Rhynchophorus ferrugineus (Olivier), RPW displays remarkable color variation across its range, and consequently has a taxonomic history littered with new species descriptions and synonymization. We compared DNA sequences of the mitochondrial cytochrome oxidase subunit I (COI) gene from RPW populations throughout the native and invaded ranges, to investigate the specific status and invasion history of this serious economic pest, and to identify possible common routes of entry. Analyses of COI haplotype data provide conclusive support, corroborated by sequences of additional nuclear gene regions, for the existence of at least two predominantly allopatric species. The true R. ferrugineus is native only to the northern and western parts of continental southeast Asia, Sri Lanka and the Philippines, and is responsible for almost all invasive populations worldwide. In contrast, the second species, which is currently synonymized under R. ferrugineus and should be resurrected under the name R. vulneratus (Panzer), has a more southern distribution across Indonesia, and is responsible for only one invasive population; that in California, U.S.A. The distribution of COI haplotypes is used to discuss the possible existence of further cryptic species, sources and routes of entry of different invasive populations, and the implications of our findings for current control methods.The red palm weevil (RPW) is a major pest of palms. It is native to southeast Asia and Melanesia, but in recent decades has vastly expanded its range as the result of multiple accidental anthropogenic introductions into the Middle East, Mediterranean Basin, Caribbean, and U.S.A. Currently regarded as a single species,  Rhynchophorus ferrugineus (Olivier 1790) (Coleoptera: Curculionidae), is widely considered to be the most damaging insect pest of palms (Aracaceae) in the world . Alm. AlmR. fpongsiri  providespongsiri  for refeRhynchophorus (and the related genus Dynamis), which was published in 1966 [schach as a synonym of vulneratus), concluding that ferrugineus and vulneratus were the only valid species. Wattanapongsiri [R. ferrugineus and R. vulneratus could be distinguished from each other primarily by the shape of the pronotum, and to a lesser extent by the color of the body. However, the specific status of R. ferrugineus and R. vulneratus was again brought into question in the 1990s, when researchers attempting to isolate aggregation pheromones, reported finding no differences in the chemical composition of pheromones produced by these species, or in the response of each species to the pheromones [R. ferrugineus and R. vulneratus (approximately 10% of captured specimens) [R. ferrugineus and R. vulneratus which included: re-examination of Wattanapongsiri’s morphological characters [R. ferrugineus and R. vulneratus were alike in their morphological characters, mitochondrial DNA sequences , and RAPD banding patterns [R. ferrugineus taking priority [This historical confusion eventually led Wattanapongsiri to conduct a thorough taxonomic revision of the genus eromones ,9. At thecimens) . In theiecimens)  returnedpatterns . Fertilepriority . R. ferrugineus has continued and over the last decade, interest in genetic variation, particularly among invasive populations of RPW, has increased, driven largely by the devastating effect of the pest on the date palm industry in the Middle East and Maghreb region of north Africa, and on ornamental Canary Island palms in the south east Mediterranean Basin. Early studies utilized RAPD methods to characterize genetic relationships among: different color-morphs drawn from a single collection site in Egypt [Debate over the specific status of in Egypt  and Saudin Egypt ; individin Egypt ; and, inin Egypt . Collectb (Cytb) gene, but again with very small sample sizes, corroborated this finding, recovering two closely related haplotypes present in Middle Eastern and Pakistani populations, and a third more distantly related haplotype that was the only haplotype present in Mediterranean, Egyptian and surprisingly KSA populations, which had grouped with the rest of the Middle East using RAPDs [In 2011, El-Mergawy et al.  made a mng RAPDs . The latng RAPDs .c oxidase sub-unit 1 (COI), and for the first time considered a reasonable number of samples; 310 specimens from 52 geographic localities across 14 countries in the invaded range [R. ferrugineus.A third study, also published in 2011, considered variation in the DNA sequence of another mitochondrial gene, Cytochrome ed range . The stued range , but wased range . One pared range ,20, agaiR. vulneratus as a valid species, highlight the possibility of additional cryptic species identifiable at the molecular level, and provide insight into the origins of the different invasive populations.In several cases, interpretation of existing studies that have attempted to examine molecular genetic variation in RPW, is hampered by their small sample sizes (see above). However, and more importantly, in every one of the published studies, the geographic range from which the samples were taken was also restricted. The molecular (and cross-breeding) data that contributed to Hallett et al.’s synonymization  was baseOnly one permit was required to complete the collections included in this study. Said permit was required for Singapore, where we had no official cooperators and collected only via traps placed on the balcony of a hotel room. Permit number NP/RP12-071 was issued by Jeremy Woon, Singapore National Parks Board. All other collections were made either with the direct permission of cooperating land owners , or with the aid of university scientists and Ministry of Agriculture officials who had arranged access to their own study sites, or the private properties of cooperating landowners . In addition, a lot of material was sent to us by university researchers, government cooperators, and farm owners . To the best of our knowledge none of the collections included herein were from National Parks or otherwise protected wilderness areas. Furthermore, these weevils are most certainly not an endangered species.R. ferrugineus lure  with an ethyl-acetate synergist , and were baited with either fermenting dates (in approximately 500 mL of water), or palm hearts extracted from trees (no water added) [Containers used to house this material varied depending on the local availability of materials, but included 2 L plastic soda bottles, 5 L and 25 L plastic buckets, all of which had holes cut into them to allow RPW access to the lure and bait. In addition, or as an alternative, with the landowner's consent (and assistance), infested palms  were felled and "dissected" with chainsaws and machetes to reveal larvae, pupae, and adult RPW. Finally, in Thailand, RPW were also collected from commercial RPW production facilities where larvae are mass produced for food.Collection sites throughout the native and invaded range varied greatly and included date plantations , forests , oil palm plantations , coconut plantations , coconuts in oil palm plantations , and even the balconies of hotel rooms as high as the 18th floor  . As a rer added) . Contain All RPW specimens were placed in labeled 50 mL, screw-capped conical centrifuge tubes , and euthanized by the addition of 95% ethanol. Each tube typically held 3-5 RPW specimens. The ethanol was replaced at least twice over the next 24-48h to ensure complete dehydration of tissues, thereby promoting adequate conditions for DNA preservation. Preserved samples were returned to our laboratory at the University of California Riverside (UCR), USA, and on receipt, RPW specimens were transferred to individual 20 mL clear PET sample vials , containing fresh 95% ethanol, and stored at -20 °C. vulneratus color-morph of RPW. On arrival at UCR, these specimens were instead found to match the description of R. bilineatus, common in PNG, but for confirmation and comparison, we included them in our study anyway. Finally, again to allow wider comparison, we also obtained samples of R. cruentatus and R. palmarum from Florida, U.S.A. and Tijuana, Mexico, respectively. In addition to our field collected samples, a tissue sample  was obtained from each of eight RPW specimens held in the California State Collection of Arthropods, CDFA, Sacramento, that were collected in Laguna Beach, California, in 2010 . While c3) of muscle tissue was dissected from a single tibia using flame-sterilized forceps, and allowed to air dry for 1 min. For larvae, a similar quantity of tissue was dissected from the head capsule and allowed to air dry. The tissue was transferred to a sterile 0.6 mL microcentrifuge tube and ground up in 6 µL proteinase-K  using a micropestle. To this was added 120 µL of a 5% (w/v) suspension of Chelex® 100 resin  and the reaction was incubated at 55 °C for 1 h followed by 10 min at 99 °C. The remainder of each extracted specimen  is deposited in the Entomology Research Museum collection at UC Riverside .Whole genomic DNA was extracted from individual specimens using Chelex® 100 resin . For adu2, 200 µM each dATP, dCTP, dGTP, 400 µM dUTP, 4% (v/v) BSA (NEB), 1 U Taq polymerase (NEB), and 0.2 µM of each PCR primer. Initial reactions utilized the primers Bron and Simon  but it quickly became clear that no single primer pair worked with all our samples. Consequently, the majority of reactions used the primers C1-J-1718 and C1-N-2329 [® ep gradient S thermocycler  using one profile for all 3 primer combinations: an initial denaturing step of 2 min at 94 °C; followed by five cycles of 30 s at 94 °C, 1 min 30 s at 45 °C, and 1 min at 72 °C; followed by a further 35 cycles of 30 s at 94 °C, 1 min 30 s at 51 °C, and 1 min at 72 °C; and, a final extension of 5 min at 72 °C. Amplification was confirmed by standard agarose gel electrophoresis and PCR products were cleaned using the Wizard® PCR Preps DNA purification system  and direct-sequenced in both directions at the Institute for Integrative Genome Biology, UCR. PCR primers were trimmed and sequences were aligned using SEQUENCHER 4.9 . The absence of pseudogenes was confirmed by translating each sequence using the online EMBOSS Transeq tool [ The polymerase chain reaction (PCR) was used to amplify a section of the mitochondrial gene (mtDNA) cytochrome oxidase c subunit 1 (COI) from each specimen. PCR was performed in 25 µL reactions containing 2 µL of DNA template (concentration not determined), 1X ThermoPol PCR Buffer , an additional 1 mM MgClseq tool .® (accessions KF311358-KF311740). Based on the outcome of genealogical analyses of the COI sequences (see below and Results), we also examined sequence variation in two sections of nuclear ribosomal RNA (rRNA) for a subset of 46 specimens. The D2 domain of 28S rRNA (28S-D2) is generally highly conserved across related taxa, and small differences may be indicative of species boundaries . SimilarR. bilineatus were generated in this study. These were combined with, and trimmed to match, 310 existing RPW sequences [Rhynchophorus, five species from different genera in the same sub-family (Dryopthorhinae), and a “rooting” taxon from the sister sub-family (Scolytinae), were retrieved from GenBank , and a clear signal in the geographic distribution of COI haplotypes within each lineage , the shape of the pronotum of 89 sequenced adult specimens across lineages L1 and L3 (Wattanpongsiri  suggeste1 and L3  was inveR. bilineatus (see methods). Furthermore, this lineage grouped with an existing GenBank accession for R. bilineatus (HM043664) in the ML analysis , collecanalysis  and therR. bilineatus was distinct from both L1 and L3 with a 24bp deletion between positions 397 and 420 inclusive, and by several further substitutions (GenBank accessions KF311695-KF311740). Taken together, this is very strong evidence that the L1 and L3 represent different species.The remaining two lineages  also displayed strong geographic structure . L1 contWithin each of the COI lineages, strong phylogeographic structure was also evident in the distribution of haplotypes , which wAcross specimens, there was a large amount of variation in all three estimates of pronotal shape . Within Rhynchophorus ferrugineus [In recent decades, RPW has undergone a huge range expansion, and now poses a serious threat to commercial date groves, ornamental landscape plantings and native stands of palm trees worldwide. Fundamental steps in any attempt to address this "threat" include a reliable understanding of the taxonomy of the pest, and identification of sources and routes of entry of invasive populations. In the taxonomic literature, RPW is currently considered to be a single species, rugineus . The preRhynchophorus bilineatus. In our phylogenetic analyses, R. bilineatus fell between the remaining two lineages, and was consistently placed as a sister clade to lineage L3, and a more distant relative of lineage L1  lineages . The samneage L1 .R. ferrugineus and R. vulneratus respectively. In our study, the only detected geographic overlap between the two lineages occurred on the Thai-Malay Peninsula, around the border between Thailand and Malaysia , in light of the phylogeographic evidence, we propose that the name Rhynchophorus vulneratus (Panzer) be reinstated and applied to palm weevils from Singapore, Sumatra, Java and Bali. In so doing, we also propose that palm weevils to the north and east of the Thai-Malay Peninsula (i.e. lineage L1) are the "true" Rhynchophorus ferrugineus (Olivier) (but see below). Interestingly, the zone of overlap between the species (or lineages) is also close to the proposed site of two ancient seaways that bisected the Thai-Malay Peninsula, for durations in excess of 1 million years, during the Miocene (24-23 Mya) and Pliocene (5.5-4.5 Mya) eras; an area known as the Isthmus of Kra [R. ferrugineus and R. vulneratus. Wattanapongsiri [R. vulneratus in the Philippines, but we were only able to sample a single location on the island of Luzon, the northernmost region of the archipelago. Thus, it remains possible that R. vulneratus is found in southern parts of the Philippines .There was also very clear and correlative geographic division in the distribution of COI haplotypes between the L1 and L3 lineages . Within Malaysia . Again, s of Kra . These as of Kra ,35, restR. ferrugineus (L1) lineage, dividing it into 3 sub-groups which differed from each other by 2.5 - 3.2% (R. vulneratus (L3) haplotypes across the Indonesian islands of Sumatra, Java, and Bali, with each of the 50 haplotypes detected in this region, being restricted to a single island, and haplotypes from Sumatra, and those from Java and Bali combined, forming separate clades  accounts for almost everything . RPW was Support for a "bridgehead" population in KSA also comes from a second haplotype, H17, which was only found in KSA and Israel, where it didn't establish until 1999 . Regardl Secondary translocation of RPW from Egypt or the Mediterranean Basin is also the most parsimonious explanation for the presence of the El-Mergawy H8 haplotype on the island of Curaҫao in the Caribbean. However, a second haplotype (H20) was unique to the neighboring island of Aruba. At least three scenarios could account for the presence of this haplotype. First, the Caribbean was invaded just once and H20 is simply a very rare haplotype that was not detected in the combined dataset of sequences from Egypt, KSA or the countries of the Mediterranean Basin. Alternatively, since H20 differs from El-Mergawy H8 by only a single nucleotide substitution, the former haplotype may have arisen as the result of a mutation that occurred post-invasion. This would account for its absence elsewhere in our sample. Finally, perhaps the least likely scenario is that H20 is evidence of a second invasion event in the Caribbean, that coincidentally originated from a similar part of the native range. While the last scenario may be an unlikely explanation for a rare haplotype in the Caribbean, it may account for another rare haplotype in the invaded range. Haplotype H33 was found only in a single specimen (collected with others) from Limasol, Cyprus. Again, this haplotype clusters with El-Mergawy H8 (present in the other Cypriot specimens) but this time it differs from that haplotype at 11 positions (2.1%). This haplotype was not detected in our samples from the native range, but ML analyses indicate that it is most closely related to haplotypes from the Philippines . R. ferrugineus  was found among 8 specimens from California, and yet again, we were unable to detect an exact haplotype match in native populations of this species. However, Rv61 was very closely related to a group of haplotypes (Rv26-Rv62) from the Indonesian islands of Java and Bali, the latter island providing the closest match (a single nucleotide substitution between Rv61 and Rv62). The introduction of R. vulneratus seems unlikely to have resulted from permitted movement of live palm trees  since there have been are no palm plantings in the Laguna Beach area, and the USDA banned all palm imports at the beginning of 2010 . Palm smuggling is also an unlikely conduit since these weevils require large palms in which to live and breed. Thus, it is again possible that the weevils, in this case R. vulneratus, were deliberately introduced to the Laguna Beach area for food. Thankfully, at the time of publication, there had been no reported captures of RPW in Laguna Beach since January 2012 despite an extensive trapping effort from June-November of the same year. Furthermore, the recent removal and inspection (27th March 2013) of a Canary Island palm that had been previously inspected and treated for R. vulneratus infestation in 2011, found no evidence of weevil activity [R. vulneratus population in Laguna Beach may have gone extinct. Finally, and in contrast to all other invasive populations, we can confirm that the palm weevils that invaded Laguna Beach, California, U.S.A., in 2010, were not activity . Thus, iR. ferrugineus, in light of our findings, it seems most likely that ferrugineol was actually isolated from R. vulneratus. This raises the issue of why it works. It is possible that there are shared compounds in the aggregation pheromones of the two species that result in a similar end-product, which in the invaded range, since there is no alternative, R. ferrugineus is attracted to regardless. However, it is also possible that differing blends of these shared compounds, or the addition of further compounds, may produce a lure that is even more attractive to R. ferrugineus. Consequently, we strongly suggest that the aggregation pheromone for R. ferrugineus should be isolated, identified, synthesized, and compared to the commercially-available pheromone that was derived from R. vulneratus and is marketed for R. ferrugineus control. In many invaded areas, mass trapping has been used to reduce RPW densities ,3,10,39.


An effective pain therapy to block or modify the physiological responses to stress has become an essential component of modern pediatric anesthesia and surgical practice.The goal of this study was to compare the analgesic effects of the spray forms of; lidocaine, morphine, ketamine, and normal saline on post-tonsillectomy pain scores in children.P value less than 0.05 was considered significant.A total of 120 children, American Society of Anesthesiologist (ASA) class I–II, scheduled for elective tonsillectomy were enrolled in this double-blind, clinical trial study. They were randomly divided into 4 groups, each receiving one of the following drugs at the end of operation; lidocaine spray (2 mg/kg); morphine spray (0.05 mg/kg); ketamine spray (0.5 mg/kg); or normal saline spray (8 puffs). For comparison of postoperative pain; the face, legs, activity, cry, consolability (FLACC) pain scale was evaluated during the first one hour of recovery period at 20 minutes intervals. The data was transferred to SPSS-10 software and analyzed statistically with the Scheffe test and Dunnett’s T3 test. P > 0.05). Finally, at 60 minutes, the FLACC scale scores of the ketamine and morphine groups were lower than in the other groups.In the early postoperative period (time: 0) and at 20, 40 and 60 minutes of recovery time, FLACC scale scores in the control group were higher than in the three other groups. At 20 minutes, the FLACC scale score in the lidocaine group was lower than in the other groups. At 40 minutes, the statistical differences between FLACC scales of the lidocaine, morphine and ketamine groups were not significant (The results of this study showed that lidocaine spray had the best pain controlling effect at 20 minutes in the recovery room, but after 40 minutes, ketamine and morphine sprays were more effective than the lidocaine spray. Pain is an unpleasant sensory and emotional experiences associated with actual or potential tissue damage , 2.Undergoing treatment may result in the occurrence of post-operative pain and this triggers biochemical and physiological stress responses. It also causes impairments in; pulmonary, cardiovascular, neuroendocrinal, gastrointestinal, immunological, and metabolic functions , 3. ChilAn effective pain therapy to block or modify the physiological responses to stress has become an essential component of modern pediatric anesthesia and surgical practice .The Society for Pediatric Anesthesia, clearly defined the alleviation of pain as a “basic human right”, irrespective of age and medical condition .Realistic aims for pediatric post-operative pain management are to recognize pain in children, to minimize moderate and severe pain safely in all children, to prevent pain where it is predictable, to bring pain rapidly under control and to continue pain control after discharge from hospital –10.Tonsillectomy is a common pediatric surgical procedure associated with significant postoperative pain that is a challenge to treat –15. InadAnalgesic spray is a novel administration for postoperative pain control. It is delivered by a pump or pressurized container. Such sprays are topical, meaning that they are applied to the surfaces of the body, most commonly the skin, but sometimes to the mucous membranes, such as the throat. A common reason for using an analgesic spray or other topical painkiller, rather than a painkiller taken by mouth, is that topical treatments work directly on the affected area. Topical administration of analgesic drugs such as morphine produces a localized analgesic effect in inflamed skin or mucosal tissue. Transnasal butorphanol spray (a synthetic opioid agonist-antagonist drug) produces rapid pain alleviation in patients undergoing oropharyngeal surgery .Farhex spray (chlorhexidine gluconate 0.12% and benzydamine HCl 0.15%) is a topical agent that exhibits antiseptic, anti-inflammatory, and analgesic effects, it is used for postoperative pain treatment in tonsillectomy. In this study researchers concluded that pain scores in the study group were lower than in the control group at different times .Therefore, we conducted the present study, in which we compared the efficacies of four different medications in spray form including; lidocaine, morphine, ketamine, and normal saline for decreasing post-tonsillectomy pain scores in children.After approval by the Medical Ethics Committee and obtaining written informed consent from the parents of the participants, 120 children, American Society of Anesthesiologists (ASA) I–II  scheduled to undergo elective tonsillectomy in a pediatric hospital in Qazvin, Iran, were enrolled in this double-blind, controlled clinical trial study. They were randomly assigned (using colored cards) to; lidocaine, morphine, ketamine, and normal saline groups.This study was powered on the basis of previous results showing a 50% incidence of post-tonsillectomy pain in the control group. A sample size of 30 patients in each group was calculated to detect a decrease in the incidence of post-tonsillectomy pain down to 15% with α = 0.05 and β = 0.2.Patients with a positive history of asthma, drug allergy to lidocaine or morphine, and consumers of anticonvulsive, analgesic or anti-inflammatory drugs were excluded from this study.For premedication, 0.02 mg/kg midazolam, 1 μg/kg fentanyl and 0.02 mg/kg atropine were administered intravenously to all patients. They also received 5 mg/kg sodium thiopental and 0.5 mg/kg atracurium intravenously for induction of anesthesia and isoflurane (1%) with O2 and N2O (50% – 50%) during the operation for maintenance of the anesthesia. At the end of the operation, one anesthesiologist applied spray forms of lidocaine 10% (2 mg/kg), morphine 0.1% (0.05 mg/kg), ketamine 1% (0.5 mg/kg) or normal saline (8 puffs) in the tonsillar fossa.After deep extubation and transferring the patient to the recovery room, a blinded researcher carried out assessment of postoperative pain by the; face, legs, activity, cry, consolability (FLACC) pain scaling system for one hour at twenty-minute intervals.The FLACC pain scaling system is a behavioral pain assessment scale, which is used to assess pain in children or individuals who are unable to communicate their pain. The scale has 5 criteria and each is assigned a score of; 0, 1 or 2. It is scored between a range of 0–10 with 0; representing no pain, relaxed and comfortable, 1–3; mild discomfort, 4–6; moderate pain, 7–10; severe discomfort or pain or both .In our study, in patients with a FLACC score of 4 or over, we used intravenous meperidine (0.5 mg/kg) for the treatment of postoperative pain.P value less than 0.05 was considered significant.All data was transferred to SPSS-10 software and analyzed statistically with Scheffe test and Dunnett’s T3 test. The clinical trial registration number is: IRCT201104236256N1Table 1).Demographic data  were not significantly different between the four groups (Table 2).Immediately after the patients transfer to the recovery room, there was no significant statistical difference between the FLACC scores of patients in the morphine or the control group, but the difference was significant between the; ketamine-control, lidocaine-control and ketamine-lidocaine groups .In the early postoperative period (time: 0) and at 20, 40 and 60 minutes of recovery time, the FLACC scores in the control group were higher than in the three other groups .Patients in the lidocaine, morphine and ketamine groups did not have a FLACC scale score of 4 or more, and therefore they did not receive meperidine, but intravenous meperidine was administered to twelve patients in the control group (In our study, ketamine, morphine and lidocaine sprays were more effective than a placebo for controlling postoperative pain, but these three medications had a different action onset.At the beginning of the recovery period, lidocaine produced the best analgesia, ketamine led to lesser analgesia than lidocaine, but morphine did not have any analgesic effect at this time.At 20 minutes, lidocaine still produced the best analgesia, but ketamine and morphine produced similar analgesia effects. At 40 minutes, the three medications had the same effect in producing analgesia, but at 60 minutes, morphine and ketamine produced the most significant analgesia.The main limitation of our study was its short duration. In order to increase the accuracy of the study results, we instructed only one researcher to evaluate the FLACC scale scores. We thought that a longer study duration may create a bias due to the assessment of FLACC scores by more than one researcher.Tonsillectomy produces large areas of exposed muscle in the oropharynx, resulting in considerable pain from muscle spasm and irritation of the nerve endings. Also excessive dissection and use of cautery-hemostasis may produce an even larger amount of inflammation and post-operative pain .The most important factors which determine postoperative outcomes are known to be; incisional pain, nausea and vomiting, preoperative anxiety and discomfort from intravenous injection. It has been determined that more than 60% of children who have had an operation exhibit negative behavioral changes in the two weeks after this experience –24. ThusThe development of alternative methods of drug administration has improved the ability of physicians to manage specific problems. Practitioners recognize the rapid onset, relative reliability, and the general lack of patient discomfort when drugs are administered by the transmucosal and transdermal routes. They have administered sedatives, narcotics, and a variety of other medications by; transdermal, sublingual, nasal, rectal, and even tracheal-mucosal routes in a variety of practice settings .Drug absorption through a mucosal surface is generally efficient because the mucosal surfaces are usually rich in blood supply, providing the means for rapid drug transport to the systemic circulation and avoiding, in most cases, degradation by first-pass hepatic metabolism , 26.The oral transmucosal route has been used for many years to provide rapid blood nitrate levels for the treatment of angina pectoris. The fentanyl buccal tablet was developed to take advantage of oral transmucosal absorption for the painless administration of an opioid in a formulation acceptable to children .et al. that investigated the analgesic efficacy of topical tramadol in the control of postoperative pain in children after tonsillectomy, they concluded that topical 5% tramadol with its local anesthetic effect seems to be an easy, safe, and comfortable approach for pain management in children undergoing tonsillectomy (In one study by Akbay llectomy .In another study by Atef and Fawaz concerning the effect of intravenous paracetamol, they concluded that it provides rapid and effective analgesia in tonsillectomy .In several studies about the reduction of post-tonsillectomy pain by local infiltration of bupivacaine, the authors concluded that marcaine can produce effective analgesia , 30.In conclusion, the present study found that, lidocaine spray is suitable for producing early analgesia; however, morphine spray and ketamine spray lead to later analgesia. Therefore, we suggest that future researchers study the analgesic effects of the combination of lidocaine spray with one of the morphine or ketamine sprays, in order to find better methods for producing post-tonsillectomy analgesia in children.


Compared with baseline, patients' serums FSH and LH were decreased, E2 was increased, and SAS score and Kupperman score were decreased. Four patients resumed menstrual cycle after treatment and two resumed during follow-up. No serious adverse events were found in all patients. The results indicate that acupuncture may decrease serums FSH and LH level, raise serum E2 level, relieve anxiety, reduce mental stress, and improve the menopausal symptoms.To investigate the effect of acupuncture on women with premature ovarian failure (POF), prospective consecutive case series study was applied. 31 women with POF were included; all patients were treated with acupuncture once every other day, three times a week for three months. Acupoints, GV 20, GV 24, GB 13, CV 3, CV 4, BL 23, BL 32, ST 25, ST 28, ST 29, ST 36, SP 6, KI 3, and LR 3, were selected. Serums FSH, E Premature ovarian failure (POF) is a common cause of infertility in women and is characterized by amenorrhea before the age of 40. Menopause before the age of 40 is considered to be premature and is nonphysiological disorder. POF, also known as premature menopause or premature ovarian insufficiency, is defined by the presence of menopausal-level serum follicle-stimulating hormone (FSH) in women younger than 40 years –3; the mWomen with POF have been reported to have diminished general and sexual well-being, are less satisfied with their sexual lives, have increased risk for low bone density, earlier onset osteoporosis and fractures, impaired endothelial function, earlier onset of coronary heart disease, and increased cardiovascular mortality and total mortality, and have more anxiety, depression, somatization, sensitivity, hostility, and psychological distress than normal women –7. The Complete Book of Effective Prescriptions for Diseases of Women, said that acupuncture and Chinese Herbal Medicine usually led to satisfying symptom relieving effects in treating some gynaecology disorders, such as endometriosis, infertility, amenorrhea, and menopausal syndrome [2) level and Kupperman scores of perimenopause patients [ in vitro fertilization (IVF) from summarized data of several previously published meta-analysis and lots of clinical trials [POF was not nominally recorded in Traditional Chinese Medicine (TCM). However, according to TCM theory, POF can be pertained to amenorrhea according to the clinical manifestations. As early as in 1237 A.D., the first book about gynaecology and obstetrics of Chinese Medicine,syndrome . In recesyndrome  and womesyndrome –12 and spatients . Acupuncl trials , 15. AltHowever, there is less evidence on the effectiveness of acupuncture for patients with POF. This study, therefore, was designed to assess the feasibility and safety of acupuncture for POF patients on the basis of TCM theory, which includes local and distal acupoints to reinforce liver and kidney, to regulate Qi and Blood, and to adjust mental activity.2, and luteinizing hormone (LH) level, Self-Rating Anxiety Scale (SAS) [This was a prospective consecutive case series study performed at the Hospital of Acupuncture and Moxibustion of China Academy of Chinese Medical Sciences. Participants received 3 sessions of acupuncture treatment, delivered 3 times a week for 3 months. The data from patients include the serums FSH, Ele (SAS) , and Kuple (SAS) , (The SAle (SAS) , 19.) ThThe institute ethics committee approved this treatment protocol for women with POF (Institute of Acupuncture and Moxibustion Beijing (ethics) approval number: 20111117), and all patients signed informed consent before study participation. Acupuncture was performed by one therapist with more than 20 years of experience and Chinese medicine practitioner license from the Ministry of Health of the People's Republic of China. Data coordination, monitoring, analysis, and source verification were done by the researchers who did not take part in the clinical treatment. Present study recruited patients through the following ways: (1) publish recruiting advertisement on the website of the Hospital of Acupuncture and Moxibustion of China Academy of Chinese Medical Sciences; (2) publish recruiting notification on the largest Chinese doctor information website; (3) place recruiting advertisement in registration hall of our hospital. Informed consent was obtained before participant enrollment according to a clinical trial protocol. Recruitment was performed from December 2011 to January 2013, and 31 cases of POF were recruited.Inclusion criteria were as follows: (1) the patients meet the POF diagnosis criteria, mainly with amenorrhea for four months or longer and FSH above 40 IU/L as detected on at least two occasions with at least one month apart –22; (2) Acupuncture Needles. Sterile, silver-handle, prepacked needles  without guide tubes .All acupoints were selected and localized according to WHO Standardized Acupuncture Point Location  Table 1Table 1. For acupuncture at BL 32 , patients should have a strong soreness sensation which radiates to the lower abdomen. For the other points, mild reinforcing-reducing method was used, and all patients should have the “De Qi” sensation (in which patients experience a radiating feeling considered to be indicative of effective needling).The needles were administered for a maximum of 20–30 minutes, and acupuncture treatment was administered once every other day  for three months.2, and LH level, SAS, and Kupperman score, at baseline and after 3-month treatment. Additionally, patients' menstrual cycles were recorded according to individuals' reports during one-month follow-up. Adverse events were tracked for 3 months from initial acceptance of acupuncture treatment to the end of treatment.The data collected including the serums FSH, Et-test was used firstly for serums FSH, E2, and LH level, SAS, and Kupperman score. For the measurement data fitting normal distribution, using Two-Related-Samples Tests. If the measurement data did not fit the normal distribution, using Two-Related-Samples Tests Wilcoxon.All analyses were done with SPSS software package (Version 17.0) using before and after measurements. Baseline characteristics of the patients were analyzed with conventional group descriptive statistics. From December 2011 to May 2013, a total of 40 patients with POF visited the Hospital of Acupuncture and Moxibustion of China Academy of Chinese Medical Sciences seeking for acupuncture treatment. Of these patients, nine were excluded from the study with the following reasons: three patients declined to participate; two had incomplete FSH data; two did not meet inclusion criteria; two did not complete the whole session of treatment. Of these 31 patients, 25 had not been treated by acupuncture in the past, and six had been treated by acupuncture at least one month ago. And in the six, there were four received acupuncture treatment for cervical spondylosis, and two received acupuncture treatment for menstrual problem.The baseline characteristics of the participants are shown in Z = 4.68, P = 0.001).Changes in mean serum FSH level from baseline to 3 months after final acupuncture treatment session are presented in t = 5.519, P = 0.001).Changes in mean serum LH level from baseline to 3 months after the last time acupuncture treatment session are presented in 2 level from baseline to 3 months after final acupuncture session are presented in 2 level at the end of treatment .Changes in mean serum EZ = 4.82, P = 0.000).Z = 4.71, P = 0.000).After 3-month treatment, six patients had improvement on menstruation . Four of them had menstruation after treatment, and two of them experienced menstruation during the one-month follow-up. Of the 6 patients who regained menstruation, 2 patients regained normal color, duration, and volume of period, and 4 patients had decreased menstrual flow but with normal color and duration as compared with normal menstrual bleeding.During the 3-month treatment, two adverse events were reported by 2 patients . No serious adverse events were documented.Although POF was not nominally recorded in TCM, its clinical manifestations can be classified into amenorrhea according to TCM theory. The TCM etiology of amenorrhea includes insufficient transformation of blood of the spleen and stomach, severe consumption of yin blood and exhaustion of blood source, and blockage of blood stasis in the meridians and vessels due to retention of pathogenic factors in the uterus. In this study, local and distal acupoints with functions of reinforcing liver and kidney, regulating Qi and blood, and adjusting mental activity were selected according to the amenorrhea etiology of TCM theory.2, and LH level and improve patients' SAS score and Kupperman score. The serum FSH level dropped to  48 ± 16.6 IU/L from baseline to the end of treatment (P = 0.001), the serum E2 level rose to  68.24 ± 36.15 pmol/L (P = 0.001), and the serum LH level dropped to  17.01 ± 11.66 (P = 0.001). The changes of hormones produced by acupuncture in present study were similar to the previous investigation using EA [2, and LH level may partially explain the effects of acupuncture in treating POF, which is also observed in acupuncture improving other gynecological disorders [The present results indicate that the acupuncture treatment can adjust patients' serums FSH, Eisorders .Four patients regained menstrual cycle after treatment and two during one-month follow-up period of this study. Such result of present study is similar to the gaining of menstruation in a top athlete reported in a Japanese acupuncture study .P = 0.000 as compared with baseline), and Kupperman score decreased to 12 ± 2 (P = 0.000 as compared with baseline). The change of SAS and Kupperman score indicated that acupuncture may relieve anxiety, reduce mental stress, and improve menopausal symptoms .Patients' psychological comorbidities, signs, and symptoms were objectively measured with standard questionnaires by SAS and Kupperman score. The SAS score decreased to 41 ± 7  was not fully recorded, we could not compare those two acupuncture regimens. This is a methodological drawback of present study. Thus, the detailed relevant information about previous treatment of participants should be fully and meticulously recorded in future study. Meanwhile, in order to increase the objectivity and fairness of observational study, inclusion and exclusion criteria of future study should be stricter. Excluding those patients who have had other treatments may reduce confounding factors.Commonly used acupuncture formulas for amenorrhea in China normally include acupoints with functions of reinforcing liver and kidney and regulating Qi and blood. Compared to the commonly used formulas, our acupuncture regimen added acupoints for adjusting mental activity. This may partially explain the different therapeutic effects between the two patients' previous formula and ours.2, and LH level in this study were most likely due to acupuncture effects, those serum hormones' levels did still not reach the normal level after treatment. To test the therapeutic effectiveness of acupuncture, further randomized control trials are needed.Although the significant changes of serums FSH, E2 level, relieve anxiety, reduce mental stress, and improve the menopausal symptoms. No serious side effects were found.The present results showed the feasibility and safety of acupuncture for the treatment of POF in China. These findings suggest that acupuncture may decrease serums FSH and LH level, raise serum E


Objective. Elderly patients are becoming an increasingly larger proportion of our population, and there is a paucity of data regarding the epidemiology of geriatric patients refusing transport. Treatment refusal rates range from 5% to 15% in many studies. This study sought to test the hypothesis that geriatric patients constituted an increasing proportion of those persons refusing prehospital transport. Methods. This study was a retrospective analysis of data from a query of a large urban EMS service. Results. There were a total of 22,347 adult transport refusals recorded during the 16-month study period. Multivariate logistic regression incorporating covariates for sex, race, season, chief complaint, metropolitan region, and whether any treatment occurred prior to transport refusal confirmed the increasing likelihood of Period 2 patients being geriatric, as compared with Period 1 . Conclusion. This data shows that despite controlling for these covariates, patients refusing transport in the second period of this study were nearly 25% more likely to be geriatric as compared to those in the initial 8 months of the study. Emergency medical services (EMSs) are the system that is responsible for the prehospital treatment and transportation. When EMS is activated, they appropriately respond by arriving to give on the scene care. Of course, patients then have the right to receiving treatment and transportation or refuse one or both, against the advice of the treating paramedic (AMA). Treatment refusal rates range from 5% and 15%, in many studies . RefusalDespite an increased emphasis on geriatric care, the health status of this age range is still meager. Elderly patients are becoming an increasingly larger proportion of our population, and there is a paucity of data regarding the epidemiology of geriatric patients refusing transport. This would be an alarming trend if found and would then require further study to look at the etiology of the refusal. This study sought to test the hypothesis that geriatric patients constituted an increasing proportion of those persons refusing prehospital transport.This study was a retrospective analysis of data from a query of a large urban EMS service associated with the Oklahoma City, OK, and Tulsa, OK, metropolitan areas. The study includes all EMS interactions from January 1, 2010, to May 31, 2011, with patients who were at least 18 years old. There were no exclusions for gender, race, or diagnoses. The data includes EMS vehicle region (Eastern or Western), month and year of EMS interaction, response outcome , chief complaint, gender, age in years, and race. No patient identifiers such as encounter number, medical record number, or name were included.P was set at 0.05 for all analyses and 95% confidence intervals (CIs) were calculated for odds ratios (ORs).All adult transport refusals over 16 months were included, with the study timeline of 16 months divided into the first 8 months (Period 1) and the second 8 months (Period 2). Periods 1 and 2 patients were assessed with univariate categorical analysis for proportions with chi-square testing. Next, multivariate logistic regression was used to determine association between the study period and geriatric status (age 65 or older), after adjustment for covariates such as sex, chief complaint, metropolitan region (of the two areas served by the study EMS service), race, season, and whether any treatment occurred prior to transport refusal. Analyses were conducted with STATA 11 MP ; P < .001) with respect to proportions of geriatric patients . Multivariate logistic regression incorporating covariates for sex, race, season, chief complaint, metropolitan region, and whether any treatment occurred prior to transport refusal confirmed the increasing likelihood of Period 2 patients being geriatric, as compared with Period 1 . P < .001).There were a total of 22,347 adult transport refusals recorded during the 16-month study period. Total refusals of 10,622 (48.0%) versus 11,725 (52.0%) occurred during Period 1 and Period 2, respectively. Of the total transport refusals 4,723 (21.1%) were ≥65 years old . Patient characteristics of transport refusals are presented in Of the 22,347 transport refusals, no treatment was given before transport refusal in 19,552 instances . Treatment was given before refusal in the remaining 2,795 instances. There was no significance found for the presence of treatment on transport refusal rates .Prior anecdotal evidence suggests an increasing prevalence of geriatric patients refusing EMS transport –3. The d


Echinococcus multilocularis infection within fox populations in a large area in France. The parasite is much more widely distributed than hitherto thought, spreading west, with a much higher prevalence than previously reported. The parasite also is present in the large conurbation of Paris.During 2005–2010, we investigated  Echinococcus multilocularis is the causative agent of the parasitic zoonosis alveolar echinococcosis. The adult stage of this cestode is found mostly in the digestive tract of the red fox (Vulpes vulpes) .During 2005–2010 (time span needed to cover the study area) and during the months more favorable for infection ; that laboratory also confirmed any unrecognized specimens. For time- and cost-effectiveness during the analysis, we used the segmental and sedimentation counting technique , which represents a mean of 1.56 foxes per 100 km2 (± SD 0.57). For 4 departments, , full sampling could not be completed because of technical and/or administrative reasons. Urban areas, such as departments 93, 95, and 91, also were undersampled because of human population density and high urbanization, all factors preventing easy fox sampling.A total of 3,307 foxes were collected . Eighty-E. multilocularis in foxes in 35 departments  (Our study confirms the presence of  and 77)  amountinWe believe that the public needs to be proactively informed and protected, including through awareness initiatives among urban residents and, in specific areas (


HLA and PTPN22, account for less than half of the genetic susceptibility to disease; therefore, additional genetic factors have yet to be identified. The purpose of this study was to perform a systematic search of the genome to identify novel susceptibility loci for JIA.Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease of childhood. Two well-established genetic factors known to contribute to JIA susceptibility, A genome-wide association study using Affymetrix GeneChip 100K arrays was performed in a discovery cohort (279 cases and 184 controls). Single-nucleotide polymorphisms (SNPs) showing the most significant differences between cases and controls were then genotyped in a validation sample of cases (n = 321) and controls, combined with control data from the 1958 UK birth cohort . In one region in which association was confirmed, fine-mapping was performed .HLA region, while the second strongest association was with a SNP within the VTCN1 gene. Fine-mapping of that gene was performed, and 10 SNPs were found to be associated with JIA.Of the 112 SNPs that were significantly associated with JIA in the discovery cohort, 6 SNPs were associated with JIA in the independent validation cohort. The most strongly associated SNP mapped to the VTCN1 gene defined an additional susceptibility locus for JIA and implicates a novel pathway in the pathogenesis of this chronic disease of childhood.This study is the first to successfully apply a SNP-based genome-wide association approach to the investigation of JIA. The replicated association with markers in the  Juvenile idiopathic arthritis (JIA) is a generic term for arthritis that persists for more than 6 weeks and has an onset before the age of 16 years. It is the most common chronic rheumatic disease of childhood, with a prevalence of 1 in 1,000 persons. The clinical phenotype of JIA is complex. In the current International League of Associations for Rheumatology (ILAR) classification system, the disease is divided into 7 clinical subgroups, and outcome varies according to phenotype  were genotyped in the remaining JIA cases  and in an independent cohort of population controls. Genotype frequencies in a further control population were available from public databases, and these data were combined with the data from the latter group of controls . Genotype frequencies were compared between the validation cases and controls. For one region where association was confirmed in this independent cohort, fine-mapping was performed to refine the region of association.A multistage case–control association study was undertaken. In the first stage, genotype frequencies in a subset of JIA cases were compared with those in population controls (discovery cohort), using an Affymetrix GeneChip 100K array . SNPs showing evidence of association in that dataset , extended oligoarthritis (n = 80), rheumatoid factor (RF)–negative polyarthritis (n = 57), and RF-positive polyarthritis (n = 9). The controls consisted of 184 subjects with no history of inflammatory arthritis; 48% of them were female.The 321 JIA cases in the validation set had a mean age at onset of 6.3 years, and 79% were female. JIA subtypes were as follows: persistent oligoarthritis (n = 74), extended oligoarthritis (n = 67), RF-negative polyarthritis (n = 120), and RF-positive polyarthritis (n = 60). Controls comprised 544 individuals with no history of inflammatory arthritis, as well as up to 1,480 individuals from the 1958 UK birth cohort.The 654 JIA cases in the fine-mapping cohort had a mean age at onset of 6.9 years, and 68% were female. This cohort represents a combined set of all ILAR JIA subgroups, as follows: persistent oligoarthritis (n = 194), extended oligoarthritis (n = 86), RF-negative polyarthritis (n = 138), RF-positive polyarthritis (n = 35), systemic JIA (n = 115), enthesitis-related JIA (n = 28), psoriatic JIA (n = 51), and unclassified (n = 7). Controls comprised 367 individuals with no history of inflammatory arthritis, as well as up to 1,480 individuals from the 1958 UK birth cohort. This is not an independent data set, and some of the cases and controls in this set were included in the discovery and validation cohorts.http://www.affymetrix.com). Samples with a <93% genotype call rate were dropped from the analysis. SNPs that had a minor allele frequency of <5%, that failed to genotype in >5% of samples, or that had a Hardy-Weinberg equilibrium P value of <0.0001 in controls were excluded from the analysis.The samples in the discovery cohort (n = 463) were processed according to the instructions provided in the Affymetrix GeneChip Human Mapping 100K Assay Manual .SNPs showing evidence of an association with JIA in the discovery cohort at http://www.HapMap.org) in the CEPH population  were used to determine pairwise tagging SNPs, using the Tagger software (online at http://www.broad.mit.edu/tools/software.html). The fine-mapping cohort was genotyped using Sequenom MassArray genotyping technology, as in the validation cohort.The genotype data from the HapMap project (online at http://pngu.mgh.harvard.edu/~purcell/plink/) software. The Armitage test for trend was used to test for association. Stratification by ILAR subtype for associated VTCN1 SNPs was also performed.Genotype and allele frequencies were compared between cases and controls using Stata version 9 SE  and Plink . A further 1,883 SNPs were excluded because of failure to genotype in >5% of samples, and 224 SNPs were excluded because of significant deviation from Hardy-Weinberg equilibrium. A total of 88,682 autosomal SNPs were therefore analyzed for association with JIA, and 84,235 of these SNPs (95%) had >98% complete genotype data.P ≤ 0.001, and these SNPs were selected for genotyping in the validation cohort.  One SNP (rs2187684) was situated in the HLA region on chromosome 6p21. Two SNPs that mapped to the PTPN22 region, which were almost perfectly correlated with each other but which showed only modest correlation with the known PTPN22 functional variant , were weakly associated with JIA (P = 0.015 for rs1217407 and P = 0.014 for rs1217380).One hundred twelve autosomal SNPs were associated with JIA at P > 0.001). Of these 102 SNPs, 47 had been directly genotyped in the 1958 UK birth cohort controls, whereas imputed data were available for the remaining 55 SNPs , while the second strongest association was with a SNP that mapped to the VTCN1 gene, rs2358820. The VTCN1 gene was therefore investigated further.Of the 102 SNPs tested, 11 were associated with JIA at VTCN1 gene, but only 27 were required to tag the region in order to provide 100% coverage of all nongenotyped SNPs at an r2 level of >0.8. Of these 27 SNPs selected for genotyping, assays could not be designed for 2. The 25 remaining SNPs captured 96% of the known variation across the gene. For these 25 SNPs, 7 had been genotyped directly in the 1958 UK birth cohort controls, whereas imputed data were available for the remaining 18 SNPs  lay within intron 1, rs2051047 lay within intron 3, rs2358817 lay within intron 4, and rs6673837 lay in the 3′ region of the gene . However, this finding should be viewed with caution, since the confidence score for the imputed genotypes in the control population was <95%, suggesting that this may have introduced some bias.There was only moderate linkage disequilibrium across the gene as a whole, but the associated SNPs appeared to map to 3 regions within the gene. The SNPs showing the strongest association (rs10923223 and rs12046117) are situated in intron 1 and demonstrated moderate linkage disequilibrium with each other (r2 = 0.83).A second group of SNPs in intron 1 showed modest evidence of association, in which the major allele was associated with disease. SNPs rs2358817 and rs2051047 showed stronger evidence of association and mapped to introns 3 and 4, respectively. They demonstrated a strong correlation with each other and probably represent a single effect This analysis was performed in all JIA subtypes. Reanalysis using only the JIA subtypes included in the original discovery stage did not alter the results. Comparison of genotype counts for VTCN1 gene.In this study, we used a whole-genome association approach to identify novel JIA susceptibility loci, and for one of these regions, we performed fine-mapping analysis to refine the extent of association. We identified associations between JIA and polymorphisms mapping to the The possibility that this finding could represent a false-positive result requires consideration. This could arise as a result of population stratification. However, the Wellcome Trust Case Control Consortium study previously established that there was very little evidence of this across the UK . They foP < 0.001), accepting that the majority of SNPs showing association would be false-positives and would therefore fail to be replicated in independent cohorts. We performed no corrections for multiple testing, but instead, took the approach of validation of any significant results in independent cohorts. Using this approach, strong evidence for an association with HLA was detected, serving as a proof-of-concept that established JIA susceptibility factors could be identified.We used a modest threshold for significance . Furthermore, the Affymetrix 100K GeneChip Array is only estimated to capture ∼35% of known variation across the genome, and it is therefore likely that a number of JIA susceptibility loci remain to be identified. Nonetheless, there have been notable successes in identifying genes that underlie complex diseases using a staged approach in modest sample sizes and with the same SNP density as in this study. Examples include the complement factor H gene, which has been widely confirmed as a susceptibility gene for age-related macular degeneration ; nonetheless, this is the most comprehensive genome-wide association study of JIA to date. The sample size used in the discovery cohort was selected based on its power to detect effect sizes equivalent to the confirmed JIA susceptibility causal variant within the VTCN1 gene with JIA was detected and replicated. The gene is an interesting candidate for this autoimmune disease, since it is part of a recently identified inhibitory pathway that is important in the prevention of detrimental inflammatory responses, such as the autoimmune response seen in the joints of children with JIA. VTCN1, which is also known as B7-H4, is expressed on activated T cells, B cells, monocytes, and dendritic cells (VTCN1 is the B and T lymphocyte attenuator, an inhibitory receptor on T cells. Therefore, it may be involved in the attenuation of inflammatory responses in peripheral tissue (Despite these limitations, association of the ic cells , and evil tissue . All 10 VTCN1 gene. Although confirmation of this association in different populations will be important, the identification of VTCN1 as a JIA susceptibility locus represents a novel pathway by which to explore more about the cause of the disease. In turn, this may lead to novel therapies for this disabling, chronic arthritis of childhood.In summary, we identified 6 regions where there is replicated evidence of association with susceptibility to JIA, including the Dr. Hinks had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Study design. Hinks, Barton, Kennedy, John, Worthington, Thomson.Acquisition of data. Hinks, Eyre, Bowes, Cargill, Wang, Kennedy, Thomson.Analysis and interpretation of data. Hinks, Barton, Shephard, Eyre, Cargill, Wang, Kennedy, John, Worthington, Thomson.Manuscript preparation. Hinks, Barton, Ke, Kennedy, John, Thomson.Statistical analysis. Hinks, Shephard, Cargill, Ke, John.


We started diagnosing Bundle Branch Block about 100 years ago on dog models .Today, we have conventional criteria for diagnosing LBBB, including QRS duration>120 msec, QS or rS in lead V1, Monophasic R wave with no Q wave in lead V6 and I3, ACC/AHA/HRS added notched R wave in lead I,aVL, V5, and V6, and occasional RS pattern in V5 and V6 (In case rate dependent LBBB develops, you can see the disappearance of the q wave in V6, then initial slurring of R wave and delayed increased intrinsicoid deflection. More complete LBBB causes notched plateau after initial peaked R wave .LBB has anterior fascicle, posterior fascicle, and sometimes a septal fascicle .Blocking the left bundle may cause septal force to disappear; therefore, no initial R wave can be detected in V1 or Q wave in I, V5, and V6, but that is not always the case (Sometimes, septal MI causes initial Q in the lateral leads and initial R wave in V1. Also, Grants and Doge found initial septal force in 40% of their cases with LBBB .Accordingly, initial septal force should not be considered as a diagnostic criterion for LBBB. Widening of QRS may occur in LBBB as well as many other conditions, such as LVH, RVH, and IVCD. Sometimes, LBBB also causes minimally increased width in QRS named incomplete LBBB.Wilson compared dogs and humans and suggested 120 msec. as the cut-off point for diagnosing LBB .They showed that when LBB is blocked, 40 msec. are required for septal depolarization, then 50 msec to reach the posterolateral wall, and finally 50 msec to complete posterolateral wall activations. Moreover, they suggested 140 msec. for males and 130 msec. for females for diagnosis of LBBB. The most consistent finding in LBBB patients seems to be mid QRS notching or slurring which is best seen in I, aVl, V5, and V6 (This mid QRS notching shows two vectors that are in the relatively same direction but one is minimally delayed. The first vector shows depolarization of endocardium of the left ventricle, while the second one seem to show depolarization of epicardium of the posterolateral wall .Diagnosis of LBBB using ECG may be accompanied by some errors as high as 30 % of cases. Therefore, LBBB is better to be confirmed through intracardiac mapping techniques. However, only a limited number of studies have investigated the issue. Josephson nicely mapped about 40 patients and his consistent finding was nearly 40-msec delay between RV endocardium and LV endocardium in LBBB patients .Furthermore, Vassallo et al. showed that only ⅔ of the LBBB patient diagnosed on ECG had more than 40 msec. trans-septal activation on intracardiac mapping; thus, the accuracy of the routine criteria for diagnosis of LBBB was only 70% .In 2004, Auricchio performed 3-dimensional contact and noncontact mapping for LBBB patient and his results showed the same accuracy as the conventional ECG criteria .All these lead us to wrong diagnosis of LBBB in ⅓ of our patients and this is the exact number of non-responders in CRT patients where diagnosis of LBBB is a pre- requisites .Considering what was mentioned above, new criteria for LBBB are needed and the best suggestions include:QRS more than 140 msec for males and 130 msec for femalesNotching of peak QRS in at least two leads from I,avL, V1, V2, V5, and V6QS or rS in lead V1 .This new definition can be used for picking up the cases of CRT implantation and the patients follow up may solve the mystery of non-responders in CRT patients.


Prehypertension is common in China and is associated with an increased risk of cardiovascular disease. The present study estimated the current prevalence of prehypertension and its association with clustering of other modifiable cardiovascular risk factors (CRFs) among adults in suburban Beijing.A cross-sectional survey of a representative sample of 19 003 suburban adults aged 18 to 76 years was carried out in 2007. Questionnaire data and information on blood pressure, anthropometric characteristics, and laboratory measurements were collected.The age-standardized prevalence of prehypertension was 35.7% (38.2% in men and 31.8% in women) among adults in suburban Beijing. The prevalence of overweight/obesity, diabetes, dyslipidemia, and physical inactivity was higher in participants with prehypertension  as compared with normotensive participants , and in participants with hypertension as compared with those with prehypertension. Overall, 85.3%, 49.8%, and 17.8% of prehypertensive men had 1 or more, 2 or more, and 3 or more CRFs . These proportions were higher than those in normotensive men  and lower than those in men with hypertension . Similar results were found when women with prehypertension were compared with women who were normotensive or hypertensive.A high prevalence of prehypertension and clustering of other modifiable CRFs are common among prehypertensive adults in suburban Beijing. More-effective population-based lifestyle modifications are required to prevent progression to hypertension and reduce the increasing burden of cardiovascular disease in China. This category was suggested due to evidence indicating that overall cardiovascular risk and end-organ damage were already elevated in individuals with prehypertension, when compared with those with a BP less than 120/80 mm Hg.2 JNC-7 recommended close follow-up and possible intervention for individuals with prehypertension, which frequently progresses to actual clinical hypertension over several years,3 because, in addition to hypertension, prehypertension was found to have a strong, continuous, and graded relationship with the risk of major cardiovascular events.1,4Prehypertension is a category between normotension and hypertension that was proposed by the Seventh Report of the Joint National Commission on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) in 20035 Three independent cross-sectional surveys of residents aged 35 to 74 years in the same rural Chinese area in 1991, 2002, and 2007 showed a prehypertension prevalence of 33.8%, 61.5%, and 54.6%, respectively.6 Several recent studies in China also indicate that prehypertension is common6,7 and that it is associated with an increased risk of cardiovascular disease.4 However, the association of prehypertension with clustering of other modifiable cardiovascular risk factors (CRFs) among Chinese adults has been rarely reported, particularly in more urbanized areas. The present study estimated the current prevalence of prehypertension among suburban adults in Beijing and evaluated the association of prehypertension with clustering of CRFs to provide a context for policy planners and health education programs.With the recent rapid economic growth and urbanization of China, the prevalences of prehypertension and hypertension have significantly increased.8In 2007, a cross-sectional population survey of CRFs was carried out among adults in suburban Beijing. In brief, 3-stage stratified sampling was used to select a representative sample of the general population. In stage 1, 5 towns were randomly selected. In the second stage of sampling, 30 villages/neighborhoods were randomly selected from 76 villages/neighborhoods. In the final stage, individuals were randomly chosen from the selected townships/neighborhoods.Approximately 2 531 000 suburban residents lived in Beijing in 2007, 225 416 lived in the 5 towns we selected, and 98 512 lived in the 30 villages/neighborhoods we selected. A total of 20 655 people aged 18 to 76 years were randomly selected from the 30 primary sampling units (villages or neighborhoods) and invited to participate in the study. Of these, 968 declined to participate, 514 did not complete the study, and 180 had incomplete information. Therefore, 19 003 people (7148 men and 11 855 women) completed the survey and examinations and were eligible to be included in the analysis. The overall response rate was 92.0%. The age and sex distribution of the sample was similar to that of the total population of Beijing.Institutional review boards or ethics committees at all participating institutes approved the study protocol. Written informed consent was obtained from each participant before data collection. Participants with untreated conditions identified during the examination were referred to a primary health care provider.Data collection was conducted in examination centers at local health stations or in community clinics in the participant’s residential area. During the study visit, trained research staff administered a standardized questionnaire to obtain each subject’s demographic information, medical history, and family history, and to ascertain physical activity, alcohol use, dietary habits, and tobacco use.9 Quality control measures for BP included repeated measures, supervisor observation of data collection, and a sphygmomanometer maintenance program. Body weight and height were measured twice during the interview. Weight was measured in light indoor clothing without shoes on electronic scales placed on a firm, level surface to the nearest 0.1 kg. Height was measured without shoes with a wall-mounted stadiometer to the nearest 0.1 cm.Three consecutive measurements of BP (first and fifth Korotkoff sounds) were taken on the right arm using a calibrated mercury sphygmomanometer after the participant had been resting in a seated position for at least 5 minutes; the average of these 3 measurements was used in the analysis. The room temperature was maintained at 22°C to minimize the effects of temperature and weather. Participants were advised to avoid cigarette smoking, alcohol, caffeinated beverages, and exercise for at least 30 minutes before the measurement. One of 4 cuff sizes  was chosen on the basis of the participant’s arm circumference.10 Lipid measurements were standardized according to the criteria of the Centers for Disease Control and Prevention–National Heart, Lung, and Blood Institute Lipid Standardization Program.11 For participants with a triglyceride level less than 4.5 mmol/L, low-density lipoprotein (LDL) cholesterol levels were calculated by using the Friedewald equation (LDL cholesterol = TC − HDL cholesterol − TG/5).12Venous blood samples were obtained after an overnight fast and analyzed for serum lipids and plasma glucose. Participants who had not completed an overnight fast were asked to visit centers later, when their duration of fasting was longer than 10 hours. Blood samples were centrifuged at 3000 rpm for 30 minutes at 4°C, and plasma was stored at −70°C until laboratory assay. Plasma glucose and lipid levels were measured using a modified hexokinase enzymatic method . Concentrations of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were analyzed enzymatically with commercially available reagents.2 or higher.13Body mass index (BMI) was calculated as body weight (in kilograms) divided by height (in meters) squared. Overweight/obesity was defined as a BMI of 25 kg/m14Diabetes was defined as a fasting plasma glucose (FPG) level of 7.0 mmol/L or higher or self-reported current treatment with antidiabetes medication .1 recommendations. Normal BP was defined as an SBP less than 120 mm Hg and a DBP less than 80 mm Hg without use of antihypertensive medication; prehypertension as an SBP of 120 to 139 mm Hg or a DBP of 80 to 89 mm Hg without use of antihypertensive medication; and hypertension as an SBP of 140 mm Hg or higher, a DBP of 90 mm Hg or higher, or use of antihypertensive medication in the previous 2 weeks.BP was classified according to JNC711Dyslipidemia was defined as self-reported current treatment with cholesterol-lowering medication or having 1 or more of the following: a TC level of 5.2 mmol/L or higher, a TG level of 1.7 mmol/L or higher, an HDL cholesterol level less than 1.0 mmol/L, or an LDL cholesterol level of 3.4 mmol/L or higher.15Participants who answered affirmatively to the question, “Do you smoke cigarettes now?”, and had smoked for 6 months or longer during their lifetime were classified as current smokers.A participant was classified as physically active if they took part in an exercise activity for at least 30 minutes an occasion at least 3 times per week; all other participants were classified as physically inactive.t test and analysis of variance for independent samples, and prevalences for categorical variables were compared using the chi-square test and the chi-square test for trend for proportions. Odds ratios (ORs) and 95% confidence intervals (CIs)—adjusted for sex, age, family history of hypertension, and other potential confounders—were calculated by multivariate logistic regression using PROC SURVEYLOGISTIC to estimate the association between prehypertension and CRFs. All P values are 2-sided, and statistical significance was defined as P < 0.05.Data were analyzed using SAS , allowing for the complex survey design used for calculating the estimates. Weights were calculated using data from the 2000 China Population Census. Descriptive statistics were computed for all variables, including means for continuous variables, standard deviation (SD) of the mean, frequencies, and standard errors (SEs) for categorical variables. SEs were calculated using a technique appropriate to the complex survey design, which used strata to account for each town and village/street district. PROC SURVEYFREQ was used to estimate the prevalence of prehypertension and CRFs overall and within subgroups. Differences in continuous variables were tested using the P < 0.05 for all tests). The prevalence of prehypertension increased in age groups younger than 50 years and decreased in groups aged 50 years or older in both sexes .Approximately 5834, 6784, and 6385 participants were normotensive, prehypertensive, and hypertensive, respectively. As shown in Table P < 0.01), and individuals with prehypertension were more likely to be male and older than normotensive adults . BMI, FPG, TC, TG, LDL cholesterol, and the prevalence of overweight/obesity, diabetes, dyslipidemia, and physical inactivity were all significantly higher in hypertensive subjects than in prehypertensive subjects, and in prehypertensive subjects as compared with normotensive subjects . Conversely, HDL cholesterol was significantly lower in hypertensive subjects than in prehypertensive subjects, and in prehypertensive subjects as compared with normotensive subjects (P < 0.05). Smoking status did not significantly differ among the 3 groups (P > 0.05).The demographic and metabolic characteristics of the study participants stratified by BP category are shown in Table P < 0.05 for all tests), as was the case for prehypertensive adults as compared with hypertensive adults . Participants with prehypertension were more likely than normotensive participants to have 2 CRFs and 3 or more CRFs , as was the case for hypertensive adults as compared with prehypertensive adults .As shown in the P < 0.01 for all tests), and in hypertensive men as compared with prehypertensive men . The prevalence of 1 or more, 2 or more, and 3 or more CRFs was also higher in prehypertensive women  than in normotensive women , and in hypertensive women as compared with prehypertensive women . The prevalence of 1 or more, 2 or more, and 3 or more CRFs also increased in groups younger than 60 years and decreased in groups aged 60 years or older in both sexes and all BP categories .The age-standardized prevalence rates of 1 or more, 2 or more, and 3 or more major CRFs among participants stratified by BP category are shown in Table The present study estimated the current prevalence of prehypertension and its association with clustering of other modifiable CRFs among adults in suburban Beijing, China. The strengths of the present study include its enrollment of a large, representative sample of suburban dwellers in Beijing. In addition, a high response rate was achieved, standard protocols and instruments were used, training and certification requirements for data collection were strict, and a vigorous quality assurance program ensured that high-quality data were collected, all of which allowed for calculation of representative estimates.16 31% in the United States,17 31.6% in Korea,18 32% in Japan,19 35.8% in Taiwan,20 and 40% in the Ashanti region of Ghana).21 The results of these studies reveal that the prevalence of prehypertension is high in both developed and developing countries, and that prevalence in developing countries is rapidly approaching that in developed countries. Clearly, urgent attention should be paid to preventing prehypertension, particularly in developing countries experiencing changes in lifestyle. Furthermore, in the present study, the prevalence of prehypertension increased in groups younger than 50 years and decreased in those aged 50 years or older in both sexes, perhaps because most individuals in the older age groups had progressed to actual clinical hypertension. This phenomenon was also noted in a study of Americans.17Prehypertension affected about one third (35.7%) of suburban adults in Beijing, and the prevalence was higher in men than in women in all age categories, which is generally consistent with other published studies (30% in Jamaica,22 Participants with prehypertension in this study had significantly higher BMI, FPG, TG, TC, and LDL cholesterol, lower HDL cholesterol, and higher prevalences of other modifiable CRFs, including overweight/obesity, diabetes, hyperlipidemia, and physical inactivity, as compared with normotensive participants, which was consistent with several other studies.23–25 Individuals with prehypertension have an increased risk of developing hypertension and experience adverse cardiovascular consequences. Prehypertension frequently progresses to actual clinical hypertension and increases cardiovascular risk.26 On the basis of the JNC-7, prehypertension requires attention and health-promoting lifestyle modifications to prevent such progression.Prehypertension is often associated with other CRFs, such as obesity, diabetes mellitus, dyslipidemia, and phenotypes of metabolic syndrome.Our findings also showed that participants with prehypertension were more likely to have more CRFs than participants with normal BP, which indicates that the prevalence and risk of having more CRFs increases with BP. Furthermore, we found a dose-response relationship between the number of CRFs and prehypertension. That is to say, a higher number of CRFs was associated with an increased OR for prehypertension as compared with normotensive participants. These findings suggest that prehypertension results from the accumulation of CRFs.4This research is limited by its reliance on estimates derived from a cross-sectional study, which did not allow quantification of the importance of prehypertension in the clustering of CRFs. This limits our ability to establish causal relationships between prehypertension and other modifiable CRFs. However, previous studies have demonstrated the importance of prehypertension to clustering of CRFs and the development of cardiovascular disease in Chinese adults.In conclusion, prehypertension and hypertension were highly prevalent in suburban Beijing, as were clusters of other modifiable CRFs. These findings suggest that prevention of prehypertension, hypertension, and cardiovascular disease requires not only BP control, but also management of other CRFs, and that decisions on antihypertensive treatment should be made after considering overall cardiovascular risk rather than BP values alone. More-effective population-based lifestyle modifications such as smoking cessation, improved diet, increased physical activity, and increased public awareness could be the most effective interventions for individuals with prehypertension in China, especially for those living in the most industrialized and urbanized areas.


The prevalence of rotator cuff tears increases with age and several studies have shown that diabetes is associated with symptomatic shoulder pathologies. Aim of our research was to evaluate the prevalence of shoulder lesions in a population of asymptomatic elderly subjects, normal and with non insulin - dependent diabetes mellitus.The study was performed on 48 subjects with diabetes and 32 controls , who did not complain shoulder pain or dysfunction. An ultrasound examination was performed on both shoulders according to a standard protocol, utilizing multiplanar scans.vs 5.2 ± 0.7 mm, p < 0.001; Biceps Tendon: 4 ± 0.8 mm vs 3.2 ± 0.4 mm, p < 0.001). Sonographic appearances of degenerative features in the rotator cuff and biceps were more frequently observed in diabetics .Tendons thickness was greater in diabetics than in controls (Supraspinatus Tendon: 6.2 ± 0.09 mm vs 2 (3.1%), p < 0.03; Major tears: 15 (15.8%) vs 5 (7.8%), p = ns), but not in the long head of Biceps. More effusions in subacromial bursa were observed in diabetics  as well as tenosynovitis in biceps tendon .Subjects with diabetes exhibited more tears in the Supraspinatus Tendon (Minor tears: 15 (15.8%) In both groups, pathological findings were prevalent on the dominant side, but no difference related to duration of diabetes was found.Our results suggest that age - related rotator cuff tendon degenerative changes are more common in diabetics.Ultrasound is an useful tool for discovering in pre - symptomatic stages the subjects that may undergo shoulder symptomatic pathologies. Several sonographic studies, performed in the general population, show that the prevalence of rotator cuff tears increases with age. The prevalence of tears ranges widely, roughly from 0 - 15% in the 60 s to 30 - 50% in 80 s, these differences being explained by characteristics of subjects enrolled and sonographic criteria by which lesions were identified .Magnetic Resonance Imaging is a more sensitive methodology than ultrasound (US) in detecting pathological changes in asymptomatic shoulders. However, its use for epidemiological purposes is limited by higher costs and lower availability ,11.Moreover, it is well known that diabetes is a strong risk factor for rotator cuff pathologies, as shown by studies performed in symptomatic subjects -22. In aHowever, to our knowledge, there are no studies, which evaluated asymptomatic elderly subjects with diabetes. Therefore, it could be of interest to investigate whether diabetes has an additive effect on age - related tendon degeneration and whether US evaluation of the shoulder in pre - symptomatic stage could be a useful tool for discovering subjects at risk.In addition, it must be considered that the majority of sonographic studies has been focused on supraspinatus tendon tears ,2,5-9, wTherefore, aim of this study was twofold: first, to evaluate the prevalence of sonographic shoulder lesions in asymptomatic elderly subjects, normal and diabetics; second, to describe, beside supraspinatus tears, other abnormalities of anatomical structures of clinical interest which could occur in these subjects.All the subjects enrolled in the study were recruited from the Outpatients Service of the Medicine and Science of Aging Department of Chieti - Pescara University.Inclusion criteria were the following: 1) living independently in the community; 2) age > 65 years; 3) right - handedness; 4) absence of pain or acceptable discomfort in the shoulder joint, spontaneous or during usual activities of daily living; 5) no subjective dysfunction; 6) no history of trauma or surgery of the shoulder joint.Patients with rheumatic disorders, endocrinopathies, malignancies and systemic diseases , treated with steroids or NSAID, were excluded.The local Ethics Committee approved the study design and informed written consent was obtained from all the patients.The study group included 48 subjects with non insulin - dependent diabetes mellitus (NIDDM). The diagnosis of NIDDM was based on American Diabetes Association criteria .The control group was made by 32 subjects, matched for age and sex, but without NIDDM, and selected with the same inclusion/exclusion criteria.The age of onset of diabetes, current therapies and comorbidities were registered.Hypertension was diagnosed when the subjects were taking antihypertensive drugs, Coronary Arterial Disease when they suffered from angina or myocardial infarction and Peripheral Arterial Disease when Ankle Brachial Index was less than 0.90 mmHg.Subjects were also classified according their previous working activities, sports and hobbies. Home and office work was considered as light work; farm, factory and building industry work was considered heavy work.US examination was performed by the same operator (AM), by means of a multi - frequency (5 - 14 MHz) linear array probe. The examiner was not blinded to the clinical status of the subjects.Both shoulders were evaluated, according to a standard protocol, previously described by Papatheodorou et al. .The following tendons were evaluated: Supraspinatus (SST), Infraspinatus (IST), Subscapularis (SBT) and long head of the Biceps (BT). In addition, the subacromial - subdeltoid (SAD) bursa was studied.Maximal SST thickness was measured on a longitudinal view, just in front of the lateral part of the humeral head ; the thiThe presence of dishomogeneous hypo- or hyperechoic thicknening, diffuse or focal, of the tendon, associated with loss of the normal fibrillar pattern and/or irregularity of the tendon margins, was interpreted as sign of degeneration.In addition, but only in BT, which is provided of a synovial sheat, the appearance of an anechoic area around the tendon, associated or not with synovial proliferation, was considered as a sign of tenosynovitis .SST, IST and SBT tears were classified as follows:1) Partial thickness tear: focal hypoechoic discontinuity with irregular margins at the bursal or articular side or located intratendinously. A bursal - side tear produces flattening of the bursal surface, with loss of the superior convexity of the tendon, while an articular - side tear appears as a distinct hypoechoic or mixed hyper - hypoechoic defect of the articular surface, abutting the articular cartilage .2) Full thickness tear: full defect in the tendon from the bursal to the articular margin. Hypoechoic fluid may fill the tear, with loss of the normal outward convexity of the tendon at this site. Moreover, owing to the pressure applied with the transducer, the deltoid muscle can abut against the humeral head .Taken into consideration the distance between the ends of the tendon, tears were divided in small ( < 1 cm), large (more than 1 but less than 3 cm) or massive (> 3 cm).For simplicity sake, we considered a) Minor tears  and b) Major tears (including large full thickness tears and massive ruptures).For BT, a partial tear was reported as a focal hypoechoic discontinuity, with irregular borders, located intratendinously, while the non visualization of the tendon into the bicipital groove, with associated bulbous appearance of the biceps muscle, was reported as complete tear .Involvement of SAD was identified when accumulation of anechoic fluid, with or without hypoechoic swelling of the synovia, appeared within it; it was graded subjectively as normal (distension < 1 mm), slightly increased (1 - 2 mm) or clearly increased (> 2 mm).Data are reported as mean and standard deviation (mean ± SD) for continuous variables, whereas categorical and dichotomous variables are reported as frequencies and percentage. The tendon thickness and the percentage of US abnormalities found in the shoulders of diabetic subjects were compared with that observed in controls. Afterwards, the differences in tendon thickness between dominant and non - dominant side and according to diabetes duration were analyzed.t - test was used to compare continuous variables when the distribution of data was normal; the Wilcoxon's rank sum test was used otherwise. The χ 2 test was used to evaluate associations between categorical data.The significance level was determined at p < 0.05. The two - sample Student's All analyses were done using SAS statistical software, release 8.1.Demographic and clinical characteristics of diabetic and control subjects are presented in Table The subjects did not differ for age, sex and previous working activity. None of the subjects enrolled practised sports or had hobbies involving the use of shoulder joints. Cardiovascular complications , as expected, were observed more frequently in diabetics.The duration of diabetes was less than 10 years (mean 6.8 ± 1.9) in 34 subjects and more than 10 years (mean 14.7 ± 2.2 years) in 14. In all the participants, HbA1c levels were < 8.0 gr/dl.SST and BT thickness was significantly greater in diabetics than in controls both in the dominant and non dominant side Figure ; Table 2In both groups, tears of SST were more frequently observed Figure . The pervs 8/68 (11.7%), p = 0.10; Major tears 6/28 (21.4%) vs 9/68 (13.2%), p = 0.31; 2) BT: Minor tears 1/28 (3.5%) vs 2/68 (2.9%), p = 0.87; Major tears 3/28 (10.7%) vs 2/68 (2.9%), p = 0.11).Subjects with diabetes duration more than 10 years exhibited more SST and BT tears, but the difference was not significant at statistical analysis: 1) SST: Minor tears 7/28 (25%) The prevalence of degenerative abnormalities in rotator cuff tendons and BT was significantly higher in diabetics.Tenosynovitis of the long head of the BT and SAD bursitis were more frequent in diabetics Figure ; Table 2Several studies have shown that the prevalence of rotator cuff tendons tears is increased in elderly subjects, with or without shoulder pain or movement limitation -9. MoreoThe results of our study suggest that, also in asymptomatic subjects, age - related rotator cuff tendon changes are more common in diabetics. This conclusion is supported by the observation of a higher prevalence of tears and of degenerative phenomena in diabetics, as well as by the increased thickness of supraspinatus and biceps tendons, which is due to the abnormal storage of collagen layers in the tissue and, therefore, is itself an expression of degenerative changes .These observations are of clinical relevance, because it has been shown by Yamaguchi et al. ,31, in aBesides tendinopathic degenerative lesions, bursal and peritendinous effusions were observed, which could be an expression of early reactive inflammation to minimal tendon tears, following minor and unrecognized traumatic events -36.Another clinical observation coming from our study is the increased prevalence of pathological findings in the dominant side, that confirms the theory that overuse may have a significant pathogenetic role ,37,38.However, due to the difficulty of getting definite information about working - related lesions, we have not been able to differentiate work - related injuries versus intrinsic diabetes - induced changes in the rotator cuff.No significant correlation was observed with the duration of diabetes. The lack of association may be explained by the difficulty in establishing the age of diabetes onset. Indeed, subjects could have glucose intolerance or mild NIDDM for a significant period of time before the clinical diagnosis of diabetes.From the pathogenetic point of view, it is likely that, in individuals with no history of significant trauma, rotator cuff tears are mainly caused by intrinsic degenerative changes, related to aging, vascular factors or mechanical impingement ,36,39,40The biochemical mechanisms of tendon degeneration are similar in ageing and diabetes.The most important abnormality is the non - enzymatic glycosylation of collagen with advanced glycation end products (AGEs) formation -43.The spontaneous condensation of glucose and metabolic intermediates  with free aminogroups in lysine, hydroxylysine or arginine leads to a covalent bond between the sugar and the aminoacid (the Amadori product), and subsequent reactions give rise to the formation of AGEs.AGEs affect physical and chemical properties of proteins, increasing the amount of intermolecular collagen cross - links. This results in reduction of the solubility of collagen that gets tougher, stiffer and weaker, loses its elasticity and is more likely to tear .Another mechanism, by which AGEs may exert noxious effects, is represented by their action on specific receptors (RAGE), which have been identified on the membrane of chondrocytes, tenocytes and fibroblasts ,46.Ligand engagement of RAGE triggers cell - specific signalling, resulting in enhanced generation of reactive oxygen species, and in the activation of the transcription of nuclear factor NF - kB ,48. ThisIn diabetes RAGE, Vascular Endothelial Growth Factor and Cytokines are overexpressed -56 and iBeside the AGE - mediated pathogenetic mechanism, microvascular disease may lead to tissue hypoxia, resulting in production of oxygen free radicals, which, in turn, leads to overproduction of growth factors and cytokines -59.Some limitations of this study must be acknowledged. Pain and functional limitation were evaluated on a self report basis, which is highly subjective. Active and passive ranges of motion of the shoulder were not measured. As matter of fact, functional impairment or pain in the extreme degrees of movements could be present in these subjects, who were yet able in performing usual activities of daily living, but who could avoid, spontaneously or unconsciously, some disturbing tasks. Spurs or other bone abnormalities were not taken into account in this study, which was mainly aimed at tendon evaluation. Therefore, we cannot state whether individuals with diabetes had a higher prevalence of lesions that could be treated surgically to prevent impingement type tears. Moreover, the examiner was not blind to whether or not the individuals had diabetes or not.Finally, it must be acknowledged that US investigation has limited reliability in detecting partial thickness tears and intra - articular tears of biceps tendon ,60,61.Our results demonstrate that NIDDM worsen the tendon degeneration in aged subjects. US imaging, beside clinical evaluation, is an useful tool for discovering in pre - symptomatic stages the subjects at risk, who may undergo to shoulder pathologies. In these subjects, that represent a growing segment of elderly population, a careful metabolic control by means of diet and anti - diabetics drugs is recommended and the progression of tear size should be monitored over time.NIDDM: Non Insulin Dependent Diabetes Mellitus; US: Ultrasound; SST: Supraspinatus; IST: Infraspinatus; SBT: Subscapularis; BT: Long head of the biceps tendon; SAD: Subacromial subdeltoid bursa; AGE: Advanced glycation end product; RAGE: Receptor advanced glycation end product; PGE2: Prostaglandin E2; NO: Nitric OxideThe authors declare that they have no competing interests.AM: Planning of the study. Echographic evaluation. Writing the paper; CS: Interpretation of US findings and bibliographic research; VS: Supervision of the study and of the final version of the paper.All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/11/278/prepub