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The Dentistry School of the University of Istanbul (IU), Istanbul, Turkey, joins Clinerion’s Patient Recruitment System platform, opening up new patient populations for patient recruitment and new clinical expertise areas for the running of clinical trials. By joining Patient Recruitment System (PRS), patients at the Dentistry School can be matched to clinical research studies seeking to recruit patients for trials. Pharmaceutical companies using Clinerion’s PRS will be able to evaluate the patient population of the dental hospital during the development of the trial protocol and the site selection steps of their drug trials, potentially bringing more international clinical research to Istanbul University. The hospital itself can rigorously identify and quickly enroll its own patients for trials using PRS. The IU Dentistry School specializes in all fields of dentistry, from Oral and Maxillofacial Surgery to Prosthodontics, from Periodontology to Pediatric Dentistry, Endodontics to Orthodontics. The hospital treated over 97,500 patients in the past year. Clinerion’s Patient Recruitment System finds patients for clinical trials by checking clinical trial requirements against patient data from the databases of connected hospitals in real-time. Clinerion’s hospital coverage in Turkey alone currently comprises hospitals in Istanbul, Konya and Malatya with a catchment area of 30 M people. PRS currently has access to over 350 M data entries. Additional use cases for PRS include Market Access Studies and Real World Data Analysis. “We see a great benefit for our patients as well as for our hospital,” says Prof. Dr. Gülsüm Ak, the Dean of the Dentistry School. “PRS will bring our patients access to innovative new treatments, while the Dentistry School will gain higher exposure and visibility for leading edge clinical research.” “The Dental Hospital of the University of Istanbul brings PRS new clinical expertise areas for the running of clinical trials and new patient populations for patient recruitment, expanding Clinerion’s hospitals coverage,” says Bariş Erdoğan, Clinerion’s Country Head Turkey. “The continued expansion of PRS in Turkey shows the productive and material benefits brought by Clinerion to clinical trials in Turkey.” “We are thrilled to welcome the Dental Hospital of Istanbul University to the Clinerion PRS platform,” says Ulf Claesson, CEO of Clinerion. “PRS will boost the number, quality and efficiency of their clinical trials activities, while also bringing their patients access to advanced medication.” For more on Clinerion’s Patient Recruitment System: www.clinerion.com/index/OverviewOurSolutions/PatientRecruitmentSystem Clinerion is an international technology services company offering highly scalable electronic patient recruitment solutions to increase efficiency and quality in clinical research. The company’s Patient Recruitment System connects to and leverages existing electronic medical records. Following international privacy and confidentiality standards, Clinerion’s solutions pseudonymize, enrich and normalize those records and facilitate real-time patient recruitment for clinical trials. Clinerion website: www.clinerion.com For more information, please contact:


By joining Patient Recruitment System (PRS), patients at the Dentistry School can be matched to clinical research studies seeking to recruit patients for trials. Pharmaceutical companies using Clinerion’s PRS will be able to evaluate the patient population of the dental hospital during the development of the trial protocol and the site selection steps of their drug trials, potentially bringing more international clinical research to Istanbul University. The hospital itself can rigorously identify and quickly enroll its own patients for trials using PRS. The IU Dentistry School specializes in all fields of dentistry, from Oral and Maxillofacial Surgery to Prosthodontics, from Periodontology to Pediatric Dentistry, Endodontics to Orthodontics. The hospital treated over 97,500 patients in the past year. Clinerion’s Patient Recruitment System finds patients for clinical trials by checking clinical trial requirements against patient data from the databases of connected hospitals in real-time. Clinerion’s hospital coverage in Turkey alone currently comprises hospitals in Istanbul, Konya and Malatya with a catchment area of 30 M people. PRS currently has access to over 350 M data entries. Additional use cases for PRS include Market Access Studies and Real World Data Analysis. “We see a great benefit for our patients as well as for our hospital,” says Prof. Dr. Gülsüm Ak, the Dean of the Dentistry School. “PRS will bring our patients access to innovative new treatments, while the Dentistry School will gain higher exposure and visibility for leading edge clinical research.” “The Dental Hospital of the University of Istanbul brings PRS new clinical expertise areas for the running of clinical trials and new patient populations for patient recruitment, expanding Clinerion’s hospitals coverage,” says Bariş Erdoğan, Clinerion’s Country Head Turkey. “The continued expansion of PRS in Turkey shows the productive and material benefits brought by Clinerion to clinical trials in Turkey.” “We are thrilled to welcome the Dental Hospital of Istanbul University to the Clinerion PRS platform,” says Ulf Claesson, CEO of Clinerion. “PRS will boost the number, quality and efficiency of their clinical trials activities, while also bringing their patients access to advanced medication.” For more on Clinerion’s Patient Recruitment System: http://www.clinerion.com/index/OverviewOurSolutions/PatientRecruitmentSystem Clinerion is an international technology services company offering highly scalable electronic patient recruitment solutions to increase efficiency and quality in clinical research. The company's Patient Recruitment System connects to and leverages existing electronic medical records. Following international privacy and confidentiality standards, Clinerion's solutions pseudonymize, enrich and normalize those records and facilitate real-time patient recruitment for clinical trials. Clinerion website: http://www.clinerion.com For more information, please contact: Le Vin Chin Head of Marketing and Communications Clinerion Ltd Margarethenstrasse 47, CH-4053 Basel, Switzerland Tel.: +41 61 865 60 54 media(at)clinerion(dot)com


News Article | December 7, 2016
Site: www.eurekalert.org

A study headed by Salvador Aznar Benitah, ICREA researcher at the Institute for Research in Biomedicine (IRB Barcelona), and published today in Nature identifies metastasis-initiating cells through a specific marker, namely the protein CD36. This protein, which is found in the membranes of tumour cells, is responsible for taking up fatty acids. CD36 activity and dependence on lipid (fat) metabolism distinguish metastasis-initiating cells from other tumour cells. The researchers discovered the metastatic CD36+ cells in samples from patients with oral cancer with different degrees of aggressiveness, provided as part of a collaboration with the Hospital Vall d'Hebrón de Barcelona. In the mouth tumours analysed, very few cells were found to have metastasis-initiating capacity. The addition of CD36 expression to tumours that did not cause metastasis made them become metastatic. Furthermore, the researchers have demonstrated that the effect exerted by CD36 on metastasis is the same for melanoma cells and luminal breast cancer cells. Likewise, statistical analyses of samples from patients reveal that the metastasis of ovarian, bladder and lung cancer are also dependent on CD36. "Although we have not yet tested this in all tumour types, we can state that CD36 is a general marker of metastatic cells, the first marker I know of that is generally specific to metastasis," says Salvador Aznar Benitah, head of the Stem Cell and Cancer Lab at IRB Barcelona. "We can now obtain metastatic cells in the laboratory. This will allow us to trace them and to study, for example, their distribution in the tumour, where they anchor when they leave it, or why they are so sensitive to fat, among other questions," adds the first author of the study Gloria Pascual. Dr. Aznar-Benitah pointed that "We expect this study to have a big impact on the scientific community and to further advances in metastasis research, and we hope to be able to validate the potential of CD36 as an anti-metastasis treatment. Things like this don't happen every day." Given the involvement of lipid metabolism in metastasis and the function of CD36 in this process, the next logical question for the researchers was: does fat intake have a direct effect on metastasis? The researchers provided mice with a high-fat diet (15% more fat that normal, equivalent to what a so-called "cafeteria diet"). They then inoculated them with a type of oral cancer, which in standard dietary conditions would lead to 30% of the animals developing metastasis. Strikingly, under the high-fat diet and thus with a greater amount of lipids in blood, around 80% of the mice developed many more and larger metastases. They also tested the effect of a specific fatty acid, palmitic acid, on metastasis. This plant-derived fatty acid is the main component of palm oil, and in lower proportions, of coconut and other oils, and is used in many kinds of processed food. The researchers treated the oral tumours with palmitic acid for two days and then injected them into mice on a standard diet,.An increase from 50 to 100% was observed in the frequency of the metastatic tumour. That is to say, all the mice developed metastasis in a CD36-dependent manner. "In mice inoculated with human tumour cells, there appears to be a direct link between fat intake and an increase in metastatic potential through CD36. More studies are needed to unravel this intriguing relationship between diet and metastasis, above all because industrialised countries are registering an alarming increase in the consumption of saturated fats and sugar," warns Aznar Benitah. "Fat is necessary for the function of the body, but uncontrolled intake can have an effect on health, as already shown for some tumours such as colon cancer, and in metastasis, as we demonstrate here," explains the researcher. The study demonstrates the anti-metastatic effect of blocking the CD36 protein, both in immunodepressed mice and in mice with intact immune systems. Figures were similar for all tests. The inhibition of CD36 when the animals were inoculated with the tumour cells completely eliminated their metastatic potential. In addition, the administration of CD36-blocking antibodies to mice with already established metastases led to total removal of the metastases in 20% of the animals, while for the others it brought about a dramatic reduction of 80-90% in the number of metastatic foci and their size. The mice tolerated the treatment in the therapeutic window required to achieve an anti-metastasis effect and no intolerable side-effects were observed in autopsies, and blood and tissue analyses. IRB Barcelona has applied for IP protection of the results, and the researchers are working with MRC Technology in the UK to co-develop new antibody-based therapeutics against CD36 that are suitable for treatment of patients in a range of cancers. If the development of the novel therapeutic was successful, a new product could be available in 5-10 years. The study has been possible thanks to the collaboration of the Service of Oral and Maxillofacial Surgery, the Service of Pathology Anatomy and the biobank of the Hospital Vall d'Hebrón de Barcelona, with the participation of Coro Bescós and Juan Antonio Hueto from the Vall d'Hebron Institut de Recerca (VHIR). The study is thus the result of collaboration between basic and clinical research and it aims to transform research results into useful treatments for patients. This work has been supported by the Fundació La Marató de TV3, two project grants from the World Wide Cancer Research of the UK, and Fundación Botín and Banco Santander, through Santander Universidades. Furthermore, the laboratory is supported by funding from the European Research Council, the Ministry of Science and Innovation, and the Generalitat de Catalunya (Government of Catalonia).


News Article | September 1, 2016
Site: www.chromatographytechniques.com

A fear of pain causes many people with dental phobias to avoid or delay needed treatment. In some cases, the injection of a numbing agent can be the most painful part of the visit. But with a new United States Food and Drug Administration-approved anesthetic that is administered with a brief nasal spray, that injection may not be necessary to achieve pain relief. The spray, a drug called Kovanaze, was deemed safe and effective in a recent Phase 3 clinical trial led by University of Pennsylvania School of Dental Medicine researchers. The results of the study were published in the Journal of the American Dental Association. “There is really nothing else like this out there,” said Elliot V. Hersh, the study’s lead author and a professor in the Department of Oral and Maxillofacial Surgery/Pharmacology at Penn Dental Medicine. “This is obviously a great thing for needle-phobic individuals, and it can reduce inadvertent needle-stick injuries in the clinic as well.” The double-blind, randomized trial found that the compound, a combination of the local anesthetic tetracaine and the nasal decongestant oxymetazoline, was effective at preventing pain during a single restorative procedure in an upper bicuspid, canine or incisor in 88 percent of patients, a rate comparable to the success of commonly used injectable numbing agents. The most common side effects were runny nose and nasal congestion; no serious side effects were reported. Kovanaze was developed by St. Renatus and received FDA approval on June 29. The idea for Kovanaze, or K305, emerged when St. Renatus co-founder Mark Kollar was hit in the chin playing basketball, requiring 21 stitches. A fellow player happened to be an ear nose and throat specialist, who placed the sutures and also diagnosed Kollar with a deviated nasal septum. The ENT performed the septum repair and, when Kollar returned to his office for a follow-up visit, gave him a nasal spray containing tetracaine to remove a nasal stent. Once the stent was removed, Kollar noticed his teeth were numb. The ENT said a few other patients had reported the same sensation. Kollar, who happened to be a practicing dentist, went to his office to test his teeth with a dental electronic pulp stimulator and found that they were indeed numb. The serendipitous discovery led Kollar to found a company together with his business partner and co-founder Jim Mulvahill. Shortly after the project was initiated, Kollar and Mulvahill became aware that Bryan Clay, an ENT from Jackson, Miss., had a patent issued on the idea of an intranasal dental anesthetic. Mulvahill, Kollar and Clay combined their resources, with Kollar taking the lead in formulation and scientific development. Kollar’s research refined the anesthesia formula, leading to the invention of  Kovanaze and additional patent protection. To lead the Phase 3 trial, St. Renatus reached out to Penn Dental Medicine and Hersh, who had previously evaluated the safety and efficacy of a number of analgesic drugs including an early safety study on Kovanaze. The trial recruited 150 adults who passed a health screening and were set to undergo a single dental filling in an upper bicuspid, canine or incisor. One hundred patients were assigned Kovanaze and 50 were assigned a placebo. Patients received one spray, waited four minutes, received a second spray, waited 10 minutes and then a test drilling was performed. If the patients experienced pain at that point, they received a third spray. Patients who still experienced pain at that point received a rescue injection of local anesthetic to complete the procedure. Patients’ heart rate and blood pressure were recorded at various times throughout the visit. Eighty-eight percent of the people who received Kovanaze were able to have the dental restorative procedure completed without a rescue injection, compared to 28 percent for the placebo vehicle spray. Before receiving the spray, all patients were given what’s known as an alcohol sniff test to measure baseline sense of smell. Repeating the test just after the procedure and again a day later, the researchers found that the drug caused minimal changes in olfaction. The K305 treatment had a small effect on blood pressure, causing it to rise slightly. Some patients reported nasal congestion, nasal discomfort, throat pain and irritation, headache and eye watering, but no serious adverse events were reported. To follow up on the study, Hersh said the company will likely pursue additional investigations to see if more intensive dental procedures can be performed using this anesthetic, such as root canals or oral tissue biopsies. It’s likely that further studies will also evaluate whether the drug can be safely administered to children. Currently the FDA has approved the drug for use only in individuals weighing at least 40 kilograms, roughly 88 pounds. “It would certainly make for a more stress-free dental office visit for children as well as adults if we could replace some of these anesthetic injections with a simple spray,” Hersh said. “It may also keep some children out of the operating room, which would be a major cost savings to the child’s family and reduce potential morbidity associated with general anesthetic procedures.”


News Article | November 21, 2016
Site: www.prweb.com

Celebrate Frederick, Inc. is excited to announce the 31st Annual Candlelight House Tour on Saturday, December 3 from 5 to 9 PM and Sunday, December 4 from Noon to 4 PM. This year’s self-guided tour will feature the following eight homes in historic Downtown Frederick, built between the late 1700’s and the mid 1900’s, featuring distinct architectural style and design decorated to inspire your holiday senses. Home of Lauren Kremers – Family, friends and fond memories form the heart of this 1844 row house. The owner, who moved here in 2009, has merged much-loved furnishings and accessories with comfortable seating, artwork of personal significance and warm tones to create a welcoming ambiance. Home of Fred and Jane Branski – This charming row house has architectural details dating back to 1865, with a hint of 21st century style. The parlor reflects an old English heritage, while the kitchen has a modern yet cozy look with its stainless steel appliances and warm yellow walls. Previous owners extended the house to form a space that the Branskis use as sitting room. Windows and a French door open to the garden, which offers an established landscape and the borrowed beauty of neighbors’ trees. Home of Will and Cathie Duncan – Given its location within the city, it’s hard to believe this property was once part of a farm. In 1921, the lot was carved out of the Neidig farm to create a new subdivision called Maple Park. The house –which possesses elements of American Foursquare and Craftsman architecture—was built in 1924. The home remained largely unimproved until six decades later, when the Duncans bought it and began bringing it into the 20th century. Home of Dreda and Bernie Kelley - This 1818 Federal home features Flemish bond brickwork and original interior decorative woodwork and paneling. The gracious foyer, with its elegant three story staircase, offers entrances to the living room, dining room and kitchen. The dining room is home to a brass and crystal chandelier from the 1920’s French era, and the patio and garden were featured in this year’s Beyond the Garden Gate tour. Home of Greg Campbell and Thom Francis - The front of this house was expanded in 1855 from a more modest structure. The Italianate-style, three-bay façade boasts wide cornices, decorative brackets and arched windows. The European gas lantern is the inspiration for the home’s moniker, “Gaslight House”, while twelve-foot ceilings, an impressive staircase and substantial moldings continue the sense of importance inside. Home of Michael Smith and Brian Ward – Visitors who expect this new-construction, Federal-style home will have a traditional interior are in for a surprise. At the urging of interior designer Steven Corbeile, the owners have opted for a modern décor that mixes glamorous textiles and sumptuous hues. Royal blue walls, a marble coffee table and leather wingback chairs are just some of the beautiful details found in this home. Home of Kendell and Brek Prior- This 1930 Dutch Colonial-style home has a fresh lease on life thanks to its young owners, who moved in during the summer of 2014. The home is ready for entertaining guests thanks to its cozy library and 12-foot reclaimed wood trestle table found in the dining room. Industrial lighting and midcentury- style Wishbone chairs help to complete the mood. Home of Mary “Sam” and John Reeves – This 1952 rancher is decorated with more than a hundred crystals from old chandeliers, glittering white lights and greenery, including tiny trees of unknown species that volunteer in their backyard. Their eclectic style can be seen from the Asian influence in the living room, as well as a Venetian styled dining room. Tickets for the tour are $25 in advance or $30 the days of the tour. Tickets may be purchased for $25 through Friday, December 2 online at CelebrateFrederick.com or at the following Downtown Frederick retail locations: Fabulous Finds, 24 E. Patrick Street, Tiara Day, 153 N. Market Street, Frederick Basket Company, 12 N. East Street or the Frederick Visitors Center, 151 S. East Street. For those tour goers who frequent our Beyond the Garden Gates Tour in the spring, be sure to take advantage of the opportunity to save over 10% by purchasing a Home and Garden Ticket Package for $40. Package sales are available exclusively online at CelebrateFrederick.com. Day of tour ticket purchases can be made at the Hospitality Center located at the Talley Recreation Center, 121 N. Bentz Street on Saturday, December 3 from 4 to 9 PM and Sunday, December 4 from 11 AM to 3:30 PM. All tour guests are invited to take advantage of the Hospitality Center where light refreshments will be available. The Candlelight House Tour proceeds help to fund a variety of Celebrate Frederick’s free public events help throughout the year, including the Frederick’s 4th Celebration, the Sunday night Summer Concert Series, the Thursday morning Summerfest Family Theatre, In The Street, and other Holidays events. In addition to helping fund these events, a portion of the proceeds also benefits beautification and community projects in Downtown Frederick. Over the 30 years of this tour, more than $100,000 has been donated to beautify the Frederick community. In 2016, a portion of the tour proceeds will benefit the Culler Lake Project, Garden Club of Frederick, Green-walled Garden Club and the Men’s Garden Club of Frederick. The Candlelight House Tour and Holidays in Historic Frederick event series would not be possible without the hard work of the volunteers of the Holidays in Historic Frederick Committee, and the following community-minded businesses: Spires Sponsor – Nymeo; Carillon Sponsors – 106.9 The Eagle, BGE Home, Key 103, Sandy Spring Bank and Weis Markets; Bandshell Sponsors – Frederick Magazine, Mid-Maryland Oral and Maxillofacial Surgery, Roy Rogers, The Frederick News-Post, The Plamondon Companies and WHAG. Event Sponsors – The City of Frederick, Frederick County Bank and Friends Meeting School. For more information about the tour, or any of the Celebrate Frederick holiday events, please call The City of Frederick Office of Special Events at 301-600-2841 or visit our website at CelebrateFrederick.com.


News Article | December 20, 2016
Site: www.prweb.com

Researchers have found another potential medical use for botulinum toxin, commercially known as Botox, when they injected the drug into the inflamed salivary glands of a patient suffering from Sjögren’s Syndrome, an autoimmune disorder affecting nearly 4 million Americans. Published in the December issue of the Journal of Oral and Maxillofacial Surgery, the case study focuses on a 65-year-old woman who had been suffering for 10 years with weekly bouts of parotitis – inflammation of the major salivary glands located on either side of the face – associated with her 30-year history of Sjögren’s Syndrome. Her successful treatments led the authors to conclude in the official journal of the American Association of Oral and Maxillofacial Surgeons (AAOMS) that Botox is a “safe and effective alternative to surgical management of recurrent parotitis” resulting from Sjögren’s Syndrome. The patient’s parotitis flare-ups had been requiring regular antibiotic therapy and caused pain, swelling and tenderness. The authors at the University of Sydney in New South Wales, Australia, said current conservative treatments for parotitis typically include a combination of antibiotics, drugs that promotes the secretion of saliva, anti-inflammatories, steroids, warm compresses and massaging – or “milking” – the salivary glands. The physicians decided to offer their patient botulinum toxin injections on the “theoretical basis that reducing saliva production may reduce the likelihood of saliva accumulation and subsequent parotitis.” Botox is being used to reduce saliva production in patients suffering from other disorders, they said. The patient had injections initially every three months and then at four-month intervals. At the 36-month mark, the authors reported that she has no signs or symptoms of parotitis, “remarkably” has not needed a course of antibiotics since her second injection and has not reported any complications or side effects from the treatments. Patients with Sjögren’s Syndrome produce immune cells that may infiltrate their salivary glands and destroy or dilute the ducts that produce saliva. That accumulation of saliva can lead to chronic gland infections and result in a limited production of saliva. If nonsurgical options are not effective, surgery to remove the salivary gland – called a parotidectomy – may be performed. “Botulinum Toxin for the Management of Sjögren Syndrome-Associated Recurrent Parotitis,” is authored by Luke M. O’Neil, MBBS, Carsten E. Palme, MBBS, Faruque Riffat, MBBS, and Neil Mahant, MBBS, Ph.D. The full article can be accessed at http://www.joms.org/article/S0278-2391(16)30487-6/fulltext. ________________ The Journal of Oral and Maxillofacial Surgery is published by the American Association of Oral and Maxillofacial Surgeons to present to the dental and medical communities comprehensive coverage of new techniques, important developments and innovative ideas in oral and maxillofacial surgery. Practice-applicable articles help develop the methods used to handle dentoalveolar surgery, facial injuries and deformities, TMJ disorders, oral and head and neck cancer, jaw reconstruction, anesthesia and analgesia. The journal also includes specifics on new instruments and diagnostic equipment, and modern therapeutic drugs and devices.


News Article | December 19, 2016
Site: www.prweb.com

Intense and regular physiotherapy – including exercises and special equipment to temporarily keep the jaw open – is critical to the recovery of pediatric patients who suffer complications from maxillofacial trauma, according to a new scientific study. The study’s recommended treatment plan can help young patients who suffer from post-traumatic restricted mouth openings prevent permanent disabilities, including future TMJ-related disorders, jaw growth problems, functional issues, and the development of chronic pain and joint stiffness. The study was published in the December issue of the Journal of Oral and Maxillofacial Surgery – the official journal of the American Association of Oral and Maxillofacial Surgeons (AAOMS). Working with 86 patients ages 3 to 17 who had suffered mandibular (jawbone) or midface fractures or trauma, the researchers found those who followed a regular program of exercises and used mouth props to keep their jaw open for an hour several times a day recovered more quickly and completely than those who were not provided such treatment. To ensure patient cooperation, especially for children younger than 12, researchers stressed that treatments be performed under the close supervision of their surgeons. In addition, parents were motivated to ensure compliance after being informed of the permanent disabilities the treatment could prevent by maintaining muscle function while preventing adhesion (internal scar tissue) formation and contraction of soft tissues. In addition to difficulties with patient cooperation, researchers said children create special challenges for maxillofacial surgeons because their facial skeletons differ significantly from those of adults. These differences include the small bone and sinus size, growth potential, a quicker healing process and a high incidence of temporomandibular joint (TMJ) issues. Patients who followed the study’s recommended treatment plan returned to their preoperative mouth opening size at the fourth month, with fixed normal measurements at the sixth month. The study results led researchers to conclude that a vigorous physiotherapy treatment plan is critical in the recovery of restricted mouth openings and prevention of bone stiffness for pediatric trauma patients. “Physiotherapy Maneuver Is Critical to Recover Mouth Opening After Pediatric Trauma” is authored by Ghada Amin Khalifa, M.D., Naglaa Shawki El-Kilani, M.D., and Hanan Mohamed Shokier, M.D. The full article can be accessed at http://www.joms.org/article/S0278-2391(16)30649-8/fulltext. ____________ The Journal of Oral and Maxillofacial Surgery is published by the American Association of Oral and Maxillofacial Surgeons to present to the dental and medical communities comprehensive coverage of new techniques, important developments and innovative ideas in oral and maxillofacial surgery. Practice-applicable articles help develop the methods used to handle dentoalveolar surgery, facial injuries and deformities, TMJ disorders, oral and head and neck cancer, jaw reconstruction, anesthesia and analgesia. The journal also includes specifics on new instruments and diagnostic equipment, and modern therapeutic drugs and devices.

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