Stricture dilation via balloon-assisted endoscopy in Crohn's disease: approach and intraprocedural outcomes with the single-balloon and double-balloon systems.

Background: Despite recent emerging literature involving the utility of endoscopic balloon dilation (EBD) of strictures via balloon-assisted endoscopy (BAE), specifically regarding the management of Crohn's disease (CD), the optimal clinical approach with balloon systems has been largely neglected in academic literature. Objectives: This study assesses the intra-procedural success and safety of EBD via BAE for small bowel CD strictures while detailing our clinical approach and technique. Secondarily, we compare the single-balloon endoscope (SBE) and double-balloon endoscope (DBE) systems for EBD-related outcomes. Design: Retrospective consecutive patient cohort analysis. Methods: We retrospectively assessed a consecutive small bowel CD patient cohort undergoing BAE at the University of Alberta Hospital endoscopy unit from 2013 to 2020. The primary endpoint discerned the safety and immediate success rate of EBD during endoscopy, and comparisons of the dilation parameters and efficacy of SBE versus DBE were assessed as secondary outcomes. Results: During the study period, 87 patients (44 male) with a mean age of 56 ± 14.7 years underwent 179 endoscopic procedures (92 DBE and 87 SBE). Of 358 strictures encountered, 320 (89.4%) were successfully dilated and traversed. The mean maximum dilation diameter was 15.76 ± 2.10 mm. There were no perforations or major adverse events. Conclusion: EBD via BAE is a safe procedure in small bowel CD with a high intraprocedural success rate. Overall, SBE had a higher success rate in traversing strictures before and after dilation using our technique. This analysis is limited by the retrospective nature of our study and must be balanced against the inherent benefits of the DBE system.

Outcome and approach of small-bowel stricture dilation using balloon-assisted endoscopy in patients with Crohn's disease This study investigated the safety and success of using balloon-assisted endoscopy as a method to dilate small bowel strictures in patients with Crohn's disease. As a secondary outcome, we compared the overall safety and success between two different types of endoscopic systems: the single- and double-balloon systems.

Paleolakes and socioecological implications of last glacial "greening" of the South African interior.

Determining the timing and drivers of Pleistocene hydrological change in the interior of South Africa is critical for testing hypotheses regarding the presence, dynamics, and resilience of human populations. Combining geological data and physically based distributed hydrological modeling, we demonstrate the presence of large paleolakes in South Africa's central interior during the last glacial period, and infer a regional-scale invigoration of hydrological networks, particularly during marine isotope stages 3 and 2, most notably 55 to 39 ka and 34 to 31 ka. The resulting hydrological reconstructions further permit investigation of regional floral and fauna responses using a modern analog approach. These suggest that the climate change required to sustain these water bodies would have replaced xeric shrubland with more productive, eutrophic grassland or higher grass-cover vegetation, capable of supporting a substantial increase in ungulate diversity and biomass. The existence of such resource-rich landscapes for protracted phases within the last glacial period likely exerted a recurrent draw on human societies, evidenced by extensive pan-side artifact assemblages. Thus, rather than representing a perennially uninhabited hinterland, the central interior's underrepresentation in late Pleistocene archeological narratives likely reflects taphonomic biases stemming from a dearth of rockshelters and regional geomorphic controls. These findings suggest that South Africa's central interior experienced greater climatic, ecological, and cultural dynamism than previously appreciated and potential to host human populations whose archaeological signatures deserve systematic investigation.

Ripples at edges of blooming lilies and torn plastic sheets.

Ripples arise at edges of petals of blooming Lilium casablanca flowers and at edges of torn plastic sheets. In both systems, ripples are a consequence of excess length along the edge of a sheet. Through the use of time-lapse videos of blooming lilies and published images of torn plastic sheets, we find that ripples in both systems are well described by the scaling relationship a∝w(L-w), where a is amplitude, w is wavelength, and L is arc length. A phenomenological relationship previously reported for self-similar ripple patterns, namely ⟨a⟩∝⟨w⟩, can be recovered by assuming that buckling stress is constant. Excess length along petal edges can also influence their overall Gaussian curvature, such that petals invert from a cup shape to a saddle shape upon blooming. Previous simulations of these shape changes have assumed that petal thickness decreases at least quadratically. Here, we evaluate tomograms of several varieties of lily buds and find that this assumption is valid along the short axis of the buds, but not the long axis. A challenge of employing traditional tomography methods to measure petal thickness is that the sample is destroyed; a single bud cannot be followed through the entire blooming process. To address this challenge, we provide proof of principle that the nondestructive, label-free method of x-ray tomography produces high-contrast three-dimensional scans on time scales short enough to follow lily blooming.

Aroma Acupoint Therapy for Symptom Management with Adolescent Patients: Early Experiences from School-Based Health Centers.

Objectives: The American Academy of Pediatrics has long recognized a need for more resources for integrative medicine for health care providers and for patients. The aim of this study was to introduce Aroma Acupoint Therapy (AAT)-a relatively new integrative medicine modality using essential oils to activate acupoints-and to describe the early experiences of providers using AAT for adolescents at school-based health centers (SBHCs). Materials and Methods: This was a case series of 15 adolescents treated with 1 of 2 AAT specific protocols plus standard medical therapy between April 2018 and February 2019 at SBHCs. Of these 15 patients, ages 12-19, 14 were female. Clinical characteristics and treatment courses were abstracted by retrospective review of the patients' electronic medical records. The main outcomes and measures for this research were clinical characteristics, treatment courses and pre- and post-treatment pain scores for adolescents treated with AAT. Results: All 15 patients had nonspecific symptoms, including headaches, menstrual cramps, nausea, shortness of breath, chest pain, back pain, or dizziness. Pain scores were recorded in 8 of 15 encounters, and suggested improvements in most patients. Subjective documentation by the providers also suggested that most of these patients had reduced symptoms. Conclusions: With the call for nonopiate and integrative approaches to pain management, there is an urgent need to study the effectiveness of such modalities, such as AAT. It is safe, inexpensive, easy to learn, and is well-received by both health care providers and patients.

Electronic cigarettes: A position statement from the Thoracic Society of Australia and New Zealand.

The TSANZ develops position statements where insufficient data exist to write formal clinical guidelines. In 2018, the TSANZ addressed the question of potential benefits and health impacts of electronic cigarettes (EC). The working party included groups focused on health impacts, smoking cessation, youth issues and priority populations. The 2018 report on the Public Health Consequences of E-Cigarettes from the United States NASEM was accepted as reflective of evidence to mid-2017. A search for papers subsequently published in peer-reviewed journals was conducted in August 2018. A small number of robust and important papers published until March 2019 were also identified and included. Groups identified studies that extended, modified or contradicted the NASEM report. A total of 3793 papers were identified and reviewed, with summaries and draft position statements developed and presented to TSANZ membership in April 2019. After feedback from members and external reviewers, a collection of position statements was finalized in December 2019. EC have adverse lung effects and harmful effects of long-term use are unknown. EC are unsuitable consumer products for recreational use, part-substitution for smoking or long-term exclusive use by former smokers. Smokers who require support to quit smoking should be directed towards approved medication in conjunction with behavioural support as having the strongest evidence for efficacy and safety. No specific EC product can be recommended as effective and safe for smoking cessation. Smoking cessation claims in relation to EC should be assessed by established regulators.

The lipoprotein Pal stabilises the bacterial outer membrane during constriction by a mobilisation-and-capture mechanism.

Coordination of outer membrane constriction with septation is critical to faithful division in Gram-negative bacteria and vital to the barrier function of the membrane. This coordination requires the recruitment of the peptidoglycan-binding outer-membrane lipoprotein Pal at division sites by the Tol system. Here, we show that Pal accumulation at Escherichia coli division sites is a consequence of three key functions of the Tol system. First, Tol mobilises Pal molecules in dividing cells, which otherwise diffuse very slowly due to their binding of the cell wall. Second, Tol actively captures mobilised Pal molecules and deposits them at the division septum. Third, the active capture mechanism is analogous to that used by the inner membrane protein TonB to dislodge the plug domains of outer membrane TonB-dependent nutrient transporters. We conclude that outer membrane constriction is coordinated with cell division by active mobilisation-and-capture of Pal at division septa by the Tol system.

Nascent ß Structure in the Elongated Hydrophobic Region of a Gerstmann-Sträussler-Scheinker PrP Allele.

Prion diseases are neurodegenerative disorders caused by the misfolding of the cellular prion protein (PrPC). Gerstmann-Sträussler-Scheinker syndrome is an inherited prion disease with one early-onset allele (HRdup) containing an eight-amino-acid insertion; this LGGLGGYV insert is positioned after valine 129 (human PrPC sequence) in a hydrophobic tract in the natively disordered region. Here we have characterized the structure and explored the molecular motions and dynamics of HRdup PrP and a control allele. High-resolution NMR data suggest that the core of HRdup has a canonical PrPC structure, yet a nascent ß-structure is observed in the flexible elongated hydrophobic region of HRdup. In addition, using mouse PrPC sequence, we observed that a methionine/valine polymorphism at codon 128 (equivalent of methionine/valine 129 in human sequence) and oligomerization caused by high protein concentration affects conformational exchange dynamics at residue G130. We hypothesize that with the ß-structure at the N-terminus, the hydrophobic region of HRdup can adopt a fully extended configuration and fold back to form an extended ß-sheet with the existing ß-sheet. We propose that these structures are early chemical events in disease pathogenesis.

Reductions in emergency department visits after primary healthcare use of the UK National Poisons Information Service.

BACKGROUND: Suspected poisoning is a common cause of hospital admission internationally. In the United Kingdom, the National Poisons Information Service (NPIS), a network of four poisons units, provides specialist advice to health professionals on the management of poisoning by telephone and via its online poisoning information and management database, TOXBASE®. OBJECTIVE: To demonstrate the impact of NPIS telephone advice and TOXBASE® guidance on poisoning-related referrals to emergency departments (ED) from primary healthcare settings. METHODS: A telephone survey of primary healthcare providers calling the NPIS and an online survey of TOXBASE® primary care users were conducted to evaluate the effect of these services on poisoning-related ED referrals. Enquirers were asked to indicate whether referral was needed before and after using these information sources. RESULTS: The number of cases considered by enquirers appropriate for ED referral was reduced from 1178 (58.1%) before to 819 (40.4%) after the provision of telephone advice for 2028 cases (absolute reduction 17.7%, 95% CI 14.6, 20.7%) and from 410 (48.2%) before to 341 (40.1%) after consideration of TOXBASE® guidance for 851 cases (absolute reduction 8.1%, 95% CI 3.3, 12.9%). By extrapolating these figures over a full year, it is estimated that these services prevent approximately 41,000 ED referrals annually. CONCLUSIONS: The use of NPIS services significantly reduced ED referrals from primary healthcare services with resulting avoided healthcare costs exceeding the current annual NPIS budget. Further studies are needed to evaluate other potential benefits of accessing NPIS services.

Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression.

Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.

Abnormal vocal cord movement treated with botulinum toxin in patients with asthma resistant to optimised management.

BACKGROUND AND OBJECTIVE: Abnormal vocal cord movement may coexist with asthma and cause additional upper/middle airway obstruction. The condition may be a form of muscular dystonia that could contribute to asthma resistant to optimised treatments. Botulinum toxin causes temporary paralysis of muscle and may be an effective local treatment that improves asthma control. METHODS: In an observational study, we evaluated the benefits of unilateral vocal cord injection with botulinum toxin in 11 patients (total 24 injections). Subjects had asthma resistant to optimised treatment and abnormal vocal cord movement. Responses after botulinum toxin treatment were assessed using asthma control test (ACT) scores, vocal cord narrowing quantified by computerised tomography (CT) of the larynx and spirometry. Side-effects were recorded. RESULTS: ACT scores improved overall (9.1 ± 2.4 before and 13.5 ± 4.5 after treatment; difference 4.4 ± 4.2; P < 0.001). There was also an improvement in airway size on CT larynx (time below lower limit of normal at baseline 39.4 ± 37.63% and improved to 17.6 ± 25.6% after injection; P = 0.032). Spirometry was not altered. One patient experienced an asthma exacerbation but overall side-effects were moderate, chiefly dysphonia and dysphagia. CONCLUSIONS: Although a placebo effect cannot be ruled out, local injection of botulinum toxin may be an effective treatment for intractable asthma associated with abnormal vocal cord movement. Further mechanistic studies and a double-blind randomised controlled trial of botulinum toxin treatment are merited.

Conformation of the critical pH sensitive region of troponin depends upon a single residue in troponin I.

The calcium sensitivity of cardiac and skeletal muscle is reduced during cytosolic acidosis, and this inhibition is more pronounced in cardiac muscle. Replacing cardiac troponin I with skeletal troponin I reduces the pH sensitivity of cardiac muscle. This diminished pH sensitivity depends on a single amino acid difference in troponin I: an alanine in cardiac and a histidine in skeletal. Studies suggested that when this histidine is protonated, it forms an electrostatic interaction with glutamate 19 on the surface of cardiac troponin C. Structures of the skeletal and cardiac troponin complexes show very different conformations for the region of troponin I surrounding this residue. In this study, we determined the structure of skeletal troponin I bound to cardiac troponin C. Skeletal troponin I is found to bind to cardiac troponin C with histidine 130 in close proximity to glutamate 19. This conformation is homologous to the crystal structure of the skeletal troponin complex; but different than in the cardiac complex. We show that an A162H variant of cardiac troponin I adopts a conformation similar to the skeletal structure. The implications of these structural differences in the context of cardiac muscle regulation are discussed.

Lung T-cell responses to nontypeable Haemophilus influenzae in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation that persists after the cessation of smoking. T cells have a major role in driving inflammation in patients with COPD and are activated by specific antigens to produce mediators, such as cytokines. The antigens that activate lung T cells have not been clearly defined. Nontypeable Haemophilus influenzae (NTHi) is the dominant bacterium isolated from the lungs of patients with COPD. OBJECTIVE: We sought to measure the response of lung tissue T cells to stimulation with NTHi. METHODS: We obtained lung tissue from 69 subjects having lobectomies for lung cancer. Of the group, 39 subjects had COPD, and 30 without COPD were classified as control subjects. The lung tissue was dispersed into single-cell suspensions and stimulated with live NTHi. Cells were labeled with antibodies for 5 important inflammatory mediators in patients with COPD and analyzed by using flow cytometry. RESULTS: NTHi produced strong activation of both TH cells and cytotoxic T cells in the COPD cohort. The COPD cohort had significantly higher levels of cells producing TNF-α, IL-13, and IL-17 in both T-cell subsets. When control subjects were divided into those with and without a significant smoking history and compared with patients with COPD, there was a progressive increase in the numbers of T cells producing cytokines from nonsmoking control subjects to smoking control subjects to patients with COPD. CONCLUSION: NTHi activates lung T cells in patients with COPD. This proinflammatory profibrotic response might be a key cause of inflammation in patients with COPD and has implications for treatment.

Tsetse-transmitted trypanosomes--their biology, disease impact and control.

Tsetse-transmitted trypanosome infections of man and animals occur across large areas of sub-Saharan Africa and are a major cause of ill-health and death. Although many details of the biology of tsetse-transmitted trypanosomes and the diseases they cause have been clearly established their control has proved extremely difficult. In part this is because trypanosomes show amazing antigenic variation of their surface coat and this has prevented the development of an effective vaccine. Also the few drugs which are available for treatment are unsatisfactory and often have severe side-effects. Significant progress has been made through tsetse control but such programmes are expensive and frequently re-infestation occurs. There is an urgent need for more effective disease diagnostic methods, new safer drugs and more sustained international support for integrated control programmes.

Chest pain and exacerbations of bronchiectasis.

BACKGROUND: Bronchiectasis is a common disease and a major cause of respiratory morbidity. Chest pain has been described as occurring in the context of bronchiectasis but has not been well characterized. This study was performed to describe the characteristics of chest pain in adult bronchiectasis and to define the relationship of this pain to exacerbations. SUBJECTS AND METHODS: We performed a prospective study of 178 patients who were followed-up for 8 years. Subjects were reviewed on a yearly basis and assessed for the presence of chest pain. Subjects who had chest pain at the time of clinical review by the investigators were included in this study. Forty-four patients (25%) described respiratory chest pain at the time of assessment; in the majority of cases 39/44 (89%), this occurred with an exacerbation and two distinct types of chest pain could be described: pleuritic (n = 4) and non-pleuritic (n = 37), with two subjects describing both forms. The non-pleuritic chest pain occurred most commonly over both lower lobes and was mild to moderate in severity. The pain subsided as patients recovered. CONCLUSION: Non-pleuritic chest pain occurs in subjects with bronchiectasis generally in association with exacerbations.