Antidepressants fine-tune brain reward pathway to lessen neuropathic pain

first_imgThe study suggests that antidepressants that target monoamines, signaling chemicals in the brain that regulate chronic pain and depression, act in the nucleus accumbens, a part of the brain’s reward system, and likely through pathways that pass on messages to nerve cells through RGS9-2.“Our data reveals that antidepressants that target specific neurotransmitters in the brain, particularly TCAs and SNRIs, regulate chronic pain and depression-related symptoms through actions in the nucleus accumbens,” said Venetia Zachariou, PhD, Associate Professor in the Fishberg Department of Neuroscience and the Friedman Brain Institute, Icahn School of Medicine at Mount Sinai. “We don’t yet know if the typical pain-processing pathways in the spinal cord and the pathways we’ve identified in the brain reward center are directly linked, but we now know more about the cellular pathways that need to be activated in order to achieve pain relief and that effective therapeutics must target both pathways.”In the treatment of pain, a common course is to treat patients with opioid medications, but these medications show limited effectiveness for neuropathic pain and come with safety and addiction issues. Because antidepressant medications are not addictive, they have become increasingly prescribed to treat neuropathic pain and related depression. Earlier research identified that antidepressants act in the spinal cord to control pain transmission, but little is known about their pain-controlling actions in the brain.“We found that the molecular pathways required for recovery from neuropathic pain are controlled by RGS9-2,” says Vasiliki Mitsi, a PhD student in the Zachariou lab at the Icahn School of Medicine at Mount Sinai. “In addition, we discovered that by inhibiting RGS9-2, the function of hundreds of other molecules that are important for pain-relief and mood-elevation was boosted,”The study suggests that therapeutic treatments should target both the brain reward center as well as the previously identified pain-transmitting pathways in the spine. Insight from this study will be used to develop new targets for the treatment of this debilitating disorder. Share LinkedIn Pinterest Share on Twittercenter_img Email Commonly used antidepressant drugs change levels of a key signaling protein in the brain region that processes both pain and mood, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published August 24 in the Proceedings of the National Academy of Sciences (PNAS). The newly understood mechanism could yield insights into more precise future treatments for nerve pain and depression.The study was conducted in mice suffering from chronic neuropathic pain, a condition which is caused in mice and humans by nerve damage. Chronic neuropathic pain is often related to diabetes, infection or trauma – and it persists even after the original source of the pain is gone. Past studies have shown that such pain often leads to depression, but brain mechanisms underlying this connection were previously unknown, as were the mechanisms by which common antidepressant drug classes -tricyclic (TCA) antidepressants or Selective Serotonin-Norepinephrine inhibitors (SNRIs) – counter both pain and depression-related symptoms.The current study found that the molecular adaptations required for “recovery” from pain and depression are controlled by a gene (RGS9), and the protein it codes for, named RGS9-2. Mice that lacked the gene responsible for encoding RGS9-2 responded much earlier to very low doses of antidepressants, showed significant improvement of sensory deficits and had no signs of depression-related behaviors. Share on Facebooklast_img read more

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News Scan for Aug 06, 2020

first_imgCase series: Mild illness, good outcomes in infants hospitalized with COVID-19A small single-center case series published today in Pediatrics describes only mild illness in seven hospitalized infants in New York City with COVID-19 and fever, with none requiring supplemental oxygen, mechanical ventilation, or intensive care.Columbia University researchers conducted a mixed retrospective and prospective study of infants 60 days old and younger (range, 11 to 56 days) hospitalized from Mar 1 to Apr 15 with confirmed infection with SARS-CoV-2, the virus that causes COVID-19.In three of the seven infants (43%), fever was the only symptom at hospital admission. None of the newborns were ill or in respiratory distress. Two infants had underlying Escherichia coli urinary tract infections (UTIs), but it was not clear whether their fever was a result of the UTI or coronavirus infection.Median hospitalization length was 2 days. None of the newborns were readmitted by 7 days, but one infant was hospitalized again at 14 days for fever and again tested positive for COVID-19 but was later released.”Our result, although based on small numbers, suggests that infants with SARS-CoV-2 generally have mild presentations, similar to typical viral illness with other coronaviruses,” the authors wrote. “This benign clinical course was also observed for the 2 infants in our study with underlying medical illnesses.” Aug 6 Pediatrics case series Penicillin allergy delabeling linked to more appropriate antibiotic useA combination of direct delabeling and oral penicillin challenge in patients with reported penicillin allergies resulted in improved antibiotic prescribing at two Australian hospitals, Australian researchers reported yesterday in Clinical Infectious Diseases.In the study, patients with a reported penicillin allergy were offered a single-dose oral penicillin challenge or direct removal of the penicillin allergy label based on their history. The primary end point of the study was the proportion of patients delabeled. The secondary end points were the use of narrow-spectrum penicillins, restricted antibiotics, and appropriate antibiotics in delabeled patients compared with both the pre-testing period and non-delabeled patients.During the study period (January through August 2019), investigators at the two hospitals assessed 1,779 patients reporting 2,135 allergies and found 1,272 with a penicillin allergy. Of the 1,225 patients analyzed, 355 were delabeled: 161 by direct delabeling and 194 by oral challenge. Ninety-seven percent (194 of 200) of patients were negative upon oral challenge.In the delabeled patients, the investigators observed an increase in narrow-spectrum penicillin usage (adjusted odds ratio [OR], 10.51; 95% confidence interval [CI], 5.39 to 20.48), improved antibiotic prescribing (adjusted OR, 2.13; 95% CI, 1.45 to 2.13), and a reduction in restricted antibiotic usage (adjusted OR, 0.38; 95% CI, 0.27 to 0.54) in the post-testing period compared with the pre-testing period.In the propensity score analysis, they noted an increase in narrow-spectrum penicillins (OR, 10.89; 95% CI, 5.09 to 23.31) and beta-lactam/beta-lactamase inhibitors (OR, 6.68; 95% CI, 3.94 to 11.35) and a reduction in restricted antibiotic use (OR, 0.52; 95% CI, 0.36 to 0.74) and inappropriate prescriptions (relative risk ratio, 0.43; 95% CI, 0.26 to 0.72) in the delabeled group compared with the patients who retained their allergy label.”Our study in hospitalized inpatients demonstrated, at an individual and propensity-adjusted level, a dramatic increase in appropriate and narrow-spectrum penicillin use in those delabeled, without an increase in total antibiotic consumption,” the authors of the study wrote. “The strategy provided here should enable clinicians globally to implement and incorporate similar antibiotic allergy delabeling programs into their health service as a novel medication safety and AMS [antimicrobial stewardship] intervention with minimal additional resources.”Aug 5 Clin Infect Dis abstract German data show significant drop in pediatric antibiotic prescribingAn analysis of national outpatient antibiotic prescribing data in Germany shows a significant reduction in antibiotic prescribing for children and adolescents over the last decade, German researchers reported today in Eurosurveillance.In a cross-sectional analysis of annual antibiotic prescription rates among insured children ages 0 to 14 from 2010 through 2018, researchers from Germany’s Central Research Institute of Ambulatory Health Care found that the age-standardized antibiotic prescription rate fell by 43%, from 746 prescriptions per 1,000 people in 2010 to 428 per 1,000 in 2018 (P < 0.001). The highest reductions were observed in children ages 0 to 1 (49%) and 2 to 5 (44%). The 2-to-5 age-group had the highest prescription rate, with 683 prescriptions per 1,000 people in 2018, while children ages 10 to 14 had the lowest, with 273 prescriptions per 1,000. Rates declined strongly in all regions of the country.With the exception of penicillins with a beta-lactamase inhibitor, prescription rates of all antibiotic subgroups decreased markedly. But second- and third-generation cephalosporins accounted for 32% of prescribed antibiotics, which is high compared with other European countries.The authors of the study say the reductions may have been driven by rising public awareness of antibiotic resistance in Germany, an increasingly critical view of the use of antibiotics, and an increasing focus on judicious prescribing among German physicians. But they also note that there is room for improvement, as the antibiotic prescribing rate in German children remains roughly 70% higher than it is in Norway and the Netherlands.Aug 6 Eurosurveill studylast_img read more

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Los Alamos Firefighters Assist Hikers On Deer Trap Mesa

first_imgScene this evening of Los Alamos Firefighters and EMTs responding to a couple of hikers in need of help getting out of Deer Trap Mesa near the trailhead. Initial reports indicate there are no serious injuries. Deer Trap Mesa extends east from Barranca Mesa and is named for a game pit found close to the start of the trail. The mesa is a natural area with fragile soil and it is not an appropriate spot for bicycles or horses. Its relative isolation makes it an attractive location for wildlife viewing, studying wildflowers and simply enjoying the view. Walking is easy, except for a short section of rock stairs near the trailhead. Courtesy photolast_img

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Town CPF Fund Buys Noyac Land

first_imgA Noyac parcel in a wetland preservation target area will be acquired by Southampton Town.Town board members unanimously approved a resolution to purchase the land from Rotondi Properties LLC and amend the Community Preservation Fund list to include the 1.7 acres of land on Noyac Road that it will buy for $1.75 million. Town-protected Trout Pond is immediately south of the parcel and drains north into Mill Creek,which feeds into Peconic Bay.“Acquisition of this property protects vital wetlands, and can also provide recreational access to Mill Creek via the existing catwalk and dock area,” CPF coordinator Mary Wilson said on October 9. “The property also provides an opportunity to extend the trail system to include a scenic water view.”Supervisor Jay Schneiderman said while there is parking at Trout Pond, he thought the area could provide some additional parking spaces for those accessing the marina, especially since crossing the road from Trout Pond to the dock is dangerous.“They could walk down to the water,” he said. “And we could use the vista being protected to see the water over the property.”The land has been cleared prior to the sale, Wilson said, but would be restored with native grasses and monitored to make sure no non-native species gained a foothold. “You can see the water heading northeast,” Wilson said. “Particularly if you’re enjoying Trout Pond from the vista, it’s a nice view.”desiree@indyeastend.com Sharelast_img read more

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Leybold highlights innovations

first_imgThe Germany-based company recognises the vacuum technology functions almost as a heart in most systems and enables processes to run.Fore vacuumTo serve its customers efficiently, Leybold’s ECODRY series offers a clean, silent, compact and low-maintenance pump for use in analytical or research laboratories.The pump class lies in the transition area between small laboratory devices and large machines. However, the most significant innovation is the reduction of noise level.“The pump is compact, low-vibration, powerful, easy to operate and very quiet in its design,” said Alexander Kaiser, Product Manager at Leybold.High vacuumLeybold’s devices in the TURBOLAB series are plug-and-play high vacuum pump systems and offer a wide range of variants. They are compact, fully assembled and can be put into operation immediately.Different configurations cover the vacuum requirements of applications in the R&D markets and analytic applications.The oil-free hybrid bearing of the TURBOVAC i/iX turbopumps and the choice of the different dry-compressing fore vacuum pumps allow hydrocarbon-free operation.MeasureLeybold’s TURBOLAB systems can be equipped with THERMOVAC TTR fore vacuum gauges and PENNINGVAC PTR high vacuum sensors. Connected sensors are detected and pressure readings are automatically shown on the display.All critical parameters and operating conditions such as errors, warnings etc. are automatically recorded in an internal memory based on a standard time interval and can be adjusted by the user directly on site.A full portfolio of sensors and controllers makes the measurement and control of the process easy.Leybold offers innovations with its sensors for vacuum measurements in numerous applications in the pressure range of 2000 to 10-12 mbar.The measure devices offer precision, an extended measure range, improved reproducibility and process stability.Leybold offers sensors of various designs with the own characteristic measuring ranges. A distinction is made between direct and indirect pressure measurements.Read more like this – subscribe todayEnjoyed this story? Subscribe to gasworld today and take advantage of even more great insights and exclusives in industrial gases.Visit www.gasworld.com/subscribe to access all content and choose the right subscription for you.last_img read more

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On the beach

first_imgStay at the forefront of thought leadership with news and analysis from award-winning journalists. Enjoy company features, CEO interviews, architectural reviews, technical project know-how and the latest innovations.Limited access to building.co.ukBreaking industry news as it happensBreaking, daily and weekly e-newsletters To continue enjoying Building.co.uk, sign up for free guest accessExisting subscriber? LOGIN Subscribe now for unlimited access Get your free guest access  SIGN UP TODAY Subscribe to Building today and you will benefit from:Unlimited access to all stories including expert analysis and comment from industry leadersOur league tables, cost models and economics dataOur online archive of over 10,000 articlesBuilding magazine digital editionsBuilding magazine print editionsPrinted/digital supplementsSubscribe now for unlimited access.View our subscription options and join our communitylast_img read more

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A building is not just for Christmas, it’s for life

first_imgSubscribe now for unlimited access Get your free guest access  SIGN UP TODAY To continue enjoying Building.co.uk, sign up for free guest accessExisting subscriber? LOGIN Stay at the forefront of thought leadership with news and analysis from award-winning journalists. Enjoy company features, CEO interviews, architectural reviews, technical project know-how and the latest innovations.Limited access to building.co.ukBreaking industry news as it happensBreaking, daily and weekly e-newsletters Subscribe to Building today and you will benefit from:Unlimited access to all stories including expert analysis and comment from industry leadersOur league tables, cost models and economics dataOur online archive of over 10,000 articlesBuilding magazine digital editionsBuilding magazine print editionsPrinted/digital supplementsSubscribe now for unlimited access.View our subscription options and join our communitylast_img read more

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Polet in pair of Latin America firsts

first_imgThe flight was the first time the airline had operated into South America and the first time the four-engined long haul widebody IL-96-400T freighter had been involved on a commercial flight onto the continent.The 58 tonne payload aircraft was chartered to move an urgent cargo of aircraft equipment from the UK.Polet sales manager Khaydar Khasanzyanov commented: “It will be quite right to admit that from the beginning it seemed to be not an easy task having a very short period of time for flight preparation and procedures. The request from our customer came very urgently and the transportation required immediate performance.”In a further historical twist, the aircraft used, RA 96103, was the last IL-96-400T produced.www.poletairlines.comlast_img

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When science doesn’t have the answer

first_img James Morton is a writer and former criminal defence solicitor The sad story of the couple found dead in the swimming pool reminded me of one case which forensic science failed to solve. This concerned New Zealand-born Rhodes scholar and scientist Gilbert Stanley Bogle, who was found dead along with his companion, Margaret Chandler, at around 8am on 1 January 1963 in Lane Cove, River Park, Sydney. Both married, they had been to a New Year’s Eve party in Chatswood and left together. When found, Bogle was wearing a shirt and tie, shoes and socks, and was covered with a piece of dirty carpet. Chandler’s button-down dress was open and she was naked from the waist down. She had been covered with a cardboard beer carton. The pair had been poisoned, but the toxin has never been identified. Suggestions included LSD (traces were found in their bodies), arecoline hydrobromide (used for worming dogs) and yohimbine (a herbal Viagra). Theories ranged from an accident, to taking a drug as a sex aid, to suicide, to poisoning by Chandler’s husband Geoffrey (a rumour he has always denied, writing a book, So You Think I Did It? to dispel it) or Bogle’s jealous ex-lover Margaret Fowler. Other suggestions have included FBI involvement and an attempt to stop Bogle inquiring too deeply into the death of scientist Dr Clifford Dalton. In her book Without Hardware, Dalton’s wife claimed her husband had been killed by the Australian Security Intelligence Organisation spraying nerve gas in his face. Margaret Fowler left Australia immediately after the inquest and died in London in 1977. Geoffrey Chandler wrote his own account of the case later. Bogle’s FBI file remains classified. In 2006, a new suggestion by filmmaker Peter Butt in the documentary Who Killed Dr Bogle & Mrs Chandler? was that the couple’s deaths were due to hydrogen sulfide: a gas from a polluted riverbed caused by waste dumped there by a local factory. At first, the pair would have smelt and seen nothing, and by the time they did their respiratory systems would have already been shutting down, as the gas binds reduces blood’s ability to carry oxygen. As for the covering of the bodies, it was suggested that a local greyhound trainer exercising his dogs had come across the bodies first by accident and covered them for modesty’s sake.last_img read more

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Alarm as Strasbourg backs bugging of lawyers’ client meetings

first_imgRecording meetings between a man convicted of terrorist offences and his lawyers was justified, the European Court of Human Rights (ECtHR) has said in a ruling that could have far-reaching implications for the confidentiality of lawyer-client relationships.The Strasbourg ruling, in Öcalan v Turkey, a case concerning militant leader Abdullah Öcalan, was based on the reasoning that national authorities should be able to impose ‘lawful restrictions’ on people charged with terrorist activities when such restrictions are ‘strictly necessary to protect society against violence’.However the Law Society’s human rights committee is concerned that, if left unchallenged, the decision could undermine legal professional privilege in countries subject to the European Convention on Human Rights.The UN Basic Principles on the Rules for Lawyers compel governments to recognise the confidentiality of lawyer-client communications.Professor Sara Chandler, chair of the committee, said: ‘As it stands, the ECtHR decision allows legal professional privilege to be ignored in circumstances where the state expresses the view that confidentiality may lead to the commission of violent crimes.’This stance is open to misuse by governments and, while the protection of society from violence must be paramount, respect for privileged communications between lawyers and their clients is essential except in the most extreme circumstances.‘This exception by the ECtHR to allow a government to record a lawyer-client meeting unfairly identifies the lawyer with the client’s activities, and, to an extent, undermines the UN Basic Principles on the Role of Lawyers.‘We are hopeful that this decision will be reviewed by the Grand Chamber of the ECtHR so that more detailed consideration is given to the issue of when, if ever, legal professional privilege can be compromised.’last_img read more

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