Identification of circRNA-miRNA-mRNA networks contributes to explore underlying pathogenesis and therapy strategy of gastric cancer.
Circular RNAs (circRNAs) are a new class of noncoding RNAs that have gained increased attention in human tumor research. However, the identification and function of circRNAs are largely unknown in the context of gastric cancer (GC). This study aims to identify novel circRNAs and determine their action networks in GC. A comprehensive strategy of data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology were conducted to discover novel circRNAs and to explore their potential mechanisms in GC. Promising therapeutic drugs for GC were determined by connectivity map (CMap) analysis. Six overlapped differentially expressed circRNAs (DECs) were screened from selected microarray and RNA-Seq datasets of GC, and the six DECs were then validated by sanger sequencing and RNase R treatment. Subsequent RT-qPCR analysis of GC samples confirmed decreased expressions of the six DECs (hsa_circ_0000390, hsa_circ_0000615, hsa_circ_0001438, hsa_circ_0002190, hsa_circ_0002449 and hsa_circ_0003120), all of which accumulated preferentially in the cytoplasm. MiRNA binding sites and AGO2 occupation of the six circRNAs were predicted using online databases, and circRNA-miRNA interactions including the six circRNAs and 33 miRNAs were determined. Then, 5320 target genes of the above 33 miRNAs and 1492 differently expressed genes (DEGs) from The Cancer Genome Atlas (TCGA) database were identified. After intersecting the miRNA target genes and the 889 downregulated DEGs, 320 overlapped target genes were acquired. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these target genes were related to two critical tumor-associated signaling pathways. A protein-protein interaction network with the 320 target genes was constructed using STRING, and fifteen hubgenes (ATF3, BTG2, DUSP1, EGR1, FGF2, FOSB, GNAO1, GNAI1, GNAZ, GNG7, ITPR1, ITPKB, JUND, NR4A3, PRKCB) in the network were identified. Finally, bioactive chemicals (including vorinostat, trichostatin A and astemizole) based on the fifteen hubgenes were identifed as therapeutic agents for GC through the CMap analysis. This study provides a novel insight for further exploration of the pathogenesis and therapy of GC from the circRNA-miRNA-mRNA network perspective.


Distinguishing features of Long COVID identified through immune profiling.
SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID 1-3 . Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions 1-3 ; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.


Localization of dopamine D2 receptor mRNA with non-radioactive in situ hybridization histochemistry.
A digoxigenin-labeled antisense 42-mer oligonucleotide was used for the localization of the dopamine D2 receptor mRNA in the rat brain. The digoxigenin label was identified with alkaline phosphatase conjugated sheep-anti-digoxigenin. In good analogy with the known terminal fields of the dopaminergic system, various nuclei throughout the brain were labeled. Positive in situ hybridization signals were also found in dopamine cell groups of the substantia nigra and ventral tegmental area and in regions where a dopaminergic innervation is controversial, like the cerebellar cortex and the hippocampus. The non-radioactive in situ hybridization procedure described, shows the localization of the dopamine D2 receptor mRNA with a very high contrast and an optimal histological resolution.


Retinal pathology occurring after excimer laser surgery or phakic intraocular lens implantation: evaluation of possible relationship.
The increasing number of patients undergoing refractive surgery has led to an awareness of the potential retinal complications of these procedures. The purpose of this review is to summarize the reports of retinal pathology and myopic maculopathy that have occurred after excimer refractive surgery or implantation of phakic intraocular lenses, and to evaluate theoretical pathogenetic mechanisms. We found it reasonable to conclude that retinal detachments and macular hemorrhages are not caused by laser surgery, but are rather characteristic of the natural history in the myopic eye. However, although there is no clear-cut evidence for a cause-and-effect relationship between excimer laser surgery and retinal pathology, it is very important to inform patients that refractive surgery only corrects the refractive aspect of myopia, and that the myopia itself still has the potential for serious complications.


Examining factors that shape use and access to diverted prescription opioids during an overdose crisis: A qualitative study in Vancouver, Canada.
Prescription opioid (PO) diversion is widely regarded as a driver of overdose mortality. However, less is known about the rationale for using diverted POs during an overdose epidemic and how contextual factors (e.g., poverty, drug policies) may affect this practice. Therefore, we sought to examine this phenomenon. We conducted qualitative interviews with 24 participants who accessed diverted POs in Vancouver, Canada. Participants were recruited from ongoing cohort studies of people who use drugs (PWUD). Participants preferred a variety of POs due to their known contents and lower overdose risk compared to street drugs and used them for pain relief and pleasure. Participants reported barriers in accessing POs from physicians, with some being cut off or having insufficient prescriptions. Prices for diverted POs varied and affected access among impoverished participants. These access challenges led some to acquire fentanyl. Some participants reported concerns over the contents of counterfeit pills, while others relied on trusted sources or using visual cues to identify legitimate pills. Our findings demonstrate that diverted POs are being used by PWUD with the goal of reducing opioid-related harms, although PO use comes with challenges associated with limited accessibility and risks posed by counterfeit pills. Poverty also limited PO accessibility, leading some to purchase more toxic, yet affordable, street drugs. Given the risks and barriers affecting people seeking to use diverted POs, our findings emphasize the need for the continued implementation and evaluation of safer drug supply initiatives, including those providing access to various drug types.


The number of valvular insufficiency is a strong predictor of cardiovascular and all-cause mortality in hemodialysis patients.
To investigate the relationship between the number of valvular insufficiency (VI) and emergency hospitalization or mortality in maintenance hemodialysis (HD) patients. The maintenance HD patients with cardiac ultrasonography were included. According to the number of VI ≥ 2 or not, the patients were divided into two groups. The difference of emergency hospitalized for acute heart failure, arrhythmia, acute coronary syndrome (ACS) or stroke, cardiovascular mortality, and all-cause mortality between the two groups were compared. Among 217 maintenance HD patients, 81.57% had VI. 121 (55.76%) patients had two or more VI, and 96 (44.24%) with one VI or not. The study subjects were followed up for a median of 47 (3-107) months. At the end of the follow up, 95 patients died (43.78%), of whom 47 (21.66%) patients died because of cardiovascular disease. Age (HR 1.033, 95% CI 1.007-1.061, P = 0.013), number of VI ≥ 2 (HR 2.035, 95% CI 1.083-3.821, P = 0.027) and albumin (HR 0.935, 95% CI 0.881-0.992, P = 0.027) were independent risk factors for cardiovascular mortality. The three parameters were also independent risk factors for all-cause mortality. The patients with number of VI ≥ 2 were more likely to be emergency hospitalized for acute heart failure (56 [46.28%] vs 11 [11.46%], P = 0.001). On the contrary, the number of VI was not associated with emergency hospitalized for arrhythmia, ACS or stroke. Survival analysis results showed that probability of survival was statistically different in the two groups (P < 0.05), no matter based on cardiovascular mortality or all-cause mortality. Based on age, number of VI ≥ 2 and albumin, nomogram models for 5-year cardiovascular and all-cause mortality were built. In maintenance HD patients, the prevalence of VI is prominently high. The number of VI ≥ 2 is associated with emergency hospitalized for acute heart failure, cardiovascular and all-cause mortality. Combining age, number of VI ≥ 2, and albumin can predict cardiovascular and all-cause mortality.


Prevalence of asymptomatic coronary disease in fibrosing idiopathic interstitial pneumonias.
Because of growing body of interest on the association between fibrosing idiopathic interstitial pneumonias (f-IIP) and ischaemic heart disease, we initiated this prospective study to evaluate the prevalence of asymptomatic coronary artery disease (CAD) in patients with f-IIP. Forty-two patients with f-IIP underwent noninvasive screening for CAD that included (a) a chest CT examination enabling calculation of the coronary artery calcium (CAC) score, then depiction of coronary artery stenosis; and (b) stress myocardial perfusion scintigraphy (MPS). Patients with significant coronary abnormalities, defined by a CAC score >400 or coronary artery stenosis >50% at CT and/or perfusion defect >5% at MPS, were referred to the cardiologist. Coronary angiography was indicated in presence of a perfusion defect >10% at MPS or significant left main or proximal left anterior descending stenosis whatever MPS findings. Combining CT and MPS, significant abnormalities were detected in 32/42 patients (76%). The cardiologist: (a) did not consider further investigation in 21 patients (CT abnormalities but no ischaemia at MPS: 12/21; false-positive findings at MPS: 3/21; poor respiratory condition: 6/21); (b) proceeded to coronary angiography in 11 patients which confirmed significant stenoses in 5 patients (5/42; 12%). In the worst-case-scenario (i.e., inclusion of 6 patients with significant coronary artery abnormalities who were not investigated due to poor respiratory condition), the prevalence of CAD reached 26% (11/42). In the studied population of patients with f-IIP, asymptomatic CAD ranged between 12% and 26%.


Cardiac Arrest in Acute Myocardial Infarction: Concept of Circulatory Support With Mechanical Chest Compression and Impella to Facilitate Percutaneous Coronary Intervention.
Cardiogenic shock in the context of acute ST-elevation myocardial infarction (STEMI) remains a challenge to manage and results in significant mortality and morbidity, cardiac arrest in this setting even more so. The increase in myocardial oxygen demand and consumption with the use of inotropes is recognised as increasing mortality. Alternatives include the intra-aortic balloon pump (IABP), which has yet to be shown to improve outcomes, and extracorporeal membrane oxygenation (ECMO), which requires super-specialised techniques not widely available. We report a case of Anterior STEMI from a left main stem occlusion suffering with cardiac arrest on reaching the catheter laboratory table necessitating external mechanical compression with an Autopulse™. The patient remained in pulseless electrical activity (PEA) throughout, and was Autopulse dependent despite successful percutaneous coronary intervention (PCI). An Impella® was inserted for additional mechanical support and facilitated successful weaning from cardiopulmonary resuscitation (CPR). Despite 105minutes without a spontaneous output, we describe the first documented case of simultaneous use of Impella with mechanical CPR with a successful outcome; demonstrating a potential technique of good mechanical haemodynamic support to aide early revascularisation that may have potential utility in the treatment of cardiogenic shock and arrest.


Involvement of the Escherichia coli RNA polymerase alpha subunit in transcriptional activation by the bacteriophage lambda CI and CII proteins.
Escherichia coli cells harbouring the rpoA341 mutation produce an RNA polymerase which transcribes inefficiently certain operons subject to positive control. Here, we demonstrate that the rpoA341 allele also prevents lysogenization of the host strain by bacteriophage lambda, a process dependent upon the action of two phage-encoded activators. This phenomenon was shown to arise from an inability to establish an integrated prophage rather than a failure to maintain the lysogenic state. The inability of the rpoA341 host to support lysogenization could be completely reversed by CII-independent expression of int and cI in trans. These results led us to propose that the inhibition of lysogenization arises from a defective interaction between the phage lambda transcriptional activator CII and the mutant RNA polymerase at the phage promoters pI and pE. Finally, we also provide genetic evidence for impaired transcription of the cI gene from the CI-activated promoter, pM in the rpoA341 background.


Taphonomic criteria for identifying Iberian lynx dens in quaternary deposits.
For decades, taphonomists have dedicated their efforts to assessing the nature of the massive leporid accumulations recovered at archaeological sites in the northwestern Mediterranean region. Their interest lying in the fact that the European rabbit constituted a critical part of human subsistence during the late Pleistocene and early Holocene. However, rabbits are also a key prey in the food webs of Mediterranean ecosystems and the base of the diet for several specialist predators, including the Iberian lynx (Lynx pardinus). For this reason, the origin of rabbit accumulations in northwestern Mediterranean sites has proved a veritable conundrum. Here, we present the zooarchaeological and taphonomic study of more than 3000 faunal and 140 coprolite remains recovered in layer IIIa of Cova del Gegant (Catalonia, Spain). Our analysis indicates that this layer served primarily as a den for the Iberian lynx. The lynxes modified and accumulated rabbit remains and also died at the site creating an accumulation dominated by the two taxa. However, other agents and processes, including human, intervened in the final configuration of the assemblage. Our study contributes to characterizing the Iberian lynx fossil accumulation differentiating between the faunal assemblages accumulated by lynxes and hominins.


Biomechanical analysis of temporomandibular joints during mandibular protrusion and retraction motions: A 3d finite element simulation.
Temporomandibular disorders (TMDs) represent a wide range of musculoskeletal disorders associated with the maxillofacial system, which negatively affect the daily activities of patients. TMD symptoms are caused by the temporomandibular joint (TMJ) overloading. TMJ motions are frequent and can trigger overloading and imbalanced loads on the TMJs, which are assumed to be dangerous. The condyles move forward a lot during mandibular protrusion, which is possibly harmful to the biomechanical environment of the TMJs. The aim of this study was to investigate the biomechanical behavior of TMJs during mandibular protrusion and retraction. Six three-dimensional maxillofacial system models from asymptomatic subjects were established through computed tomography (CT) and magnetic resonance imaging (MRI). The mandibular protrusion and retraction were recorded using an optical tracking system. Finite element analysis was used to simulate the biomechanical behaviors of the TMJs during the movements. The simulation results were validated to be effective by comparison with the MRIs. The results indicated that the stresses during the protrusion and retraction were approximately equal at the same condylar displacement. Meanwhile the discal stresses, relatively correlated with the condylar displacement, increased as the condylar displacement increased during the protrusion and decreased as the condylar displacement decreased in the retraction. In addition, the average peak maximum and minimum principal stresses of the discs were 0.186 and -0.192 MPa, respectively. The models were reasonable for the investigation of the TMJs motion. Based on the results, three quadratic polynomials were proposed to describe the relationship between the stresses and the condylar displacements. In clinical diagnosis, the functions are helpful in the prediction of the discal stresses by measuring the condylar displacement.


Design of synthetic retinoids.
This chapter has been conceived as an introductory text to aid in the understanding of the key design strategies for the development of synthetic analogs of endogenous retinoids as ligands for the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). The structure and binding characteristics of the endogenous retinoids are first explained to put the main chemical design challenges in context. Existing biochemical and structural data is then used to describe the guiding principles used to develop agonists and antagonists of the RARs and RXRs. In light of the increasing proliferation of biophysical methods that employ fluorescence measurements or molecular tags, we also examine the application of retinoids as probes and the chemical principles required to develop these tools.


Strong ALK and PD-L1 positive IHC expression related ALK amplification in an advanced lung sarcomatoid carcinoma: A therapeutic trap?
Immunohistochemistry (IHC) is considered as a screening method for ALK rearrangement thanks to its excellent sensitivity. Strong marking on immunohistochemistry give the go-ahead to start ALK tyrosine kinase inhibitors (ALK TKI). Lack of therapeutic response may then lead to the suspicion of molecular alterations other than ALK rearrangements. We present a patient with strong ALK and PD-L1 positive IHC expression lung sarcomatoid carcinoma with initial life-threatening disease progression after beginning ALK TKI. We also review the literature to summarize ALK amplification clinical features and therapeutic management in lung cancers. Fluorescence in situ Hybridization (FISH) revealed ALK amplification on the initial anatomopathological samples. Lack of ALK rearrangement and strong PD-L1 positive IHC expression led to the initiation of immune checkpoint inhibitor (ICI) as a second line of treatment, with an excellent response. We demonstrated that IHC positive test, in these cases, must be interpreted with caution. FISH analysis has to be recommended to confirm IHC results in case of unusual phenotype, such as smoker or lung cancer other than adenocarcinoma. Although lung carcinoma with ALK rearrangement seems to be not sensitive to ICI, further investigations should be conducted on other types of ALK molecular alterations. ALK amplifications, as observed in the present case, should not be an impediment to taking into account the PD-L1 marking for the initiation of treatment by immunotherapy.


Chlamydial Pgp3 Seropositivity and Population-Attributable Fraction Among Women With Tubal Factor Infertility.
Chlamydial infection is associated with tubal factor infertility (TFI); however, assessment of prior chlamydial infection and TFI is imperfect. We previously evaluated a combination of serological assays for association with TFI. We now describe the chlamydial contribution to TFI using a newer Chlamydia trachomatis Pgp3-enhanced serological (Pgp3) assay. In our case-control study of women 19 to 42 years old with hysterosalpingogram-diagnosed TFI (cases) and non-TFI (controls) in 2 US infertility clinics, we assessed possible associations and effect modifiers between Pgp3 seropositivity and TFI using adjusted odds ratios with 95% confidence intervals (CIs) stratified by race. We then estimated the adjusted chlamydia population-attributable fraction with 95% CI of TFI. All Black (n = 107) and 618 of 620 non-Black women had Pgp3 results. Pgp3 seropositivity was 25.9% (95% CI, 19.3%-33.8%) for non-Black cases, 15.2% (95% CI, 12.3%-18.7%) for non-Black controls, 66.0% (95% CI, 51.7%-77.8%) for Black cases, and 71.7% (95% CI, 59.2%-81.5%) for Black controls. Among 476 non-Black women without endometriosis (n = 476), Pgp3 was associated with TFI (adjusted odds ratio, 2.6 [95% CI, 1.5-4.4]), adjusting for clinic, age, and income; chlamydia TFI-adjusted population-attributable fraction was 19.8% (95% CI, 7.7%-32.2%) in these women. Pgp3 positivity was not associated with TFI among non-Black women with endometriosis or among Black women (regardless of endometriosis). Among non-Black infertile women without endometriosis in these clinics, 20% of TFI was attributed to chlamydia. Better biomarkers are needed to estimate chlamydia TFI PAF, especially in Black women.


Intraoperative functional MRI using a real-time neurosurgical navigation system.
A 42-year-old-man had focal left hand motor seizures. MR studies demonstrated a right posterior frontal brain tumor. Functional MRI was performed, localizing the motor cortex posterior to the lesion. The functional images were integrated with a neurosurgical navigation computer. A real-time intraoperative display of the anatomic and functional images was produced, registered to a neurosurgical probe. Excellent correlation was demonstrated between the functional maps and invasive electrophysiologic mapping performed at the time of craniotomy.


Qualitative assessment of the impacts of the COVID-19 pandemic on migration, access to healthcare, and social wellbeing among Venezuelan migrants and refugees in Colombia.
Colombia hosts a large number of Venezuelan migrants and refugees who are uniquely vulnerable and have been markedly impacted by the COVID-19 pandemic. It is necessary to understand their experiences to inform future policy decisions both in Colombia and during disease outbreaks in other humanitarian contexts in the future. As part of a larger study focused on HIV among Venezuelans residing in Colombia, qualitative interviews were conducted to understand this population's experiences and access to healthcare. Interviews were conducted with Venezuelan migrants and refugees as well as stakeholders such as care providers, humanitarian workers, and government officials. Interviews were recorded, transcribed, and coded using thematic content analysis. Select quotes were translated and edited for length and/or clarity. Venezuelan migrants and refugees reported high levels of housing instability, job instability, increased barriers to accessing healthcare, and complications in engaging in the HIV care continuum, among other impacts of the COVID-19 pandemic. Stakeholders reported complications in provision of care and obtaining medicines, difficulty maintaining contact with patients, increased discrimination and xenophobia targeting Venezuelan migrants and refugees, increased housing instability among Venezuelan migrants and refugees, and other impacts as a result of the COVID-19 pandemic. This study demonstrates the unique impacts of the COVID-19 pandemic among Venezuelans residing in Colombia by both compounding extant vulnerabilities and introducing new challenges, such as high rates of eviction. Colombia has enacted increasingly inclusive migration policies for Venezuelan refugees and migrants within the country; findings from this study underscore the necessity for such policies both in and outside of the Colombian context.


The good, the bad, and the why: How do Arabic-speaking migrant men perceive and experience information and services related to sexual and reproductive health in Sweden?
Although migrant men constitute a large and growing proportion of men in Sweden, literature exploring migrant men's experiences in sexual and reproductive health (SRH) services is scarce. We aimed to explore how Arabic-speaking migrant men perceive and experience information and services related to SRH in Sweden. We conducted 13 semi-structured interviews with Arabic-speaking migrant men and analysed the data using reflexive thematic analysis. We developed four themes: 1) SRH is 'something essential in life'; 2) the good: a transition to a 'new open society'; 3) the bad: barriers to sexual education and health services; and 4) the why: blaming oneself or the system. SRH services and sexual education/information were perceived as needs and rights, and the participants were content with the new possibilities and the 'new open society'. However, sexual education was not provided to most migrants, and SRH services provided to men had shortcomings that deprived some migrant men from fulfilling their needs. Moreover, internalised and cultural racism created a challenge to receive adequate/acceptable SRH services. There is a need to provide comprehensive sexual education for all, strengthen SRH services provided to men, and develop an action plan to reinforce the anti-discrimination/racism policies in healthcare and society.


[Adhesion patterns in diffusely adherent Escherichia coli (DAEC) strains isolated from children with and without diarrhea].
Diffusely adherent E. coli (DAEC) is the sixth recognized group of diarrheagenic E. coli. However, its association with diarrhea remains controversial. Variability in the adherence patterns of clinical strains is unknown. To compare the adherence patterns between strains isolated from children with and without diarrhea. A total of 31 DAEC strains were analyzed, 25 from children with diarrhea and 6 from asymptomatic (control) children, isolated from a cohort study of children under one year of age in the southern districts of Lima. DAEC were identified by PCR (daaD gene). The pattern and adherence score in HEp-2 cell culture were evaluated, Actin polimerization was determined by fluorescence actin staining (FAS) and motility was evaluated by conventional microbiology methods. Diffuse adherence pattern was found in 88% of diarrhea samples and in the total of control strains. The number of bacteria adhered per cell was significantly lower in diarrhea samples (p<0.05). However, actin polymerization was greater in diarrhea samples (60% vs. 17%). Motility test was positive in 60% of the diarrhea samples and in all control samples. Our findings suggest a difference between adherence patterns, actin polymerization and motility between DAEC strains corresponding to diarrhea and control groups. The significance of these results must be confirmed with a bigger number of strains and determining the presence of virulence genes in the strains.


Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution.
Generating the appropriate protonation states of drug-like molecules in solution is important for success in both ligand- and structure-based virtual screening. Screening collections of millions of compounds requires a method for determining tautomers and their energies that is sufficiently rapid, accurate, and comprehensive. To maximise enrichment, the lowest energy tautomers must be determined from heterogeneous input, without over-enumerating unfavourable states. While computationally expensive, the density functional theory (DFT) method M06-2X/aug-cc-pVTZ(-f) [PB-SCRF] provides accurate energies for enumerated model tautomeric systems. The empirical Hammett-Taft methodology can very rapidly extrapolate substituent effects from model systems to drug-like molecules via the relationship between pK(T) and pK(a). Combining the two complementary approaches transforms the tautomer problem from a scientific challenge to one of engineering scale-up, and avoids issues that arise due to the very limited number of measured pK(T) values, especially for the complicated heterocycles often favoured by medicinal chemists for their novelty and versatility. Several hundreds of pre-calculated tautomer energies and substituent pK(a) effects are tabulated in databases for use in structural adjustment by the program Epik, which treats tautomers as a subset of the larger problem of the protonation states in aqueous ensembles and their energy penalties. Accuracy and coverage is continually improved and expanded by parameterizing new systems of interest using DFT and experimental data. Recommendations are made for how to best incorporate tautomers in molecular design and virtual screening workflows.


Edge-to-Edge Repair Versus Secondary Cord Cutting During Septal Myectomy in Patients With Hypertrophic Obstructive Cardiomyopathy: A Pilot Randomised Study.
To evaluate whether the Alfieri technique improves clinical and haemodynamic results and compare it with transaortic mitral valve secondary cord cutting in patients scheduled for septal myectomy for severely symptomatic hypertrophic obstructive cardiomyopathy. Forty-eight (48) patients with moderate-to-severe systolic anterior motion (SAM)-mediated mitral regurgitation were randomly assigned to the Alfieri or Cutting groups in addition to septal myectomy. The primary endpoint was postoperative mean transmitral pressure gradient (TPG). The secondary endpoints were residual left ventricular outflow tract (LVOT) gradient after procedure, residual mitral regurgitation (MR), postoperative SAM, repeating bypass, and survival. There were no 30-day mortality and ventricular septal defects. The postoperative LVOT gradient was 15.4±7.6 mmHg and 11.1±4.9 mmHg (p=0.078) in the Alfieri and Cutting groups, respectively. The Alfieri technique was associated with higher peak (7.8±3.3 vs 4.7±2.8 mmHg; p=0.014) and mean (3.9±1.7 vs 2.1±1.6 mmHg; p=0.013) TPG. The Cutting group was associated with higher mild MR rate at discharge (six vs no patients; p=0.009). One (1) patient (4.2%) in the Alfieri group required pacemaker implantation owing to conduction disturbances (p=0.312). Two-year (2-year) freedom from late mortality and sudden cardiac death rates were 95.5%±4.4% and 100% for the Alfieri and Cutting groups, respectively (log rank, p=0.317). No patients had New York Heart Association functional class III or IV or moderate or severe MR. The maximum LVOT gradient was 20.4±15.2 mmHg and 16.7±10.4 mmHg, respectively (p=0.330). There were no reoperations during follow-up. Both techniques with septal myectomy effectively eliminated SAM-induced MR and LVOT obstructions in hypertrophic cardiomyopathy patients.


A Visual Analytic Tool (VIADS) to Assist the Hypothesis Generation Process in Clinical Research: Mixed Methods Usability Study.
Visualization can be a powerful tool to comprehend data sets, especially when they can be represented via hierarchical structures. Enhanced comprehension can facilitate the development of scientific hypotheses. However, the inclusion of excessive data can make visualizations overwhelming. We developed a visual interactive analytic tool for filtering and summarizing large health data sets coded with hierarchical terminologies (VIADS). In this study, we evaluated the usability of VIADS for visualizing data sets of patient diagnoses and procedures coded in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). We used mixed methods in the study. A group of 12 clinical researchers participated in the generation of data-driven hypotheses using the same data sets and time frame (a 1-hour training session and a 2-hour study session) utilizing VIADS via the think-aloud protocol. The audio and screen activities were recorded remotely. A modified version of the System Usability Scale (SUS) survey and a brief survey with open-ended questions were administered after the study to assess the usability of VIADS and verify their intense usage experience with VIADS. The range of SUS scores was 37.5 to 87.5. The mean SUS score for VIADS was 71.88 (out of a possible 100, SD 14.62), and the median SUS was 75. The participants unanimously agreed that VIADS offers new perspectives on data sets (12/12, 100%), while 75% (8/12) agreed that VIADS facilitates understanding, presentation, and interpretation of underlying data sets. The comments on the utility of VIADS were positive and aligned well with the design objectives of VIADS. The answers to the open-ended questions in the modified SUS provided specific suggestions regarding potential improvements for VIADS, and the identified problems with usability were used to update the tool. This usability study demonstrates that VIADS is a usable tool for analyzing secondary data sets with good average usability, good SUS score, and favorable utility. Currently, VIADS accepts data sets with hierarchical codes and their corresponding frequencies. Consequently, only specific types of use cases are supported by the analytical results. Participants agreed, however, that VIADS provides new perspectives on data sets and is relatively easy to use. The VIADS functionalities most appreciated by participants were the ability to filter, summarize, compare, and visualize data. RR2-10.2196/39414.


Influence of pericoronary adipose tissue on local coronary atherosclerosis as assessed by a novel MDCT volumetric method.
Pericoronary adipose tissue (PCAT) may create a pro-inflammatory state, contributing to the development of coronary artery disease (CAD). We sought to evaluate the feasibility of a novel volumetric PCAT quantification method using a novel threshold based computed tomography approach. In addition we determined the relation between PCAT volumes and CAD. In 51 patients (49.5±5.1 years, 64.8% male) who underwent 64-slice MDCT, we measured threshold-based PCAT volumes using distance and anatomic-based methods. Using the most reproducible method, we performed the proximal 40-mm distance measurement in three groups as stratified by coronary plaque and high-sensitivity C-reactive protein (hs-CRP) levels: Group 1 (presence of coronary plaque, hs-CRP >2.0 mg/L); an intermediate group (Group 2, no plaque, hs-CRP >2.0 mg/L); and Group 3 (no plaque, hs-CRP<1.0 mg/L). We compared PCAT volumes to the presence of coronary plaque on a patient (n=51) and vessel (n=153) basis. On a subsegment basis (n=1224), we compared PCAT volume to the presence of plaque as well as plaque morphology. Distance-based PCAT volume measurements yielded excellent reproducibility with intra-observer intraclass correlation (ICC) of 0.997 and inter-observer ICC of 0.951. On a both a per-patient and per-vessel analysis, adjusted PCAT volume was greater in patients with plaque (Group 1) than without plaque (Groups 2 and 3, p<0.001). No difference in PCAT volume was seen between high and low hs-CRP groups without plaque (p=0.51). Adjusted PCAT volumes were higher in subsegments with plaque as compared without (p<0.001). Additionally, adjusted PCAT volume was greatest in subsegments with mixed plaque followed by non-calcified plaque, calcified plaque, and the lowest volume in segments with no plaque (p<0.001). In this proof-of-concept study, threshold based PCAT volume assessment is feasible and highly reproducible. PCAT volume is increased in patients and vessels with coronary plaques. Surrounding vessel subsegments with coronary plaque, particularly mixed plaques, have greatest PCAT volume and highlight the effect of local PCAT in the development of coronary atherosclerosis.


Phenotypic study of peripheral blood leucocytes in HTLV-I-infected individuals from Minas Gerais, Brazil.
The human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) associated with the HTLV-I is a well-defined clinical-pathological entity in which the virus and host immune responses contribute to the pathological mechanism. In this study, flow cytometric analysis of whole peripheral blood leucocytes (PBL) was performed to evaluate the immunological status of HTLV-I-infected individuals in an effort to better understand the role of the immune system in the development of HAM/TSP. We have evaluated three groups of infected patients including asymptomatic (AS = 18), ambulatory/oligosymptomatic (AM = 14) and hospitalized HAM/TSP individuals (HO = 42). Noninfected healthy blood donors were used for the control group (NI = 32). Our results demonstrated that the HO group presents an increased percentage of circulating T cells and a decreased percentage of B and natural killer (NK) cells, leading to the highest T/B-cell ratio in comparison with the other groups. Interestingly, while an increased percentage of activated CD4+HLA-DR+ T lymphocytes was observed in both AM and HO, only HO presented higher percentage of activated CD8+HLA-DR+ in combination with the highest CD18 surface expression. This was true for all cell populations analysed, including T lymphocytes, monocytes and neutrophils. Moreover, the HO group was distinguished by a dramatic decrease in the percentage of CD8+CD28+ lymphocytes. Taken together, these findings demonstrate a potent cellular immune activation response involving primarily CD8+ T cells that is concomitant with disease progression in HAM/TSP. We also show that an upregulation of CD18 expression, a hallmark for increased cell migratory potential, might play a critical role in the development/maintenance of HAM/TSP.


Impact of arrhythmias on health-related quality of life in adults with congenital cardiac disease.
Health-related quality of life in adults with congenital cardiac disease appears to be impaired, but the determinants of this alteration remain largely unknown. The aim of our study was to examine the impact of arrhythmias on quality of life in patients late after the atrial redirection operation for transposition, or after complete correction of tetralogy of Fallot. We enrolled 32 patients with transposition, and 35 patients with tetralogy of Fallot, in a prospective study. Quality of life was assessed using RAND-36 questionnaires. Quality of life data were compared with those of an age-matched control population. Patients underwent 24-hour and 7-day electrocardiographic recordings, echocardiography, and exercise testing. Patients without arrhythmias had quality of life comparable to that of the general population. All 8 domains in the questionnaire showed scores 22 to 51 percent lower in 12 patients with atrial tachyarrhythmias, and/or sinus nodal dysfunction, requiring insertion of a pacemaker in comparison with 55 patients without arrhythmias. In patients with transposition, low scores were not only associated with arrhythmias, but also correlated with impaired exercise capacity. Atrial tachyarrhythmias, and sinus nodal dysfunction, requiring insertion of a pacemaker, were associated with impaired quality of life in adults late after atrial surgical correction of transposition or correction of tetralogy of Fallot.


Sex differences in brain structure in geriatric depression.
In an exploratory study, authors compared patients with late-life major depression (MDD) and age-matched control subjects to examine sex differences in frontal and orbito-frontal (OFC) regional brain volumes. The study sample comprised 41 patients with MDD and 41 controls. Subjects underwent comprehensive neuropsychiatric examinations and magnetic resonance imaging (MRI) scans. Corrected frontal and OFC gray-matter volumes were compared among men and women in both groups. The depression group had lower MMSE scores, greater severity of medical burden, apathy, psychomotor retardation, and poor health-related quality of life than the controls. Men in both groups had a greater severity of medical burden, apathy, and psychomotor retardation than women. The depression group had smaller OFC total and gray-matter volumes than the controls after matching for age. Men had smaller frontal-matter volumes than women in both groups. The diagnosis x sex interaction in brain regional volumes was observed only after controlling for medical burden. Sex differences in brain neuroanatomy may be important in the pathophysiology of geriatric depression. Men may be susceptible to atrophy in frontal subregions. Medical burden may contribute to the diagnosis x sex interaction in brain regional volumes.


A mechanism for extremely weak SpaP-expression in Streptococcus mutans strain Z1.
Streptococcus mutans surface-protein antigen (SpaP, PAc, or antigen I/II) has been well known to play an important role in initial attachment to tooth surfaces. However, strains with weak SpaP-expression were recently reported to be found in natural populations of S. mutans. The S. mutans gbpC-negative strain Z1, which we previously isolated from saliva and plaque samples, apparently expresses relatively low levels of SpaP protein compared to S. mutans strains MT8148 or UA159. To elucidate the mechanism for weak SpaP-expression in this strain, the spaP gene region in strain Z1 was amplified by polymerase chain reaction (PCR) and analyzed. Allelic exchange mutants between strains Z1 and UA159 involving the spaP gene region were constructed. The SpaP protein expressed in the mutants was detected with Coomasie Brilliant Blue (CBB)-staining and Western blot analysis following SDS-PAGE. The 4689 bp spaP gene coding sequence for Z1 appeared to be intact. In contrast, a 20 bp nucleotide sequence appeared to be deleted from the region immediately upstream from the Z1 spaP gene when compared to the same region in UA159. The 216 bp and 237 bp intergenic fragments upstream from the spaP gene, respectively, from Z1 and UA159 were isolated, modified, and transformed into the other strain by allelic replacement. The resultant UA159-promoter region-mutant exhibited extremely weak SpaP-expression similar to that of strain Z1 and the Z1 complemented mutant expressed Spa protein levels like that of strain UA159. These results suggest that weak SpaP-expression in strain Z1 resulted from a 20 bp-deletion in the spaP gene promoter region.


TLR4/TRAF6/NOX2 signaling pathway is involved in ventilation-induced lung injury via endoplasmic reticulum stress in murine model.
In ventilation-induced lung injury (VILI), prolonged nonpathogen-mediated inflammation is triggered as a result of alveolar hyperinflation. In our previous study, we suggested that endoplasmic reticulum (ER) stress-mediated inflammation was involved in VILI, but how ER stress is triggered remains unknown. Toll-like receptor 4 (TLR4) activation plays an important role in mechanical ventilation (MV)-induced lung inflammation, however, it is unknown whether ER stress is activated by TLR4 to participate in VILI. In this study, C57BL/6 mice were exposed to MV with high tidal volumes (HTV 20 ml/kg). Mice were pretreated with TAK-242 the TLR4 inhibitor, C25-140, the TRAF6 inhibitor, or GSK2795039, the NOX2 inhibitor. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected to measure lung injury, inflammatory responses and mRNA/protein expression associated with ER stress and the TLR4/TRAF6/NOX2 signaling pathway. Our results indicate that MV with HTV caused the TLR4/TRAF6/NOX2 signaling pathway activation and production of large amounts of ROS, which led to ER stress and NF-κB mediated inflammation in VILI. Furthermore, TLR4/TRAF6/NOX2 signaling pathway inhibition attenuated ER stress response and alleviate lung injury in mice.


Correction: Xiao, H., et al. Social Distancing among Medical Students during the 2019 Coronavirus Disease Pandemic in China: Disease Awareness, Anxiety Disorder, Depression, and Behavioral Activities. Int. J. Environ. Res. Public Health 2020, 17, 5047.
In our recently published article [...].


Continuous Glucose Monitoring and Glycemic Control in Patients With Type 2 Diabetes Mellitus and CKD.
The accuracy of glycated hemoglobin (HbA1c) level for assessment of glycemic control in patients with chronic kidney disease (CKD) is uncertain. This study assessed the accuracy of HbA1c level using continuous glucose monitoring. Diagnostic test study of HbA1c and serum fructosamine. The continuous glucose monitor was worn for 14 days. Glucose was measured every 15 minutes (up to 1,344 measurements). Average glucose concentration was calculated for each patient from the patient's continuous glucose monitor measurements. Linear regression was applied to estimate the relationship between average glucose concentration and HbA1c and serum fructosamine levels. The influence of patient characteristics on the relationship between HbA1c and average glucose concentrations was examined in a multivariate regression model. Patients with type 2 diabetes and CKD (estimated glomerular filtration rate, 7-45 mL/min, not receiving dialysis) seen in an academic nephrology clinic. The accuracy of HbA1c level for assessment of chronic glycemia. A secondary objective was to study serum fructosamine levels. The degree of correlation between continuous glucose monitoring-derived average glucose concentration and HbA1c level; serum fructosamine level was studied as a secondary outcome. 80 patients wore the continuous glucose monitor for a mean of 12.7 ± 2.9 days. Average glucose concentration of all patients was 151.5 ± 55.7 mg/dL. Mean HbA1c level was 7.2% ± 1.5%. HbA1c level was highly correlated with average glucose concentration, described by the equation: average glucose concentration = 30.48 × HbA1c - 68.48; r = 0.82; P < 0.001. Serum fructosamine level was also significantly correlated with average glucose concentration; r = 0.55; P < 0.001. The strong correlation between average glucose concentration and HbA1c level was not affected by the severity of CKD, whereas the performance of serum fructosamine level, in contrast, degraded among patients with more severe CKD. Relatively small sample size. HbA1c is an accurate measure of glycemic status among patients with CKD and type 2 diabetes. This relationship appears to hold true among patients with more severe CKD.


Endovascular management of lost or misplaced intravascular objects: experiences of 12 years.
This paper reports our experience with endovascular techniques for the retrieval of lost or misplaced intravascular objects. Over 12 years, 78 patients were referred for interventional retrieval of intravascular foreign objects. In this retrospective study, radiological procedure records and patients' medical records were reviewed to determine the exact removal procedure in every case, to report success rates, and to identify significant procedure-related complications. Written, informed consent was obtained from all patients prior to the intervention; this retrospective analysis was performed according to the guidelines of the Institutional Review Board. Thirty-six of seventy-eight foreign objects (46%) were located in the venous system, 27 of 78 (35%) in the right heart, and 15 of 78 (19%) in the pulmonary arteries. For foreign object removal, in 71 of 78 (91%) cases a snare loop was used, in 6 of 78 (8%) cases a sidewinder catheter combined with a snare loop was used, and in 1 case (1%) a sidewinder catheter alone was used for foreign object removal. In 68 of 78 (87%) cases, primary success was achieved. In 3 of 78 cases (4%), foreign objects were successfully mobilized to the femoral vessels and surgically removed. In 7 of 78 cases (9%), complete removal of the foreign object was not possible. In 5 of 78 cases (6%), minor complications occurred during the removal procedure. In conclusion, endovascular retrieval of lost or misplaced intravascular objects is highly effective, with relatively few minor complications. On the basis of our findings, these techniques should be considered as the therapy of choice.


Postprandial variations in ST-segment in a patient with Brugada syndrome and partial gastrectomy.
A 74-year-old man with a history of partial gastrectomy presented with an electrocardiogram consistent with Brugada syndrome and marked meal related fluctuations in the ST segment. ST-segment elevation was prominently attenuated at 30 minutes and increased at 120 minutes after meals. Analysis of heart rate variability revealed a relationship between postprandial heightened parasympathetic activity and increase in Brugada-type ECG abnormality. A rapid postprandial increase in blood glucose may initially stimulate sympathetic nervous activity and secondarily increase parasympathetic tone. Food intake can be associated with fluctuations in ST-segment elevation in patients with the Brugada syndrome.


What factors are associated with improvements in productivity in clinical laboratories in the Asia Pacific Region?
Clinical laboratories usually have a quality management system such as ISO 15189, which provides a framework for quality and competence to perform medical testing and internal systems such as audit and nonconformance to ensure consistent processes. However, organizations need to have access to internal procedures and external competitors' performance to improve their operations. These are often seen as commercial or areas where it is difficult to agree on an acceptable goal. In 2019, 1158 laboratories from 17 countries/regions in the Asia Pacific Region answered the survey, including 399 Chinese sites. The survey collected information on quality, turnaround time and productivity. Median productivity for laboratories in the Asia Pacific Region not including Chinese sites was 25 samples/FTE/day for small laboratories (workload: <250 samples/day), 100 for medium-sized laboratories (workload: 251-1000 samples/day) and 220 for large laboratories (workload: >1001 samples/day). The parameters associated with increased productivity in some laboratories were automation, middleware, Lean Six Sigma quality improvement activities and International Accreditation. This survey provides evidence of an association of quality improvement activities on laboratory productivity. There are differences in the effect of these activities in Chinese and non-Chinese laboratories in the Asia Pacific Region. The survey confirmed that the implementation of automation is associated with increased median productivity in all sites. Implementation of Lean Six Sigma and International Accreditation is associated with increased productivity in large laboratories.


Adiaspiromycosis in south Australian hairy-nosed wombats (Lasiorhinus latifrons).
Spherical organisms, with an average diameter of about 22 microns, were detected in the lungs of adult and pouched young hairy-nosed wombats (Lasiorhinus latifrons). Although infections of up to 640 X 10(3) organisms per cubic centimeter were detected, their presence produced only limited pathological change. In-vitro growth was obtained at 30 C but not at 37 C or 40 C. However, at the higher temperatures, typical chlamydospore spherules were produced by colonies initially grown at 30 c. This report presents the first record of adiaspiromycosis in Australia and in wombats.


Loss of positional specificity in the aminoacylation of Escherichia coli tRNAGly.
The positional specificity in the aminoacylation of Escherichia coli tRNAGly by its cognate aminoacyl-tRNA synthetase has been studied using tRNAGlys terminating in 2'- or 3'-deoxyadenosine under conditions believed to alter tRNA conformation. Although E. coli tRNAGly terminating in 3'-deoxyadenosine has been reported not to be a good substrate for activation by the homologous glycyl-tRNA synthetase, by systematic variation of the conditions employed for aminoacylation it was possible to activate this tRNA to essentially the same extent as unmodified tRNAGly. Activation of tRNAGly terminating in 3'-deoxyadenosine was carried out optimally at 45 degrees C in an incubation mixture containing 0.3-0.4 M NaCl; 10% methanol, ethanol, and dimethyl sulfoxide were found to facilitate activation of the modified tRNA. Interestingly, the conditions employed to enhance activation of this modified tRNAGly had no effect on the activation of unmodified tRNAGly or tRNAGly terminating in 2'-deoxyadenosine. These experiments afford insight into the activation of tRNAGly by glycyl-tRNA synthetase and provide facile access to positionally defined, isomeric glycl-tRNAGlys.


The effect of timing of influenza vaccination and sample collection on antibody titers and responses in the aged.
Antibody responses, B cell subset distribution in blood and the blood transcriptome were analyzed in younger and aged human subjects before and after vaccination with the inactivated influenza vaccine. In the aged, but not the younger, individuals we saw a clear difference in antibody titers including those at baseline depending on the time of vaccination and sample collection. Differences in baseline titers in aged individuals treated in the morning or afternoon in turn affected responsiveness to the vaccine. In both younger and aged individuals, the time of sample collection also affected relative numbers of some of the B cell subsets in blood. A global gene expression analysis with whole blood samples from the aged showed small but statistically significant differences depending on the time of sample collection. Our data do not indicate that timing of vaccination affects immune responsiveness of the aged, but rather shows that in clinical influenza vaccine trials timing of collection of samples can have a major and potentially misleading influence on study outcome. In future vaccine trials, timing of vaccination and sample collection should be recorded carefully to allow for its use as a study covariant.


The temporal gene expression profiles of calcium and phosphorus transporters in Hy-Line Brown layers.
Calcium and phosphorus homeostasis is crucial for the performance and bone health of laying hens. The calcium and phosphorus transporters play an important role in calcium and phosphorus absorption, reabsorption, and excretion. In the present study, Hy-Line Brown layers were sampled at brooding period (1, 4, 6 wk), growing and developing period (12, 18 wk) and laying period (20, 28, 80 wk) respectively, and the calcium transporters CaBP-D28k and PMCA1b and phosphorus transporters NPt2a and NPt2b were respectively measured in duodenum, jejunum, ileum and kidney. The result showed that serum calcium increased (P < 0.0001) and phosphorus level fluctuated (P = 0.0019), while alkaline phosphatase activity decreased with age (P < 0.0001). The mRNA and protein expressions of CaBP-D28k in small intestine elevated after maturity (P ≤ 0.0001). In contrast, the PMCA1b mRNA showed a trend to increase with age in jejunum (P = 0.0059) and ileum (P = 0.0825) whereas there was a decrease for PMCA1b protein in 12-18 wk (P ≤ 0.0009). The peak of NPt2b mRNA were observed at 28 wk in duodenum (P = 0.0001) and jejunum (P = 0.0622) and 1 wk in ileum (P < 0.0001). The NPt2b protein expression reached the top point at 4 or 6 wk and 20 wk and decreased to the lowest point around 12 wk (P ≤ 0.0850). In kidney, CaBP-D28k mRNA was not influenced by age (P = 0.4999), while PMCA1b highly expressed in 6-12 wk (P = 0.0003). The protein expressions of CaBP-D28k (P = 0.0148) and PMCA1b (P = 0.0003) decreased with age and lowly expressed in 12-18 wk and increased thereafter. In contrast, NPt2a expression increased steadily with age and decreased at 80 wk (P < 0.0001). In conclusion, the expressions of intestinal calcium and phosphorus transporters were changed by age, intestinal CaBP-D28k and renal NPt2a showed a dramatic increase after maturity, which coincide with the increased calcium and phosphorus requirement for egg production.


Transduction in microbial biosensors using multiplexed bioluminescence.
The enormous diversity of genetic responses in living microbes to their environment is an attractive resource on which to base biosensor designs. In particular, there is much interest in microbial sensors for environmental monitoring where toxicity can be ascertained directly by its action on cellular physiology. However, due to the complexities of living systems, the utility of genetic-based microbial sensors has been limited by the ability to accurately transduce the activities of specific genetic sensing systems into readily measurable signals. We present here a strategy for employing an additional signal in the sensor design, to provide an internal baseline control upon which to reliably interpret sensor responses. The strategy relies on using beetle luciferases capable of emitting optical signals of different wavelengths; the optical signals are a sensitive real-time indicator of genetic activity within the cells. The different wavelengths allow both a target and control signal to be incorporated into each cell, providing a means of differentiating between specific effects of a genetic sensing system and other non-specific interfering influences.


Blaschko lines and other patterns of cutaneous mosaicism.
The lines of Blaschko represent a classic pattern of cutaneous mosaicism that can be observed in a wide variety of congenital and acquired skin disorders. This contribution reviews the clinicopathologic spectrum of skin lesions that follow Blaschko lines. Four other patterns of mosaicism are also discussed: blocklike, phylloid, large patches without midline separation, and lateralization. We emphasize the differential diagnoses, clues to correct categorization, and associated findings of inflammatory, hypopigmented, and hyperpigmented lesions with a mosaic distribution. Clinical examples are used to illustrate genetic concepts such as functional X-chromosome mosaicism, type 1 and 2 segmental manifestations of autosomal dominant skin diseases, paradominant inheritance, and twin spotting.


Separation of tryptophan and related indoles by micellar electrokinetic chromatography with KrF laser-induced fluorescence detection.
Micellar electrokinetic chromatography (MEKC) was applied for the separation of tryptophan and related indoles. Using a 5 mM sodium borate buffer (pH 9.2) containing 50 mM sodium dodecyl sulfate and 5% acetonitrile, eleven indoles were baseline separated in under 17 min. Most of the indoles were detected at the nM level by native fluorescence using KrF laser-induced fluorescence (LIF), which was approximately 100 times more sensitive than UV absorption detection at 200 nm. Preliminary results show that the MEKC-LIF with direct sample injection is a feasible method for assessing indole profiles in diluted urine and serum.


3α-diol administration decreases hippocampal PKA (II) mRNA expression and impairs Morris water maze performance in adult male rats.
The effect of testosterone and its metabolites on learning and memory has been the subject of many studies. This study used the Morris water maze task to investigate the effect of intra-hippocampal injection of 3α-diol (one of the metabolites of testosterone) on acquisition stage of spatial memory in adult male rats. During the experiment we observed that 3α-diol, significantly impaired Morris water maze performance in treated rat's compared with controls. Because signaling event mediated by protein kinase A (PKA) especially PKA (II) are critical for many neuronal functions such as learning and memory, the hippocampus was analyzed for mRNA expression of PKA (II) using TaqMan real time RT-PCR. The results indicated that the transcription levels of PKA (II) were significantly decreased in animals treated with 3α-diol compared with controls. Thus, the findings suggest that administration of 3α-diol in hippocampus of adult male rats impairs memory function, possibly via down-regulation of PKA.


Health-related quality of life in children after surgical treatment of non-syndromal craniosynostosis.
Craniosynostosis is a premature ossification of the fibrous sutures in a skull which results in a changing of the growth pattern of the skull with abnormal head shapes, midface hypoplasia, and neurofunctional disorders. Surgical correction of craniosynostosis by opening the ossified cranial sutures is usually made in the infant phase to avoid compression of the brain and mental deficits. However, little is known regarding the health-related quality of life among children after surgical treatment of diverse forms of craniosynostosis. The purpose of this study was to evaluate the quality of life of adolescent patients who anderwent a surgical correction of non-syndromal craniosynostosis in infancy. The study population included 48 adolescents with an average age of 12.1 ± 4.3 years. The KINDL questionnaire, which was specifically validated for children, was used to estimate different dimensions of quality of life and the impact of various factors on it. In the investigated group, boys were more likely to be affected by non-syndromal craniosynostosis than were girls. Children and their parents showed a high degree of correlation in each of the investigated dimensions of the KINDL questionnaire. Sex, the type of craniosynostosis, surgical technique, and surgical result did not seem to have an influence on the quality of life. A negative correlation between the time of surgery and the family-related quality of life could be shown. None of the patients in the study had relevant limitations or impairments in their later life. In our study, patients with simple non-syndromic craniosynostoses who anderwent operative correction of craniosynostosis in infancy do not show any quality-of-life limitations in their later life compared to the average population.


Preparation of monolithic polymer-magnetite nanoparticle composites into poly(ethylene-co-tetrafluoroethylene) tubes for uses in micro-bore HPLC separation and extraction of phosphorylated compounds.
This paper describes the fabrication of a novel microbore monolithic column modified with magnetite nanoparticles (MNPs) prepared in a poly(ethylene-co-tetrafluoroethylene) (EFTE) tubing, and its application as stationary phase for the chromatographic separation of phosphorylated compounds. In order to obtain the composite column, a two-step procedure was performed. The formation of a glycidyl methacrylate-based monolith inside the activated ETFE tube was firstly carried out. Then, two incorporation approaches of MNPs in monoliths were investigated. The generic polymer was modified with 3-aminopropyltrimethoxysilane (APTMS) to be subsequently attached to MNP surfaces. Alternatively, APTMS-coated MNPs were firstly prepared and subsequently used for attachment onto the monolith surface through reaction of epoxy groups present in the generic monolith. This last strategy gave a reproducible layer of MNPs coated onto the polymer monolith as well as robust and permeable chromatographic columns. The retention behaviour of this MNP-based composite monolithic column was studied by using small phosphorylated compounds (adenosine phosphates). It was found that the retention of model analytes was ruled by partitioning and adsorption HILIC mechanisms. The columns also exhibited satisfactory performance in the separation of these target compounds, showing good chromatographic behaviour after two months of continued use. These composite monolithic columns were also successfully applied to the extraction of a tryptic digest of β-casein.


Genomics, expression, and function analyses of XB3 family genes in cotton.
XANTHOMONAS RESISTANCE 21-binding protein3 (XB3) is the first characterized XA21 interacting protein required for plant immunity. We isolated GhXB32A that is similar to XBAT32 and was induced during inoculation of Verticillium dahliae in cotton. 32 putative XB3 family genes were identified in G. hirsutum, G. arboreum, and G. raimondii. Cis-Acting elements related to growth, stresses, and phytohormone were detected in the promoter regions. GhXB3s were ubiquitously expressed in different cotton tissues with different patterns. Most GhXB3s were down-regulated by cold stress, but up-regulated by heat, salt, PEG, V. dahliae, ethylene, and some were up-regulated by SA or MeJA. Silencing GhXB32A and GhXB32D greatly improved resistance to Verticillium wilt, while silencing GhXB35A(D) or GhXB37A(D) made them more susceptible to V. dahliae. The interacting proteins of GhXB32A and GhXB32D were functionally enriched in response to abiotic and/or biotic stresses, and photosynthesis. XB3 family genes are potential stress resistance genes for cotton improvement.


Carbohydrate expression profile of colorectal cancer cells is relevant to metastatic pattern and prognosis.
Carbohydrate expression of cancer cells is closely related to the metastatic nature of colorectal cancer. In the present study we investigated the relevance of carbohydrate expression profiles of colorectal cancer cells in the primary lesion to metastatic distribution patterns as well as prognosis in 134 cases. Carbohydrate expression was estimated by histochemistry with 17 kinds of lectins and 3 kinds of Lewis-related monoclonal antibodies (MAbs), and correlations between the staining and clinicopathological parameters were examined. The results showed that lymphatic invasion, lymph node metastasis, and peritoneal metastasis correlated with staining with lectins that bind galactose/N-acetylgalactosamine residues (Gal/GalNAc) such as Maclura pomifera (MPA), Arachis hypogaea (PNA), Helix pomatia (HPA), and Vicia villosa (VVA). In contrast, hepatic metastasis correlated with staining with Anguilla anguilla lectin (AAA), anti-LewisX (LEX-2), anti-sialyl Lewisa (NS 19-9), and anti-sialyl-dimeric LewisX (FH-6) MAbs, all of which bind preferentially to fucosylated carbohydrate chains. The five-year survival rate of patients was related to the staining of cancers with MPA, HPA, FH-6 or NS19-9, and MPA- and FH-6 staining were independent prognostic factors. We conclude that carbohydrate expression profiles of cancer cells are relevant to the route of tumor cell dissemination, metastatic pattern as well as prognosis of colorectal cancer.


How opening two chronic total occlusions may be easier than just one.
Recanalization of chronic total occlusions (CTOs) via grafts has been described previously. However, the insertion of the graft into the distal vessel is often characterized by an unfavorable entry angle which renders an antegrade approach challenging. In the present case, we describe how retrograde recanalization of the proximal right coronary artery (RCA) via a right internal mammary artery graft facilitated antegrade revascularization of the CTO of the RCA.


Pediatric Interfacility Transport Curriculum: Its Impact on the Pediatric Intensive Care and Emergency Medicine Fellows' Performance and Confidence.
Pediatric interfacility transports are frequent. Despite the absence of a formal pediatric transport curriculum in eastern Canada, directly managing patients during transport and medical direction of the referring center and transport team are part of the pediatric critical care medicine (PCCM) and pediatric emergency medicine (PEM) program requirements. The authors developed a pediatric interfacility transport curriculum and measured its impact on fellows' confidence and performance. This was a pilot interventional prospective study in Montreal, Canada. Postcurriculum surveys were used to measure confidence, and high-fidelity simulations were used to measure performance. A target threshold for confidence was defined before implementation, and pre- and post values were compared. The simulation scenario and assessment checklist were locally developed. The participants were 11 PCCM and 3 PEM fellows. The content of the curriculum and educational methods were selected based on the literature and a needs assessment survey. All participants rated themselves as confident at the end of the curriculum. Eighty-three percent of the participants were deemed proficient with a perfect interrater agreement. The pediatric transport curriculum had a positive impact on PEM and PCCM fellows' confidence and performance in transport. Further studies should look at the impact of such a curriculum on participants' real-life performance and patient care.


High prevalence of intermediate resistance to ciprofloxacin in Salmonella enterica isolated from a Brazilian poultry production chain, located in Minas Gerais state.
We characterized the distribution and diversity of antimicrobial-resistance Salmonella enterica isolated from a poultry production chain in Minas Gerais, Brazil, with special attention to ciprofloxacin and multidrug resistance (MDR). S. enterica (n = 96) of different serotypes and from different processing steps were subjected to broth dilution assay to estimate the minimum inhibitory concentration (MIC) for 12 antibiotics (8 classes) and screened using PCR for the presence of 17 antimicrobial-resistance genes. Isolates presented mainly resistance to ampicillin (11/96), and most presented intermediate resistance to ciprofloxacin (92/96). Roughly one-third (33/96) were resistant to streptomycin based on our interpretive criteria. Most strains resistant to streptomycin and ciprofloxacin were PCR-positive for aphA (51/96) and qnrB (94/96), respectively. Ciprofloxacin resistance was further investigated through high-resolution melting qPCR (HRM-qPCR) and sequencing of quinolone resistance-determining region (QRDR: gyrA, gyrB, parC, and parE). Minor differences were identified in melting temperatures (Tm), and a Thr57Sr mutation was observed in parC. MDR isolates harboring acrA and capable of expressing the AcrAB-TolC multidrug efflux pump were resistant to ethidium bromide at 0.4 mg/mL. The intermediate resistance to ciprofloxacin may be associated with qnrB, and the potential role of Thr57Ser mutation warrants further investigation. The high prevalence of antibiotic related genes and its association with the observed intermediary resistance to ciprofloxacin indicates the widespread of this hazard in the studied poultry production chain.


Incidence of previously unknown cardiac malformations in asymptomatic children after prenatal obstetric ultrasound screening.
Cardiac murmurs may be frequently found in otherwise asymptomatic children. Obstetric ultrasound screening for congenital heart disease is increasingly used to provide an antenatal diagnosis and an early treatment; thus, the incidence of cardiac anomalies in children has changed. We evaluated cardiac murmurs in otherwise healthy children referred to a level I pediatric cardiology institution. Echocardiography data from a cohort of 2045 patients from 2000 to 2009 were evaluated and the incidence and type of a newly diagnosed congenital heart disease have been determined. The majority of the children with a cardiac murmur were found to have an innocent murmur, chordae tendinae, or a minor lesion. Children born after obstetric screening are nevertheless associated with a small risk of severe congenital heart disease. We found 14.9% with a previously unknown congenital cardiac malformation; 1.4% required medical treatment and 0.6% of the patients had either a catheter or a surgical intervention. This study provides evidence that the use of obstetric screening for congenital heart disease reduces the occurrence of severe heart disease. Otherwise healthy children with murmurs still bear a small risk of having a cardiac defect, even if a prenatal study was negative. Therefore, the evaluation of children with a murmur by a pediatric cardiologist is recommended in an antenatally-screened population.


In situ gelation of thiolated poly(aspartic acid) derivatives through oxidant-free disulfide formation for ophthalmic drug delivery.
Efficient topical treatment of ocular diseases requires a prolonged residence time of drug formulations. An in situ gelling, mucoadhesive system can provide improved residence time while keeps the installation of the formulation easy and accurate due to its low initial viscosity. We synthesized a two-component, biocompatible water-based liquid formulation showing in situ gelation upon mixing. S-protected, preactivated derivatives of thiolated poly(aspartic acid) (PASP-SS-MNA) were synthesized by coupling the free thiol groups of thiolated poly(aspartic acid) (PASP-SH) with 6-mercaptonicotinic acid (MNA). The amount of protecting groups was 242, 341, and 530 µmol/g depending on the degree of thiolation of PASP. The chemical interaction between PASP-SS-MNA and mucin was proven, indicating the mucoadhesive properties. Disulfide cross-linked hydrogels were formed in situ without an oxidizing agent by mixing the aqueous solutions of PASP-SS-MNA and PASP-SH. The gelation time was controlled between 1 and 6 min, while the storage modulus was as high as 4-16 kPa depending on the composition. Swelling experiments showed that hydrogels with no residual thiol groups are stable in phosphate-buffered saline at pH = 7.4. In contrast, the presence of free thiol groups leads to the dissolution of the hydrogel with a rate depending on the excess of thiol groups. The biological safety of the polymers and MNA was confirmed on Madin-Darby Canine Kidney cell line. Furthermore, a prolonged release of ofloxacin was observed at pH = 7.4 compared to a conventional liquid formulation, supporting the potential of the developed biopolymers in ophthalmic drug delivery.


The mean platelet volume in patients with non-dipper hypertension compared to dippers and normotensives.
Increased platelet activation plays an important role in the development of atherosclerosis. Mean platelet volume (MPV) is a determinant of platelet activation. In our study, we aimed to determine whether MPV levels are elevated in non-dipper patients compared with dippers and healthy controls. In addition, we tried to find out if MPV levels are correlated with blood pressure measurements in hypertensive patients. This cross-sectional study included 56 hypertensive patients; 27 age- and sex-matched healthy volunteers were enrolled to study as a control subjects. Ambulatory blood pressure monitoring was performed for all patients. Hypertensive patients were divided into two groups: 28 dipper patients (10 male, mean age 51 +/-8 years) and 28 non-dipper patients (11 male, mean age 53+/-10 years). MPV was measured in a blood sample collected in EDTA tubes and was also used for whole blood counts in all patients. In non-dipper patients, 24-h systolic blood pressure (141.5+/-10.21 vs 132.3+/-7.7 mmHg, p<0.001), 24-h diastolic blood pressure (88.2+/-8.5 vs 81.0+/-8.2 mmHg, p<0.01) and 24-h average blood pressure (105.7+/-8.5 vs 97.7+/-7.4 mmHg, p<0.001) are significantly higher than dippers. Whereas daytime measurements were similar between dippers and non-dippers, there was a significant difference between each group during night-time measurements (night-time systolic 137.1 +/-11.0 vs 120.2+/-8.0 mmHg, p<0.001; night-time diastolic 85.3+/-8.0 vs 72.8+/-7.9 mmHg, p<0.001). Non-dipper patients (9.61 +/-0.42 fl) demonstrated higher levels of MPV compared with dippers (9.24+/-0.35 fl) and normotensives (8.87+/-0.33 fl) (p<0.001 and p<0.001, respectively). There was significant correlation between MPV and ambulatory diastolic and systolic blood pressure in non-dipper hypertensives. Our results suggest that MPV, a determinant of platelet activation, has a positively correlation with blood pressure and elevated in non-dipper compared with dippers and controls. Increased platelet activation could contribute to increase the atherosclerotic risk in non-dipper patients compared with dippers.


Immunohistochemical demonstration of viral antigens in Japanese encephalitis.
Japanese encephalitis virus antigens were immunohistochemically demonstrated in formalin-fixed paraffin sections from an autopsied brain. Glial nodules were always associated with antigen-positive cell debris. Glia shrubs in the cerebellar cortex appeared to be formed along the apical dendrite of Purkinje cells. Most, but not all, of the neurons involved in neuronophagia were viral antigen positive. Antigenic masses were occasionally encountered in the center of so-called acellular plaques. Neurons with strong viral antigens were sporadically found in normal-appearing regions in the thalamus and cerebral cortex. Viral antigens were demonstrable only in neurons and not in glial or vascular endothelial cells.


Bridging the Behavioral Health Gap in Serious Illness Care: Challenges and Strategies for Workforce Development.
Comorbidity with behavioral health conditions is highly prevalent among those experiencing serious medical illnesses and is associated with poor outcomes. Siloed provision of behavioral and physical healthcare has contributed to a workforce ill-equipped to address the often complex needs of these clinical populations. Trained specialist behavioral health providers are scarce and there are gaps in core behavioral health competencies among serious illness care providers. Core competency frameworks to close behavioral health training gaps in primary care exist, but these have not extended to some of the distinct skills and roles required in serious illness care settings. This paper seeks to address this issue by describing a common framework of training competencies across the full spectrum of clinical responsibility and behavioral health expertise for those working at the interface of behavioral health and serious illness care. The authors used a mixed-method approach to develop a model of behavioral health and serious illness care and to delineate seven core skill domains necessary for practitioners working at this interface. Existing opportunities for scaling-up the workforce as well as priority policy recommendation to address barriers to implementation are discussed.


Differential inactivation analysis of diploid yeast exposed to radiation of various LET. I. Computerized single-cell observation and preliminary application to X-ray-treated Saccharomyces cerevisiae.
This series of investigations was designed to observe growth and division of single, diploid yeast cells within the first four generations after irradiation with ionizing radiation. Evidence exists that cell reactions important for the final cell fate occur during this period, and therefore the analysis of cell kinetics and of stationary forms of inactivated cells can be performed. A large number of experiments is necessary to obtain statistically confirmed results of single-cell observation. An automatically steered microphotographic registration device has been developed to facilitate the collection of large numbers of observations. Optical data scanned by a TV camera and digitally stored in a computer are processed by pattern recognizing programs to achieve the correct correlation of newly built cells to existing ones and to deliver a pedigree over four generations of at least eight cells for every irradiated single cell. The pooled data of many pedigrees of this kind allow the analysis of the differential behavior of a total population. From the analysis of X-irradiated cells one can conclude that a single cell that produces at least a microcolony of five cells is eventually able to form a microcolony and thus can be considered a survivor. That means the division probability of cells to go from generation zero to three corresponds to the survival curve of the colony-forming ability test. Therefore this method is suitable for the differential description of the important phenomenological cell reactions after irradiation.


Interaction of colloidal particles of NH(4)(+)-montmorillonite with activated carbon.
The interaction between negative colloidal particles of NH(4)(+)-montmorillonite and particles of activated carbon was studied as a function of particle concentration, pH, and time of contact. The results show that carbon particles act as a support/bridge for clay particles, the type of resulting clay/carbon/clay associations depending on the pH and the clay/carbon ratio in the system. The relation between clay and carbon particles can be described by equations of the Langmuir type. For the same carbon particle concentration in the system, the relation varies from 6820 to 36,100 and is dependent on pH. The interaction coefficients at pH 6.5 correspond to reaction of pseudo-first (k(1)=4.14 x 10(-3) to 1.93 x 10(-3) s(-1)) and pseudo-second order (k(2)=9.36 x 10(-14) to 2.47 x 10(-14) cm(3)s(-1)) for different clay/carbon ratios. By using the Dubinin-Radushkevich equation, the interaction energy (+/-22.42, +/-685.0, and +/-14.63 J mol(-1)) was obtained for three different pH values (5, 6.7, and 7.6), demonstrating that the reaction is mainly physical.


Measurable residual disease (MRD) testing for acute leukemia in EBMT transplant centers: a survey on behalf of the ALWP of the EBMT.
Detectable measurable residual disease (MRD) is a key prognostic factor in both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients. Thus, we conducted a survey in EBMT transplant centers focusing on pre- and post-allo-HCT MRD. One hundred and six centers from 29 countries responded. One hundred had a formal strategy for routine MRD assessment, 91 for both ALL and AML. For ALL (n = 95), assessing MRD has been routine practice starting from 2010 (range, 1990-2019). Techniques used for MRD assessment consisted of PCR techniques alone (n = 27), multiparameter flow cytometry (MFC, n = 16), both techniques (n = 43), next-generation sequencing (NGS) + PCR (n = 2), or PCR + MFC + NGS (n = 7). The majority of centers assessed MRD every 2-3 months for 2 (range, 1-until relapse) years. For AML, assessing MRD was routine in 92 centers starting in 2010 (range 1990-2019). Assessment of MRD was by PCR (n = 23), MFC (n = 13), both PCR and MFC (n = 39), both PCR and NGS (n = 3), and by all three techniques (n = 14). The majority assesses MRD for AML every 2-3 months for 2 (range, 1-until relapse) years. This survey is the first step in the aim to include MRD status as a routine registry capture parameter in acute leukemia.


Surgical vs wire-guided cricothyroidotomy: a randomised crossover study of cuffed and uncuffed tracheal tube insertion.
Using an airway mannequin and artificial lung model, we compared surgical cricothyroidotomy with a 6.0-mm cuffed Portex tracheostomy tube with wire-guided cricothyroidotomy using a 5.0-mm cuffed Melker or 6.0-mm uncuffed Melker tube. The trial was carried out by 27 anaesthetists using a randomised, crossover design. Surgical cricothyroidotomy proved significantly faster (mean (SD) time to first breath 44.3 (12.5) s for Portex surgical, 87.2 (21.6) s for cuffed Melker, 87.8 (19.2) s for uncuffed Melker, p < 0.001). With a standardised ventilator model, the cuffed tubes provided more effective ventilation (mean (SD) tidal volume 446 (41) ml Portex, 436 (52) ml cuffed Melker, 19 (5) ml uncuffed Melker, p < 0.001). Fourteen of the participants preferred the wire-guided system. We conclude that, in this model, a cuffed device is preferable when cricothyroidotomy is needed. In addition, the surgical method is quicker than a wire-guided approach.


Myosin-II puts the squeeze on asymmetric cell division.
Asymmetric cell division--where two dissimilar daughter cells are produced--relies on asymmetric positioning of the telophase spindle midzone, which specifies the cleavage furrow. Ou et al. (2010) now report in Science a mechanism of asymmetric midzone positioning driven by a polarized cortical distribution of the contractile motor myosin-II.


The use of voided urine temperature in the determination of basal body temperature.
The temperature of freshly voided urine has been shown to be a reliable predictor of body temperature. This relationship was confirmed for the measurement of BBT. A method was described for patients to obtain their BBT in a way that they may find more convenient than obtaining either oral or rectal temperature. The BBT graph patterns generated from the temperature of freshly voided urine closely paralleled those generated by oral temperature.


Concern about developing Alzheimer's disease or dementia and intention to be screened: An analysis of national survey data.
Early diagnosis of Alzheimer's disease (AD) or dementia is important so that patients can express treatment preferences, subsequently allowing caregivers to make decisions consistent with their wishes. This study explored the relationship between people's concern about developing AD/dementia, likelihood to be screened/tested, if experiencing changes in cognitive status or functioning, and concerns about sharing the diagnostic information with others. A descriptive study was conducted using Porter Novelli's SummerStyles 2013 online survey data. Of the 6105 panelists aged 18+ who received the survey, 4033 adults responded (response rate: 66%). Chi squares were used with case-level weighting applied. Almost 13% of respondents reported being very worried or worried about getting AD/dementia, with women more worried than men (p<.001), and AD/dementia caregivers more worried than other types of caregivers (p=.04). Women were also more likely than men to agree to be screened/tested if experiencing changes in memory and/or thinking (p<.001). The greater the worry, the more likely respondents would agree to be screened/tested (p<.001). Nearly 66% of respondents were concerned that sharing a diagnosis would change the way others think/feel about them, with women reporting greater concern than men (p=.003). Findings demonstrate that level of worry about AD/dementia is associated with the reported likelihood that individuals agree to be screened/tested. This information will be useful in developing communication strategies to address public concern about AD/dementia that may increase the likelihood of screening and early detection.


Multiple steps in DNA recognition by restriction endonuclease from E. coli K.
The process of DNA recognition by the activated form of the restriction endonuclease from E. coli K involves three enzyme-DNA complexes which can be differentiated experimentally. These are: an initial complex formed at a nonspecific site; a recognition complex involving the host specificity site; and a cleavage complex dependent on the presence of ATP.


Impact of pre-existing type 2 diabetes with and without cardiovascular disease on patients with COVID-19.
To compare adverse outcomes among COVID-19 patients with pre-existing type 2 diabetes (T2D) only, T2D and cardiovascular disease (CVD), or neither. This retrospective cohort study used administrative claims, laboratory and mortality data from the HealthCore Integrated Research Database. Patients with COVID-19 were identified from 3 January 2020 to 31 May 2021 and stratified by the presence of T2D and CVD. Outcomes included hospitalization, intensive care unit (ICU) admission, mortality and complications following COVID-19 infection. Propensity score matching and multivariable analyses were performed. A total of 321 232 COVID-19 patients were identified (21 651 T2D + CVD, 28 184 T2D only, and 271 397 neither) with a mean (SD) follow-up of 5.4 (3.0) months. After matching, 6 967 patients were identified for each group, and residual baseline differences remained. Adjusted analyses showed that COVID-19 patients with T2D + CVD were 59% more probable to be hospitalized, 74% more probable to be admitted to the ICU, and had a 26% higher mortality risk than those with neither. COVID-19 patients with T2D only were 28% and 32% more probable to be admitted to the hospital and ICU than those with neither, respectively. Among all T2D + CVD patients, acute respiratory distress syndrome (31%) and acute kidney disease (24%) were observed. Our study highlights the incrementally poorer outcomes associated with pre-existing T2D + CVD in COVID-19 patients compared with those without T2D/CVD and suggests consideration of a more optimal management approach in these patients.


Studies on the mechanism of action of Riley virus. 3. Replication of Riley's plasma enzyme-elevating virus in vitro.
A study was made of the replication of Riley virus in various tissue cultures. It was observed that Riley virus replicated in primary mouse embryo cultures for 8 to 12 days. As they aged primary cultures became less susceptible to Riley virus infection, and subcultured cells were not susceptible. Suspensions of virus, in the absence of cells, were inactivated at 36.5 degrees C. Serial passage by transfer of supernatant fluids to fresh embryo cultures was not successful. Replication of the virus was more active in mouse embryo liver cultures than in the cultures of the embryo minus the livers. In cultures of mouse macrophages, the supernatants remained infective throughout the life of the cultures (21 days). The virus was passed 23 times through fresh macrophage cultures over a period of 80 days, during which the original inoculum (10(6.0)ID(50)/ml) was theoretically diluted to 10(-14). The possibility that the cells of the RES are involved in Riley virus replication is discussed.


Clinical applications of perforator-based propeller flaps in upper limb soft tissue reconstruction.
A propeller flap is an island flap that moves from one orientation to another by rotating around its vascular axis. The vascular axis is stationary, and flap movement is achieved by revolving on this axis. Early propeller flaps relied on a thick, subcutaneous pedicle to maintain vascularity, and this limited the flap rotation to 90°. With increasing awareness of the location and the vascular territory perfused by cutaneous perforators, it is now possible to design propeller flaps based on a single perforator, so-called "perforator-based propeller flaps." These flaps permit flap rotation up to 180°. We present the results of upper limb soft tissue reconstruction using perforator-based propeller flaps. We constructed a treatment strategy based on the location of the soft tissue defect and the perforator anatomy for expedient wound coverage in 1 stage. All perforator-based propeller flaps derived from 3 institutions that were used for upper limb soft tissue reconstruction were retrospectively analyzed. The parameters studied included the size and location of the defect, the perforator that was used, the size and shape of the flap, the direction (ie, clockwise or counter-clockwise) of flap rotation, the degree of twisting of the perforator, the management of the donor site (ie, linear closure or skin grafting), and flap survival (recorded as the percentage of the flap area that survived). Twelve perforator-based propeller flaps were used to reconstruct upper limb soft tissue defects in 12 patients. Six different perforators were used as vascular pedicles. The donor defects of 11 flaps could be closed primarily. One flap was partially lost in a patient with electrical burns. Perforator-based propeller flaps provide a reliable option for covering small- to medium-size upper limb soft tissue defects.


Metagenomic analysis reveals indole signaling effect on microbial community in sequencing batch reactors: Quorum sensing inhibition and antibiotic resistance enrichment.
Indole is an essential signal molecule in microbial studies. However, its ecological role in biological wastewater treatments remains enigmatic. This study explores the links between indole and complex microbial communities using sequencing batch reactors exposed to 0, 15, and 150 mg/L indole concentrations. A concentration of 150 mg/L indole enriched indole degrader Burkholderiales, while pathogens, such as Giardia, Plasmodium, and Besnoitia were inhibited at 15 mg/L indole concentration. At the same time, indole reduced the abundance of predicted genes in the "signaling transduction mechanisms" pathway via the Non-supervised Orthologous Groups distributions analysis. Indole significantly decreased the concentration of homoserine lactones, especially C14-HSL. Furthermore, the quorum-sensing signaling acceptors containing LuxR, the dCACHE domain, and RpfC showed negative distributions with indole and indole oxygenase genes. Signaling acceptors' potential origins were mainly Burkholderiales, Actinobacteria, and Xanthomonadales. Meanwhile, concentrated indole (150 mg/L) increased the total abundance of antibiotic resistance genes by 3.52 folds, especially on aminoglycoside, multidrug, tetracycline, and sulfonamide. Based on Spearman's correlation analysis, the homoserine lactone degradation genes which were significantly impacted by indole negatively correlated with the antibiotic resistance gene abundance. This study brings new insights into the effect of indole signaling on in biological wastewater treatment plants.


Predictability of adverse outcomes in hypertensive disorders of pregnancy: a multicenter prospective cohort study.
To explore variables associated with adverse maternal/fetal/neonatal outcomes among pregnant/postpartum patients admitted to ICU for hypertensive disorders of pregnancy (HDP). Multicenter, prospective, national cohort study. Variables independently associated with maternal/fetal/neonatal mortality among 172 patients were as follows: Acute Physiology and Chronic Health Evaluation-II (APACHE-II)(OR1.20[1.06-1.35]), gestational age (OR0.698[0.59-0.82]) and aspartate aminotransferase (AST)(OR1.004[1.001-1.006]). Positive likelihood ratio for headache, epigastric pain, and visual disturbances to predict composite adverse outcomes were 1.23(1.16-1.30), 0.76(0.59-1.02), and 1.1(0.98-1.2), respectively. Maternal/fetal mortality due to HDP was independently associated with severity of illness on admission, gestational age, and elevated AST. Accuracy of clinical symptoms to predict composite adverse outcomes was low.


Efficacy of herbal tea preparation in infantile colic.
We evaluated the effect of an herbal tea preparation on infantile colic in a prospective double-blind study. The use of tea eliminated the colic in 19 (57%) of 33 infants, whereas placebo was helpful in only 9 (26%) of 35 (p < 0.01). The mean colic score was significantly improved in tea-treated infants. No significant differences were noted between groups regarding number of night wakings.


Way to efficient microbial paclitaxel mass production.
The microbial synthesis of paclitaxel is attractive for its short-cycle, cost-effectiveness, and sustainability. However, low paclitaxel productivity, depleted capacity during subculture and storage, and unclear biosynthesis mechanisms restrain industrial microbial synthesis. Along with the isolation of various paclitaxel-producing microorganisms and the development of versatile molecular tools, tremendous promises for microbial paclitaxel synthesis have become increasingly prominent. In this review, we summarize the progress of microbial synthesis of paclitaxel in recent years, focusing on paclitaxel-producing endophytes and representative engineering microorganism hosts that were used as chassis for paclitaxel precursor synthesis. Numerous wide-type microbes can manufacture paclitaxel, and fermentation process optimization and strain improvement can greatly enhance the productivity. Engineered microbes can efficiently synthesize precursors of paclitaxel by introducing exogenous synthetic pathway. Mining paclitaxel synthetic pathways and genetic manipulation of endophytes will accelerate the construction of microbial cell factories, indefinitely contributing to paclitaxel mass production by microbes. This review emphasizes the potential and provides solutions for efficient microbial paclitaxel mass production.


Articulatory effects on perceptions of men's status and attractiveness.
Research on heterosexual mating has demonstrated that acoustic parameters (e.g., pitch) of men's voices influence their attractiveness to women and appearance of status and formidability to other men. However, little is known about how men's tendency to clearly articulate their speech influences these important social perceptions. In the current study, we used a repeated-measures design to investigate how men's articulatory clarity or conformity influenced women's (N = 45) evaluations of men's attractiveness for both short- and long-term relationships, and men's (N = 46) evaluations of physical formidability and prestige. Results largely supported our hypotheses: men who enunciated phonemes more distinctly were more attractive to women for long-term relationships than short-term relationships and were perceived by other men to have higher prestige than physical dominance. These findings suggest that aspects of articulatory behavior that influence perceptions of prestige and long-term mating attractiveness may indicate an early social history characterized by high socioeconomic status, likely owing to crystallization of articulatory patterns during the critical period of language development. These articulatory patterns may also be honest signals of condition or disposition owing to the nature of complex, multicomponent traits, which deserve further empirical attention.