Case report: A patient with HHV-6 and HHV-7 combined with Whipple's trophoblast infection and streptococcal pneumonia.

Adult respiratory distress syndrome due to viral pneumonia occurs predominantly in immunodeficient populations; adult respiratory distress syndrome secondary to human herpesvirus HHV-6 and HHV-7 pneumonia is extremely rare. Whipple's disease, caused by Tropheryma whipplei, a Gram-positive bacillus and obligate intracellular pathogen, is clinically challenging to diagnose. Whipple's disease is a chronic multisystem infectious disease caused by T. whipplei, most often affecting the gastrointestinal tract and joints, seldom the lungs. Both pathogens are opportunistic. We report a case of mixed infectious pneumonia in a patient with type 2 diabetes mellitus. The patient presented with dyspnea and intermittent fever. Imaging revealed multiple large patchy consolidations in the left lung. Routine anti-infective therapy was ineffective. Metagenomic next generation sequencing of bronchoalveolar lavage fluid indicated HHV-6 and HHV-7 pneumonia concurrent with T. whipplei and Streptococcus co-infections. Meropenem was administered to improve treatment. This case represents a rare mixed lung infection by multiple uncommon pathogens, and is of particular clinical significance.

Correction: Development of a Humanized Antibody with High Therapeutic Potential against Dengue Virus Type 2.

[This corrects the article DOI: 10.1371/journal.pntd.0001636.].

A bivalent inhibitor against TDRD3 to suppress phase separation of methylated G3BP1.

The formation of membrane-less organelles is driven by multivalent weak interactions while mediation of such interactions by small molecules remains an unparalleled challenge. Here, we uncovered a bivalent inhibitor that blocked the recruitment of TDRD3 by the two methylated arginines of G3BP1. Relative to the monovalent inhibitor, this bivalent inhibitor demonstrated an enhanced binding affinity to TDRD3 and capability to suppress the phase separation of methylated G3BP1, TDRD3, and RNAs, and in turn inhibit the stress granule growth in cells. Our result paves a new path to mediate multivalent interactions involved in SG assembly for potential combinational chemotherapy by bivalent inhibitors.

Understanding the role of lipids in aroma formation of circulating non-fried roasted chicken using UHPLC-HRMS-based lipidomics and heat transfer analysis.

The role of lipids in aroma formation of circulating non-fried roasted (CNR) chicken with different roasting times was studied using ultra-high performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS)-based lipidomics and heat transfer analysis. Thirteen odorants were confirmed as important aroma compounds of CNR chicken, including dimethyl trisulfide, 3,5-dimethyl-2-ethylpyrazine, nonanal, and 1-octen-3-ol. A comprehensive lipidomics analysis identified 1254 lipids in roasted chickens, classified into 23 distinct lipid categories that included 281 phosphatidylcholines (PC), 223 phosphatidylethanolamines (PE), and 202 triglycerides (TG). Using OPLS-DA analysis, the lipid PG (18:1_18:1) showed promise as a potential biomarker for distinguishing between chickens subjected to CNR treatments with varying roasting times. The lipids PC, PE, and their derivatives are likely to play a crucial role in the formation of aroma compounds. In addition, TGs that contributed to the retention of key odorants in roasted chicken included TG (16:0_16:0_18:1), TG (16:0_16:0_18:0), and TG (16:0_18:1_18:1). Findings further showed that lower water activity and specific heat capacity promoted the formation and retention of aroma compounds during the CNR process. This study contributed to a better understanding of the formation of aroma compounds through lipid oxidation in roasted chicken.

Long-term quality-of-care score for predicting the occurrence of acute myocardial infarction in patients with type 2 diabetes mellitus.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death globally, and diabetes mellitus (DM) is a well-established risk factor. Among the risk factors for CVD, DM is a major modifiable factor. In the fatal CVD outcomes, acute myocardial infarction (AMI) is the most common cause of death. AIM: To develop a long-term quality-of-care score for predicting the occurrence of AMI among patients with type 2 DM on the basis of the hypothesis that good quality of care can reduce the risk of AMI in patients with DM. METHODS: Using Taiwan's Longitudinal Cohort of Diabetes Patient Database and the medical charts of a medical center, we identified incident patients diagnosed with type 2 DM from 1999 to 2003 and followed them until 2011. We constructed a summary quality-of-care score (with values ranging from 0 to 8) with process indicators (frequencies of HbA1c and lipid profile testing and urine, foot and retinal examinations), intermediate outcome indicators (low-density lipoprotein, blood pressure and HbA1c), and co-morbidity of hypertension. The associations between the score and the incidence of AMI were evaluated using Cox regression models. RESULTS: A total of 7351 patients who had sufficient information to calculate the score were enrolled. In comparison with participants who had scores ≤ 1, those with scores between 2 and 4 had a lower risk of developing AMI [adjusted hazard ratio (AHR) = 0.71; 95% confidence interval (95%CI): 0.55-0.90], and those with scores ≥ 5 had an even lower risk (AHR = 0.37; 95%CI: 0.21-0.66). CONCLUSION: Good quality of care can reduce the risk of AMI in patients with type 2 DM. The quality-of-care score developed in this study had a significant association with the risk of AMI and thus can be applied to guiding the care for these patients.

Identification of oxidosqualene cyclases associated with saponin biosynthesis from Astragalus membranaceus reveals a conserved motif important for catalytic function.

INTRODUCTION: Triterpenoids and saponins have a broad range of pharmacological activities. Unlike most legumes which contain mainly oleanane-type scaffold, Astragalus membranaceus contains not only oleanane-type but also cycloartane-type saponins, for which the biosynthetic pathways are unknown. OBJECTIVES: This work aims to study the function and catalytic mechanism of oxidosqualene cyclases (OSCs), one of the most important enzymes in triterpenoid biosynthesis, in A. membranaceus. METHODS: Two OSC genes, AmOSC2 and AmOSC3, were cloned from A. membranaceus. Their functions were studied by heterologous expression in tobacco and yeast, together with in vivo transient expression and virus-induced gene silencing. Site-directed mutagenesis and molecular docking were used to explain the catalytic mechanism for the conserved motif. RESULTS: AmOSC2 is a ß-amyrin synthase which showed higher expression levels in underground parts. It is associated with the production of ß-amyrin and soyasaponins (oleanane-type) in vivo. AmOSC3 is a cycloartenol synthase expressed in both aerial and underground parts. It is related to the synthesis of astragalosides (cycloartane-type) in the roots, and to the synthesis of cycloartenol as a plant sterol precursor. From AmOSC2/3, conserved triad motifs VFM/VFN were discovered for ß-amyrin/cycloartenol synthases, respectively. The motif is a critical determinant of yield as proved by 10 variants from different OSCs, where the variant containing the conserved motif increased the yield by up to 12.8-fold. Molecular docking and mutagenesis revealed that Val, Phe and Met residues acted together to stabilize the substrate, and the cation-π interactions from Phe played the major role. CONCLUSION: The study provides insights into the biogenic origin of oleanane-type and cycloartane-type triterpenoids in Astragalus membranaceus. The conserved motif offers new opportunities for OSC engineering.

Wide-Scope Multi-residue analysis of pesticides in beef by gas chromatography coupled with quadrupole Orbitrap mass spectrometry.

Increasing pesticide contamination in foods of animal origin has made the wide-scope multi-residue analysis of pesticides an international concern. By using 191 pesticides, this study investigates a sensitive and reliable method for multi-residue analysis of pesticides in beef to determine the extent of the application of this method. The QuEChERS method was employed to extract and purify the pesticides as C18 was utilized as the absorbents. Then, the purified pesticides were analysed using gas chromatography - quadrupole orbitrap mass spectrometry (GC-Q-Orbitrap-MS). The validation test results revealed that this method was satisfactorily sensitive since its screening detection limit (SDL) ranged from 0.2 to 100 µg∙kg-1. The recovery tests implemented at three spiking levels, namely 100, 200, and 500 µg∙kg-1, generated the results of 71.95 %-113.97 %, while the intra- and inter-day precisions were 0.27 %-17.94 %, indicating that this method had excellent accuracy and precision.

Copy number variations of the KAT6A gene are associated with body measurements of Chinese sheep breeds.

Copy number variation (CNV) is one kind of genomic structure variations and presents as gains and losses of genomic fragments. More recently, we have made an atlas of CNV maps for livestock. In the future, it is a primary focus to determine the phenotypic effects of candidate CNVs. Lysine Acetyltransferase 6 A (KAT6A) is a protein coding gene and plays a critical role in many cellular processes. However, the effects of KAT6A CNVs on sheep body measurements remains unknown. In this study, we performed quantitative polymerase chain reaction (qPCR) to detect the presences and distributions of three CNV regions within KAT6A gene in 672 sheep from four Chinese breeds. Association analysis indicated that the three CNVs of KAT6A gene were significantly associated with body measurement(s) in Small-tailed Han sheep (STH) and Hu sheep (HU) (p < 0.05), while no effects on Large-tailed Han sheep (LTH) were observed (p > 0.05) were observed. Additionally, only one CNV was significantly associated with body measurement (body length) in Chaka sheep (CK) (p < 0.05). Our study provided evidence that the CNV(s) of KAT6A gene could be used as candidate marker(s) for molecular breedings of STH, HU, and CK breeds.

The multidisciplinary management of a mechanical mitral valve thrombosis in pregnancy: a case report and review of the literature.

Background: The management of anticoagulation for mechanical heart valves during pregnancy poses a unique challenge. Mechanical valve thrombosis is a devastating complication for which surgery is often the treatment of choice. However, cardiac surgery for prosthetic valve dysfunction in pregnant patients confers a high risk of maternofetal morbidity and mortality. Case summary: A 39-year-old woman in her first pregnancy at 30 weeks gestation presented to hospital with a mechanical mitral valve thrombosis despite therapeutic anticoagulation with low-molecular-weight heparin. She underwent an emergent caesarean section followed immediately by a bioprosthetic mitral valve replacement. This occurred after careful planning and organization on the part of a large multidisciplinary team. Discussion: A proactive, rather than reactive, approach to the surgical management of a mechanical valve thrombosis in pregnancy will maximize the chances of successful maternal and fetal outcomes.

Modification and application of highly active alkaline pectin lyase.

Alkaline pectate lyase has developmental prospects in the textile, pulp, paper, and food industries. In this study, we selected BacPelA, the pectin lyase with the highest expression activity from Bacillus clausii, modified and expressed in Escherichia coli BL21(DE3). Through fragment replacement, the catalytic activity of the enzyme was significantly improved. The optimum pH and temperature of the modified pectin lyase (PGLA-rep4) were 11.0 and 70 °C, respectively. It also exhibited a superior ability to cleave methylated pectin. The enzyme activity of PGLA-rep4, measured at 235 nm with 0.2% apple pectin as the substrate, was 554.0 U/mL, and the specific enzyme activity after purification using a nickel column was 822.9 U/mg. After approximately 20 ns of molecular dynamics simulation, the structure of the pectin lyase PGLA-rep4 tended to be stable. The root mean square fluctuation (RMSF) values at the key catalytically active site, LYS168, were higher than those of the wildtype PGLA. In addition, PGLA-rep4 was relatively stable in the presence of metal ions. PGLA-rep4 has good enzymatic properties and activities and maintains a high pH and temperature. This study provides a successful strategy for enhancing the catalytic activity of PGLA-rep4, making it the ultimate candidate for degumming and various uses in the pulp, paper, and textile industries.

Evaluating the effectiveness of drug and therapeutics committees (DTCs) in controlling irrational drug use: A retrospective analysis.

WHAT IS KNOWN AND OBJECTIVE: This study aimed to explore methods to optimize the function of Drug and Therapeutics Committees (DTCs) in controlling irrational drug use. Clinical pharmacologists contribute their specific knowledge and skills to DTCs and help guide rational therapeutics. The DTC is the highest organization of hospital pharmacy management. METHODS: From January 2016 to August 2021, the DTC promoted the optimization of clinical drug treatment schemes and reduced unreasonable drug use by improving the organizational framework, clarifying the division of functions, regularly monitoring drug use, organizing expert comments, scientific decision-making and functional intervention. During this time, we statistically analysed typical management cases, irrational drug use and drug cost to evaluate the effectiveness of the DTC's management. RESULTS AND DISCUSSION: The DTC's intervention led to a significant reduction in prescribing errors (65.98%, p < 0.05); the intervention acceptance rate increased by 16.37%; and the rate of problem resolution increased by 45.84% (p < 0.05). The level of drug treatment was improved, and the proportion of patients' drug expenses was reduced. WHAT IS NEW AND CONCLUSION: The DTC carried out a series of continuous improvement work that played a significant normative role in clinical drug use. Giving more power to the DTCs can significantly improve the level of drug treatment and reduce unreasonable drug use, which reduces unnecessary drug expenses.

Public perceptions and interactions with UK COVID-19 Test, Trace and Isolate policies, and implications for pandemic infectious disease modelling

The efforts to contain SARS-CoV-2 and reduce the impact of COVID-19 have been supported by Test, Trace and Isolate (TTI) systems in many settings, including the United Kingdom. The mathematical models underlying policy decisions about TTI make assumptions about behaviour in the context of a rapidly unfolding and changeable emergency. This study investigates the reported behaviours of UK citizens in July 2021, assesses them against how a set of TTI processes are conceptualised and represented in models and then interprets the findings with modellers who have been contributing evidence to TTI policy. We report on testing practices, including the uses of and trust in different types of testing, and the challenges of testing and isolating faced by different demographic groups. The study demonstrates the potential of input from members of the public to benefit the modelling process, from guiding the choice of research questions, influencing choice of model structure, informing parameter ranges and validating or challenging assumptions, to highlighting where model assumptions are reasonable or where their poor reflection of practice might lead to uninformative results. We conclude that deeper engagement with members of the public should be integrated at regular stages of public health intervention modelling.

Characterization of key lipids for binding and generating aroma compounds in roasted mutton by UPLC-ESI-MS/MS and Orbitrap Exploris GC.

Lipids are the key aroma formation substrates and retainers relevant to the flavor quality. The lipids in the roasted mutton were investigated by UPLC-ESI-MS/MS and Orbitrap Exploris GC. The results showed that a total of 2488 lipids from 24 subclasses were identified in the roasted mutton, including 28.21% triglyceride (TG), 14.87% phosphatidylcholine (PC), and 11.03% phosphatidylethanolamine (PE). TG (16:0_18:1_18:1) and TG (18:0_18:0_18:1) might be the predominant lipids for binding aroma compounds. 488 Differential lipids from 20 subclasses were observed based on VIP > 1 and p < 0.05. The 61 out of 488 differential lipids, especially PC and PE, might predominantly contribute to the formation of aroma compounds. A total of 13 aroma compounds were determined as the characteristic odorants in the roasted mutton, including hexanal, heptanal, and 1-octen-3-ol. PC (30: 6) and PC (28: 3) were the potential markers for the discrimination of roasted mutton.

A sheep in wolf's clothing: Elaphe xiphodonta sp. nov. (Squamata, Colubridae) and its possible mimicry to Protobothrops jerdonii.

Based on combined morphological and osteological characters and molecular phylogenetics, we describe a new species of the genus Elaphe that was discovered from the south slope of the Qinling Mountains, Shaanxi, China, namely Elaphe xiphodonta sp. nov. It is distinguished from the other congeners by a combination of the following characters: dorsal scales in 21-21-17 rows, the medial 11 rows keeled; 202-204 ventral scales, 67-68 subcaudals; two preoculars (including one subpreocular); two postoculars; two anterior temporals, three posterior temporals; reduced numbers of maxillary teeth (9+2) and dentary teeth (12); sharp cutting edges on the posterior or posterolateral surface of the rear maxillary teeth and dentary teeth; dorsal head yellow, three distinct markings on the head and neck; a distinct black labial spot present in supralabials; dorsum yellow, 46-49 complete (or incomplete) large black-edged reddish brown blotches on the body and 12-19 on the tail, two rows of smaller blotches on each ventrolateral side; ventral scales yellow with mottled irregular black blotches, a few irregular small red spots dispersed on the middle of the ventral. Based on molecular phylogenetic analyses, the new species forms the sister taxon to E. zoigeensis. The discovery of this new species increases the number of the recognized species in the genus Elaphe to 17.

Pharmacist-led, prescription intervention system-assisted feedback to reduce prescribing errors: A retrospective study.

WHAT IS KNOWN AND OBJECTIVE: Prescribing errors are prevalent in hospital settings, with provision of feedback recommended to support prescribing by doctors. To evaluate the impact of a pharmacist-led prescription intervention system on prescribing error rates and to measure intervention efficiency. METHODS: All prescribers in Shandong Provincial Third Hospital received feedback from ward pharmacists using a pharmacist-led prescription intervention system. The prescribing error rate was calculated from Oct 2019 to December 2020. After the intervention was applied, the rates of PASS 1 (System pass), PASS 2 (Pharmacist pass) and PASS 3 (Pharmacist-doctor pass) events and the feedback time were calculated each month. RESULTS AND DISCUSSION: Irrational use of drugs was reduced and the prescription rate increased significantly. The error rate reduced from 6.94% to 1.96%, representing an estimated 71.76% decrease overall (p < 0.05). The PASS 1 rate gradually increased from 88% to 96% (p < 0.05), the PASS 2 rate gradually decreased from 5.06% to 2.04% (p < 0.05), the PASS 3 rate gradually decreased from 6.94% to 1.96% (p < 0.05). WHAT IS NEW AND CONCLUSION: The pharmacist-led prescription intervention system has the potential to reduce prescribing errors and improve prescribing outcomes and patient safety.

Ultrasound-guided platelet-rich plasma injections for post-traumatic greater occipital neuralgia: study protocol for a pilot randomized controlled trial.

BACKGROUND: Post-traumatic headaches (PTH) are a common sequelae of traumatic brain injury (TBI) and greatly impact patient function and quality of life. Post-traumatic greater occipital neuralgia (GON) is a type of post-traumatic headache. Conventional treatment includes steroid/anesthetic injections which typically alleviate pain but have a short duration of effect. Platelet-rich plasma (PRP) is an emerging biological treatment for numerous degenerative disorders, including peripheral nerve disorders. The primary aim of this pilot study is to evaluate whether a randomized control trial of PRP for the treatment of GON in patients with post-traumatic headaches is feasible in regard to recruitment, adherence, retention, and adherence and adverse events. Exploratory aims include improvement in pain, function, and quality of life in patients with post-traumatic GON receiving PRP compared to steroid/anesthetic and normal saline injections. METHODS: Thirty adults (over 18 years of age) with post-traumatic GON will be randomized into one of three groups: (1) autologous PRP injection, (2) steroid/anesthetic injection (standard care), or (3) placebo injection with normal saline. Injections will be performed to the greater occipital nerve under ultrasound guidance by a trained physician. Daily headache intensity and frequency data will be collected pre-injection and for the duration of the study period. Feasibility will be defined as greater than 30% recruitment, 70% completion of intervention, 70% retention, and less than 2 minor adverse events. Exploratory outcomes will be explored using the Headache Impact Test-6 (HIT-6, a valid and reliable 6-item questionnaire for assessment of the impact of headaches across different diagnostic groups of headaches) and the quality of life in following brain injury questionnaire (QOILIBRI). DISCUSSION: This pilot study will be the first to evaluate the feasibility of PRP as a potential treatment of GON in patients with post-traumatic headache. TRIAL REGISTRATION: ClinicalTrials.gov - NCT04051203 (registered August 9, 2019).

Phylogeographic study of the Bufo gargarizans species complex, with emphasis on Northeast Asia.

We conduct a phylogeographic and population genetic study of the Asiatic toad (Bufo gargarizans) to understand its evolutionary history, and the influence of geology and climate. A total of 292 individuals from 94 locations were genotyped for two mitochondrial loci (cytb, ND2) and five nuclear introns (Sox9-2, Rho-3, CCNB2-3, UCH-2, and DBI-2), and we performed a suite of phylogenetic, population genetic, and divergence dating analyses. The phylogenetic trees constructed using mitochondrial loci inferred B. gargarizans being divided into two major groups: China mainland and Northeast Asia (Northeast China, Russia, and Korean Peninsula). As with previous studies of this species, we recover population genetic structure not tied to geographic region. Additionally, we discover a new genetic clade restricted to Northeast Asia that points towards the Korean Peninsula being a glacial refugium during the Pleistocene. The weak phylogeographic pattern of B. gargarizans is likely the result of multiple biological, anthropogenic, and historical factors - robust dispersal abilities as a consequence of physiological adaptations, human translocation, geologic activity, and glacial cycles of the Pleistocene. We highlight the complex geologic and climatic history of Northeast Asia and encourage further research to understand its impact on the biodiversity in the region.

A definition of the Goniurosaurus yingdeensis group (Squamata, Eublepharidae) with the description of a new species.

A definition of the Goniurosaurus yingdeensis group is presented in this study, on the basis of morphological and phylogenetic analyses based on a series of additional specimens. Moreover, a new species of this group, Goniurosaurus varius sp. nov., is proposed for northern Guangdong Province, China. The new species can be distinguished from the other two congeners of this group by the following unique characters: one or two internasals; enlarged supraorbital tubercles absent; paravertebral tubercles between limb insertions 27-29; dorsal tubercle rows at midbody 21-24; ten precloacal pores in males and absent in females; body bands with black spots; iris orange-red.

Engagement and adherence trade-offs for SARS-CoV-2 contact tracing

Contact tracing is an important tool for allowing countries to ease lock-down policies introduced to combat SARS-CoV-2. For contact tracing to be effective, those with symptoms must self-report themselves while their contacts must self-isolate when asked. However, policies such as legal enforcement of self-isolation can create trade-offs by dissuading individuals from self-reporting. We use an existing branching process model to examine which aspects of contact tracing adherence should be prioritised. We consider an inverse relationship between self-isolation adherence and self-reporting engagement, assuming that increasingly strict self-isolation policies will result in fewer individuals self-reporting to the programme. We find that policies that increase the average duration of self-isolation, or that increase the probability that people self-isolate at all, at the expense of reduced self-reporting rate, will not decrease the risk of a large outbreak and may increase the risk, depending on the strength of the trade-off. These results suggest that policies to increase self-isolation adherence should be implemented carefully. Policies that increase self-isolation adherence at the cost of self-reporting rates should be avoided.

A new species of the Rana japonica group (Anura, Ranidae, Rana) from China, with a taxonomic proposal for the R. johnsi group.

Rana jiulingensis sp. nov., a new species from Hunan and Jiangxi, southeastern China, is described. The new species is assigned to the R. japonica group. The clade comprising R. jiulingensis sp. nov. and R. dabieshanensis from Anhui is the sister taxon of R. omeimontis from Sichuan. Rana jiulingensis sp. nov. can be distinguished by the significant divergences in the 16S and COI genes, and the combination of following morphological characters: body size medium, SVL 48.3-57.8 mm in adult males and 48.2-57.5 mm in adult females; dorsolateral fold straight; digits without circummarginal grooves; dorsal skin smooth; tibio-tarsal articulation reaching forward beyond the tip of snout; heels overlapping; webbing formula of toes: I 1⅓ - 2 II 1⅓ - 2⅓ III 1½ - 2⅔ IV 3 - 1⅓ V; absence of vocal sacs in males; and presence of creamy white nuptial pad with tiny hoar spines on the finger I and reddish tubercles on loreal and temporal regions in breeding males. Furthermore, based on our results and the previous literature, R. zhengi is synonymized with R. sangzhiensis, and a new species group, the Rana johnsi group, is proposed for the R. johnsi and R. sangzhiensis. Currently, the Rana contains 41 recognized species, and the phylogenetic placements of several species remain unresolved.