Repeat exercise normalizes the gas-exchange impairment induced by a previous exercise bout in asthmatic subjects

Twenty-one subjects with asthma underwent treadmill exercise to exhaustion at a workload that elicited approximately 90% of each subject's maximal O2 uptake (EX1). After EX1, 12 subjects experienced significant exercise-induced bronchospasm [(EIB+), %decrease in forced expiratory volume in 1.0 s = -24.0 +/- 11.5%; pulmonary resistance at rest vs. postexercise = 3.2 +/- 1.5 vs. 8.1 +/- 4.5 cmH2O.l(-1).s(-1)] and nine did not (EIB-). The alveolar-to-arterial Po2 difference (A-aDo2) was widened from rest (9.1 +/- 6.7 Torr) to 23.1 +/- 10.4 and 18.1 +/- 9.1 Torr at 35 min after EX1 in subjects with and without EIB, respectively (P < 0.05). Arterial Po2 (PaO2) was reduced in both groups during recovery (EIB+, -16.0 +/- -13.0 Torr vs. baseline; EIB-, -11.0 +/- 9.4 Torr vs. baseline, P < or = 0.05). Forty minutes after EX1, a second exercise bout was completed at maximal O2 uptake. During the second exercise bout, pulmonary resistance decreased to baseline levels in the EIB+ group and the A-aDo2 and PaO2 returned to match the values seen during EX1 in both groups. Sputum histamine (34.6 +/- 25.9 vs. 61.2 +/- 42.0 ng/ml, pre- vs. postexercise) and urinary 9alpha,11beta-prostaglandin F2 (74.5 +/- 38.6 vs. 164.6 +/- 84.2 ng/mmol creatinine, pre- vs. postexercise) were increased after exercise only in the EIB+ group (P < 0.05), and postexercise sputum histamine was significantly correlated with the exercise PaO2 and A-aDo2 in the EIB+ subjects. Thus exercise causes gas-exchange impairment during the postexercise period in asthmatic subjects independent of decreases in forced expiratory flow rates after the exercise; however, a subsequent exercise bout normalizes this impairment secondary in part to a fast acting, robust exercise-induced bronchodilatory response

Gas exchange during exercise in habitually active asthmatic subjects

We determined the relations among gas exchange, breathing mechanics, and airway inflammation during moderate- to maximum-intensity exercise in asthmatic subjects. Twenty-one habitually active (48.2 +/- 7.0 ml.kg(-1).min(-1) maximal O2 uptake) mildly to moderately asthmatic subjects (94 +/- 13% predicted forced expiratory volume in 1.0 s) performed treadmill exercise to exhaustion (11.2 +/- 0.15 min) at approximately 90% of maximal O2 uptake. Arterial O2 saturation decreased to < or =94% during the exercise in 8 of 21 subjects, in large part as a result of a decrease in arterial Po2 (PaO2): from 93.0 +/- 7.7 to 79.7 +/- 4.0 Torr. A widened alveolar-to-arterial Po2 difference and the magnitude of the ventilatory response contributed approximately equally to the decrease in PaO2 during exercise. Airflow limitation and airway inflammation at baseline did not correlate with exercise gas exchange, but an exercise-induced increase in sputum histamine levels correlated with exercise Pa(O2) (negatively) and alveolar-to-arterial Po2 difference (positively). Mean pulmonary resistance was high during exercise (3.4 +/- 1.2 cmH2O.l(-1).s) and did not increase throughout exercise. Expiratory flow limitation occurred in 19 of 21 subjects, averaging 43 +/- 35% of tidal volume near end exercise, and end-expiratory lung volume rose progressively to 0.25 +/- 0.47 liter greater than resting end-expiratory lung volume at exhaustion. These mechanical constraints to ventilation contributed to a heterogeneous and frequently insufficient ventilatory response; arterial Pco2 was 30-47 Torr at end exercise. Thus pulmonary gas exchange is impaired during high-intensity exercise in a significant number of habitually active asthmatic subjects because of high airway resistance and, possibly, a deleterious effect of exercise-induced airway inflammation on gas exchange efficiency

Glucagon receptor gene mutations with hyperglucagonemia but without the glucagonoma syndrome

Pancreatic neoplasms producing exclusively glucagon associated with glucagon cell hyperplasia of the islets and not related to hereditary endocrine syndromes have been recently described. They represent a novel entity within the panel of non-syndromic disorders associated with hyperglucagonemia. This case report describes a 36-year-old female with a 10 years history of non-specific abdominal pain. No underlying cause was evident despite extensive diagnostic work-up. More recently she was diagnosed with gall bladder stones. Abdominal ultrasound, computerised tomography and magnetic resonance imaging revealed no pathologic findings apart from cholelithiasis. Endoscopic ultrasound revealed a 5.5 mm pancreatic lesion. Fine needle aspiration showed cells focally expressing chromogranin, suggestive but not diagnostic of a low grade neuroendocrine tumor. OctreoScan(®) was negative. Serum glucagon was elevated to 66 pmol/L (normal: 0-50 pmol/L). Other gut hormones, chromogranin A and chromogranin B were normal. Cholecystectomy and enucleation of the pancreatic lesion were undertaken. Postoperatively, abdominal symptoms resolved and serum glucagon dropped to 7 pmol/L. Although H and E staining confirmed normal pancreatic tissue, immunohistochemistry was initially thought to be suggestive of alpha cell hyperplasia. A count of glucagon positive cells from 5 islets, compared to 5 islets from 5 normal pancreata indicated that islet size and glucagon cell ratios were increased, however still within the wide range of normal physiological findings. Glucagon receptor gene (GCGR) sequencing revealed a heterozygous deletion, K349_G359del and 4 missense mutations. This case may potentially represent a progenitor stage of glucagon cell adenomatosis with hyperglucagonemia in the absence of glucagonoma syndrome. The identification of novel GCGR mutations suggests that these may represent the underlying cause of this condition

The magnetic nature of disk accretion onto black holes

Although disk accretion onto compact objects - white dwarfs, neutron stars, and black holes - is central to much of high energy astrophysics, the mechanisms which enable this process have remained observationally elusive. Accretion disks must transfer angular momentum for matter to travel radially inward onto the compact object. Internal viscosity from magnetic processes and disk winds can in principle both transfer angular momentum, but hitherto we lacked evidence that either occurs. Here we report that an X-ray-absorbing wind discovered in an observation of the stellar-mass black hole binary GRO J1655-40 must be powered by a magnetic process that can also drive accretion through the disk. Detailed spectral analysis and modeling of the wind shows that it can only be powered by pressure generated by magnetic viscosity internal to the disk or magnetocentrifugal forces. This result demonstrates that disk accretion onto black holes is a fundamentally magnetic process.Comment: 15 pages, 2 color figures, accepted for publication in Nature. Supplemental materials may be obtained by clicking http://www.astro.lsa.umich.edu/~jonmm/nature1655.p

Standardization of epidemiological surveillance of acute rheumatic fever

Acute rheumatic fever (ARF) is a multiorgan inflammatory disorder that results from the body’s autoimmune response to pharyngitis or a skin infection caused by Streptococcus pyogenes (Strep A). Acute rheumatic fever mainly affects those in low- and middle-income nations, as well as in indigenous populations in wealthy nations, where initial Strep A infections may go undetected. A single episode of ARF puts a person at increased risk of developing long-term cardiac damage known as rheumatic heart disease. We present case definitions for both definite and possible ARF, including initial and recurrent episodes, according to the 2015 Jones Criteria, and we discuss current tests available to aid in the diagnosis. We outline the considerations specific to ARF surveillance methodology, including discussion on where and how to conduct active or passive surveillance (eg, early childhood centers/schools, households, primary healthcare, administrative database review), participant eligibility, and the surveillance population. Additional considerations for ARF surveillance, including implications for secondary prophylaxis and follow-up, ARF registers, community engagement, and the impact of surveillance, are addressed. Finally, the core elements of case report forms for ARF, monitoring and audit requirements, quality control and assurance, and the ethics of conducting surveillance are discussed

Efficacy of tunnel technique in the treatment of localized and multiple gingival recessions: A systematic review and metaâ analysis

BackgroundTunnel technique (TUN) has recently gained popularity among clinicians for its promising clinical and esthetic results in treating gingival recession (GR) defects. However, evidence regarding the efficacy of the TUN is not yet conclusive. Therefore, the aim of the present systematic review and metaâ analysis was to investigate the predictability of TUN and its comparison to the coronally advanced flap (CAF) procedure.MethodsA literature search on PubMed, Cochrane libraries, EMBASE, and handâ searched journals through November 2017 was conducted to identify clinical studies investigating TUN for root coverage procedures. Only randomized controlled trials (RCTs) were considered for the metaâ analysis comparing TUN to CAF.ResultsA total of 20 articles were included in the systematic review and six in the metaâ analysis. The overall calculated mean root coverage (mRC) of TUN for localized and multiple GR defects was 82.75 ± 19.7% and 87.87 ± 16.45%, respectively. Superior results were found in maxillary and in Miller Class I and II GR defects. TUN outcomes may have been enhanced by splitâ thickness flap preparation and microsurgical approach. TUN and CAF had comparable mRC, complete root coverage (CRC), keratinized tissue gain, and root coverage esthetic score when varying combinations of graft material were evaluated. However, CAF demonstrated superior outcomes to TUN when the same graft (connective tissue or acellular dermal matrix) was used in both techniques.ConclusionsTUN is an effective procedure in treating localized and multiple GR defects. Limited evidence is available comparing TUN to CAF; however, CAF seemed to be associated with higher percentage of CRC than was TUN when the same grafts (connective tissue or acellular dermal matrix) were used in both techniques.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145520/1/jper10154.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145520/2/jper10154_am.pd

Interpersonal psychotherapy (IPT) for late-life depression in general practice: uptake and satisfaction by patients, therapists and physicians

<p>Abstract</p> <p>Background</p> <p>Interpersonal Psychotherapy (IPT) is recommended in most depression treatment guidelines and proved to be a suitable treatment for elderly depressed patients. Despite the favorable results of IPT in research populations, the dissemination to general practice is surprisingly limited. Little is known about uptake and satisfaction when this therapy is introduced into real-life general practice.</p> <p>Methods</p> <p>Motivation and evaluation of patients, GPs and therapists were recorded and organizational barriers described alongside a randomized controlled trial. IPT, given by mental health workers, was compared with usual general practitioner (GP) care. Included were patients (≥55 years) who met the DSM-IV criteria for major depressive disorder.</p> <p>Results</p> <p>Patients were motivated for the psychotherapy intervention: of the 205 eligible patients, 143 (70%) entered the study, and of the 69 patients who were offered IPT, 77% complied with the treatment. IPT proved to be an attractive therapy for patients as well as for therapists from mental health organizations. General practitioners evaluated the intervention positively afterwards, mainly because of the time-limited and structured approach. Organizational barriers: no IPT therapists were available; an IPT trainer and supervisor had to be trained and training materials had to be developed and translated. Additionally, there was a lack of office space in some general practices; for therapists from private practices it was not feasible to participate because of financial reasons. IPT was superior to usual care in patients with moderate to severe depression.</p> <p>Conclusion</p> <p>As we succeeded in delivering IPT in primary care practice, and as IPT was superior to usual care, there are grounds to support the implementation of IPT for depressed elderly patients within general practice, as long as the practices have room for the therapists and financial barriers can be overcome. Consolidation may be achieved by making this intervention available through practice nurses or community psychiatric nurses who deliver IPT as part of a more comprehensive depression management program.</p

Trial Protocol: Randomised controlled trial of the effects of very low calorie diet, modest dietary restriction, and sequential behavioural programme on hunger, urges to smoke, abstinence and weight gain in overweight smokers stopping smoking

Background\ud Weight gain accompanies smoking cessation, but dieting during quitting is controversial as hunger may increase urges to smoke. This is a feasibility trial for the investigation of a very low calorie diet (VLCD), individual modest energy restriction, and usual advice on hunger, ketosis, urges to smoke, abstinence and weight gain in overweight smokers trying to quit. \ud \ud Methods\ud This is a 3 armed, unblinded, randomized controlled trial in overweight (BMI > 25 kg/$m^2$), daily smokers (CO > 10 ppm); with at least 30 participants in each group. Each group receives identical behavioural support and NRT patches (25 mg(8 weeks),15 mg(2 weeks),10 mg(2 weeks)). The VLCD group receive a 429-559 kcal/day liquid formula beginning 1 week before quitting and continuing for 4 weeks afterwards. The modest energy restricted group (termed individual dietary and activity planning(IDAP)) engage in goal-setting and receive an energy prescription based on individual basal metabolic rate(BMR) aiming for daily reduction of 600 kcal. The control group receive usual dietary advice that accompanies smoking cessation i.e. avoiding feeling hungry but eating healthy snacks. After this, the VLCD participants receive IDAP to provide support for changing eating habits in the longer term; the IDAP group continues receiving this support. The control group receive IDAP 8 weeks after quitting. This allows us to compare IDAP following a successful quit attempt with dieting concurrently during quitting. It also aims to prevent attrition in the unblinded, control group by meeting their need for weight management. Follow-up occurs at 6 and 12 months. \ud \ud Outcome measures include participant acceptability, measured qualitatively by semi-structured interviewing and quantitatively by recruitment and attrition rates. Feasibility of running the trial within primary care is measured by interview and questionnaire of the treatment providers. Adherence to the VLCD is verified by the presence of urinary ketones measured weekly. Daily urges to smoke, hunger and withdrawal are measured using the Mood and Physical Symptoms Scale-Combined (MPSS-C) and a Hunger Craving Score (HCS). 24 hour, 7 day point prevalence and 4-week prolonged abstinence (Russell Standard) is confirmed by CO < 10 ppm. Weight, waist and hip circumference and percentage body fat are measured at each visit. \ud \ud Trial Registration\ud Current controlled trials ISRCTN83865809\ud \u

Galaxy Harassment and the Evolution of Clusters of Galaxies

Disturbed spiral galaxies with high rates of star formation pervaded clusters of galaxies just a few billion years ago, but nearby clusters exclude spirals in favor of ellipticals. ``Galaxy harassment" (frequent high speed galaxy encounters) drives the morphological transformation of galaxies in clusters, provides fuel for quasars in subluminous hosts and leaves detectable debris arcs. Simulated images of harassed galaxies are strikingly similar to the distorted spirals in clusters at $z \sim 0.4$ observed by the Hubble Space Telescope.Comment: Submitted to Nature. Latex file, 7 pages, 10 photographs in gif and jpeg format included. 10 compressed postscript figures and text available using anonymous ftp from ftp://ftp-hpcc.astro.washington.edu/pub/hpcc/moore/ (mget *) Also available at http://www-hpcc.astro.washington.edu/papers

Interface modification of clay and graphene platelets reinforced epoxy nanocomposites: a comparative study

The interface between the matrix phase and dispersed phase of a composite plays a critical role in influencing its properties. However, the intricate mecha-nisms of interface are not fully understood, and polymer nanocomposites are no exception. This study compares the fabrication, morphology, and mechanical and thermal properties of epoxy nanocomposites tuned by clay layers (denoted as m-clay) and graphene platelets (denoted as m-GP). It was found that a chemical modification, layer expansion and dispersion of filler within the epoxy matrix resulted in an improved interface between the filler mate-rial and epoxy matrix. This was confirmed by Fourier transform infrared spectroscopy and transmission electron microscope. The enhanced interface led to improved mechanical properties (i.e. stiffness modulus, fracture toughness) and higher glass transition temperatures (Tg) compared with neat epoxy. At 4 wt% m-GP, the critical strain energy release rate G1c of neat epoxy improved by 240 % from 179.1 to 608.6 J/m2 and Tg increased from 93.7 to 106.4 �C. In contrast to m-clay, which at 4 wt%, only improved the G1c by 45 % and Tg by 7.1 %. The higher level of improvement offered by m-GP is attributed to the strong interaction of graphene sheets with epoxy because the covalent bonds between the carbon atoms of graphene sheets are much stronger than silicon-based clay