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Cannabis use is more prevalent among youth at clinical high-risk (CHR) for psychosis than healthy controls (HC). There is mixed evidence as to whether cannabis use is associated with increased severity of attenuated psychotic symptoms (APS) or whether current cannabis use is associated with the transition to psychosis. This study aims to assess cannabis use differences between CHR youth and HC and the impact of cannabis use on APS, clinical status, and transition to psychosis. Participants were from the North American Prodrome Longitudinal Study-3, a prospective longitudinal study including 710 individuals, age 12-30, meeting criteria for a psychosis risk syndrome based on the Structured Interview for Psychosis-Risk Syndromes, and 96 HC. Cannabis use, frequency, and severity of use were assessed with the Alcohol Use Scale/Drug Use Scale. Current and past cannabis use disorders were assessed with the Structured Clinical Interview for DSM-5. Compared to HC, CHR individuals reported significantly increased lifetime cannabis use, during the past six months, and at baseline; greater frequency and severity of cannabis use; and increased prevalence of cannabis use disorder. Relative to CHR youth without cannabis use, CHR cannabis users had significantly higher ratings on baseline grandiosity and lower 12-months social anhedonia. Severity of cannabis was unrelated to clinical status at 2-years, and it did not differentiate CHR individuals who transitioned to psychosis from those who did not. However, a major limitation was that the current number of CHR cannabis users was small, and survival analyses resulted in a smaller power than the 80 % recommended.

The heterogeneity of schizophrenia (SCZ) regarding psychopathology, illness trajectory and their inter-relationships with underlying neural substrates remain incompletely understood. In a bid to reduce illness heterogeneity using neural substrates, our study aimed to replicate the findings of an earlier study by Chand et al. (2020). We employed brain structural measures for subtyping SCZ patients, and evaluate each subtype's relationship with clinical features such as illness duration, psychotic psychopathology, and additionally deficit status.

Overall, 240 subjects (160 SCZ patients, 80 healthy controls) were recruited for this study. The participants underwent brain structural magnetic resonance imaging scans and clinical rating using the Positive and Negative Syndrome Scale. Neuroanatomical subtypes of SCZ were identified using "Heterogeneity through discriminative analysis" (HYDRA), a clustering technique which accounted for relevant covariates and the inter-group normalized percentage changes in brain volume were also calculated.

As replicated, two neuroanatomical subtypes (SG-1 and SG-2) were found amongst our patients with SCZ. The subtype SG-1 was associated with enlargements in the third and lateral ventricles, volume increase in the basal ganglia (putamen, caudate, pallidum), longer illness duration, and deficit status. The subtype SG-2 was associated with reductions of cortical and subcortical structures (hippocampus, thalamus, basal ganglia).

These replicated findings have clinical implications in the early intervention, response monitoring, and prognostication of SCZ. Future studies may adopt a multi-modal neuroimaging approach to enhance insights into the neurobiological composition of relevant subtypes.

These replicated findings have clinical implications in the early intervention, response monitoring, and prognostication of SCZ. Future studies may adopt a multi-modal neuroimaging approach to enhance insights into the neurobiological composition of relevant subtypes.

Clavicular and scapular orientations vary between neck pain patients as do clinical features and responses (changes in pain and rotation range) to scapular repositioning. Associations between these factors are unknown.

To identify subgroups of neck pain patients based on three-dimensional (3D) measures of clavicular and scapular orientations and differences between subgroups in clinical characteristics and responses to scapular repositioning.

Cross-sectional study.

Eligible participants were recruited as part of a larger study. The 3D clavicular and scapular orientations were analyzed on the more painful side of the neck using a hierarchical cluster analysis. Clinical characteristics were neck pain location, intensity, duration, disability and presence of headache. Responses to scapular repositioning were classified as "yes and no".

Fifty-eight participants (29 responsive; 29 non-responsive to scapular repositioning) participated in the study. Analysis identified two distinct subgroups subgroup1 had greater clavicular retraction and scapular downward rotation (n=26) and subgroup2 had greater clavicular elevation and scapular internal rotation and anterior tilt (n=32). Headache and dominant pain in the upper neck were more frequent in subgroup 1 while dominant pain in the lower neck was frequent in subgroup 2 (p<0.01). Most participants who responded positively to scapular repositioning (88.5%) were in subgroup1 and most non-responsive participants (81.2%) in subgroup2.

The 3D clavicular and scapular orientations identified two subgroups of neck pain patients. Participants with predominantly downward scapular rotation were distinguished by pain in the upper neck, presence of headache and a positive response to scapular repositioning.

The 3D clavicular and scapular orientations identified two subgroups of neck pain patients. Participants with predominantly downward scapular rotation were distinguished by pain in the upper neck, presence of headache and a positive response to scapular repositioning.The early intervention is essential, and later development cannot compensate for this initial generation of an antibody drug. Especially for sequence variants (SVs), should cause concern during the early bioprocess development. The advancement of bioprocess development is paralleled by development of state-of-the-art analytical methods that will provide further information. In the present study, a mass spectrometry (MS)-based multi-attribute method (MAM) was used to simultaneously monitor the SVs and other quality attributes in the early bioprocess development of ofatumumab, and a sequence variant (SV) was detected by a subunit-based MAM. Subsequently, the variant was further identified by MS/MS and confirmed by adding a synthetic peptide. Tacedinaline order Furthermore, the content of the SV was detected via DNA sequencing. The levels of the variant (T175A mutant) in the light chain were demonstrate to be nearly consistent at the DNA and protein levels, suggesting that the mutation may have negligible effect on both the transcriptional and translational levels. Collectively, these results indicate that broad-spectrum, rapid, and accurate platform such as MS-based MAM should be implemented to quality control for the early development of therapeutic proteins, it will also be important to establish an effective and integrated MAM to control SVs during therapeutic proteins development.The plasma concentration of lamotrigine (LTG) and its metabolites has great interindividual variability. An UHPLC-MS/MS method for simultaneous determination of LTG and lamotrigine N2-glucuronide (LTG N2-GLUC), lamotrigine N2-oxide was developed, validated, and applied in 58 plasma samples. The ion transition was m/z 256.0 > 144.9 for LTG, 432.1 > 256.0 for LTG N2-GLUC, 272.2 > 241.9 for LTG N2-oxide, and 259.1 > 144.8 for LTG-13C3 (internal standard). The flow rate was 0.4 mL/min with a run time of 3 min. The calibration range was 0.025-2 mg/L for LTG and LTG N2-GLUC, and 0.000625-0.05 mg/L for LTG N2-oxide. For all analytes, the intra-day and inter-day bias and imprecision were -11.7-5.7 % and less than 14.3 %, and the internal standard normalized recovery and matrix factor were 91.7-101.5 % and 98.1-110.1 % with CV less then 13. 7%. Ten- and twenty-fold dilution with blank plasma did not affect the analysis. All analytes were stable in plasma at room temperature for 8 h, at -80 °C for 80 days, and after 3 freeze-thaw cycles. The LTG N2-GLUC/LTG ratio was 0.44 in LTG monotherapy group. The ratio was reduced to 0.17 when co-administrated with valproic acid, while elevated to 0.82 when co-administrated with enzyme inducer. In conclusion, this method is suitable for simultaneous determination of LTG, LTG N2-GLUC and LTG N2-oxide in human plasma.Polysaccharides from natural medicines, being safe and effective natural mixtures, show great potential to be developed into botanical drugs. However, there is yet one polysaccharide-based case that has fulfilled the Botanical Guidance definition of a botanical drug product. One of the reasons is the analytical methods commonly used for qualitative and quantitative analysis of polysaccharides fall far behind the quality control criteria of botanical drugs. Here we systemically reviewed the recent advances in analytical methods. A critical evaluation of the strength and weaknesses of these methods was provided, together with possible solutions to the difficulties. Mass spectrometry with or without robust chromatographic separation was increasingly employed. And scientists have made significant progress in simplifying polysaccharide quantification by depolymerizing it into oligosaccharides. This oligosaccharides-based strategy is promising for qualitative and quantitative analysis of polysaccharides. And continuous efforts are still needed to develop a standardized quality control method that is specific, accurate, repeatable, and applicable for analyzing individual components in natural medicine formulas.Bictegravir (BIC), an integrase inhibitor, and doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor, were recently approved by the US FDA for HIV treatment and are recommended first line treatment options. Because certain clinical scenarios warrant using them in combination, we developed a fully validated LC-MS/MS method for simultaneous measurement of BIC and DOR, along with a legacy integrase inhibitor, raltegravir (RAL), in human plasma over a clinically relevant 1000-fold range for each analyte. These analytes were extracted from the plasma by protein precipitation with their stable, isotopically labeled internal standards (BIC-d5, 13C6-DOR, and RAL-d6). Following extraction, samples were analyzed by reverse phase chromatography on a Waters Atlantis T3 C18 (50 ×2.1 mm, 3 µm particle size) column with subsequent detection by electrospray ionization in positive ion mode on an AB Sciex API-5000 triple quadrupole mass spectrometer. The assay was linear (R2 >0.994) over the selected calibration ranges (20.0-20,000 ng/mL (BIC), 3.00-3000 ng/mL (DOR), and 10.0-10,000 (RAL)). The assay was accurate (inter-assay %Bias ≤ ± 8.5) and precise (inter-assay %CV ≤11.4). This method was validated according to FDA guidance for industry and can be used to assess the pharmacokinetics of two newly approved antiretrovirals, or to support therapeutic drug monitoring for modern antiretroviral therapy.

This study aimed to explore symptom clusters at different time points among patients with gynecological cancer undergoing chemotherapy.

A longitudinal design was used to explore the patterns of symptom clusters four times during prechemotherapy (T0), first (T1), second (T2), and third (T3) cycles of chemotherapy. The Memorial Symptom Assessment Scale was used to assess the dimension of symptoms. The study was conducted in Indonesia. Exploratory factor analysis was used to analyze the structures of symptom clusters across time.

A total of 120 subjects provided baseline data, and 82 were retained at T3. Before chemotherapy, the most prevalent symptoms were pain and difficulty in sleeping. However, after starting chemotherapy, the patients suffered from chemotherapy-related side effects, including nausea, change in taste, lack of appetite, hair loss, fatigue, and feeling of "I don't look like myself." Six symptom clusters were identified in patients with gynecological cancer across four time points during chemotherapy pain-related, nutritional, emotional, hormonal-related, fatigue-related, and body-image symptom clusters.