Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle

Background: Acetylcholine, the primary parasympathetic neurotransmitter in the airways, plays an important role in bronchoconstriction and mucus production. Recently, it has been shown that acetylcholine, by acting on muscarinic receptors, is also involved in airway inflammation and remodelling. The mechanism(s) by which muscarinic receptors regulate inflammatory responses are, however, still unknown. Methods: The present study was aimed at characterizing the effect of muscarinic receptor stimulation on cytokine secretion by human airway smooth muscle cells (hASMc) and to dissect the intracellular signalling mechanisms involved. hASMc expressing functional muscarinic M(2) and M(3) receptors were stimulated with the muscarinic receptor agonist methacholine, alone, and in combination with cigarette smoke extract (CSE), TNF-alpha, PDGF-AB or IL-1 beta. Results: Muscarinic receptor stimulation induced modest IL-8 secretion by itself, yet augmented IL-8 secretion in combination with CSE, TNF-alpha or PDGF-AB, but not with IL-1 beta. Pretreatment with GF109203X, a protein kinase C (PKC) inhibitor, completely normalized the effect of methacholine on CSE-induced IL-8 secretion, whereas PMA, a PKC activator, mimicked the effects of methacholine, inducing IL-8 secretion and augmenting the effects of CSE. Similar inhibition was observed using inhibitors of I kappa B-kinase-2 (SC514) and MEK1/2 (U0126), both downstream effectors of PKC. Accordingly, western blot analysis revealed that methacholine augmented the degradation of I kappa B alpha and the phosphorylation of ERK1/2 in combination with CSE, but not with IL-1b in hASMc. Conclusions: We conclude that muscarinic receptors facilitate CSE-induced IL-8 secretion by hASMc via PKC dependent activation of I kappa B alpha and ERK1/2. This mechanism could be of importance for COPD patients usin

Will emergency and surgical patients participate in and complete alcohol interventions? A systematic review

<p>Abstract</p> <p>Background</p> <p>In the everyday surgical life, staff may experience that patients with Alcohol Use Disorders (AUDs) seem reluctant to participate in alcohol intervention programs. The objective was therefore to assess acceptance of screening and intervention as well as adherence to the intervention program among emergency department (ED) and surgical patients with AUDs.</p> <p>Methods</p> <p>A systematic literature search was followed by extraction of acceptance and adherence rates in ED and surgical patients. Numbers needed to screen (NNS) were calculated. Subgroup analyses were carried out based on different study characteristics.</p> <p>Results</p> <p>The literature search revealed 33 relevant studies. Of these, 31 were randomized trials, 28 were conducted in EDs and 31 evaluated the effect of brief alcohol intervention. Follow-up was mainly conducted after six and/or twelve months.</p> <p>Four in five ED patients accepted alcohol screening and two in three accepted participation in intervention. In surgical patients, two in three accepted screening and the intervention acceptance rate was almost 100%. The adherence rate was above 60% for up to twelve months in both ED and surgical patients. The NNS to identify one eligible AUD patient and to get one eligible patient to accept participation in alcohol intervention varied from a few up to 70 patients.</p> <p>The rates did not differ between randomized and non-randomized trials, brief and intensive interventions or validated and self-reported alcohol consumption. Adherence rates were not affected by patients' group allocation and type of follow-up.</p> <p>Conclusions</p> <p>Most emergency and surgical patients with AUD accept participation in alcohol screening and interventions and complete the intervention program.</p

NOAA-GFDL/FMS: 2023.03

&lt;h2&gt;[2023.03] - 2023-10-27&lt;/h2&gt; &lt;h3&gt;Known Issues&lt;/h3&gt; &lt;ul&gt; &lt;li&gt;GCC 9 and below as well as GCC 11.1.0 are unsupported due to compilation issues. See prior releases for more details.&lt;/li&gt; &lt;li&gt;&lt;code&gt;NO_QUAD_PRECISION&lt;/code&gt; macro is no longer set by FMS, the &lt;code&gt;ENABLE_QUAD_PRECISION&lt;/code&gt; macro has replaced prior usage of &lt;code&gt;NO_QUAD_PRECISION&lt;/code&gt;. &lt;code&gt;-DENABLE_QUAD_PRECISION&lt;/code&gt; should be set if quad precision is to be used, otherwise FMS will not use quad precision reals where applicable.&lt;/li&gt; &lt;/ul&gt; &lt;h3&gt;Added&lt;/h3&gt; &lt;ul&gt; &lt;li&gt;UNIT_TESTS: New unit tests have been created or and existing ones expanded on for any modules utilizing mixed precision support.&lt;/li&gt; &lt;/ul&gt; &lt;h3&gt;Changed&lt;/h3&gt; &lt;ul&gt; &lt;li&gt;MIXED PRECISION: Most subroutines and functions in FMS have been updated to simultaneously accept both 4 byte and 8 byte reals as arguments. This deprecates the &lt;code&gt;--enable-mixed-mode&lt;/code&gt; option, which enabled similar functionality but was limited to certain directories and was not enabled by default. To facilitate easier testing of these code changes, the CMake precision options for default real size were left in (along with an equivalent &lt;code&gt;--disable-r8-default&lt;/code&gt; flag for autotools). The resulting libraries will support mixed-precision real kinds regardless of default real size. It should also be noted that many routines that accept real arguments have been moved to include files along with headers in order to be compiled with both kinds. Most module level variables were explicitly declared as r8_kind for these updates.&lt;/li&gt; &lt;li&gt;Some type/module changes were made to facilitate mixed precision support. They are &lt;strong&gt;intended&lt;/strong&gt; to have minimal impact to other codebases:&lt;ul&gt; &lt;li&gt;COUPLER_TYPES: In coupler_types.F90, &lt;code&gt;coupler_nd_field_type&lt;/code&gt; and &lt;code&gt;coupler_nd_values_type&lt;/code&gt; have been renamed to indicate real kind value: &lt;code&gt;coupler_nd_real4/8_field_type&lt;/code&gt; and &lt;code&gt;coupler_nd_real4/8_values_type&lt;/code&gt;. The &lt;code&gt;bc&lt;/code&gt; field within &lt;code&gt;coupler_nd_bc_type&lt;/code&gt; was modified to use r8_kind within the value and field types, and an additional field added &lt;code&gt;bc_r4&lt;/code&gt; to use r4_kind values.&lt;/li&gt; &lt;li&gt;TRIDIAGONAL: Module state between r4 and r8 calls are distinct (ie. subsequent calls will only be affected by calls of the same precision). This behaviour can be changed via the &lt;code&gt;save_both_kinds&lt;/code&gt; optional argument to &lt;code&gt;tri_invert&lt;/code&gt;.&lt;/li&gt; &lt;/ul&gt; &lt;/li&gt; &lt;li&gt;CODE_STYLE: has been updated to reflect the formatting used for the mixed precision support updates.&lt;/li&gt; &lt;/ul&gt; &lt;h3&gt;Fixed&lt;/h3&gt; &lt;ul&gt; &lt;li&gt;DIAG_MANAGER: Tile number (ie. tileX) will now be added to filenames for sub-regional diagnostics.&lt;/li&gt; &lt;li&gt;MPP: Bug affecting non-intel compilers coming from uninitialized pointer in the &lt;code&gt;nest_domain_type&lt;/code&gt;&lt;/li&gt; &lt;li&gt;MPP: Bug fix for unallocated field causing seg faults in &lt;code&gt;mpp_check_field&lt;/code&gt;&lt;/li&gt; &lt;li&gt;FMS2_IO: Fixed segfault occuring from use of cray pointer remapping along with mpp_scatter/gather&lt;/li&gt; &lt;li&gt;TEST_FMS: Added various fixes for different compilers within test programs for fms2_io, mpp, diag_manager, parser, and sat_vapor_pres.&lt;/li&gt; &lt;li&gt;INTERPOLATOR: Deallocates fields in the type that were previously left out in &lt;code&gt;interpolator_end&lt;/code&gt;&lt;/li&gt; &lt;/ul&gt; &lt;h3&gt;Removed&lt;/h3&gt; &lt;ul&gt; &lt;li&gt;CPP MACROS:&lt;ul&gt; &lt;li&gt;&lt;code&gt;no_4byte_reals&lt;/code&gt; was removed and will not set any additional macros if used. &lt;code&gt;no_8byte_integers&lt;/code&gt; is still functional.&lt;/li&gt; &lt;li&gt;&lt;code&gt;NO_QUAD_PRECISION&lt;/code&gt; was removed. It was conditionally set if ENABLE_QUAD_PRECISION was undefined. ENABLE_QUAD_PRECISION should be used in model components instead (logic is flipped)&lt;/li&gt; &lt;li&gt;&lt;code&gt;use_netCDF&lt;/code&gt; was set by autotools previously but wasn't consistently used in the code. FMS should always be compiled with netcdf installed so this was removed with the exception of its use in deprecated IO modules.&lt;/li&gt; &lt;/ul&gt; &lt;/li&gt; &lt;li&gt;DRIFTERS: The drifters subdirectory has been deprecated. It will only be compiled if using the &lt;code&gt;-Duse_drifters&lt;/code&gt; CPP flag.&lt;/li&gt; &lt;/ul&gt; &lt;h3&gt;Tag Commit Hashes&lt;/h3&gt; &lt;ul&gt; &lt;li&gt;2023.03-beta1 06b94a7f574e7794684b8584391744ded68e2989&lt;/li&gt; &lt;li&gt;2023.03-alpha3 b25a7c52a27dfd52edc10bc0ebe12776af0f03df&lt;/li&gt; &lt;li&gt;2023.03-alpha2 9983ce308e62e9f7215b04c227cebd30fd75e784&lt;/li&gt; &lt;li&gt;2023.03-alpha1 a46bd94fd8dd1f6f021501e29179003ff28180ec&lt;/li&gt; &lt;/ul&gt