Real-World Dispensing of Buprenorphine in California during Prepandemic and Pandemic Periods.

INTRODUCTION: The opioid overdose crisis in the United States has become a significant national emergency. Buprenorphine, a primary medication for individuals coping with opioid use disorder (OUD), presents promising pharmacokinetic properties for use in primary care settings, and is often delivered as a take-home therapy. The COVID-19 pandemic exacerbated the scarcity of access to buprenorphine, leading to dire consequences for those with OUD. Most existing studies, primarily focused on the immediate aftermath of the COVID-19 outbreak, highlight the challenges in accessing medications for opioid use disorder (MOUDs), particularly buprenorphine. However, these studies only cover a relatively short timeframe. METHODS: To bridge this research gap, in our study, we utilized 33 months of California's prescription drug monitoring program (PDMP) data to provide insights into real-world buprenorphine dispensing trends since the onset of the pandemic from 2018 to 2021, focusing on outcomes such as patient counts, prescription volumes, prescriber involvement, days' supply, and dosage. Statistical analysis employed interrupted time series analysis to measure changes in trends before and during the pandemic. RESULTS: We found no significant impact on patient counts or prescription volumes during the pandemic, although it impeded the upward trajectory of prescriber numbers that was evident prior to the onset of the pandemic. An immediate increase in days' supply per prescription was observed post-pandemic. CONCLUSION: Our findings differ in comparison to previous data regarding the raw monthly count of patients and prescriptions. The analysis encompassed uninsured patients, offering a comprehensive perspective on buprenorphine prescribing in California. Our study's insights contribute to understanding the impact of COVID-19 on buprenorphine access, emphasizing the need for policy adjustments.

Potential apply of hydrogel-carried chlorhexidine and metronidazole in root canal disinfection.

Microorganisms may persist in the root canal system after root canal therapy (RCT). The purpose of this study was to explore the metronidazole (MTR)- and chlorhexidine (CHX)-loaded hydrogels as the potential application in intracanal medicaments for root canal disinfection. Ultraviolet cross-linked hydrogels (gGels) were synthesized by GelMA solution and photoinitiator, which were loaded with MTR (MTR@gGels) and CHX (CHX@gGels). gGels, MTR@gGels and CHX@gGels were characterized by scanning electron microscopy. The antimicrobial activity against E. faecalis, S. mutans and P. intermedia was assessed. Meanwhile, the biocompatibility of human dental pulp stem cells (hDPSCs) was evaluated. DCT, CCK-8, CFU and live/dead-stained biofilm results showed that the viability of E. faecalis, S. mutans and P. intermedia was significantly reduced in MTR@gGels and CHX@gGels in vitro. CCK-8 results showed considerable biocompatibility with hDPSCs. The filling and clearance of gGels in root canals were demonstrated in vivo. Therefore, MTR- and CHX-loaded hydrogels may be a potential application in intracanal medicaments for root canal disinfection.

Algorithms and Applications to Weighted Rank-one Binary Matrix Factorization.

Many applications use data that are better represented in the binary matrix form, such as click-stream data, market basket data, document-term data, user-permission data in access control, and others. Matrix factorization methods have been widely used tools for the analysis of high-dimensional data, as they automatically extract sparse and meaningful features from data vectors. However, existing matrix factorization methods do not work well for the binary data. One crucial limitation is interpretability, as many matrix factorization methods decompose an input matrix into matrices with fractional or even negative components, which are hard to interpret in many real settings. Some matrix factorization methods, like binary matrix factorization, do limit decomposed matrices to binary values. However, these models are not flexible to accommodate some data analysis tasks, like trading off summary size with quality and discriminating different types of approximation errors. To address those issues, this article presents weighted rank-one binary matrix factorization, which is to approximate a binary matrix by the product of two binary vectors, with parameters controlling different types of approximation errors. By systematically running weighted rank-one binary matrix factorization, one can effectively perform various binary data analysis tasks, like compression, clustering, and pattern discovery. Theoretical properties on weighted rank-one binary matrix factorization are investigated and its connection to problems in other research domains are examined. As weighted rank-one binary matrix factorization in general is NP-hard, efficient and effective algorithms are presented. Extensive studies on applications of weighted rank-one binary matrix factorization are also conducted.

Optimization of the Parameters of Different Purification Techniques and Comparison of Their Purification Efficiency and Their Effects on the Metabolic Activity of Adipose Tissue in Autologous Fat Transplantation.

There is still no unified standardized or optimal procedure for lipoaspirate purification and we explored the optimal parameters of 3 purification techniques and compared their efficiencies and effects on the metabolic activity of adipose tissue. The purification efficiency of each technique was compared by analyzing the composition ratio of the processed compounds. The effects of the purification techniques on the dynamic metabolic activity of adipose tissue were evaluated in vitro using the glucose transfer assay. We found that the cotton pad adsorption technique displayed the greatest ability to remove aqueous and oil fractions, followed by centrifugation and sedimentation techniques (P < 0.01). The in vitro metabolic activity of adipose tissue peaked at 4 hours. The glucose transfer rates in the cotton pad group and the sedimentation group were significantly higher (P < 0.05) than that of the centrifugation group, and the centrifugation method exerted the greatest effect on the metabolic activity of adipose tissue. To sum up, the optimal processing parameters were the following: sedimentation technique, 30 minutes of sedimentation; centrifugation technique, 3 to 5 minutes of centrifugation and centrifugation force of 200 g; and cotton pad adsorption technique, contact area of 5 cm/mL and contact time of 5 minutes. The cotton pad adsorption technique yielded the best purification of the aqueous and oil fractions, followed by the centrifugation technique, whereas the sedimentation technique exhibited the lowest efficiency. The in vitro metabolic activity of adipose tissue peaked at 4 hours, and the cotton pad and sedimentation technique exerted decreased effects on metabolic activity than the centrifugation technique.

The role of Bag2 in neurotoxicity induced by the anesthetic sevoflurane.

Sevoflurane is the most commonly used general anesthetic in pediatric patients. But preclinical studies indicate that sevoflurane could have neurotoxicity in newborn and old animals, and this raises concern regarding its safety. In this study, we explored the potential mechanisms of sevoflurane-induced neurotoxicity in human SH-SY5Y neuronal cells. We showed that prolonged exposure to 2% sevoflurane caused a significant increase in the Bag family protein Bag2 in a time- and dose-dependent manner. We investigated the possible role of Bag2 upon exposure to sevoflurane by silencing Bag2 in neuronal cells. Knockdown of Bag2 caused increased overall reactive oxygen species (ROS) and generation of lipid peroxidation products 4-hydroxynonenal (4-HNE). Upon sevoflurane exposure, Bag2-silent cells have reduced glutathione (GSH) and glutathione peroxidase activity. Under the sevoflurane treatment, Bag2-deficient cells have reduced mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) production, while knockdown cells have less viability and higher lactic dehydrogenase (LDH) release as well as a higher percentage of apoptotic cells. The knockdown cells also had higher levels of mitochondrial cytochrome C release, a higher ratio of Bax/Bcl-2 and increased caspase cleavage by sevoflurane. Overall, our data support an important role of Bag2 in sevoflurane-induced neurotoxicity.

A neonatal murine model for evaluation of enterovirus E HY12 virus infection and pathogenicity.

BACKGROUNDS: HY12 viruses are enteroviruses recently isolated from cattle characterized by severe respiratory and digestive disease with high morbidity and mortality in China. While the viruses exhibit unique biological and molecular characters distinct from known enterovirus E, the pathogenicity and viral pathogenesis remains largely unknown. METHODS: Neonatal mice of Balb/C, ICR, and Kunming strain are infected with HY12 to determine the susceptible mouse strain. The minimal infection dose, the virus infection routes, the pathogenicity and tissue tropism for HY12 were determined by infecting susceptible mice with HY12 viruses, and confirmed by different approaches including virus isolation and recovery, virus detection, histopathology, and immunohistochemistry. RESULTS: A murine model for HY12 infection was successfully established and employed to investigate the pathogenicity of HY12 viruses. ICR mouse strain is the most susceptible strain for HY12 infection with a minimal infective dose as 2×106TCID50/mouse. HY12 viruses have the capability of infecting ICR suckling mice via all infection routes including intranasal administration, oral administration, intraperitoneal injection, subcutaneous injection, and intramuscular injection, which are confirmed by the isolation and recovery of viruses from HY12-infected mice; detection of viruses by RT-PCR; observations of pathological lesions and inflammatory cell infiltrations in the intestine, lung, liver, and brain; uncovering of HY12 virus antigens in majority of tissues, especially in intestine, lung, and infected brain of mice by immunohistochemistry assay. CONCLUSIONS: A neonatal murine model for HY12 infection is successfully established for determining the susceptible mouse strain, the minimal infective dose, the infection route, the viral pathogenicity and the tropism of HY12, thus providing an invaluable model system for elucidating the pathogenesis of HY12 viruses and the elicited immunity.

A novel enterovirus species identified from severe diarrheal goats.

BACKGROUNDS: The Enterovirus genus of the family of Picornaviridae consists of 9 species of Enteroviruses and 3 species of Rhinoviruses based on the latest virus taxonomy. Those viruses contribute significantly to respiratory and digestive disorders in human and animals. Out of 9 Enterovirus species, Enterovirus E-G are closely related to diseases affecting on livestock industry. While enterovirus infection has been increasingly reported in cattle and swine, the enterovirus infections in small ruminants remain largely unknown. METHODS: Virology, molecular and bioinformatics methods were employed to characterize a novel enterovirus CEV-JL14 from goats manifesting severe diarrhea with morbidity and mortality respectively up to 84% and 54% in China. RESULTS: CEV-JL14 was defined and proposed as a new Enterovirus species L within the genus of Enterovirus of the family Picornaviridae. CEV-JL14 had a complete genome sequence of 7461 nucleotides with an ORF encoding 2172 amino acids, and shared 77.1% of genomic sequence identity with TB4-OEV, an ovine enterovirus. Comparison of 5'-UTR and structural genes of CEV-JL14 with known Enterovirus species revealed highly genetic variations among CEV-JL14 with known Enterovirus species. VP1 nucleotide sequence identities of CEV-14 were 51.8%-53.5% with those of Enterovirus E and F, 30.9%-65.3% with Enterovirus G, and 43.8-51. 5% with Enterovirus A-D, respectively. CEV-JL14 was proposed as a novel species within the genus of Enterovirus according to the current ICTV demarcation criteria of enteroviruses. CONCLUSIONS: CEV-JL14 clustered phylogenetically to neither Enterovirus E and F, nor to Enterovirus G. It was defined and proposed as novel species L within the genus of Enterovirus. This is the first report of caprine enterovirus in China, the first complete genomic sequence of a caprine enterovirus revealed, and the unveiling of significant genetic variations between ovine enterovirus and caprine enterovirus, thus broadening the current understanding of enteroviruses.

A fatal suppurative pneumonia in piglets caused by a pathogenic coagulase-positive strain of Staphylococcus hyicus.

Staphylococcus hyicus is one of the opportunistic pathogens that cause infections to animals. Early studies have demonstrated that S. hyicus is the causative agents of exudative epidermitis in pigs, arthritis in horses and chicken, mastitis in cow, and bacteremia, sepsis and multiple organ failure in humans. Here, we report the isolation and identification of a representative S. hyicus isolate, named JLHN15, from a pig farm with a disease characterized by bacteremia, suppurative pneumonia and fibrinous pericarditis. Our results indicate that JLHN15 is a pathogenic coagulase-positive Staphylococcus. To the best knowledge, this is the first report of S. hyicus causing an infection characterized by suppurative pneumonia and sepsis.

Molecular Characterization of a Novel Bovine Viral Diarrhea Virus Isolate SD-15.

As one of the major pathogens, bovine viral diarrhea virus caused a significant economic loss to the livestock industry worldwide. Although BVDV infections have increasingly been reported in China in recent years, the molecular aspects of those BVDV strains were barely characterized. In this study, we reported the identification and characterization of a novel BVDV isolate designated as SD-15 from cattle, which is associated with an outbreak characterized by severe hemorrhagic and mucous diarrhea with high morbidity and mortality in Shandong, China. SD-15 was revealed to be a noncytopathic BVDV, and has a complete genomic sequence of 12,285 nucleotides that contains a large open reading frame encoding 3900 amino acids. Alignment analysis showed that SD-15 has 93.8% nucleotide sequence identity with BVDV ZM-95 isolate, a previous BVDV strain isolated from pigs manifesting clinical signs and lesions resembling to classical swine fever. Phylogenetic analysis clustered SD-15 to a BVDV-1m subgenotype. Analysis of the deduced amino acid sequence of glycoproteins revealed that E2 has several highly conserved and variable regions within BVDV-1 genotypes. An additional N-glycosylation site (240NTT) was revealed exclusively in SD-15-encoded E2 in addition to four potential glycosylation sites (Asn-X-Ser/Thr) shared by all BVDV-1 genotypes. Furthermore, unique amino acid and linear epitope mutations were revealed in SD-15-encoded Erns glycoprotein compared with known BVDV-1 genotype. In conclusion, we have isolated a noncytopathic BVDV-1m strain that is associated with a disease characterized by high morbidity and mortality, revealed the complete genome sequence of the first BVDV-1m virus originated from cattle, and found a unique glycosylation site in E2 and a linear epitope mutation in Erns encoded by SD-15 strain. Those results will broaden the current understanding of BVDV infection and lay a basis for future investigation on SD-15-related pathogenesis.