes processing and responding to sensory information more difficult. A person with Sensory Processing Disorder may be more or less sensitive than most people to any or all of the senses. Sensory Processing Disorder is not yet widely understood by the majority of people. Most people have an idea about what Autism is or ADHD, but people often do not know about Sensory Processing Disorder. Many school professionals have not learned about it and do not understand it. Many parents have never heard of it. If you have any concerns that your child may have difficulty with sensory processing, I strongly recommend The Out-of-Sync Child: Recognizing and Coping with Sensory Processing Disorder, Revised Edition This book was explains the various types of sensory processing and helps parents to understand what their child may be feeling. It is transformative for a parent to finally understand what is going on with their child. Strategies for the Classroom:

 Often making small changes to the environment can help a child regulate his own body and focus in the classroom. A seating disk fits on a chair and is filled with air. It allows a child to wiggle in his seat, without moving around and causing a distraction. The bumps and the movement can provide the sensory input needed to help a child focus better. The ball chair also allows movement and is good for low tone as well. Weighted lap pads help provide proprioceptive input that helps establish increased body awareness, improves attention span and concentration, and has calming benefits.   Strategies for home: Trampolines provide deep pressure. Also, it is great exercise. For some children, when they start having difficulty regulating his or her body, jumping on the trampoline helps provide the needed pressure and will calm the body after a few minutes. The Body Sock is made of tight material that pushes back against the child's movement. This can help children with coordination and spatial positioning.

 Disclaimer: I am not an Occupational Therapist and am not an expert in this area. I am writing this article to raise awareness in sensory issues that can have a huge impact in the classroom and within a family. Sometimes, minor accommodations can make significant improvements in the life of a child, which I have witnessed firsthand. I encourage any parents who think his or her child may have a sensory issue to seek help through an Occupational Therapist. In most cases, this will fall outside of Special Education and schools, unless the sensory issues are associated with a disability, such as Autism. Some schools are more proactive than others and have more Occupational Therapy support than others. Because OT services are not mandated outside of an IEP or 504 Plan, many schools will not be equipped to help you with this. It is recommended that you seek support through an OT, who can provide individual strategies to use in the classroom and at home.

British scientists said Monday that an amino acid swap can help protect wheat crops from rising heat due to global warming.

Testimony of Marc Rosenblum before the Senate Committee on Homeland Security and Governmental Affairs for the March 26, 2015 hearing on the characteristics of unauthorized immigrants in the United States and how to address future flows.

Federal health officials fined a New Jersey nursing home where last month authorities discovered 17 bodies piled in a small morgue.

K-pop star Minzy shared a comeback schedule for her new solo single, "Lovely."

i even got this from pro trans page that say they have laws banning men from women's room & trans aka GD was put into mad house, & even then there been alot of time where rapists &perverted freaks been using other Gender's bath room too doesn't make it right, they go to prison if they find out

I know it's Ramadan, but I've been feeling urges for a few years now and it's just getting more and more now. I always imagine about sex and loving my to-be wife. Right now, I'm studying medicine, so my parents told me it's too early to get married (24 years old). I just don't know really what to do. I prone masturbate to get some relief. What should I do?

Hello I am a man 36 years old and, My ex girlfriend and I and I were together from January to August 2012, my ex girlfriend's daughter was very affectionate with me, I miss her what I can do I was very fond of her, what can I do ?

I’ve been talking to a man, we have mutual interest in each other. We talked on the phone for over an hour the night before last and it was an amazing conversation. The next day he had no contact with me, which in my mind it didn’t bother me and still kind of isn’t I think he just is doing his own thing and likes his personal space. I’m not too bothered or worried but still questioning why? Is it normal for a man to kinda disappear and have no contact for a day?

New Zealand drew global attention for its unity and support for the Muslim community targeted during the horrific Christchurch attacks. Yet the country's road to inclusion has been far from straightforward, and amid rising diversity it is grappling with the best way to achieve inclusion for its multiethnic population, including indigenous Māori peoples and migrants. This article outlines the opportunities and challenges to fostering multiculturalism against a backdrop of bicultural policies.

Amid ongoing debates about the costs and benefits of free movement, this MPI Europe webchat examines big-picture trends of East-West migration; considers possible policy responses at regional, national, and EU levels to alleviate some of the challenges; and reflects on realistic actions that could be taken under the incoming European Commission.

Melissa Hunfalvay feels Claudio Reyna's pain. Not the pain caused by the sprain in Reyna's knee -- an injury the captain of the defeated U.S. World Cup soccer team sustained last week while conceding a goal in an all-important match against Ghana.

Long before word recently broke that white referees in the National Basketball Association were calling fouls at a higher rate on black athletes than on white athletes, and long before studies found racial disparities in how black and white applicants get called for job interviews, researchers no...