35 research outputs found
Mindfulness-based cognitive therapy v. group psychoeducation for people with generalised anxiety disorder: randomised controlled trial
Background:
Research suggests that an 8-week mindfulness-based cognitive therapy (MBCT) course may be effective for generalised anxiety disorder (GAD).
Aims:
To compare changes in anxiety levels among participants with GAD randomly assigned to MBCT, cognitive–behavioural therapy-based psychoeducation and usual care.
Method:
In total, 182 participants with GAD were recruited (trial registration number: CUHK_CCT00267) and assigned to the three groups and followed for 5 months after baseline assessment with the two intervention groups followed for an additional 6 months. Primary outcomes were anxiety and worry levels.
Results:
Linear mixed models demonstrated significant group × time interaction (F(4,148) = 5.10, P = 0.001) effects for decreased anxiety for both the intervention groups relative to usual care. Significant group × time interaction effects were observed for worry and depressive symptoms and mental health-related quality of life for the psychoeducation group only.
Conclusions:
These results suggest that both of the interventions appear to be superior to usual care for the reduction of anxiety symptoms
A Model to Induce Low Temperature Trauma for in vitro Astrogliosis Study*
Astrogliosis is an inevitable and rapid response of astrocytes to physical, chemical and pathological injuries. To study astrogliosis, we developed a reproducible in vitro model in which low temperature injury to cultured astrocytes could be induced by placing the culture dish onto a copper pipe pre-cooled by liquid nitrogen. Using this model, the relationship between the temperature decline and the severity of cellular damage was analyzed. An increase in the expression of some known injury-related proteins, such as glial fibrillary acidic protein (GFAP), immediate early response genes (IEGs), and heat shock proteins 70 (HSP70), was demonstrated in astrocytes after low temperature trauma. With the use of this low temperature trauma model, the flexibility in the temperature control and injury area may allow researchers to evaluate cryotherapy and cryosurgery, which could be applicable to future development of quality health care
Robust estimation of bacterial cell count from optical density
Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries
Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely
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Protein Isomerization in Aging Diseases: Mass Spectrometry Strategies for Identifying and Locating Isomerized Residues
Comprehending protein structures is fundamental to understanding their functions and interactions at the molecular level. Long-lived human proteins (LLPs) are susceptible to damage associated with aging-related diseases such as cataracts and Alzheimer's disease (AD). Alternation in chirality from L to D in canonical amino acids does not have any mass shift, yet, it can modify the protein structure, alter its functions, and disrupt the cellular balance. Analytical techniques such as liquid chromatography and mass spectrometry (MS) have been utilized to identify isomers in LLPs. MS is a powerful and versatile tool for proteomic studies and structural characterization. Despite peptide isomers having no mass shifts, MS can differentiate isomers through their fragmentation patterns. This dissertation presents several innovative MS-based strategies for identifying and locating peptide isomerized residues. Our statistical framework can distinguish several types of isomers, including L/D stereoisomers and Leu/Ile, even with some standard fragmentation methods, such as collision-induced dissociation (CID) and higher-energy dissociation (HCD). This method can identify peptide isomers collected via direct infusion and liquid chromatography LC-MS. We successfully identified various isomers in human eye lens lysis, which shows the potential application to other biological samples. Secondly, incorporating ion mobility spectrometry (IMS) with mass spectrometry has also been utilized for isomer differentiation. The isomeric fragment ions were separated in the gas phase and had different arrival times based on their structural differences. This arrival time shift can locate in the isomerized residues, while the fragmentation patterns can also be used to identify isomers. This method provides two-dimensional data that enables confident isomer differentiation. Lastly, an efficient and accessible method for locating isomerized residues has been introduced using tandem mass spectrometry, which includes an improved R-value method incorporated with statistical analyses. The isomerized site can be pinpointed in peptides using CID-CID or CID-HCD. This method is accessible for instruments equipped with ion traps and allows for trivial isomer identification. The efficient and accessible method allows for the quantification of isomers in a mixture, and identifying isomerized residue in LLPs may reveal the relationship between isomerization and aging diseases
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Localizing Isomerized Residue Sites in Peptides with Tandem Mass Spectrometry.
Isomerized amino acid residues have been identified in many peptides extracted from tissues or excretions of humans and animals. These isomerized residues can play key roles by affecting biological activity or by exerting an influence on the process of aging. Isomerization occurs spontaneously and does not result in a mass shift. Thus, identifying and localizing isomerized residues in biological samples is challenging. Herein, we introduce a fast and efficient method using tandem mass spectrometry (MS) to locate isomerized residues in peptides. Although MS2 spectra are useful for identifying peptides that contain an isomerized residue, they cannot reliably localize isomerization sites. We show that this limitation can be overcome by utilizing MS3 experiments to further evaluate each fragment ion from the MS2 stage. Comparison at the MS3 level, utilizing statistical analyses, reveals which MS2 fragments differ between samples and, therefore, must contain the isomerized sites. The approach is similar to previous work relying on ion mobility to discriminate MS2 product ions by collision cross-section. The MS3 approach can be implemented using either ion-trap or beam-type collisional activation and is compatible with the quantification of isomer mixtures when coupled to a calibration curve. The method can also be implemented in combination with liquid chromatography in a targeted approach. Enabling the identification and localization of isomerized residues in peptides with an MS-only methodology will expand accessibility to this important information
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Statistical Framework for Identifying Differences in Similar Mass Spectra: Expanding Possibilities for Isomer Identification
Isomeric molecules are important analytes in many biological and chemical arenas, yet their similarity poses challenges for many analytical methods, including mass spectrometry (MS). Tandem-MS provides significantly more information about isomers than intact mass analysis, but highly similar fragmentation patterns are common and include cases where no unique m/z peaks are generated between isomeric pairs. However, even in such situations, differences in peak intensity can exist and potentially contain additional information. Herein, we present a framework for comparing mass spectra that differ only in terms of peak intensity and include calculation of a statistical probability that the spectra derive from different analytes. This framework allows for confident identification of peptide isomers by collision-induced dissociation, higher-energy collisional dissociation, electron-transfer dissociation, and radical-directed dissociation. The method successfully identified many types of isomers including various d/l amino acid substitutions, Leu/Ile, and Asp/IsoAsp. The method can accommodate a wide range of changes in instrumental settings including source voltages, isolation widths, and resolution without influencing the analysis. It is shown that quantification of the composition of isomeric mixtures can be enabled with calibration curves, which were found to be highly linear and reproducible. The analysis can be implemented with data collected by either direct infusion or liquid-chromatography MS. Although this framework is presented in the context of isomer characterization, it should also prove useful in many other contexts where similar mass spectra are generated