Increasing fishing pressure on sharks stocks over recent decades has resulted in declines of many populations and led to increasing concerns for their conservation. The extent of these declines, ...however, has been highly variable—the result of the level of fishing, ocean conditions, and the life history of individual species. Two recent articles have described the collapse and possible extirpation of shark populations in the northwest Atlantic Ocean and Gulf of Mexico. Herein, we examine the results of these two papers commenting on the data sets used, comparing them to other available data sets, and critically evaluating the analyses and conclusions. We argue that these conclusions have been overstated because: (1) the analyses were based on a limited number of data sets, (2) the data sets themselves are inadequate to describe the status of all shark populations in the northwest Atlantic Ocean and Gulf of Mexico reported in these studies, (3) available data sets that could produce different conclusions were not utilized, (4) some factors were not taken into account that could have biased the results, (5) there were no alternate hypotheses presented evaluating other causes of the perceived decline, and (6) the authors did not consider any current stock assessments, which in several cases report the status of sharks to be considerably healthier than asserted.
ESGE recommends cold snare polypectomy (CSP) as the preferred technique for removal of diminutive polyps (size ≤ 5 mm). This technique has high rates of complete resection, adequate tissue sampling ...for histology, and low complication rates. (High quality evidence, strong recommendation.)
ESGE suggests CSP for sessile polyps 6 - 9 mm in size because of its superior safety profile, although evidence comparing efficacy with hot snare polypectomy (HSP) is lacking. (Moderate quality evidence, weak recommendation.)
ESGE suggests HSP (with or without submucosal injection) for removal of sessile polyps 10 - 19 mm in size. In most cases deep thermal injury is a potential risk and thus submucosal injection prior to HSP should be considered. (Low quality evidence, strong recommendation.)
ESGE recommends HSP for pedunculated polyps. To prevent bleeding in pedunculated colorectal polyps with head ≥ 20 mm or a stalk ≥ 10 mm in diameter, ESGE recommends pretreatment of the stalk with injection of dilute adrenaline and/or mechanical hemostasis. (Moderate quality evidence, strong recommendation.)
ESGE recommends that the goals of endoscopic mucosal resection (EMR) are to achieve a completely snare-resected lesion in the safest minimum number of pieces, with adequate margins and without need for adjunctive ablative techniques. (Low quality evidence; strong recommendation.)
ESGE recommends careful lesion assessment prior to EMR to identify features suggestive of poor outcome. Features associated with incomplete resection or recurrence include lesion size > 40 mm, ileocecal valve location, prior failed attempts at resection, and size, morphology, site, and access (SMSA) level 4. (Moderate quality evidence; strong recommendation.)
For intraprocedural bleeding, ESGE recommends endoscopic coagulation (snare-tip soft coagulation or coagulating forceps) or mechanical therapy, with or without the combined use of dilute adrenaline injection. (Low quality evidence, strong recommendation.)An algorithm of polypectomy recommendations according to shape and size of polyps is given (Fig. 1).
Interactions between early life and adult insults on lung function decline are not well understood, with most studies investigating prebronchodilator (pre-BD) FEV
decline.
To investigate ...relationships between adult risk factors and pre- and post-BD lung function decline and their potential effect modification by early life and genetic factors.
Multiple regression was used to examine associations between adult exposures (asthma, smoking, occupational exposures, traffic pollution, and obesity) and decline in both pre- and post-BD spirometry (forced expiratory volume in 1 s FEV
, forced vital capacity FVC, and FEV
/FVC) between ages 45 and 53 years in the Tasmanian Longitudinal Health Study (
= 857). Effect modification of these relationships by childhood respiratory risk factors, including low childhood lung function and GST (glutathione S-transferase) gene polymorphisms, was investigated.
Baseline asthma, smoking, occupational exposure to vapors/gases/dusts/fumes, and living close to traffic were associated with accelerated decline in both pre- and post-BD FEV
. These factors were also associated with FEV
/FVC decline. Occupational exposure to aromatic solvents was associated with pre-BD but not post-BD FEV
decline. Maternal smoking accentuated the effect of personal smoking on pre- and post-BD FEV
decline. Lower childhood lung function and having the GSTM1 null allele accentuated the effect of occupational exposure to vapors/gases/dusts/fumes and personal smoking on post-BD FEV
decline. Incident obesity was associated with accelerated decline in FEV
and more pronounced in FVC.
This study provides new evidence for accentuation of individual susceptibility to adult risk factors by low childhood lung function, GSTM1 genotype, and maternal smoking.
Increased levels of IL-6 are documented in asthma, but its contribution to the pathology is unknown. Asthma is characterized by airway wall thickening due to increased extracellular matrix ...deposition, inflammation, angiogenesis, and airway smooth muscle (ASM) mass. IL-6 binds to a specific membrane-bound receptor, IL-6 receptor-alpha (mIL-6Ralpha), and subsequently to the signaling protein gp130. Alternatively, IL-6 can bind to soluble IL-6 recpetor-alpha (sIL-6Ralpha) to stimulate membrane receptor-deficient cells, a process called trans-signaling. We discovered that primary human ASM cells do not express mIL-6Ralpha and, therefore, investigated the effect of IL-6 trans-signaling on the pro-remodeling phenotype of ASM. ASM required sIL-6Ralpha to activate signal transducer and activator 3, with no differences observed between cells from asthmatic subjects compared with controls. Further analysis revealed that IL-6 alone or with sIL-6Ralpha did not induce release of matrix-stimulating factors (including connective tissue growth factor, fibronectin, or integrins) and had no effect on mast cell adhesion to ASM or ASM proliferation. However, in the presence of sIL-6Ralpha, IL-6 increased eotaxin and VEGF release and may thereby contribute to local inflammation and vessel expansion in airway walls of asthmatic subjects. As levels of sIL-6Ralpha are increased in asthma, this demonstration of IL-6 trans-signaling in ASM has relevance to the development of airway remodeling.
Telehealth offers the potential to meet the needs of underserved populations in remote regions. The purpose of this study was a proof-of-concept to determine whether voice therapy can be delivered ...effectively remotely. Treatment outcomes were evaluated for a vocal rehabilitation protocol delivered under 2 conditions: with the patient and clinician interacting within the same room (conventional group) and with the patient and clinician in separate rooms, interacting in real time via a hard-wired video camera and monitor (video teleconference group). Seventy-two patients with voice disorders served as participants. Based on evaluation by otolaryngologists, 31 participants were diagnosed with vocal nodules, 29 were diagnosed with edema, 9 were diagnosed with unilateral vocal fold paralysis, and 3 presented with vocal hyperfunction with no laryngeal pathology. Fifty-one participants (71%) completed the vocal rehabilitation protocol. Outcome measures included perceptual judgments of voice quality, acoustic analyses of voice, patient satisfaction ratings, and fiber-optic laryngoscopy. There were no differences in outcome measures between the conventional group and the remote video teleconference group. Participants in both groups showed positive changes on all outcome measures after completing the vocal rehabilitation protocol. Reasons for participants discontinuing therapy prematurely provided support for the telehealth model of service delivery.
Dharmage SC, Perret JL, Burgess JA, et al. Int J Chron Obstruct Pulmon Dis. 2016;11:1911–1920. On page 1911, the author list “Shyamali C Dharmage,1 Jennifer L Perret,1,2 John A Burgess,1 Caroline J ...Lodge,1 David P Johns,3 Paul S Thomas,4 Graham G Giles,1,5 John L Hopper,1,6 Michael J Abramson,7,8 E Haydn Walters,3,9 Melanie C Matheson1” should have read “Shyamali C Dharmage,1,* Jennifer L Perret,1,2,* John A Burgess,1 Caroline J Lodge,1 David P Johns,3 Paul S Thomas,4 Graham G Giles,1,5 John L Hopper,1,6 Michael J Abramson,7,8 E Haydn Walters,3,9 Melanie C Matheson1”, and was missing the following statement “*These authors contributed equally to this work”.
Summary
Background
Markers of microbial exposure are thought to be associated with risk of allergic sensitization; however, the associations are inconsistent and may be related to gene‐environment ...interactions.
Objective
To examine the relationship between polymorphisms in the CD14 gene and allergic sensitization and whether sibling exposure, as a marker of microbial exposure, modified this relationship.
Methods
We used data from the Tasmanian Longitudinal Health Study and the Melbourne Atopy Cohort Study. Two CD14 polymorphisms were genotyped. Allergic sensitization was defined by a positive response to a skin prick test. Sibling exposure was measured as cumulative exposure to siblings before age 6 months, 2 and 4 years. Logistic regression and multi‐level mixed‐effects logistic regression were used to examine the associations. Effect estimates across the cohorts were pooled using random‐effects meta‐analysis.
Results
CD14 SNPs were not individually associated with allergic sensitization in either cohort. In TAHS, cumulative sibling exposure before age 6 months, 2 and 4 years was each associated with a reduced risk of allergic sensitization at age 45 years. A similar effect was observed in MACS. Meta‐analysis across the two cohorts showed consistent evidence of an interaction between cumulative sibling exposure before 6 months and the rs5744455‐SNP (P = 0.001) but not with the rs2569190‐SNP (P = 0.60). The pooled meta‐analysis showed that the odds of sensitization with increasing cumulative exposure to sibling before 6 months of age was 20.9% smaller in those with the rs5744455‐C‐allele than the T‐allele (OR = 0.83 vs 1.05, respectively).
Conclusion and Clinical Relevance
Cumulative sibling exposure reduced the risk of sensitization from childhood to middle age in genetically susceptible individuals.
In the yeast Saccharomyces cerevisiae, mitochondria are elongated organelles which form a reticulum around the ceil periphery. To determine the mechanism by which mitochondrial shape is established ...and maintained, we screened yeast mutants for those defective in mitochondrial morphology. One of these mutants, mmm1, is temperature-sensitive for the external shape of its mitochondria. At the restrictive temperature, elongated mitochondria appear to quickly collapse into large, spherical organelles. Upon return to the permissive temperature, wild-type mitochondrial structure is restored. The morphology of other cellular organelles is not affected in mmm1 mutants, and mmml does not disrupt normal actin or tubulin organization. Cells disrupted in the MMM1 gene are inviable when grown on nonfermentable carbon sources and show abnormal mitochondrial morphology at all temperatures. The lethality of mmm1 mutants appears to result from the inability to segregate the aberrant-shaped mitochondria into daughter cells. Mitochondrial structure is therefore important for normal cell function. Mmm1p is located in the mitochondrial outer membrane, with a large carboxyl-terminal domain facing the cytosol. We propose that Mmm1p maintains mitochondria in an elongated shape by attaching the mitochondrion to an external framework, such as the cytoskeleton
Bradyzide is from a novel class of rodent‐selective non‐peptide B
2
bradykinin antagonists (1‐(2‐Nitrophenyl)thiosemicarbazides).
Bradyzide has high affinity for the rodent B
2
receptor, displacing
...3
H‐bradykinin binding in NG108‐15 cells and in Cos‐7 cells expressing the rat receptor with K
I
values of 0.51±0.18 n
M
(
n
=3) and 0.89±0.27 n
M
(
n
=3), respectively.
Bradyzide is a competitive antagonist, inhibiting B
2
receptor‐induced
45
Ca efflux from NG108‐15 cells with a pK
B
of 8.0±0.16 (
n
=5) and a Schild slope of 1.05.
In the rat spinal cord and tail preparation, bradyzide inhibits bradykinin‐induced ventral root depolarizations (IC
50
value; 1.6±0.05 n
M
(
n
=3)).
Bradyzide is much less potent at the human than at the rodent B
2
receptor, displacing
3
H‐bradykinin binding in human fibroblasts and in Cos‐7 cells expressing the human B
2
receptor with K
I
values of 393±90 n
M
(
n
=3) and 772±144 n
M
(
n
=3), respectively. Bradyzide inhibits bradykinin‐induced
3
H‐inositol trisphosphate (IP
3
) formation with IC
50
values of 11.6±1.4 n
M
(
n
=3) at the rat and 2.4±0.3 μ
M
(
n
=3) at the human receptor.
Bradyzide does not interact with a range of other receptors, including human and rat B
1
bradykinin receptors.
Bradyzide is orally available and blocks bradykinin‐induced hypotension and plasma extravasation.
Bradyzide shows long‐lasting oral activity in rodent models of inflammatory hyperalgesia, reversing Freund's complete adjuvant (FCA)‐induced mechanical hyperalgesia in the rat knee joint (ED
50
, 0.84 μmol kg
−1
; duration of action >4 h). It is equipotent with morphine and diclofenac, and 1000 times more potent than paracetamol, its maximal effect exceeding that of the non‐steroidal anti‐inflammatory drugs (NSAIDs). Bradyzide does not exhibit tolerance when administered over 6 days.
In summary, bradyzide is a potent, orally active, antagonist of the B
2
bradykinin receptor, with selectivity for the rodent over the human receptor.
British Journal of Pharmacology
(2000)
129
, 77–86; doi:
10.1038/sj.bjp.0703012
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