Rejected

κ-Opioid receptors (KORs) play a predominant role in pain alleviation, itching skin diseases, depression and neurodegenerative disorders such as multiple sclerosis. Therefore, imaging of KOR by a fluorinated PET tracer was envisaged. Two strategies were followed to introduce a F atom into the very potent class of cis,trans-configured perhydroquinoxalines. Whereas the synthesis of fluoroethyltriazole 2 has already been reported, fluoropyrrolidines 14 (1-[2-(3,4-dichlorophenyl)acetyl]-8-[(R)-3-fluoropyrrolidin-1-yl]-perhydroquinoxalines) were prepared by S2 substitution of a cyclic sulfuric acid derivative with hydroxypyrrolidine and subsequent transformation of the OH moiety into a F substituent. Fluoropyrrolidines 14 showed similar low-nanomolar KOR affinity and selectivity to the corresponding pyrrolidines, but the corresponding alcohols were slightly less active. In the cAMP and β-arrestin assay, 14b (proton at the 4-position) exhibited similar KOR agonistic activity as U-50,488. The fluoro derivatives 14b and 14c (COCH at the 4-position) revealed KOR-mediated anti-inflammatory activity as CD11c and the IFN-γ production were reduced significantly in mouse and human dendritic cells. Compounds 14b and 14-c also displayed anti-inflammatory and immunomodulatory activity in mouse and human T cells. The PET tracer [F]-2 was prepared by 1,3-dipolar cycloaddition. In vivo, [F]-2 did not label KOR due to very fast elimination kinetics. Nucleophilic substitution of a mesylate precursor provided [F]-14c. Unfortunately, defluorination of [F]-14c occurred in vivo, which was analyzed in detail by in vitro studies.

Chronic shoulder pain is a complex and multidimensional phenomenon with multiple causative factors involved in its perpetuation. Alteration of central nervous system processing along with the central sensitization is a predominant feature in chronic pain. Reduction in physical function has an impact on the psychological well-being of an individual. The aim of the study was to compare pain, kinesiophobia, catastrophizing, disability and quality of life in chronic shoulder pain patients with and without central sensitization. Eighty chronic unilateral shoulder pain patients in the age group of 40 to 60 years were recruited. Of them, 38 were chronic shoulder pain with central sensitization and 42 without central sensitization, classified on the basis of central sensitization inventory. Pain catastrophizing was measured using the pain catastrophizing scale, kinesiophobia using Tampa scale of kinesiophobia, disability using Shoulder pain and disability index and quality of life using 36-Item Short Form Health Survey questionnaire was evaluated in both the groups. Increased pain catastrophizing (p=0.000), kinesiophobia (p=0.000) and disability (p=0.000) was observed in centrally sensitized chronic shoulder pain patients. Also, physical component summary (p=0.000) and mental component summary (p=0.000) of SF-36 quality of life were reduced in chronic shoulder pain with central sensitization as compared to without central sensitization. Hence, these components should be included during assessment which will provide a holistic and multimodal approach towards the understanding, planning and management of chronic shoulder pain patients.

Pediatric Chiari I malformation decompression is a common neurosurgical procedure. Liposomal bupivacaine (LB) is a novel formulation that can have an impact on postoperative recovery for particular procedures, but its potential role in pediatric neurosurgery is largely unexplored. The authors sought to describe and assess their initial experience with LB in pediatric Chiari I malformation decompression to better define its potential role as an analgesic agent in a procedure for which the postoperative course is often remarkably painful.

Opioids are effective analgesics in the management of chronic pain. However, their clinical use is hindered by adverse side effects such as addiction and analgesic tolerance. Naringenin is a common polyphenolic constituent of the citrus fruits and is one of the most commonly consumed flavonoids within our regular diet. However, its influences on opioid tolerance and addiction have not yet been clarified.

Superficial fungal infections (SFI) are common diseases affecting the skin, hair, nails, and mucosal membranes. They are often caused by dermatophytes and yeasts, e.g. Trichophyton, Candida, and Malassezia . Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease of the intertriginous areas associated with minor infections , peripheral vascular disease, diabetes, and smoking , the last three of which are risk factors for the development of SFI . Despite this, and the anatomical overlap between HS and types of SFI e.g. intertriginous candidiasis and tinea cruris, the possibility of an association between HS and SFI has never been investigated.

Benzodiazepines (BZDs) and related drugs (Z-drugs) are mainly taken chronically, and older people are much more likely to take them on a chronic basis despite recommendations. Withdrawal symptoms could be an obstacle to stopping BZD/Z-drug administration. The main objective of this study is to estimate the prevalence of withdrawal symptoms in patients aged 65 years and older who have experience a stop of BZD/Z-drug. The secondary objectives are to describe the withdrawal symptoms and identify factors associated.

Catheter-guided interventional implantation of cardiac valves is one of the main developments in cardiology over the past 15 years. It is characterized by a close interdisciplinary cooperation in the heart team (H-team), which consists of cardiac anesthesiologists, cardiologists and heart surgeons. This co-responsibility for anesthesia, which is demanded by the legislator (Federal Joint Committee, G‑BA, July 2015), includes not only qualified training for the cardiac anesthesiologist, including transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) but also several years of experience in cardiac anesthesia and correlates with the recommendations of the German Society for Anaesthesiology and Intensive Care Medicine. In accompaniment with the demographic development, the number of heart valve diseases increases with age. More than 50% of all heart operations are performed on patients over the age of 70 years and nearly 20% on patients over the age of 80 years. Minimally invasive procedures are outstanding opportunities for patients who were initially classified as inoperable. Therefore, anesthesiologists must have precise knowledge of the possible complications related to the procedure itself. Additionally, it challenges the anesthesiologist with unconventional situations in the care of older patients who are exposed to a higher risk. The aforementioned risks are organic functional restrictions, increasing number of comorbidities and more severe exposure due to malnutrition and frailty; however, monitoring methods are also being developed aiming for patient-specific anesthesia management and analgesia treatment. This article discusses the interventional procedures of heart valvular diseases as well as the hemodynamic changes associated with the procedures from the anesthesiologist's point of view. To present examples, we have selected transcatheter aortic valve replacement (TAVR) and the interventional procedure of mitral and tricuspid valve insufficiency called MitraClip and TricaClip. A thorough examination of the procedural risk rate shows that despite minimizing the surgical intervention by miniaturizing the devices, the presence of an experienced cardiac anesthesiologist is obligatory.

Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with persistently positive antiphospholipid antibodies. However, in APS, there are several non-thrombotic clinical manifestations such as thrombocytopenia, cardiac valve disease, microthrombotic nephropathy, skin ulcer, or cognitive dysfunction. These non-criteria manifestations are relatively common and usually are non-responsive to anticoagulation. Among the non-criteria manifestations, thrombocytopenia, skin ulcers, migraine, and heart valve lesions are the most frequent manifestations described in APS. Limited data are available on the treatment of non-criteria manifestations of APS, and most therapeutic options are based on case reports or retrospective non-randomized studies. Although there is no consensus on the treatment of non-criteria manifestations of APS, anticoagulant therapy and immunomodulatory drugs could be combined in most patients.

Low back pain (LBP) is well documented as a common health problem; it is the leading cause of activity limitation and work absence throughout much of the world, and it causes an enormous economic burden on individuals, families, communities, industry, and governments. The aim of this study was to comparatively investigate the effects of myofascial induction therapy (MIT) against pain neuroscience education (PNE) on pain and function in patients with chronic low back pain (CLBP).

The incidence of visceral pain among caesarean section can be as high as 50% in sub arachnoid block (SAB) in spite adequate sensory block, which requires conversion to general anesthesia. Different types of adjuvant have been used to augment the effect of local anesthetics but their use is limited due to adverse effects. The effect of intrathecal midazolam along with hyperbaric bupivacaine in sub arachnoid block is less known. So this randomized, double blind study was conducted to evaluate the additive effect of 0.4ml midazolam to 0.5% 3ml bupivacaine on sub arachnoid block in scheduled elective caesarean section. This study demonstrated that the addition of intrathecal 0.4ml midazolam to spinal 0.5% bupivacaine kept all the characteristics of block unaffected, furthermore pain score VAS 3.4±1.3 in Group A and 1.8±1.22 in Group B which is statistically significant, the requirement of intraoperative analgesia and also increased the duration of postoperative analgesia that is 130.3±5.4 minute in Group A, 265.1±3.6 minute in Group B and also statistically significant. Therefore addition of 2.0mg midazolam with 0.5% bupivacaine significantly reduces the VAS score, reduces the intraoperative visceral pain and need of analgesia.