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The habits of an improver

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Improving the quality of care services is an imperative for the NHS. For this to happen systematically a substantial proportion of those working in health care need to be committed to learning and changing, as well as capable of implementing and sometimes leading improvements.

Download The habits of an improver.

In this paper, Professor Bill Lucas offers a way of viewing the field of improvement from the perspective of the men and women who deliver and co-produce care on the ground – the improvers on whom the NHS depends. The paper describes 15 habits which such individuals regularly deploy, grouped under five broad headings:

  • Learning
  • Influencing
  • Resilience
  • Creativity
  • Systems thinking

It goes on to suggest that there are certain teaching and learning methods which best develop skills and knowledge for understanding and implementing improvement.

The habits of an improver has been written to promote discussion and as a possible model for all those seeking to take decisions about the best balance of attitudes, skills and knowledge – both in initial training and continuing professional development – for improvement across the NHS and beyond.

Author: Bill Lucas, Hadjer Nacer. 

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The Hunt for Better Preeclampsia Biomarkers

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Preeclampsia, a serious, potentially life-threatening hypertensive and inflammatory disorder of pregnancy, occurs in only 5%–8% of pregnant women but poses severe consequences for affected mothers and infants. In the U.S., an estimated 9% of maternal deaths and at least one-third of severe obstetric complications result from preeclampsia or its most severe manifestation, eclampsia. Adverse fetal and neonatal outcomes include intrauterine growth restriction, placental abruption, preterm delivery, respiratory distress syndrome, and necrotizing enterocolitis. Preeclampsia also puts women at risk for cardiovascular disease later in life.

The diagnostic mainstays of preeclampsia are hypertension ≥140 mmHg systolic or ≥90 mmHg diastolic and new-onset proteinuria, defined as ≥300 mg/dL in a 24-h urine collection or protein:creatinine ratio of 0.3—usually developing after 20 weeks of pregnancy. However, not all women with preeclampsia develop proteinuria, so the American College of Obstetricians and Gynecologists in 2013 updated its definition to reflect the syndrome’s complexity. In the presence of hypertension and other clinical signs as well as the absence of proteinuria, diagnostic test results indicative of preeclampsia include: thrombocytopenia, defined as a platelet count <100,000/µL; impaired liver function with enzymes “twice normal concentration”; and progressive renal insufficiency with serum creatinine concentration >1.1 mg/dL or in the absence of other renal disease.

Even with these diagnostic guideposts, clinicians would like better ways to identify preeclampsia earlier and to distinguish patients most at risk of severe complications. Diagnostic challenges arise particularly in women who have borderline symptoms, symptoms consonant with other conditions, or pre-existing diseases that mask preeclampsia until it blooms in full.

“For patients with pre-existing high blood pressure or diabetes, what’s new and what’s superimposed? It’s basically guesswork,” said Belinda Jim, MD, attending physician in the division of nephrology at Albert Einstein Medical College’s Jacobi Medical Center in the Bronx, New York.

A Complex Syndrome

The search for better preeclampsia diagnostic tools has been constrained by clinicians’ murky understanding of the disorder’s underlying causes, despite decades of research. Current models posit that maternal, fetal, and placental factors yield different manifestations of the syndrome. Abnormal vascular formation in the developing placenta, maternal endothelial dysfunction, and vascular inflammation appear to play varying roles.

Even with an imperfect understanding of preeclampsia’s pathogenesis, considerable research efforts are underway to identify biomarkers that could help clarify which women are truly at risk for progressing to full-blown preeclampsia and require early delivery, versus those unlikely to get worse.

“If these tests were positive, we could refer women to a tertiary care hospital with the potential for early detection of complications and delivery down the line,” said Ananth Karumanchi, MD, professor of medicine at Harvard Medical School and senior scientist with the department of obstetrics and gynecology at Beth Israel Deaconess Medical Center in Boston. Doctors could prescribe steroids, a common practice to help fetal lungs to prepare for early delivery. “If [tests are] negative, you could expect to prolong pregnancies by expectant management and perhaps not require mothers to remain in the hospital until they deliver,” he added.

A Promising Duo

Researchers have explored a laundry list of candidate biomarkers capturing different aspects of preeclampsia’s suspected pathophysiology, from human chorionic gonadotropin and α-fetoprotein to kallikrein and endothelin. Of these contenders, a particularly promising duo is the antiangiogenic factor soluble fms-like tyrosine kinase 1 (sFlt1) and the proangiogenic placental growth factor (PlGf).

In 2003, Karumanchi and his colleagues reported sFlt1 was more abundant in the serum of women with preeclampsia. Karumanchi noted that sFlt1 seems to be expressed by the struggling placenta.

Subsequent studies showed the potential diagnostic significance of high circulating concentrations of sFlt1 in combination with low concentrations of PlGF. Automated tests for sFlt1 and PlGF have made large-scale diagnostics a realistic option. The sFlt1:PlGF ratio has been used to diagnose and predict preeclampsia in Europe since 2009, in countries such as the U.K., Germany, Italy, and Spain.

“The sFlt1:PlGF ratio helps us to better predict and diagnose preeclampsia. It is actually the first biomarker for the disease that has been proven to be helpful in the clinical setting,” said Stefan Verlohren, MD, PhD, a consultant in obstetrics and gynecology and head of the preeclampsia research group at Charité University Medicine in Berlin, which recently formed a research alliance with LifeCodexx to accelerate development of a novel genetics-based assay to detect preeclampsia in its early stages.

He and his colleagues recently reported in the New England Journal of Medicine the results of an international multi-center study involving more than 1,000 women in which they found that the sFlt1:PlGF ratio was useful in ruling out preeclampsia in women suspected of having­ the condition (N Engl J Med 2016;374:13–22). Among women who presented with signs and symptoms of preeclampsia after 24 weeks of pregnancy, those with a sFlt1:PlGF ratio ≤38 were not likely to develop the syndrome within the subsequent week. sFlt1:PlGF had a high negative predictive value of 99.3%. If women with suspected preeclampsia had an sFlt1:PlGF-ratio >38, the positive predictive value was 36.7% for them to develop preeclampsia in the subsequent 4 weeks.

“With this test we now are able to better decide whom to hospitalize and whom to send home. In Germany, we use this test in our routine clinical work-up for preeclampsia,” said Verlohren, who pointed out that fewer days of hospitalization translate to cost savings as well.

Karumanchi compared the current state of preeclampsia biomarkers to that of cardiac care before the development of assays for creatinine kinase and troponin. The introduction of those blood tests enabled clinicians to better understand what happens in myocardial infarction and, over time, to develop better interventions, he noted.

“That’s a big reason we need better diagnostic tests,” Karumanchi said. “We could then study those patients with interventions. Preeclampsia could become a lot like cardiology. We could treat patients early and avoid long-term damage.”

Karumanchi and Verlohren hope that Food and Drug Administration-approved tests for sFlt1:PlGF in preeclampsia will become available in the U.S. in as little as 2 years, but acknowledged that licensing a new diagnostic test can be unpredictable. “I hope it is closer to two years than 10 years,” Verlohren said.

Balancing Sensitivity and Specificity

Other researchers are not as enamored with the sFlt1:PlGF ratio. “What’s really needed for a rare condition like preeclampsia is a test with high positive predictive value,” said Ann Gronowski, PhD, DABCC, FACB, professor of pathology and immunology and medical co-director of clinical chemistry at Washington University School of Medicine in St. Louis. In cases of suspected preeclampsia, the chances that a woman referred for biomarker testing will be negative is already fairly high—even in a population of women with high blood pressure. So a biomarker with a high negative predictive value, like sFlt1:PlGF ratio, isn’t a useful tool, she added.

Gronowski is eager for a biomarker with a high positive predictive value that picks up the few patients who will go on to have preeclampsia from the many pregnant women with high blood pressure and proteinuria. In a recent post on The Pregnancy Lab, a blog about laboratory tests during pregnancy, she noted that the sFlt1:PlGF negative predictive value is not much better than a coin flip.

Gronowski conceded, however, that there may be some subpopulations for which this biomarker may be better at identifying women with preeclampsia. This would make sFlt1:PlGF more valuable in those subgroups, but those subgroups have yet to be identified.

Karumanchi concurred with Gronowski about the benefits of having a preeclampsia test with a high negative predictive value. “In the absence of a specific therapy for preeclampsia, the clinical need today in the population of suspected preeclampsia is for a negative predictive test that would enable physicians to safely prolong pregnancy for several weeks in those patients who have a negative test,” he explained.

That said, he still believes sFlt1:PlGF ratio, with its relatively low positive predictive value, has a place in identifying and managing women with preeclampsia. “The natural course of the disease is interrupted by early iatrogenic delivery in this population, and so [many] don’t have time to develop full-blown preeclampsia. If we use indicated delivery as a surrogate outcome then the positive predictive values are greater than 90 percent,” said Karumanchi.

For now, testing in the U.S. will continue to rely on blood ­pressure readings and proteinuria tests, practices endorsed in April 2017 by the United States Preventive Services Task Force in its first review of preeclampsia screening since 1996. Although this influential group noted the need for new markers to screen for the disorder, it also underscored that an incomplete understanding of preeclampsia’s complex pathophysiology limits researchers’ ability to assess screening tools.

Once that understanding sharpens, the promise of making the best use of current biomarkers and of developing even more informative tests may be realized.

Author: Rina Shaikh-Lesko

Source: AACC

Helium ions reveal how viruses attack bacteria

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Bacteriophages (green) attached on E. coli bacteria (blue) on an agar substrate (brown), imaged with a helium ion microscope. Credit: Image courtesy of University of Jyväskylä

An interdisciplinary research consortium from the Nanoscience Center at University of Jyvaskyla in Finland (group leaders Dr. Lotta-Riina Sundbergand Prof. Ilari Maasilta) has found that bacteria and viruses can be imaged with helium ions in contrast to electrons which are the standard workhorse in nanoscale microscopy. Helium ions, being more massive than electrons, can be focused to a much tighter spot down to the atomic length scales. By measuring the electrons generated by the ion bombardment, an image can be formed from the sample with biological features visible below the nanometer (one billionth of a meter) length.

New solutions to study microbes and viruses

The novel technique, called helium ion microscopy (HIM), was used to image hard-to-see interaction between bacteria and viruses infecting bacteria, or so called bacteriophages. These phages are currently actively considered as a novel “smart weapon” against bacterial infections, which are becoming more and more difficult to treat with traditional antibiotics. The images demonstrated in clear images the different stages of how the phages in question attacked the bacteria (E. coli), for example showing the process where the virus has latched onto the bacterial surface, grabbing it with a tentacle like structure, and being in the process of injecting its genome into the bacterial cell.

In addition to imaging, the researchers also demonstrated that the ions can be used as a nanoscale scalpel, to cut portions off individual bacterial cells, or to reveal bacterial colonies under the surfaces of samples. They feel confident that HIM offers many more possibilities in the future to help to study microbes and viruses in their natural state, interacting with each other and other cells.

The study was funded by the Academy of Finland and Jane and Aatos Erkko Foundation. The research was published in the journal Advanced Biosystems.

Journal Reference: Miika Leppänen, Lotta-Riina Sundberg, Elina Laanto, Gabriel Magno de Freitas Almeida, Petri Papponen, Ilari J. Maasilta. Imaging Bacterial Colonies and Phage-Bacterium Interaction at Sub-Nanometer Resolution Using Helium-Ion MicroscopyAdvanced Biosystems, 2017; 1700070 DOI: 10.1002/adbi.201700070

Source: sciencedaily.com

The Clinical Urine Culture: Enhanced Techniques Improve Detection of Clinically Relevant Microorganisms

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Enhanced quantitative urine culture (EQUC) detects live microorganisms in the vast majority of urine specimens reported as “no growth” by the standard urine culture protocol. Here, we evaluated an expanded set of EQUC conditions (expanded-spectrum EQUC) to identify an optimal version that provides a more complete description of uropathogens in women experiencing urinary tract infection (UTI)-like symptoms. One hundred fifty adult urogynecology patient-participants were characterized using a self-completed validated UTI symptom assessment (UTISA) questionnaire and asked “Do you feel you have a UTI?” Women responding negatively were recruited into the no-UTI cohort, while women responding affirmatively were recruited into the UTI cohort; the latter cohort was reassessed with the UTISA questionnaire 3 to 7 days later. Baseline catheterized urine samples were plated using both standard urine culture and expanded-spectrum EQUC protocols: standard urine culture inoculated at 1 l onto 2 agars incubated aerobically; expanded-spectrum EQUC inoculated at three different volumes of urine onto 7 combinations of agars and environments. Compared to expanded-spectrum EQUC, standard urine culture missed 67% of uropathogens overall and 50% in participants with severe urinary symptoms. Thirty-six percent of participants with missed uropathogens reported no symptom resolution after treatment by standard urine culture results. Optimal detection of uropathogens could be achieved using the following: 100 l of urine plated onto blood (blood agar plate [BAP]), colistin-nalidixic acid (CNA), and MacConkey agars in 5% CO2 for 48 h. This streamlined EQUC protocol achieved 84% uropathogen detection relative to 33% detection by standard urine culture. The streamlined EQUC protocol improves detection of uropathogens that are likely relevant for symptomatic women, giving clinicians the opportunity to receive additional information not currently reported using standard urine culture techniques.

Authors: Travis K. Price,a Tanaka Dune,b Evann E. Hilt,a Krystal J. Thomas-White,a Stephanie Kliethermes,c Cynthia Brincat,b,d Linda Brubaker,b,d Alan J. Wolfe,a Elizabeth R. Mueller,b,d Paul C. Schreckenbergere

Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University, Chicago, Illinois, USAa ; Department of Obstetrics & Gynecology and Urology, Loyola University Medical Center, Maywood, Illinois, USAb ; Departments of Medicine and Public Health Sciences,c Department of Obstetrics & Gynecology and Urology,d and Department of Pathology,e Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA

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CDC Updates guidance on testing pregnant women at risk of Zika

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Current CDC guidelines call for all pregnant women to be evaluated for risk of Zika exposure and signs and symptoms of Zika. Asymptomatic pregnant women at risk of Zika are recommended to have a blood test to detect immunoglobulin M (IgM) antibodies that the body makes initially to fight Zika infections. However, recent data indicate that Zika IgM antibodies may be detected in blood for months after the initial infection in some people. That means that healthcare practitioners may not be able to tell whether an asymptomatic pregnant woman who tests positive contracted the infection before or after becoming pregnant. Knowing when the virus was contracted is important because becoming infected while pregnant can result in birth defects for the baby, including a smaller than normal head (microcephaly) and developmental delays.

The updated CDC guidelines recommend that in addition to the test for IgM antibody, a test that detects Zika virus RNA (nucleic acid test or NAT) be done at least once each trimester, unless a previous test is positive. The NAT test can be done on blood or urine and may provide a more definitive diagnosis of a current Zika infection, according to the CDC. However, having a negative test does not rule out the possibility of an infection since the amount of virus drops over time.

Among other new recommendations:

  • Zika NAT testing may be performed on amniotic fluid if an amniocentesis is done  for any reason (e.g., prenatal genetic testing).
  • Women planning a pregnancy and at risk of Zika should consider getting an IgM antibody test done prior to pregnancy to possibly detect a pre-pregnancy exposure to Zika. While the result cannot determine whether it is safe to become pregnant, it can help determine whether a woman gets infected during her pregnancy (i.e., a negative result pre-pregnancy and then a positive test after becoming pregnant). A positive result pre-pregnancy may mean that a woman has a recent Zika infection, a past Zika infection, or an infection with a similar type of virus.
  • Pregnant women who are tested should receive information from their healthcare practitioners about the limitations of testing along with their results.

The guidelines have not changed for pregnant women who have signs and symptoms or have sexual partners diagnosed with Zika infections. They should have a NAT test done immediately. Additional tests, such as ultrasounds, may be done when a pregnant woman has a positive test for Zika.

“Our [new] guidance…is part of our continued effort to share data for public health action as quickly as possible,” said Henry Walke, M.D., incident manager of the CDC’s Zika response efforts. “As we learn more about the limitations of antibody testing, we continue to update our guidance to ensure that healthcare professionals have the latest information for counseling patients who are infected with Zika during pregnancy.”

While there is yet no vaccine to prevent Zika, there are steps individuals can take to avoid mosquito bites and exposure to Zika. To learn more, see the CDC web page on Zika Virus Prevention.

Source: Lab Tests Online

A protein made by the fetus may lead to preeclampsia in moms

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People born to mothers who had the prenatal disorder were more likely to have certain DNA variations near a gene known to influence blood vessels. The results, published online June 19 in Nature Genetics, point to that gene as a possible preeclampsia culprit, and may help scientists develop ways to stop or prevent the pregnancy complication. Preeclampsia, which is marked by a dangerous spike in blood pressure, affects about 5% of pregnancies and is estimated to kill over 70,000 women a year globally.

Scientists have known that preeclampsia can run in families, but the genetics of the fetus hadn’t been scrutinized. “Over the years, people have looked at mothers’ genes,” says geneticist Linda Morgan of the University of Nottingham in England. “This is the first large study to look at babies’ genes.”

Morgan and colleagues compared DNA variations in 2,658 babies, children and adults born to mothers who had preeclampsia with those in more than 300,000 people. (This large group probably included some people born to mothers with the condition, but the vast majority were not.)

A genome-wide association study (GWAS), a technique used to comb through DNA looking for genetic variations that may be linked to a disorder, pinpointed a spot on chromosome 13, near a gene called FLT1.That gene is involved with blood vessel formation, an intricate process for the placenta as it grows into the inside wall of the uterus and merges the baby’s blood supply to the mother’s. The same genetic hot spot turned up in tests of a second group of offspring from mothers who had preeclampsia, Morgan and colleagues report. Another DNA variation near the gene also showed a link to the disorder.

Identifying FLT1 “makes a lot of sense,” says Ananth Karumanchi, a vascular biologist at Beth Israel Deaconess Medical Center in Boston, who was not involved in the study. Earlier experiments by Karumanchi and others suggest that the gene plays a role in preeclampsia.

Preeclampsia is kicked off by the placenta, an organ grown mostly from fetal cells that helps provide nutrients to the fetus. And though the details are unclear, some scientists suspect that unhealthy placentas start to pump out too much Flt-1 protein. A version of the protein called sFlt-1 can then slip into a mother’s bloodstream, where it may damage blood vessels in a way that leads to high blood pressure.

The GWAS results can’t explain the bulk of preeclampsia cases. A fetus carrying a single copy of one of the troublesome variants near FLT1 raised a mother’s risk of preeclampsia by about 20 percent, the analysis suggests. Other risk factors are known to be much stronger, Morgan says, including previous high blood pressure, former preeclampsia diagnoses or carrying twins.

Karumanchi says that the genetic results might not be strong enough on their own to make the case that the gene is involved. But other work points to FLT1. “We feel it’s the right target,” he says.

In Europe, a preliminary clinical trial is testing a filtration method that removes excess sFlt-1 protein from the blood of women with signs of preeclampsia. So far, about 20 women have undergone the procedure, says nephrologist Ravi Thadhani of Massachusetts General Hospital in Boston. Early results are “quite encouraging,” he says, and he hopes to expand the study soon.

Source: Science News

IFCC’s Forthcoming Congresses – June Issue

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Calendar of IFCC Congresses/Conferences and Regional Federation’s Congresses

Sep 17 – 22, 2017 XXIII COLABLIOCLI Congress 2017 and XI Uruguayan Congress of Clinical Biochemistry Punta del Este, UY
 

Oct 20 – 22, 2017

 

XIV International Congress of Pediatric Laboratory Medicine

 Durban, ZA
Oct 21, 2017 IFCC-POCT Satellite Meeting – WorldLab Durban 2017  Durban, ZA
Oct 22 – 25, 2017 XXIII IFCC WORLDLAB – DURBAN 2017 Durban, ZA
 Oct 26-27, 2017 IFCC Satellite Meeting “Biomarkers for Diabetes” – WorldLab Durban 2017  Durban, ZA
May 19 – 23, 2019 XXIII IFCC-EFLM EUROMEDLAB – BARCELONA 2019 Barcelona, ES
May 24 – 28, 2020 XXIV IFCC WORLDLAB – SEOUL 2020 Seoul, KR

Calendar of events with IFCC auspices

Jul 14 – 15,  2017 High Quality Specialty Training Courses in Quality Control for Laboratory Sciences- MODULE I BASIC LESSONS QC Mexico City, MX
Aug 11 – 12, 2017 High Quality Specialty Training Courses in Quality Control for Laboratory Sciences – MODULE II STATISTICAL TOOLS Mexico City, MX
Sep 08 – 09, 2017 High Quality Specialty Training Courses in Quality Control for Laboratory Sciences – MODULE III: “Technical Competence Indicators” Mexico City, MX
Sep 19 – 21, 2017 18th International Metrologie Congress Paris, FR
Sep 21 – 22, 2017 13th EFLM Symposium for Balkan Region Belgrade, SRB
Sep 26 – 29, 2017 51st Brazilian Congress of Clinical Pathology/Laboratory Medicine Sao Paulo, BR
Oct 01 – 31, 2017 Workshop and Course in clinical microbiology update.2017 Quito, EC
Oct 03 – 04, 2017 High Quality Specialty Training Courses in Quality Control for Laboratory Sciences – MODULE IV: “Breaking rules” Mexico City, MX
Oct 04 – 07, 2017 3rd International Symposium on Advances in Circulating Tumor Cells (ACTC) Rhodes, GR
Oct 04 – 07, 2017 ESPT Annual Meeting Catania, IT
Oct 05 – 06, 2017 CELME 2017 Prague, CZ
Oct 11 – 13, 2017 III Russian Congress of Laboratory Medicine Moscow, RU
Oct 11 – 14, 2017 14th Annual Congress of the German Society of Clinical Chemistry and Laboratory Medicine (DGKL) Oldenburg, DE
Oct 16 – 17, 2017 Journées Nationales 2017 de la Société Française de Biologie Clinique Paris, FR
Oct 18 – 20, 2017 LMCE 2017 & KSLM 58th Annual Meeting Seoul, KR
Oct 26, 2017 International Conference on Laboratory Medicine “Uncertainty, quality, safety and accreditation in Laboratory Medicine” Padova, IT
Nov 30, 2017 11th International Scientific Meeting of the Centree of Metrological Traceability in Laboratory Medicine (CIRME) “Measurement Uncertainty in Medical Laboratories: Friend or Foe?” Milan, IT
Dec 04 – 05, 2017 JCTLM Members & Stakeholders Meeting 2017 Paris, FR
Feb 08 – 09, 2018 International Congress on Quality in Laboratory Medicine Helsinki, FI
Jun 12 – 15, 2018 XXXVI Nordic Congress of Clinical Chemistry Helsinki, FI
Sep 30 – Oct 03, 2018 Santorini Conference “Systems medicine and personalised health & therapy” – “The odyssey from hope to practice”. Thira Santoirini, GR

Scientists reverse Huntington’s disease in mice using CRISPR

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Huntington’s disease is a fatal neurodegenerative disorder that causes the breakdown of nerve cells in the brain. It’s an inherited condition that typically begins in adulthood and is caused by a gene that produces proteins that are toxic to cells in the brain.

The research, published in the Journal of Clinical Investigation, focused on mice engineered to develop Huntington’s disease, with symptoms like impaired movement developing when they are nine months old. The team then used CRISPR to change the genes of the mice, and within three weeks, the mice were significantly improved, although not back to the level of a healthy mouse.

The genetic therapy was delivered to the mice’s brain cells using a virus. This approach called the adeno-associated virus, or AAV, has been successful in CRISPR. The viral carrier was injected in the brain striatum of the mice, the region that controls movement.

“The findings open up an avenue for treating Huntington’s as well as other inherited neurodegenerative diseases, although more testing of safety and long-term effects is needed,” senior author Professor Xiao-Jiang Li, from Emory University School of Medicine, said in a statement.

The potential long-term effects are what makes medical researchers tread carefully when it comes to CRISPR. The potential for CRISPR to be a phenomenal weapon in the medical arsenal is undeniable, but there’s still more that we need to understand.

What if by suppressing a specific gene we know is causing a disease, another gene is affected? Or what if the change leads to other long-term difficulties? The researchers showed that the gene mutations caused by CRISPR in this setup happened only in the Huntington genes and not in off-target genes.

“The long-term effects and safety of injecting AAV in the brain to express CRISPR/Cas9 remain to be rigorously tested before applying this approach to patients,” Li added.

There are no current plans to use CRISPR to fight neurodegenerative disorders in humans, although human trials to make cells able to fight cancer is currently underway in the USA and in China.

Source: IFLScience

Emerging Shigella strains show reduced antibiotic susceptibility

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Current Clinical and Laboratory Standards Institute criteria consider Shigella isolates with ciprofloxacin MIC ≤ 0.12 µg/mL as susceptible to this antibiotic. However, recent data show that some Shigella strains have a quinolone resistance gene that might lead to “clinically significant reduced susceptibility” to fluoroquinolones. CDC’s preliminary data indicates that all Shigella isolates with ciprofloxacin MICs between 0.12–1 µg/mL harbor at least one of these resistance genes. Shigella isolates without a quinolone resistance gene usually have a ciprofloxacin MIC ≤ 0.015 µg/mL.

This emerging resistance is particularly concerning because data show that many Shigella isolates with a quinolone resistance gene also are resistant to several other key antibiotics. Based on these findings, CDC recommends that physicians order stool culture and antimicrobial susceptibility testing for patients suspected of having Shigella infection. The agency emphasizes that culture-independent diagnostic testing does not provide susceptibility results.

Physicians should avoid prescribing fluoroquinolones when ciprofloxacin MIC ≥ 0.12 µg/mL, even if the isolates show susceptibility. Labs using commercially available automated systems should test Shigella isolates with susceptibility panels that include 0.12, 0.25, and 0.5 µg/mL dilutions. CDC also advised that labs include MIC values for fluoroquinolone agents in their susceptibility testing reports for Shigella, and that they report to state public health laboratories all findings about strains with ciprofloxacin MIC 0.12–1 µg/mL.

More information is available at https://emergency.cdc.gov/han/han00401.asp.

Source: AACC

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