Akupunktur & Aurikulomedizin

Kongress-Splitter

EXPERTENKURS DAVOS 2019

DICKES KNIE BEIM JOGGEN

A-DIPLOME ERFREUEN SICH GROSSER BELIEBTHEIT

FRAGEN AUS DER PRAXIS

MIT LASER TRADITIONELL STIMULIEREN

FÜR SIE GELESEN

Inhaltsverzeichnis

ZEREBRALE PHOTOBIOMODULATION — VORLÄUFIGE ERGEBNISSE ZUR REGIONALEN ZEREBRALEN OXYMETRIE UND THERMISCHEN BILDGEBUNG Zusammenfassung Ein neues Gerät für die LED-Photobiomodulation wird vorgestellt. Vorläufige Ergebnisse der regionalen zerebralen Sauerstoffsättigung und der Thermografie werden vor, während und nach der Stimulation gezeigt. Diese Verfahren bieten neue Wege, um die biologischen Wirkungen einer möglichen innovativen therapeutischen Methode zu quantifizieren. Weitere Messungen sind jedoch unbedingt erforderlich.

DER PHOENIX AUF DEM DRACHENTHRON

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Drug Safety

Correction to: Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists In the original publication of this article, the following correction should be noted in Table 1.

A Profile of Adverse Drug Reactions of Atazanavir- and Lopinavir-Based Antiretroviral Regimens in Namibia

Inflammation, Monoclonal Antibodies and Depression: Joining the Dots

Sirolimus and mTOR Inhibitors: A Review of Side Effects and Specific Management in Solid Organ Transplantation Abstract Inhibitors of mechanistic target of rapamycin (mTOR inhibitors) are used as antiproliferative immunosuppressive drugs and have many clinical applications in various drug combinations. Experience in transplantation studies has been gained regarding the side effect profile of these drugs and the potential benefits and limitations compared with other immunosuppressive agents. This article reviews the adverse effects of mTOR inhibitors in solid organ transplantation, with special attention given to mechanisms hypothesized to cause adverse events and their management strategies.

Drug-Induced Photosensitivity—An Update: Culprit Drugs, Prevention and Management Abstract Photosensitive drug eruptions are cutaneous adverse events due to exposure to a medication and either ultraviolet or visible radiation. In this review, the diagnosis, prevention and management of drug-induced photosensitivity is discussed. Diagnosis is based largely on the history of drug intake and the appearance of the eruption primarily affecting sun-exposed areas of the skin. This diagnosis can also be aided by tools such as phototesting, photopatch testing and rechallenge testing. The mainstay of management is prevention, including informing patients of the possibility of increased photosensitivity as well as the use of appropriate sun protective measures. Once a photosensitivity reaction has occurred, it may be necessary to discontinue the culprit medication and treat the reaction with corticosteroids. For certain medications, long-term surveillance may be indicated because of a higher risk of developing melanoma or squamous cell carcinoma at sites of earlier photosensitivity reactions. A large number of medications have been implicated as causes of photosensitivity, many with convincing clinical and scientific supporting evidence. We review the medical literature regarding the evidence for the culpability of each drug, including the results of phototesting, photopatch testing and rechallenge testing. Amiodarone, chlorpromazine, doxycycline, hydrochlorothiazide, nalidixic acid, naproxen, piroxicam, tetracycline, thioridazine, vemurafenib and voriconazole are among the most consistently implicated and warrant the most precaution by both the physician and patient.

Exploring the Association between Monoclonal Antibodies and Depression and Suicidal Ideation and Behavior: A VigiBase Study Abstract Introduction Several monoclonal antibodies (mAbs) have been linked to neuropsychiatric adverse effects in patients, including depression and suicidal ideation and behavior. Objective The aim of this study was to quantify and characterize spontaneously reported adverse drug reactions (ADRs) of depression and suicidal ideation and behavior related to mAb users, and to explore a possible association with their mechanism of action. Methods We included mAb ADRs that were reported in VigiBase, and identified those related to depression and suicidal ideation and behavior. Reporting odds ratios (RORs) were estimated for each mAb (bevacizumab as the reference) and according to their influence on the immune system (not directly targeting [reference], stimulating, or suppressing). Those suppressing the immune system were further divided into their intended indication (auto-immune diseases, cancer). Results Overall, 2,924,319 ADRs for 44 mAbs were included; 9455 ADRs were related to depression and 1770 were related to suicidal ideation and behavior. The association was strongest for natalizumab and belimumab, both for depression (ROR 5.7, 95% confidence interval [CI] 5.0–6.4; and ROR 5.1, 95% CI 4.2–6.2) and suicidal ideation and behavior (ROR 12.0, 95% CI 7.9–18.3; and ROR 20.2, 95% CI 12.4–33.0). Those suppressing the immune system showed higher ROR, i.e. 1.9 (95% CI 1.8–2.0) for depression and 3.6 (95% CI 3.0–4.4) for suicidal ideation and behavior. This finding was only seen for mAbs used for treating autoimmune diseases. Conclusion Depression and suicidal ideation and behavior are seen in patients using mAbs, particularly mAbs used for treating autoimmune diseases that suppress the immune system. For interpretation of these data, the indications for use and other characteristics require further consideration.

Long-Term Safety and Efficacy of Fecal Microbiota Transplant in Active Ulcerative Colitis Abstract Introduction and objective The therapeutic role of fecal microbiota transplantation in ulcerative colitis varies across different reports. This study aims to evaluate the long-term safety and efficacy of a strategy called step-up fecal microbiota transplantation for ulcerative colitis. Methods Two clinical trials (NCT01790061, NCT02560727) for moderate-to-severe ulcerative colitis (Mayo score range 6–12) were performed from November 2012 to July 2017. Both studies were pooled for analysis on the safety and efficacy of fecal microbiota transplantation in patients with ulcerative colitis over a 1-year follow-up. The step-up fecal microbiota transplantation strategy included step 1: single fecal microbiota transplantation; step 2: two or more fecal microbiota transplantations; and step 3: fecal microbiota transplantations followed by immunosuppressants. Long-term clinical efficacy and adverse events were assessed, and multiple factors related to fecal microbiota transplantation were evaluated. Results Of 134 eligible patients in this real-word study, 81.3% (109/134) were included for analysis. The follow-up ranged from 1 to 5 years. Fecal microbiota transplantation-related adverse events were observed in 17.4% (43/247) of fecal microbiota transplantation procedures including one serious adverse event (myasthenia gravis) and 56 non-serious adverse events. Multivariable logistic regression analysis showed that both the method of preparation of microbiota from stool using the automatic system and the delivery method of colonic transendoscopic enteral tubing were associated with a lower rate of fecal microbiota transplantation-related adverse events (p = 0.023, p = 0.017, respectively). In total, 74.3% (81/109) and 51.4% (56/109) of patients achieved clinical response at 1 month and 3 months after step-up fecal microbiota transplantation, respectively. Conclusions Fecal microbiota transplantation should be a safe and promising therapy for ulcerative colitis. The improved fecal microbiota preparation and colonic transendoscopic enteral tubing might reduce the rate of adverse events in ulcerative colitis. Trial registration ClinicalTrials.gov NCT01790061, NCT02560727.

Summary of Torsades de Pointes (TdP) Reports Associated with Intravenous Drug Formulations Containing the Preservative Chlorobutanol Abstract Introduction Drug-induced torsades de pointes (TdP) is a potentially lethal ventricular arrhythmia that is associated with drugs that prolong the QT interval on the electrocardiogram (ECG) due to their interference with the cardiac potassium current, IKR. Intravenous (IV) formulations of methadone have been associated with TdP and contain the preservative chlorobutanol, which, like methadone, blocks IKR. The combinations of chlorobutanol with methadone or terfenadine, another IKR blocker, produce synergistic IKR block. Objective The aim of this study was to examine and summarize the evidence available to address the question: what other IV drug formulations contain chlorobutanol and are they associated with TdP? Methods IV drug products containing the preservative chlorobutanol were identified by searching the websites DailyMed (https://dailymed.nlm.nih.gov/dailymed/index.cfm) and Drugs@FDA (https://www.accessdata.fda.gov/scripts/cder/daf/). For each drug identified, PubMed and the FDA's Adverse Event Reporting System (FAERS) were searched for reports of TdP and/or QT prolongation and FAERS data were analyzed for disproportionality of reports. Results The search found nine drugs (methadone, epinephrine, papaverine, oxytocin, vasopressin, testosterone, estradiol, isoniazid, and desmopressin) that contain chlorobutanol 2.5 (n = 1) or 5.0 mg/mL. All nine drugs had reports of QT prolongation or TdP reported in FAERS and all but estradiol, testosterone, desmopressin, and isoniazid had reports of QT prolongation or TdP in PubMed. Two of the nine drugs (epinephrine and methadone) had positive signals (by disproportionality analysis) for TdP in FAERS (EB05 2.88 and 23.81, respectively) and four (methadone, epinephrine, papaverine, and vasopressin) were reported in published articles as the suspect drugs in cases of TdP. Conclusion The pharmacologic profile of chlorobutanol (synergistic IKR block) and its association with reports of TdP and QT prolongation suggest the need for a full evaluation of its cardiac safety when used as a preservative in IV drug and vitamin formulations.

Pharmacovigilance Systems in Arab Countries: Overview of 22 Arab Countries Abstract Pharmacovigilance has received much attention in Arab countries recently due to the development of new regulations. However, there are differences in the progression of pharmacovigilance systems by regulatory agencies in these countries because only some are able to meet the requirements for conducting pharmacovigilance activities. Only 45% of Arab countries are official members of the World Health Organization (WHO) Collaborating Centre for International Drug Monitoring. Countries such as Morocco, Tunisia, Saudi Arabia, Egypt, and Jordan are considered to be advanced pharmacovigilance countries, whereas other countries such as Libya, Yemen, and Palestine remain in the very early stages of implementing and developing pharmacovigilance systems. Countries such as Somalia, Djibouti, Mauritania, and Comoros Island have no pharmacovigilance system or culture. Asian Arab countries have some advantages over those in Africa because 50% of them are a part of the Gulf Cooperation Council (GCC), meaning that most of them can utilize similar approaches for the application of the majority of activities related to the healthcare system, including pharmacovigilance. Thus, participating in the GCC enables increased connections among these countries. However, one of the strengths in Africa is that Morocco is partnering with the WHO through the WHO Collaborating Center to enhance and strengthen pharmacovigilance across the Eastern Mediterranean Region and the Francophone and Arab countries. This partnership could have a role in enhancing the pharmacovigilance culture among African Arab countries. This review provides a general overview of the current situation regarding regulatory agencies related to pharmacovigilance in Arab countries.

Use of FDA's Sentinel System to Quantify Seizure Risk Immediately Following New Ranolazine Exposure Abstract Introduction Neurological complications including seizures have been reported with ranolazine. We sought to quantify the risk of seizure-related hospitalizations or emergency department events following ranolazine exposure in the Sentinel System (2006–2015). Study Design and Setting Eligibility criteria were new use of ranolazine after 183 days washout period and absence of seizure diagnoses, anti-epileptic drugs, or seizure-related disorders during the baseline period. Results Among 52,155 ranolazine users, we identified 28 seizures in the 1–32 days after new ranolazine dispensing: 12 occurring in days 1–10 (high-risk window), 11 in days 11–20 (moderate-risk window) and 5 in the control window (days 21–32). Assuming an equal likelihood of seizure events across the 32-day observation window, we estimate an attributable risk of 0.9 excess cases per 10,000 exposed users. Using a self-controlled risk interval design with exact logistic regression, seizures were elevated in the high-risk window (relative risk [RR] 2.88 (95% confidence interval [CI] 1.01–8.33) compared with the control window. No significant increased risk was observed in the moderate window. Half of the seizure cases had a diagnosis of renal disease, although seizure risk was not significant (RR 3.20 [CI 0.82–14.01]). A majority of patients in both risk windows were 75 years or older. Conclusion Our study suggests risk among younger ranolazine patients is rare. Given the imprecision of the risk estimates, we interpret the elevated seizure risk following ranolazine exposure with caution. Further analysis in a larger elderly population is warranted.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Sport and Exercise

Career Performance Progressions of Junior and Senior Elite Track and Field Athletes Abstract Purpose To compare and assess differences in the career performance progressions of elite junior and Olympic track and field athletes. Methods Annual best performances from top 8 men and women (e.g. finalists) in track and field events at the 2000 World Junior Championships (junior cohort) and the 2000 Olympic Games (Olympic cohort) were examined. Annual bests of these finalists were tracked each year from select groups: sprints (100 m, 200 m), distance (1500 m, 5000 m), jumps (long jump, high jump), throws (discus, shot put). Age of best lifetime performance, age of final posted performance, and improvement from junior-age best to lifetime best performance were compared between groups. Results Olympic finalists achieved lifetime best performances at later ages than junior finalists [26.0 ± 4.0 years vs. 21.1 ± 3.5 years; age difference 90% CI (3.7–5.2 years), P < 0.001], and this significant age difference between cohorts was found within all four groups. Olympic finalists improved from under-20 best to lifetime best more so than junior finalists [6.1 ± 4.8% vs. 2.5 ± 2.3%; Age difference 90% CI (2.5–4.8%), P < 0.001]. Of 130 junior finalists, 54 did not improve after age 19, while 19 of 128 Olympic finalists posted no improvement after age 19. Conclusion The data suggest that these two populations have different career performance progressions and challenge the notion that achieving elite success as a junior athlete is a prerequisite for the same success at the senior level.

Editors Welcome

Commentary on Wang Y et al. "An Overview of Non-exercise Estimated Cardiorespiratory Fitness: Estimation Equations, Cross-Validation and Application"

Passive Strategies for the Prevention of Muscle Wasting During Recovery from Sports Injuries Abstract Background Recovery from sport injuries commonly involves a muscle disuse situation (i.e., reduction in physical activity levels sometimes preceded by joint immobilization) with subsequent negative effects on muscle mass and function. Purpose To summarize the current body of knowledge on the effectiveness of different physical strategies that are currently available to mitigate the negative effects of muscle disuse during recovery from sports injury. Methods A narrative review was conducted to summarize the information available on neuromuscular electrical stimulation (NMES), blood flow restriction (BFR) and vibration intervention. Results The concomitant application of BFR and low-intensity exercise has shown promising results in the prevention of disuse-induced muscle atrophy. Some benefits might also be obtained with BFR alone (i.e., with no exercise), but evidence is still inconclusive. NMES, which can be applied both passively and synchronously with exercise, can also attenuate most of the negative changes associated with disuse periods. In turn, the mechanical stimulus elicited by vibration seems effective to reduce the loss of bone mineral density that accompanies muscle disuse and could also provide some benefits at the muscle tissue level. Conclusions Different physical strategies are available to attenuate disuse-induced negative consequences during recovery from injury. These interventions can be applied passively, which makes them feasible during the first stages of the recovery. However, it would be advisable to apply these strategies in conjunction with low-intensity voluntary exercise as soon as this is feasible.

Exercise Against Aging: Darwinian Natural Selection Among Fit and Unfit Cells Inside Human Body Abstract Exercise inevitably induces damages and triggers a brief inflammation in challenged tissues of the human body. Nevertheless, regular exercise is associated with improved physical fitness and lower all-cause mortality among adults in a dose-dependent manner. The paradox between destructive nature of exercise and its anti-aging benefit can be best explained by decreasing aged cell population of the human body in a Darwinian natural selection fashion, resulting in tissue renewal. In this concept, the unfit-to-fit cell ratio of a multicellular system increases during growth (expansion of cell population and size) and decreases after exercise challenges. Inflammation serves as an innate mechanism to recognize cells in danger and triggers clearance mechanism to eliminate unhealthy cells followed by regeneration. A recent finding of decreased p16INK4a+ senescent cells together with CD68+ macrophage infiltration in human skeletal muscle after resistance exercise supports this concept. The senescent cells are mostly stem cells located in capillaries surrounding myofibers, functioning to replace short-lived endothelial cells. They can be found in young men aged 20–25 years. In this context, exercise controls weight gain (i.e. cell number and size) and decrease senescent cell proportion in capillaries of the human body, providing benefits in physical fitness and increasing life expectancy.

Resistance Exercise Increases the Regulation of Skeletal Muscle FSTL1 Consequently Improving Cardiac Angiogenesis in Rats with Myocardial Infarctions Abstract Purpose The aim of this study was to investigate whether skeletal muscle-derived follistatin-like 1 (FSTL1) reaches the heart and exerts the angiogenetic function in rats suffering myocardial infarctions (MI) after exercise intervention. Methods Forty-eight male adult Sprague–Dawley rats were randomly divided into four groups. MI was provoked by ligation of left anterior descending coronary artery. MI rats underwent adeno-associated virus injection of FST1 in tibialis anterior muscle and 4 weeks of resistance exercise via a tail-suspended incremental weight-climbing method (0–75% body weight, daily load increased by 10%; 1 h/day, 5 day/w). Heart function was evaluated by hemodynamics including LVSP, LVEDP and ± dP/dt max; the cross-sectional area of muscle cells and myocardium fibrosis were analyzed by DiI and Masson's staining, respectively; the FSTL1 expression, endothelial cell proliferation and angiogenesis were visualized by immunofluorescence staining; and protein expression was quantified by Western blotting. Results Resistance exercise reverted MI-induced skeletal muscle atrophy, increased muscle FSTL1 expression and stimulated skeletal muscle derived FSTL1 entering into the MI heart via blood circulation. The overexpression of skeletal muscle FSTL1 improved myocardial endothelial cell proliferation, increased small vessel density in the fibrotic border, inhibited myocardial fibrosis and improved heart function in the MI rats after the exercise intervention. Meanwhile, DIP2A-PI3K-Akt-mTOR, Erk1/2 and TGFβ-Smad2/3 pathways were activated in the myocardium. Conclusion Resistance exercise stimulates skeletal muscle derived FSTL1 to reach the myocardium which makes a positive contribution to cardioprotection in MI rat.

Relationships Between Estimated Hourly Energy Balance and Body Composition in Professional Cheerleaders Abstract Purpose We sought to describe and examine the interrelationships between energy intake, body composition, and estimated energy balance. Methods Using self-reported hourly food intake and formula-based energy expenditure (EE) protocols, 19 female professional cheerleaders (mean age 25.4 years) were assessed to obtain energy balance (EB) for a typical training day. Energy intake (EI) was predicted using the USDA Food Composition Database SR27, and EE was predicted using the Harris-Benedict equation plus a MET-based relative intensity activity scale. Body composition was predicted using a multi-current, 8-mode segmental bioelectrical impedance analysis system. Hourly and daily EB was calculated from EI and EE data. Results Subjects reported a 24 h EI significantly below (P < 0.001) the unadjusted predicted energy requirement (1482 kcal vs. 2199 kcal, respectively), resulting in an average negative net EB of − 720 kcal. Carbohydrate intake was significantly below the minimum recommended level (3.1 g/kg vs. 6 g/kg, P < 0.001) while protein and fat intakes met the recommended levels. Higher fat intake (g/kg) was significantly associated with a higher EI kcal/kg (r = 0.726; P < 0.001), which was significantly associated (r = − 0.55; P = 0.01) with a lower body fat percent (BF%). Using the median of BF% (20.9) as the cut point, participants with fewer hours in a negative EB had lower BF% (P = 0.043) and those with lower BF% spent more time in an EB of ± 300 kcal (P = 0.013). Conclusions These athletes reported low energy intakes that resulted in large EB deficits and/or more hours in a negative EB, which could be counterproductive for achieving a lean body composition overtime.

Experimental Investigation of the Effects of Acute Exercise on Real-World Ecological Memory Abstract Purpose To evaluate the effects of acute moderate-intensity exercise on ecological memory, as assessed from a face-name memory task. Methods A two-arm, parallel-group, randomized controlled intervention was employed. Participants (N = 40; Mage = 20.8 years) were randomized into a seated control task or a bout of acute moderate-intensity treadmill exercise (15-min). Thereafter, participants completed a 3-phase face-name memory task, involving a study phase and two test phases (immediate and delayed recall, with the delay occurring 15 min after the immediate recall). Results For the immediate memory recall, the mean (SD) scores for the exercise and control conditions, respectively, were 6.60 (2.5) and 6.20 (2.5). For the 15-min delayed assessment, the respective scores were 6.25 (2.6) and 5.75 (1.9). There was a significant main effect for time (F = 4.06, P = 0.05, \( \eta^{2}_{{p}} \)  = 0.10). However, there were no main effects for group (F = 0.33, P = 0.56, \( \eta^{2}_{{p}} \)  = 0.01) or time by group interactions (F = 0.12, P = 0.72, \( \eta^{2}_{{p}} \)  = 0.003). Conclusions Despite the exercise group having slightly higher immediate and delayed face-name memory scores, we did not observe robust evidence of acute exercise enhancing face-name memory performance.

Acute Effects of Stretching on Flexibility and Performance: A Narrative Review Abstract Passive and active stretching techniques have been shown to increase both chronic and acute range of motion (ROM). Acute ROM improvements can be countered by decreases in muscle performance, primarily after prolonged static stretching (SS) and proprioceptive neuromuscular facilitation (PNF) techniques when not incorporated into a full warm up procedure. In contrast, ballistic stretching and dynamic stretching techniques typically induce either an increase or no change in muscular force and power. This review explores studies that have investigated stretching responses on ROM, muscle functionality and performance. Collectively, the literature demonstrates that prolonged acute SS and PNF stretching can elicit the greatest changes in flexibility, but without additional dynamic activities (i.e. full warm up) can induce neuromuscular force and power output impairments, while increasing ROM and some sports specific performance. Muscle response to stretching may be determined by the manipulation of confounding variables such as duration, population, volume, test specificity and frequency. An increased dosage of some of these variables during stretching in isolation, augments ROM increases while attenuating muscle force output, except for stretching intensity which may lead to similar responses. Populations with high flexibility may have positive effects from stretching when tested on their sport specific performance, while general population may suffer greater negative effects. Not controlling these variables during stretching protocols may lead to misleading information regarding its effects on muscle performance.

Longitudinal Changes in Sarcopenia Criteria in Older Men with Low Skeletal Muscle Mass Index: A 2-Year Observational Study Abstract Purpose Declines in muscle mass and function are inevitable during the aging process. However, what is the "normal age appropriate" decline of muscle mass and function? Further, is this decline uniform for muscle mass versus functions or between different functional abilities? Using recognized Sarcopenia criteria [i.e. skeletal muscle mass index (SMI) defined as appendicular skeletal muscle mass/height (kg/m2), handgrip strength, gait velocity], the aim of the present project was to determine corresponding changes in community-dwelling men 70 years+ with low SMI over a 2-year period. Methods One hundred and seventy-seven (177) men within the lowest SMI quartile of a recent epidemiologic study (n = 965) were included in the 2-year follow-up analysis. Muscle mass was determined via direct-segmental, multi-frequency Bio-Impedance-Analysis, handgrip strength was tested with a Jamar hand-dynamometer and habitual gait speed was assessed with photo sensors applying the 10 m protocol. Results SMI, handgrip strength and gait velocity all declined significantly ( P< 0.001; effect size, d′ 0.39–1.17), however, with significantly higher reductions (P< 0.001) in functional compared with morphologic Sarcopenia criteria (P ≤ 0.006). Less expected, handgrip strength featured a fourfold higher decline compared with gait velocity (− 12.8 ± 10.9% versus − 3.5 ± 9.0%). Conclusion We provided evidence for significant non-uniform changes of Sarcopenia criteria in a cohort of community dwelling men 70 years+ with low SMI. We doubt that this result might be a particularity of the selected cohort; however, studies with other (older) cohorts should address this issue in more depth. Of practical relevance, our data further give implications for the prioritization of interventions that address Sarcopenia criteria in older community-dwelling men.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Otolaryngology and Head & Neck Surgery

Endoscopic Management of Tympanic Membrane Retraction Pockets: A Two Handed Technique with Endoscope Holder Abstract The tympanic membrane retraction pocket is a pathological invagination of tympanic membrane into the middle ear space. The most common sites for formation of retraction pocket are pars flaccida and postero-superior parts. Decision about the procedure and the timing of the treatment of retraction pockets is debatable and depends on the functional and anatomic condition of the ear. To evaluate the results of the technique of two handed endoscopic management of retraction pockets with sliced tragal cartilage. Prospective Non Randomized Clinical Study. The study included 41 ears operated with the technique of two handed endoscopic cartilage tympanoplasty for retraction pockets with endoscope holders from November 2013 to May 2016 with a follow up period ranging from 22 to 53 months. Cases of cholesteatoma and tympanic membrane perforation were excluded from the study. Pre and postoperative symptoms and air–bone gaps were recorded. The average preoperative air–bone gap in the study group was 24.53 ± 4.326 dB. 28 ears were of pars tensa retractions (stage II-4, stage III-15, and stage IV-9) and 13 were pars flaccida retractions (stage III-8 and stage IV-5). 24 ears had ossicular erosion. The follow up revealed that, the results of two handed endoscopic sliced cartilage tympanoplasty for retraction pockets were stable and there was no recurrence of the retraction and the post-operative air–bone–gap closure was achieved to 13.62 ± 4.78, 14.13 ± 5.91 dB, 14.32 ± 3.46 and 14.57 ± 3.88 dB at 6 months, 1 year, 2 years, 3 years respectively. Though, indications for surgery are based mostly on anatomic status and observation of behaviour of retraction pocket over time, we recommend early management of retraction pockets by the technique of endoscopic sliced tragal cartilage tympanoplasty with tragal cartilage of 0.5 mm thickness using endoscope holder. Level of Evidence: Level 4.

Tracheostomy: Open Surgical or Percutaneous? An Effort to Solve the Continued Dilemma Abstract Due to lack of globally standardized guidelines and clarity on indications, patient selection, intra-operative preparations, technique, complications, postoperative care and decannulation protocols, percutaneous tracheostomy (PT) has come in vogue as compared to standard open surgical tracheostomy (OST). PercuTwist and guide wire dilatational method (GWDF), techniques of PT, offer lesser operative time and ease of surgery being a bedside procedure. There seems to be paucity of Indian literature on rising trend of increasing indications, post-operative care, management of complications and outcomes of tracheostomy. And thus, there arises a felt need to envisage a study in tertiary care setup targeting these issues and to question the so far unchallenged acceptance of new techniques and technology. Our aim is to study the recent trend of indications, complications, and outcomes of both OST and PT in a cohort of Indian patients who underwent tracheostomy. 80 patients with mean age of 59.0 ± 15 years underwent tracheostomy (OST: 48 (60%), PT: 32 (40%), and among PT, PercuTwist: 16 (50%), GWDF: 16 (50%)) for various indications with objectives to compare operative time, complications and decannulation rates of tracheostomy surgery, within the follow up period of 3 months. Most common indication of elective tracheostomy was prolonged ventilation, and for emergency ones, upper airway obstruction. Mean operative time taken by all the three techniques was comparable, i.e., 16.3 v/s 15 v/s 15.3 min (Open v/s PT GWDF v/s PT PercuTwist). Most common intra-operative complication of OST was haemorrhage (16.3%) and that of PT was false passage (8.8%). Early post-operative complications were haemorrhage (OST: 3.75%, PT: 1.25%) and tube blockage and dislodgement (equal distribution among OST and PT). Late post-operative complications were stomal granulations in PT: 7.5%. Outcomes of tracheostomy were significantly better with OST (36 (45%)) than PT (14 (17.5%)). In PT group, PercuTwist fared better than GWDF in terms of lesser complications (PercuTwist: 10%, GWDF: 18.6%) and better decannulation rates (PercuTwist: 13.6%, GWDF: 3.75%). Most common indication for tracheostomy remains prolonged intubation; complication of OST is intra and early post-operative haemorrhage and that of PT being tube dislodgement and blockage. Outcomes in form of successful decannulation are with OST.

A Study on Outcome of Myringoplasty in Dry Ear (Quiescent/Inactive CSOM) Without Using Gelfoam in Middle Ear Abstract Myringoplasty is a common surgery done for patients with tympanic membrane perforation in our clinical practice. This study was done to know the outcome of myringoplasty done without using gelfoam as a scaffold material. Simultaneously other parameters influencing the outcome were analysed. In a total of 80 patients assessed over 25 months were divided into test and control group by quasi randomisation. All patients underwent endoscopic underlay myringoplasty. Control groups had gelfoam bed created with gelfoam, whereas the test group only middle ear air pocket created with a proper seal without using gelfoam. The study revealed that without using gelfoam and creating a good middle ear air pocket the results were comparable to the method of using middle ear gelfoam bed. Also few insights and understanding regarding the parameters we need to asses preoperatively were also observed. With comparable healing and hearing results without using gelfoam in the middle ear, the normal physiology is restored in the postoperative period much earlier. The result of the surgery also becomes evident in the second postoperative week when the use of gelfoam in the middle ear is avoided.

Biomarkers in Head and Neck Cancer an Update Abstract The study is aimed at establishing the purpose of tumour markers, their application, classification, diagnostic and therapeutic roles in the management of head and neck cancer. A literature review using Medline, Scopus, Google Scholar, the Cochrane Database of Systematic Reviews and the Cochrane central register of controlled trials for articles published between 1993 and 2016 on tumour markers and their role in head and neck cancer was performed. A broader search of prognostic markers in head and neck cancer was also carried out to avoid missing other pertinent markers. Natural history, tumour biology, stage and prognostic factors influence the outcome of management in patients with Head and Neck Squamous cell carcinoma (HNSCC). Evaluation of the cellular lineage and histogenic origin of diverse neoplasms can be done using tumour biomarkers. Identifying predictive tumour markers can lead to improvement in preventive management of HNSCC. There has been remarkable advancement in molecular technology with gene expression and proteomic profiling. Integration of specific tumour markers into routine clinical practice requires substantiation through well designed clinical trials. The investigation of tumour markers is imperative as they influence the prognosis of HNSCC and provide the potential to improve outcomes of treatment through targeted therapy. We have outlined recent tumour biomarkers in this review which have significant role in diagnosis, screening and prognostication in HNSCC. Recent advancement in clinical applications, therapeutic strategies of tumour markers has been highlighted.

Three Dimensional Rhinoplasty and Nasal Airway Improvement in Cleft-Nose Deformity Abstract Septorhinoplasty is particularly challenging among revision surgeries for cleft sequelae. The challenge of cleft septorhinoplasty is mainly due to the complex anatomy of nose, deformity of each of its components and the difficulty and lack of clarity in surgical management. From 2014 to 2017, 26 patients with cleft lip nose deformity were operated by the same cleft team. The study was conducted to assess the improvement in nasal airway and appearance following secondary rhinoplasty with extracorporeal septoplasty. Post operatively each patient was evaluated using the standard modified rhinoplasty outcome evaluation questionnaire, a validated instrument that aids in stratifying patients according to their subjective response. All patients reported great relief of nasal obstruction and improved breathing. More than 80% of our patients were satisfied with improved aesthetics and reported better self-confidence. Secondary cleft rhinoplasty with extracorporeal septoplasty surgery significantly improves the cosmesis and nasal airway opening, subsequently giving them improved self-confidence.

Giant Warthin's Tumour of the Parotid Gland: A Rare Case Report Abstract Warthin's tumour was first adequately described in 1929 by an American pathologist, Aldred Scott Warthin. It is synonymous with papillary cystadenoma lymphomatosum (PCL), cystadenolymphoma or adenolymphoma. Giant salivary gland tumours are usually pleomorphic adenomas. The average size of Warthin's tumour is reported to be about 2–4 cm. In the current fascinating case, an enormous disfiguring salivary gland tumour was reported which turned out to be Warthin's tumour on histopathology, which is probably the largest PCL reported till date.

Bilateral Vestibular Atelectasis with Tullio's Phenomenon Abstract Vestibular dehiscence or atelectasis is a rarity known to cause vertigo. This pathology poses many challenges especially in diagnosis and treatment simply due to the scarcity of reported cases. The etiologic factors, disease pathophysiology and complications remain unclear. We report a young adult female who presented with unsteadiness for 2 years associated with headache. Tullio's phenomenon was observed which led to a finding of bilateral vestibular dehiscence involving the medial walls on high resolution computed tomography.

Round Window Insertion in Veria Technique of Cochlear Implantation: An Essential Modification Abstract Cochlear implants have been done using various surgical approaches. The classical posterior tympanotomy approach has been practiced by majority of surgeons worldwide. An alternative approach is the transcanal Veria approach. This is non mastoidectomy approach where the electrode is threaded via a transcanal tunnel into the cochleostomy site. Majority of "Veria" surgeons are inserting the cochlear electrodes via a cochleostomy. This article focuses on round window insertion of cochlear electrode which has been proven to be a "softer "technique of electrode insertions and finds its role in preservation of residual hearing. Out of 115 cochlear implants done at AIIMS Patna between May 2014–May 2018, using the Veria approach, 52 patients have now been done using the round window insertion. Veria approach is a non-mastoidectomy technique where a special perforator is used to drill a trans canal tunnel which lodges the cochlear electrodes. All kind of implants were used and round window insertion was possible with different kind of electrodes. Out of 52 implants, 24 were MEDEL Sonata with straight electrode and flex soft electrode, 21 were Advanced Bionics Precurved 1 J electrode, 2 were (CI 24 REST) Cochlear devices standard straight array and 5 were Neurelec standard straight array devices. Insertion was uneventful in all the cases and intra op telemetry results were satisfactory post insertion. Round window insertion has now become routine for cochlear implants especially in cases where we have to preserve residual hearing. Veria approach earlier was considered to be only a "cochleostomy" approach but our successful insertion via the round window using the Veria technique is a landmark modification and alleviates any such limitation which was associated with this technique before.

Quality of Life in Patients with Nasal Septal Deviation After Septal Correction Abstract Septal Correction is an age-old procedure being practiced for the major part of a century now. The aim of this study was to assess the quality of life after Septal Correction. Fifty patients with complaints of nasal obstruction, trouble breathing via the nose, headache and facial pain were selected for the study. Initial pre-operative assessment was done based on a symptomatic score [Nasal Obstruction Symptom Evaluation Scale (NOSE Scale)]. The presence of a septal deviation was confirmed with an X-ray and computed tomography of the paranasal sinuses along with a diagnostic nasal endoscopy. Based on the extent and location of deviation, the malformed part was corrected. Post-operative assessment was done after a period of 8 weeks based on the NOSE Scale. The results were co-related and documented. It was found that the scores were better post-surgery. Thus, it can be concluded that Septal Correction as a surgical procedure is still relevant in today's World for symptomatic betterment and for a healthier lifestyle.

A Comparison of Surgical Outcomes of Carbon Dioxide Laser Versus Conventional Cold Instrument Excision of Benign Vocal Cord Lesions Abstract Benign vocal fold lesions affect the vibratory function of the vocal folds and cause dysphonia. Surgical excision has been the mainstay of management of benign vocal fold lesions for decades. This study compares the surgical outcomes of cold instruments versus carbon dioxide (CO2) laser excision of benign vocal fold lesions. A total of 49 cases diagnosed with benign vocal fold lesions were divided randomly to undergo excision either by conventional cold steel method or by CO2 laser. The postoperative assessment of the groups was done by videostroboscopy, acoustic analysis and voice handicap index. There was a significant improvement (P value < 0.05) when preoperative values of the parameters were compared with postoperative values in the individual groups. However, there was no significant difference when the two groups were compared with each other in terms of outcomes. Both the surgical techniques provide good outcomes in management of benign vocal fold lesions and each has its own advantages and disadvantages.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Addiction Medicine

Patient and Physician Perspectives on Treating Tobacco Dependence in Hospitalized Smokers With Substance Use Disorders: A Mixed Methods Study Objective: Individuals with substance use disorders have a high prevalence of smoking cigarettes. Hospitalization represents an opportunity to deliver concurrent treatment for tobacco and other substances. Using a sequential explanatory mixed methods design, we characterized practices and perspectives of patients and physicians about smoking cessation counseling during inpatient addiction medicine consultations. Methods: We abstracted data from 694 consecutive inpatient addiction consult notes to quantify how often physicians addressed tobacco dependence using the guideline-recommended 5As framework. We conducted semi-structured interviews with 9 addiction medicine physicians and 20 hospitalized smokers with substance use disorders. We analyzed transcripts to explore physicians' and patients' perspectives on smoking cessation conversations during inpatient addiction consultations, physician-perceived barriers and facilitators to engaging inpatients in tobacco treatment, and strategies to improve tobacco treatment in this context. Results: 75.5% (522/694) of hospitalized substance use disorder patients were current smokers. Among smokers, 20.9% (109/522) were offered nicotine replacement while hospitalized, but only 5.4% (28/522) received the full guideline-recommended 5As. Patients and physicians reported minimal discussion about tobacco addiction during hospitalization. Physicians cited tobacco not being an immediate health threat and the perception that quitting tobacco is not a priority to patients as barriers, often limiting thorough counseling to patients with smoking-related admissions. Physicians and patients offered strategies to integrate treatment of tobacco dependence and other substances. Conclusions: Inpatient addiction consultations represent a missed opportunity to counsel patients with substance use disorders to quit smoking. System-level changes are needed to coordinate treatment of tobacco and other drug dependence in hospitalized smokers. Send correspondence to Hasmeena Kathuria, MD, Pulmonary Center, 72 E. Concord St R304, Boston, MA 02118. E-mail: hasmeena@bu.edu. Received 10 July, 2018 Accepted 14 November, 2018 Primary Source of Funding: This work was supported by the Boston University Evans Center for Implementation and Improvement Sciences (CIIS) and supported in part by resources from the Edith Nourse Rogers Memorial VA Hospital. Conflicts of interest: Dr. Kathuria has consulted for Remedy Partners on relevance of codes for pulmonary services. The authors have no other conflicts of interests to disclose. Disclaimer: The views expressed in this article do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. The funding organizations had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. © 2019 American Society of Addiction Medicine

Opioid Toxidrome Following Grapefruit Juice Consumption in the Setting of Methadone Maintenance Background: Methadone is a synthetic mu-opioid receptor agonist used in the treatment of chronic pain and opioid dependence. Methadone is metabolized by several cytochrome P450 isoenzymes; primarily CYP3A4, CYP2B6, and CYP2D6 before renal and fecal elimination. Exposure to substances like grapefruit juice, that inhibit these isoenzymes may result in increased blood levels of methadone, and thus may manifest clinically as unexpected opioid toxicity. Case: A 51-year-old male was found unresponsive. He was hypoxic and bradypneic with pinpoint pupils. Multiple boluses followed by infusion of naloxone were required before improvement of respiratory status. Upon awakening, the patient reported participating in an opioid treatment program where he is administered 90 mg of oral methadone daily and denied any other substance use. On further questioning, he admitted to drinking grapefruit juice (estimated to be approximately 500 mL/day) every day for 3 consecutive days before presentation. The patient was discharged home after being counseled to stop drinking grapefruit juice. Discussion: Grapefruit juice is known to be an inhibitor of the CYP3A4 isoenzyme. Various studies demonstrate that through CYP3A4 inhibition, grapefruit juice increases serum levels of opioids, such as methadone, though no clinically significant effects have been reported. Conclusions: Grapefruit juice inhibits the metabolism of methadone, raising its serum levels. To our knowledge, this is the first reported case in which the interaction between grapefruit juice and methadone was significant enough to cause an opioid toxidrome. It is, therefore, recommended that opioid treatment programs (OTPs) advise patients about this interaction before administering methadone. Send correspondence to Muhammed Ershad, MD, Hahnemann University Hospital, Philadelphia, PA 19102. E-mail: docershad@gmail.com Received 4 February, 2019 Accepted 11 March, 2019 The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

Multivisceral Failure in a Context of Serotonin Syndrome Induced by MDMA: The Investigation of a Unique and Nationwide Network The occasional ingestion of 3,4-methylenedioxy-N-methylamphetamine (MDMA) presents serious risks of side effects including death through multivisceral failure in a context of serotonin syndrome. The significant increasing evolution of illicit MDMA street dosages over the past 2 decades and the difficulty for physicians to know what quantity the patients may have consumed, make MDMA a drug with unpredictable effects. Through this case report of a 16-year-old Caucasian, we made use of a unique and nationwide French health monitoring system called TREND (Recent Trends and New Drugs)—SINTES (National Identification System for Drugs and Substances), which, combined with the hair follicle test, can assist medical practitioners in rapidly establishing a precise diagnosis and consequently provide the most appropriate treatment for each individual case in a timely manner. Send correspondence to Redwan Maatoug, MD, MSc, PhD Candidate, Psychiatrist, Addictologist, La Pitié Salêtrière Hospital, 47-83 Boulevard de l'hôpital, 75013 Paris, France. E-mail: redwanmaatoug@gmail.com Received 13 December, 2018 Accepted 19 April, 2019 Disclosure: All authors declare no competing interest. © 2019 American Society of Addiction Medicine

Adolescent SBIRT Practices Among Pediatricians in Massachusetts Objectives: Adolescent Screening, Brief Intervention, and Referral to Treatment (SBIRT) in primary care is a key strategy to prevent, identify, and respond to substance use problems and disorders, including opioid and other drug addictions. Despite substantial investment in recent years to increase its implementation, few studies have reported on recent levels of SBIRT implementation among pediatricians. We aimed to assess self-reported use of the SBIRT framework with adolescent patients among Massachusetts pediatricians, and describe trends since an earlier survey. Methods: We analyzed responses to a cross-sectional survey mailed in 2017 to a representative sample of pediatricians in Massachusetts. We computed response frequencies for all SBIRT practice questions. We used the chi-square test to compare current data to data collected in 2014, as we found no demographic differences between the 2 samples. Results: Nearly all pediatricians in the 2017 sample (n = 160) reported annual screening of their adolescent patients (99%). The majority reported giving positive reinforcement (87%), brief advice (92%), counseling (90%), and referral to treatment (66%) in response to screen results. Compared with 2014, a significantly higher proportion of pediatricians in 2017 referred patients who screened positively for problematic alcohol use, but perceived barriers to screening and follow-up remain, such as insufficient time to screen and patient refusal to return. Conclusions: Among respondents to a Massachusetts pediatrician survey, we found high rates of delivering SBIRT in accordance with published guidelines, though barriers remain. Whether the content of the counseling adheres to guidelines is unknown. Send correspondence to Sharon Levy, MD, MPH, Director, Adolescent Substance Use and Addiction Program, Boston Children's Hospital, 300 Longwood Avenue, Mailstop 3114, Boston, MA 02115. E-mail: Sharon.Levy@childrens.harvard.edu. Received 7 November, 2018 Accepted 5 May, 2019 Author contributions: Dr Straus, Ms Fluett, and Ms Strother designed the survey and collected data. Dr Harris carried out data analysis. Ms Wiseblatt carried out data analysis and drafted the initial manuscript. Dr Levy designed the survey, collected data, and drafted the initial manuscript. All authors reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Funding: Centers for Medicaid and Medicare Service, State Innovation Model grant to the Commonwealth of Massachusetts (CMS-1G1-12-001) provided support for the administration of the 2014 and 2017 survey and the analysis of results. The authors have no conflicts of interest to disclose. © 2019 American Society of Addiction Medicine

Poverty and Excess Length of Hospital Stay in Neonatal Opioid Withdrawal Syndrome Objectives: To study the impact of sociodemographic factors on length of stay (LOS) for infants with neonatal opioid withdrawal syndrome (NOWS) secondary to fetal opioid exposure. Methods: In this retrospective cohort study, we included term infants with NOWS, excluding those with other significant medical issues. Comprehensive clinical and sociodemographic data were collected. Multivariate regression modeling was used to identify factors which contributed to excess LOS, which was defined as the number of days beyond the standard monitoring and/or treatment protocol. Results: In all, 129 infants were identified; mean gestational age of 37.9 ± 1.3 weeks and mean body weight of 2880 ± 496 g. Among them, 68% of infants were exposed to opioids; 27% were exposed to methadone; and 67% required pharmacologic treatment. The degree of poverty was assessed using the Area Deprivation Index (ADI) based on the mother's address at the time of birth. Median LOS for treated infants was 23 days versus 8 days for those who did not need pharmacologic treatment. The median excess LOS was 4 days (range 0–24). Excess hospital days were strongly correlated with degree of deprivation in the mother's community (r = 0.55, P < 0.01). ADI remained a strong predictor of excess LOS, even when controlling for pharmacologic treatment, placement in state's custody, race, and gestational age at birth. Conclusions: These results suggest poverty is associated with excess LOS and that early allocation of resources for at-risk families may help to reduce overall length of hospital stay. Send correspondence to: Zachary A. Vesoulis, MD, Department of Pediatrics, Washington University School of Medicine, 1 Children's Place, St. Louis, MO 63110. E-mail: vesoulis_z@kids.wustl.edu. Received 10 January, 2019 Accepted 11 March, 2019 Funding: This work was supported by the following grants: Washington University Institute of Clinical and Translational Sciences KL2 Training Program (NIH/NCATS KL2 TR000450); the Barnes-Jewish Hospital Foundation and the Washington University Institute of Clinical and Translational Sciences Clinical and Translational Funding Program (NIH/NCATS UL1 TR000448). The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

How Might Maternal Poverty Impact the Course of Neonatal Opioid Withdrawal Syndrome? Neonatal Opioid Withdrawal Syndrome (NOWS) is an increasing problem in the midst of the current opioid epidemic, frequently associated with pharmacologic treatment and prolonged hospitalizations. NOWS is a highly variable condition with many clinical and genetic variables contributing to the clinical course. Social variables such as maternal poverty remain understudied. In this commentary, we review one of the first studies of the association between maternal poverty and infant hospital length of stay in infants with NOWS. This has important implications for designing population level interventions to improve NOWS outcomes. Send correspondence to Elisha M. Wachman, MD, Boston Medical Center, 771 Albany Street, Dowling 4103, Boston, MA 02118. E-mail: Elisha.Wachman@bmc.org Received 26 March, 2019 Accepted 31 March, 2019 Financial disclosures: No funding was provided for this manuscript. Dr Wachman has no conflicts of interest to disclose. © 2019 American Society of Addiction Medicine

The Role of Hospitalists in Treating Opioid Use Disorder No abstract available

The Role of Hospitalists in Treating Opioid Use Disorder No abstract available

Exploring the Effects of Vitamin D Supplementation on Cognitive Functions and Mental Health Status in Subjects Under Methadone Maintenance Treatment Objectives: Vitamin D deficiency may be linked to several mental complications including cognitive deficits, depression, and anxiety in patients under methadone maintenance treatment (MMT). This study was designed to explore the effect of vitamin D supplementation on cognitive functions and mental health parameters in subjects under MMT. Methods: This randomized, double-blinded, placebo-controlled clinical trial was carried out among 64 patients under MMT. Participants were randomly allocated to receive either 50,000 IU vitamin D supplements (n = 32) or placebo (n = 32) every 2 weeks for 24 weeks. Cognitive functions and mental health parameters were taken at baseline and posttreatment to evaluate relevant variables. Results: After the 24-week intervention, compared with the placebo, serum 25(OH) vitamin D levels significantly increased in participants who received vitamin D supplements (β 14.50; 95% confidence interval [CI], 13.17–15.83; P < 0.001). In addition, compared with the placebo, subjects who received vitamin D had a significant reduction in Iowa Gambling Task (β −6.25; 95% CI, −8.60 to −3.90; P < 0.001), and significant increases in Verbal Fluency Test (β 2.82; 95% CI, 0.78–4.86; P = 0.007), Immediate Logic Memory (β 1. 32; 95% CI, 0.27–2.37; P = 0.01), Reverse Digit Span (β 2.06; 95% CI, 1.18–2.94; P < 0.001) and visual working memory (β 0.75; 95% CI, 0.33–1.16; P = 0.001). Also, vitamin D supplementation significantly improved BDI (β −2.76; 95% CI, −3.97 to −1.55; P < 0.001) compared with the placebo. When we applied Bonferroni correction, LM-Immediate (P = 0.07) became nonsignificant, and other mental health parameters did not alter. Conclusions: Overall, taking 50,000 IU vitamin D supplements every 2 weeks for 24 weeks by patients under MMT had beneficial effects on cognitive functions and some mental health parameters. Further studies are needed to confirm our findings. Send correspondence to Zatollah Asemi, PhD, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran. E-mail: asemi_r@yahoo.com Received 8 May, 2018 Accepted 9 May, 2019 The authors report no conflicts of interest. Clinical trial registration number: www.irct.ir: IRCT2017101133079N4. © 2019 American Society of Addiction Medicine

Editor's note: Congratulations to the 2019 Author and Reviewer Award Winners No abstract available

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Applied Magnetic Resonance

Multi-frequency Dynamic Weighted Functional Connectivity Networks for Schizophrenia Diagnosis Abstract Frequency-specific functional connectivity (FC) networks based on resting-state functional magnetic resonance imaging (rs-fMRI) have been successfully applied to the analysis and diagnosis of various mental illnesses, such as schizophrenia. However, most of the existing frequency-specific FC studies just focus on investigating the static temporal properties of FC networks, ignoring the important dynamic characteristics and spatial properties of FC networks. To address these issues, we proposed novel dynamic weighted FC networks to investigate the interactions among distributed brain regions. To take full advantage of the dynamic characteristics of the networks, temporal, spatial and spatio-temporal variabilities of dynamic networks were extracted as the classification features. To validate the effectiveness of our proposed method, we performed experiments on subjects with baseline rs-fMRI data from SchizConnect database. Experimental results demonstrated that the proposed method outperforms the state-of-the-art approaches in schizophrenia identification. In addition, we found most of the discriminative features distributed in frontal and subcortical area, which coincide with the pathological regions of cognitive progressing in schizophrenia patients.

Substituent Influences on the NMR Signal Amplification of Ir Complexes with Heterocyclic Carbene Ligands Abstract A number of Ir–N-heterocyclic carbene (Ir–NHC) complexes with asymmetric N-heterocyclic carbene (NHC) ligands have been prepared and examined for signal amplification by reversible exchange (SABRE). Pyridine was chosen as model compound for hyperpolarization experiments. This substrate was examined in a solvent mixture using several Ir–NHC complexes, which differ in their NHC ligands. The SABRE polarization was created at 6 mT and the 1H nuclear magnetic resonance signals were detected at 7 T. We show that asymmetric NHC ligands, because of their favorable chemistry, can adapt the SABRE active complexes to different chemical scenarios.

A Simple, Accurate Method to Determine the Effective Value of the Magnetic Induction of the Microwave Field from the Continuous Saturation of EPR Spectra of Fremy's Salt Solutions. Representative values of $$T_{1}$$ T 1 Abstract A simple protocol to measure the effective value of the circularly polarized magnetic induction of the microwave field is proposed and demonstrated employing continuous-wave saturation of a standard sample of Fremy's salt measured under specified conditions. The fact that the doubly integrated intensity of first-derivative spectra is invariant with respect to the line shape is used to take into account the non-Lorentzian line shape to study the peak-to-peak intensity or the line width. Corrections for the use of line- rather than point-samples are developed.

EPR and Mössbauer Characteristics of Aqueous Solutions of 57 Fe-Dinitrosyl Iron Complexes with Glutathione and Hydroxyl Ligands Abstract Our electron paramagnetic resonance (EPR) studies have demonstrated that at 293 K and 77 K, the spin–lattice relaxation time, T1, of paramagnetic mononuclear dinitrosyl iron complexes (M-DNICs) with glutathione and hydroxyl ligands containing isotopes 57Fe and 56Fe notably exceeds the halflife of the Mössbauer transition, i.e., the lifetime of the 57Fe nucleus in the first excited state (10−7 s). The Mössbauer spectra of M-DNIC with hydroxyl ligands, binuclear DNIC with glutathione (B-DNIC) and sodium dithionite-treated solution of B-DNIC with glutathione did not display the presence of the magnetic hyperfine structure (MHFS) characteristic of M-DNIC with glutathione. The Mössbauer spectra of all these DNICs were characterized by quadrupole splitting. The results of a comprehensive comparative analysis of MHFS of M-DNIC with glutathione and that in DMF reduced sodium nitroprusside suggest that M-DNIC with glutathione have a low-spin (S = ½) d7 electronic configuration with the predominant localization of the unpaired electron on the d z 2 orbital of iron. This conclusion is fully consistent with the results of our previous studies of M-DNIC using the EPR method.

ESEEM Reveals Bound Substrate Histidine in the ABC Transporter HisQMP 2 Abstract Localization of substrates in membrane proteins is an important but challenging task. In this paper, we show that deuterium electron spin echo envelope modulation spectroscopy (2H ESEEM) combined with site-directed spin labeling is a powerful tool to localize the substrate, histidine-d5, in the ABC transporter HisQMP2. Based on a homology model and spin label rotamer analyses, we calculated 2H ESEEM spectra for eight possible labeling positions close to the putative substrate-binding site. Experimental 2H ESEEM spectra were determined with spin labels bound either at position 169 of HisM, for which a detectable 2H ESEEM signal was calculated, or with a spin label bound at position 54 of HisQ as a negative control. The agreement between the calculated and experimental ESEEM spectra provides strong evidence for the histidine located in a binding site primarily liganded by residues of HisM as proposed by the homology model.

Characterization of the Distribution of Spin–Lattice Relaxation Rates of Lipid Spin Labels in Fiber Cell Plasma Membranes of Eye Lenses with a Stretched Exponential Function Abstract The stretched exponential function (SEF) was used to analyze and interpret saturation recovery (SR) electron paramagnetic resonance (EPR) data obtained from spin-labeled porcine eye-lens membranes. This function has two fitting parameters: the characteristic spin–lattice relaxation rate (T1str−1) and the stretching parameter (β), which ranges between zero and one. When β =1, the function is a single exponential. It is assumed that the SEF arises from a distribution of single exponential functions, each described by a T1 value. Because T 1 −1 s are determined primarily by the rotational diffusion of spin labels, they are a measure of membrane fluidity. Since βdescribes the distribution of T 1 −1 s, it can be interpreted as a measure of membrane heterogeneity. The SEF was used to analyze SR data obtained from intact cortical and nuclear fiber cell plasma membranes extracted from the eye lenses of 2-year-old animals and spin labeled with phospholipid and cholesterol analogs. The lipid environment sensed by these probe molecules was found to be less fluid and more heterogeneous in nuclear membranes than in cortical membranes. Parameters T 1str −1 and β were also used for a multivariate K-means cluster analysis of stretched exponential data. This analysis indicates that SEF data can be assigned accurately to clusters in nuclear or cortical membranes. In future work, the SEF will be applied to analyze data from human eye lenses of donors with differing health histories.

Design and Simulation of a Helmholtz Coil for Magnetic Resonance Imaging and Spectroscopy Experiments with a 3T MR Clinical Scanner Abstract Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are non-invasive techniques for tissue characterization. MRI/MRS in small phantoms with a clinical magnetic resonance scanner requires the design and development of dedicated radiofrequency coils. This paper describes the simulation, design, and application of a 1H transmit/receive Helmholtz coil, suitable for MRI/MRS studies in small phantoms with a clinical 3T scanner. Coil inductance and resistance were analytically calculated by taking into account the conductors cross geometry while magnetic field and sample-induced resistance were calculated with magnetostatic approaches. Finally, the coil sensitivity was measured with the perturbing sphere method. Successively, a coil prototype was built and tested on the workbench and by acquisition of MRI and MRS data. Results show that such coil could provide a low cost and easy to build device for MRI/MRS experiments with a clinical scanner in small specimens.

The In Situ Study of the Fe 3 O 4 /DMSO Ferrofluid Synthesis Abstract Electron spin resonance in situ was applied to study the initial stages of ferrofluid formation in combination with the X-ray diffraction, high-resolution transmission electron microscopy and Fourier transform infrared spectroscopy studies data. The ultrafine (d = 4 nm) magnetite in dimethylsulfoxide ferrofluid with a narrow size nanoparticles distribution was obtained in a single step at room temperature by admixing butylene oxide to a solution of iron (II) and (III) chlorides in dimethylsulfoxide. It has been shown that at the first step of the ferrofluid synthesis antiferromagnetically ordered iron containing phase is formed, which can be correlated with iron hydroxides.

Towards a Model-Based Field-Frequency Lock for Fast-Field Cycling NMR Abstract Fast-field cycling nuclear magnetic resonance (FFC NMR) relaxometry allows to investigate molecular dynamics of complex materials. FFC relaxometry experiments require the magnetic field to reach different values in few milliseconds and field oscillations to stay within few ppms during signal acquisition. Such specifications require the introduction of a novel field-frequency lock (FFL) system. In fact, control schemes based only on current feedback may not guarantee field stability, while standard FFLs are designed to handle very slow field fluctuations, such as thermal derives, and may be ineffective in rejecting faster ones. The aim of this work is then to propose a methodology for the synthesis of a regulator that guarantees rejection of field fluctuations and short settling time. Experimental trials are performed for both model validation and evaluation of the closed-loop performances. Relaxometry experiments are performed to verify the improvement obtained with the new FFL. The results highlight the reliability of the model and the effectiveness of the overall approach.

Persistence of Nitroxide Radicals in Solution Abstract Data on long-term persistence of nitroxide radicals typically are focused on solid samples. Less information is available for nitroxides in fluid solution. Sealed deoxygenated solutions of a doxyl nitroxide in tetrahydrofuran and a piperidinyl nitroxide in toluene in 4 mm EPR tubes were kept in a laboratory environment at ambient temperature and without protection from light. After more than 40 years, the concentrations of the solutions had decreased by about factors of 12 and 6, respectively. The longevity in solution probably depends strongly on the purity of the solvent, but these results indicate remarkable persistence.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com