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Pharmaceuticals (Basel, Switzerland) Dec 2023Levothyroxine tablets, although highly prescribed in the United States, have been one of the most frequently recalled products. Because of the importance of the...
Levothyroxine tablets, although highly prescribed in the United States, have been one of the most frequently recalled products. Because of the importance of the medication, several efforts have been put in place by the United States Food and Drug Administration (US FDA) to control the quality of levothyroxine tablets available to patients using the drug. The choice of excipients used in the formulation has been shown to impact the hygroscopicity and microenvironment, and ultimately the stability of the levothyroxine tablets formulations. Based on information generated from the US FDA Enforcement Report database, one of the main reasons for recalls is the low potency of different batches of the product. The yearly product recall trends for levothyroxine formulations were determined using the FDA Enforcement Report database. Three brands of levothyroxine tablets were selected with excipient lists similar to those products that have been historically recalled. The samples were placed at ambient (~23 °C), accelerated stability (40 °C/75% RH), and stress (50 °C/75% RH) conditions for up to 6 months. Sample potencies were determined at 0, 1.5, 3, and 6 months using the methods for assay and impurities in the United States Pharmacopeia (USP) monograph for levothyroxine tablets. Additional sample monitoring was conducted by overlaying the initial powder X-ray diffractograms (PXRD) of the samples from 0 months with the patterns generated thereafter. There has been a decline in the number of levothyroxine tablets recalled over the years. The highest numbers of recalls were recorded in the years 2013 [33] and 2020 [23]; no recalls occurred in the years 2019 and 2022. All of the brands evaluated met the USP 95.0-105.0% assay requirements at 1.5 months under accelerated conditions; only one of the brands complied at 3 months. Under ambient conditions, two brands were stable at 6 months, with borderline assay results. For stability, levothyroxine was found in microgram quantities in the formulations and PXRD could not detect changes at these low levels. However, we found some distinguishing data for samples under stress conditions.
PubMed: 38256876
DOI: 10.3390/ph17010042 -
Frontiers in Nutrition 2024Dairy products and fermented foods have a reported association with maintained cognitive function. Camembert cheese, a dairy product fermented by the white mold , has...
Milk-based culture of and its component oleamide affect cognitive function in healthy elderly Japanese individuals: a multi-arm randomized, double-blind, placebo-controlled study.
Dairy products and fermented foods have a reported association with maintained cognitive function. Camembert cheese, a dairy product fermented by the white mold , has also been shown to enhance cognitive function . Oleamide, derived from the fermentation of the white mold, is a candidate for an active component, and expected to improve both cognitive function and sleep conditions. Thus, this study investigated whether the milk-based culture of white mold (MCW), and oleamide, could improve cognitive function and sleep state clinically. A multi-arm randomized, double-blind, placebo-controlled trial was conducted in Tokyo, Japan. 60 healthy Japanese individuals aged 50-75 who were aware of their cognitive decline were randomly and equally divided into three groups of 20 participants using computer-generated random numbers. Participants took either MCW (equivalent to 60 μg/day of oleamide), 60 μg/day of oleamide, or placebo capsules for 12 weeks. Serum BDNF, cognitive function by Cognitrax as primary and MCI Screen as secondary outcome, and sleep status using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) were assessed before and after intervention. The participants, outcome assessors and analysts, and research assistants were blinded to the group assignment. Of the 60 participants, 58 completed the study and were analyzed. No adverse events related to test foods were observed. The placebo group showed a negative rate of change in serum BDNF (-10.5% ± 19.7%), whereas the MCW and oleamide groups showed positive changes (2.0% ± 27.1% and 1.3% ± 13.5%, respectively). Cognitrax scores increased after 12 weeks in all groups. Conversely, the MPI score of the MCI Screen demonstrated a significant improvement in the MCW and oleamide groups compared to the placebo group ( = 0.013 and < 0.001, respectively). The subscales, immediate free recall and delayed free recall, also significantly increased in them compared to the placebo group. Although PSQI-J revealed no significant differences among groups, the MCW and oleamide groups showed significant improvement after intervention in overall score, subjective sleep quality, and sleep latency. Our results suggest that MCW and its component, oleamide, are safe and contribute to maintaining cognitive functions, particularly short-term and working memory, and improving sleep state. : https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054792, identifier UMIN-CTR UMIN000048084.
PubMed: 38600994
DOI: 10.3389/fnut.2024.1357920 -
ArXiv Apr 2024Tandem mass spectrometry (MS/MS) stands as the predominant high-throughput technique for comprehensively analyzing protein content within biological samples. This...
Tandem mass spectrometry (MS/MS) stands as the predominant high-throughput technique for comprehensively analyzing protein content within biological samples. This methodology is a cornerstone driving the advancement of proteomics. In recent years, substantial strides have been made in Data-Independent Acquisition (DIA) strategies, facilitating impartial and non-targeted fragmentation of precursor ions. The DIA-generated MS/MS spectra present a formidable obstacle due to their inherent high multiplexing nature. Each spectrum encapsulates fragmented product ions originating from multiple precursor peptides. This intricacy poses a particularly acute challenge in de novo peptide/protein sequencing, where current methods are ill-equipped to address the multiplexing conundrum. In this paper, we introduce DiaTrans, a deep-learning model based on transformer architecture. It deciphers peptide sequences from DIA mass spectrometry data. Our results show significant improvements over existing STOA methods, including DeepNovo-DIA and PepNet. DiaTrans enhances precision by 15.14% to 34.8%, recall by 11.62% to 31.94% at the amino acid level, and boosts precision by 59% to 81.36% at the peptide level. Integrating DIA data and our DiaTrans model holds considerable promise to uncover novel peptides and more comprehensive profiling of biological samples. DiaTrans is freely available under the GNU GPL license at https://github.com/Biocomputing-Research-Group/DiaTrans.
PubMed: 38659639
DOI: No ID Found -
Vision Research Feb 2024The capacity of visuospatial working memory (VSWM) is limited. However, there is continued debate surrounding the nature of this capacity limitation. The resource model...
The capacity of visuospatial working memory (VSWM) is limited. However, there is continued debate surrounding the nature of this capacity limitation. The resource model (Bays et al., 2009) proposes that VSWM capacity is limited by the precision with which visuospatial features can be retained. In one of the few studies of spatial working memory, Schneegans and Bays (2016) report that memory guided pointing responses show a monotonic decrease in precision as set size increases, consistent with resource models. Here we report two conceptual replications of this study that use mouse responses rather than pointing responses. Overall results are consistent with the resource model, as there was an exponential increase in localisation error and monotonic increases in the probability of misbinding and guessing with increases in set size. However, an unexpected result of Experiment One was that, unlike Schneegans and Bays (2016), imprecision did not increase between set sizes of 2 and 8. Experiment Two replicated this effect and ruled out the possibility that the invariance of imprecision at set sizes greater than 2 was a product of oculomotor strategies during recall. We speculate that differences in imprecision are related to additional visuomotor transformations required for memory-guided mouse localisation compared to memory-guided manual pointing localisation. These data demonstrate the importance of considering the nature of the response modality when interpreting VSWM data.
Topics: Animals; Mice; Memory, Short-Term; Mental Recall; Spatial Memory
PubMed: 38160653
DOI: 10.1016/j.visres.2023.108343 -
JAMA Network Open Jan 2024Kratom products, which are sold legally in most of the US, contain alkaloids with opioidergic, adrenergic, and serotonergic activity. Millions of people use kratom to...
IMPORTANCE
Kratom products, which are sold legally in most of the US, contain alkaloids with opioidergic, adrenergic, and serotonergic activity. Millions of people use kratom to relieve pain, improve mood, or self-manage substance use disorders (SUDs). Kratom use has primarily been examined via surveys, in which recall biases among satisfied users may lead to minimization of transient negative outcomes. Further prospective study of kratom use, such as with ecological momentary assessment (EMA), is needed.
OBJECTIVE
To characterize proximal motivators, effects, and patterns of kratom use and to assess whether use frequency is associated with motivations, effects, past-year criteria for SUD for kratom (KUD), or other substance use.
DESIGN, SETTING, AND PARTICIPANTS
For this prospective cross-sectional study, an intensive longitudinal smartphone-based EMA in which participants' current behaviors and experiences were repeatedly sampled in real time was conducted between July 1 and October 31, 2022. Participants comprised a convenience sample of US adults who used kratom at least 3 days per week for at least 4 weeks at the time of online screening. Criteria for past-year KUD were based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Data analysis was performed between November 2022 and November 2023.
EXPOSURE
The exposure was 13 401 kratom-use events across 15 days.
MAIN OUTCOMES AND MEASURES
A baseline survey covering demographics, health, kratom attitudes and behaviors, use motivations, other substance use, and KUD was administered before EMA. Data for the following EMA entries were then collected: event-contingent entries for kratom use (product, dose, and proximal motivations), follow-up entries (short-term effects and consequences of use events), random-prompt entries (mood), beginning-of-day entries (effects of kratom on sleep), and end-of-day entries (daily subjective descriptions of kratom effects). Bayesian regression was used to estimate means and credible intervals.
RESULTS
A total of 357 participants completed the EMA. Their mean (SD) age was 38.0 (11.1) years; more than half were men (198 [55.5%]). Participants reported overall motivators of use on the baseline survey that involved managing psychiatric and SUD problems, but proximal motivators evaluated during the EMA involved situation-specific needs such as increasing energy and productivity and decreasing pain. Acute effects were considered congruent with daily obligations. Use patterns, despite having some distinguishing features, were generally similar in their motivators and effects; participants used kratom predominantly during the daytime and seemed to find use frequencies that suited their needs. Higher use patterns were associated with symptoms of physical dependence (eg, withdrawal or tolerance). Co-used substances included caffeine, nicotine, vitamins, and cannabis.
CONCLUSIONS AND RELEVANCE
Most participants in this study reported using kratom in a seemingly nonproblematic way. When such use appeared problematic, the key element was usually that withdrawal avoidance became a proximal motivator. Longitudinal studies examining changes in kratom use patterns and effects over time are needed.
Topics: Adult; Female; Humans; Male; Bayes Theorem; Cross-Sectional Studies; Ecological Momentary Assessment; Mitragyna; Motivation; Pain; Prospective Studies; Self Report; Substance-Related Disorders; Middle Aged
PubMed: 38277146
DOI: 10.1001/jamanetworkopen.2023.53401 -
Brain Sciences Jun 2024Porcine Liver Decomposition Product (PLDP) was obtained by treating pig liver homogenate with protease and filling it into capsules. We have already confirmed from three...
Porcine Liver Decomposition Product (PLDP) was obtained by treating pig liver homogenate with protease and filling it into capsules. We have already confirmed from three clinical trials that PLDP enhances visual memory and delays memory recall, and we believe that its activity is due to various phospholipids, including phosphatidylcholine (PC). In this study, we clinically evaluated PLDP for depressive symptoms caused by a decline in cognitive function. This clinical trial was conducted using the Revised Hasegawa Dementia Scale (HDS-R). The HDS-R (maximum score is 30 points) is a test similar to the Mini-Mental State Examination (MMSE), which is commonly used in Japan. Dementia is suspected if the score falls below 20 on the HDS-R. Additionally, in a previous clinical trial, there was no change in scores in the placebo group after three doses of the HDS-R. In order to clearly confirm the effectiveness of PLDP, this study was conducted under stricter conditions (HDS-R points of 15 to 23) than previous clinical trials (all participants had scores of 20 or higher). Therefore, from ethical considerations, a clinical trial was conducted using the scores before PLDP administration as a control. In this study, PLDP was administered orally at 4 capsules per day, and the HDS-R was confirmed 2 and 4 weeks after administration. A significant increase in HDS-R scores was observed at 2 and 4 weeks after PLDP administration. Additionally, regarding each item of the HDS-R, PLDP significantly increased 2 and 4 weeks after oral administration for the question items assessing delayed recall, and the question item assessing verbal fluency tasks was recognized. From the above results, we confirmed the reproducibility of the effect of PLDP in improving the delayed recall of verbal memories. Furthermore, increasing scores on verbal fluency tasks suggest that PLDP may enhance frontal lobe function and prevent or improve depressive symptoms. The effects observed in this study may differ from the mechanisms of action of existing antidepressants, and we believe that this may lead to the discovery of new antidepressants.
PubMed: 38928586
DOI: 10.3390/brainsci14060586 -
Current Research in Food Science 2024The traceability of geographic origin is essential for guaranteeing the quality, safety, and protection of oyster brands. However, the current outcomes of traceability...
The traceability of geographic origin is essential for guaranteeing the quality, safety, and protection of oyster brands. However, the current outcomes of traceability lack credibility as they do not adequately explain the model's predictions. Consequently, we conducted a study to evaluate the efficacy of utilizing explainable machine learning combined with mineral elements analysis. The study findings revealed that 18 elements have the ability to determine regional orientation. Simultaneously, individuals should pay closer attention to the potential risks associated with oyster consumption due to the regional differences in essential and toxic elements they contain. Light gradient boosting machine (LightGBM) model exhibited indistinguishable performance, achieving flawless accuracy, precision, recall, F1 score and AUC, with values of 96.77%, 96.43%, 98.53%, 97.32% and 0.998, respectively. The SHapley Additive exPlanations (SHAP) method was used to evaluate the output of the LightGBM model, revealing differences in feature interactions among oysters from different provinces. Specifically, the features Na, Zn, V, Mg, and K were found to have a significant impact on the predictive process of the model. Consistent with existing research, the use of explainable machine learning techniques can provide insights into the complex connections between important product attributes and relevant geographical information.
PubMed: 38659973
DOI: 10.1016/j.crfs.2024.100738 -
Toxins Sep 2023The farming of shellfish plays an important role in providing sustainable economic growth in coastal, rural communities in Scotland and acts as an anchor industry,...
The farming of shellfish plays an important role in providing sustainable economic growth in coastal, rural communities in Scotland and acts as an anchor industry, supporting a range of ancillary jobs in the processing, distribution and exporting industries. The Scottish Government is encouraging shellfish farmers to double their economic contribution by 2030. These farmers face numerous challenges to reach this goal, among which is the problem caused by toxin-producing microplankton that can contaminate their shellfish, leading to harvesting site closure and the recall of product. Food Standards Scotland, a non-ministerial department of the Scottish Government, carries out a monitoring programme for both the toxin-producing microplankton and the toxins in shellfish flesh, with farms being closed when official thresholds for any toxin are breached. The farm remains closed until testing for the problematic toxin alone, often diarrhetic shellfish toxin (DST), shows the site to have dropped below the regulatory threshold. While this programme has proved to be robust, questions remain regarding the other toxins that may be present at a closed site. In this study, we tested archival material collected during site closures but only tested for DSTs as part of the official control monitoring. We found the presence of amnesic shellfish toxin (AST) in low concentrations in the majority of sites tested. In one case, the level of AST breached the official threshold. This finding has implications for AST monitoring programmes around Europe.
Topics: Marine Toxins; Shellfish; Diatoms; Seafood; Aquaculture
PubMed: 37755980
DOI: 10.3390/toxins15090554 -
Heliyon Jan 2024The Rapid Alert System for Food and Feed (RASFF) plays a pivotal role in regulating food safety in the European Union by enabling the competent authorities in each...
The Rapid Alert System for Food and Feed (RASFF) plays a pivotal role in regulating food safety in the European Union by enabling the competent authorities in each Member State to issue warnings for removing unsafe or illegal items from the market. This article undertakes a comprehensive analysis of RASFF data on Slovak food from 2002 to 2020, to investigate the trends in notifications, actions executed, hazard categories, and product categories within the food industry. Our scrutiny of the RASFF data revealed fluctuations in the counts of alerts and information notifications across years, indicating periods of heightened hazard detection and enhanced transparency within the system. Various measures, including destruction, recall, notification, and prohibition, were employed to address these hazards and ensure the safety and compliance of food products. The hazard categories exhibited sporadic patterns, underscoring the necessity for ongoing surveillance and regulatory interventions. Specific product categories, such as dietetic foods, food supplements, and fortified foods, registered higher incidences of hazards in specific years, implying the need for intensified safety precautions. These findings highlight the importance of sustained efforts in maintaining food safety and managing risks within the industry.
PubMed: 38163176
DOI: 10.1016/j.heliyon.2023.e23146 -
JAAD International Sep 2024Empirical decisions to select therapies for psoriasis (PSO) and atopic dermatitis (AD) can lead to delays in disease control and increased health care costs. However,...
BACKGROUND
Empirical decisions to select therapies for psoriasis (PSO) and atopic dermatitis (AD) can lead to delays in disease control and increased health care costs. However, routine molecular testing for AD and PSO are lacking.
OBJECTIVE
To examine (1) how clinicians choose systemic therapies for patients with PSO and AD without molecular testing and (2) to determine how often the current approach leads to patients switching medications.
METHODS
A 20-question survey designed to assess clinician strategies for systemic treatment of AD and PSO was made available to attendees of a national dermatology conference in 2022.
RESULTS
Clinicians participating in the survey (265/414, 64% response rate) ranked "reported efficacy" as the most important factor governing treatment choice ( < .001). However, 62% (165/265) of clinicians estimated that 2 or more systemic medications were typically required to achieve efficacy. Over 90% (239/265) of respondents would or would likely find a molecular test to guide therapeutic selection useful.
LIMITATIONS
To facilitate ease of recall, questions focused on systemic therapies as a whole and not individual therapies.
CONCLUSION
Clinicians want a molecular test to help determine the most efficacious drug for individual patients.
PubMed: 38774343
DOI: 10.1016/j.jdin.2024.03.019