Efficacy of Smoothing Algorithms to Enhance Detection of Visual Field Progression in Glaucoma.

Purpose: To evaluate and compare the effectiveness of nearest neighbor (NN)- and variational autoencoder (VAE)-smoothing algorithms to reduce variability and enhance the performance of glaucoma visual field (VF) progression models. Design: Longitudinal cohort study. Subjects: 7150 eyes (4232 patients), with ≥ 5 years of follow-up and ≥ 6 visits. Methods: Vsual field thresholds were smoothed with the NN and VAE algorithms. The mean total deviation (mTD) and VF index rates, pointwise linear regression (PLR), permutation of PLR (PoPLR), and the glaucoma rate index were applied to the unsmoothed and smoothed data. Main Outcome Measures: The proportion of progressing eyes and the conversion to progression were compared between the smoothed and unsmoothed data. A simulation series of noiseless VFs with various patterns of glaucoma damage was used to evaluate the specificity of the smoothing models. Results: The mean values of age and follow-up time were 62.8 (standard deviation: 12.6) years and 10.4 (standard deviation: 4.7) years, respectively. The proportion of progression was significantly higher for the NN and VAE smoothed data compared with the unsmoothed data. VF progression occurred significantly earlier with both smoothed data compared with unsmoothed data based on mTD rates, PLR, and PoPLR methods. The ability to detect the progressing eyes was similar for the unsmoothed and smoothed data in the simulation data. Conclusions: Smoothing VF data with NN and VAE algorithms improves the signal-to-noise ratio for detection of change, results in earlier detection of VF progression, and could help monitor glaucoma progression more effectively in the clinical setting. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Oropharyngeal, proximal colonic, and vaginal microbiomes of healthy Korean native black pig gilts.

BACKGROUND: Exploring the microbiome in multiple body sites of a livestock species informs approaches to promote its health and performance through efficient and sustainable modulation of these microbial ecosystems. Here, we employed 16S rRNA gene sequencing to describe the microbiome in the oropharyngeal cavity, proximal colon, and vaginal tract of Jeju Black pigs (JBP), which are native to the Korean peninsula. RESULTS: We sampled nine 7-month-old JBP gilts raised under controlled conditions. The most abundant phyla that we found within the oropharyngeal microbiota were Proteobacteria, Bacteroidetes, Fusobacteria and Firmicutes, collectively providing core features from twenty-five of their genera. We also found a proximal colonic microbial core composed of features from twenty of the genera of the two predominant phyla, Firmicutes, and Bacteroidetes. Remarkably, within the JBP vaginal microbiota, Bacteroidetes dominated at phylum level, contrary to previous reports regarding other pig breeds. Features of the JBP core vaginal microbiota, came from seventeen genera of the major phyla Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. Although these communities were distinct, we found some commonalities amongst them. Features from the genera Streptococcus, Prevotella, Bacillus and an unclassified genus of the family Ruminococcaceae were ubiquitous across the three body sites. Comparing oropharyngeal and proximal colonic communities, we found additional shared features from the genus Anaerorhabdus. Between oropharyngeal and vaginal ecosystems, we found other shared features from the genus Campylobacter, as well as unclassified genera from the families Fusobacteriaceae and Flavobacteriaceae. Proximal colonic and vaginal microbiota also shared features from the genera Clostridium, Lactobacillus, and an unclassified genus of Clostridiales. CONCLUSIONS: Our results delineate unique and ubiquitous features within and across the oropharyngeal, proximal colonic and vaginal microbial communities in this Korean native breed of pigs. These findings provide a reference for future microbiome-focused studies and suggest a potential for modulating these communities, utilizing ubiquitous features, to enhance health and performance of the JBP.

High-quality metagenome-assembled genomes from proximal colonic microbiomes of synbiotic-treated korean native black pigs reveal changes in functional capacity.

Synbiotics are feed supplements with the potential to promote health and productivity in pigs partly, through modulation of the intestinal microbiome. Our study used shotgun sequencing and 16S rRNA gene sequencing techniques to characterize the effect of a synbiotic containing three Lactobacillus species and a fructo-oligosaccharide on the proximal colonic microbiome of 4- to 7-month-old Korean native black gilts. With shotgun sequencing we constructed unique metagenome-assembled genomes of gut microbiota in Native Black Pig for the first time, which we then used for downstream analysis. Results showed that synbiotic treatment did not alter microbial diversity and evenness within the proximal colons, but altered composition of some members of the Lactobacillaceae, Enterococcaceae and Streptococcaceae families. Functional analysis of the shotgun sequence data revealed 8 clusters of orthologous groups (COGs) that were differentially represented in the proximal colonic microbiomes of synbiotic-treated Jeju black pigs relative to controls. In conclusion, our results show that administering this synbiotic causes changes in the functional capacity of the proximal colonic microbiome of the Korean native black pig. This study improves our understanding of the potential impact of synbiotics on the colonic microbiome of Korean native black pigs.

Analysis of the quality of anticoagulation with vitamin K antagonists in three clinical scenarios in Mexico.

INTRODUCTION: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. OBJECTIVE: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. METHODS: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. RESULTS: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. CONCLUSIONS: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.

INTRODUCCIÓN: Los antagonista de la vitamina K (AVK) son una alternativa terapéutica en los pacientes con enfermedad tromboembólica venosa; sin embargo, numerosos factores afectan su farmacología. OBJETIVO: Evaluar la calidad de la anticoagulación AVK durante tres diferentes periodos en México. MÉTODOS: Estudio prospectivo, anidado en cohortes de pacientes en tres escenarios clínicos entre los años 2013-2019. Se incluyeron pacientes no hospitalizados con indicación para recibir AVK por al menos 12 meses, quienes fueron manejados de acuerdo con el criterio del médico tratante. RESULTADOS: Las características generales de los pacientes fueron similares entre los grupos, excepto por la indicación para usar los AVK. Se analizaron los resultados de 4148 pacientes y 38 548 evaluaciones de INR. Los tiempos en rango terapéutico durante las tres fases del estudio y los datos acumulados fueron significativamente mayores en la clínica de anticoagulación. Solo el número de visitas de control de los pacientes se asoció significativamente con los resultados, a diferencia de la edad, el sexo y el tipo de AVK. CONCLUSIONES: Los AVK se utilizan ampliamente, pero es difícil alcanzar la meta terapéutica, sobre todo en servicios clínicos no especializados. La creación de clínicas de anticoagulación es una necesidad urgente en el sistema mexicano de salud.

A proposal for the management of COVID-19-induced coagulopathy in adults.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the cause of the coronavirus disease 2019 (COVID-19) pandemic, which has a high case fatality rate. Most severely ill patients develop a special type of coagulopathy that had not been described before and that is now considered the main cause of death. For this reason, anticoagulant treatment has become one of the cornerstones of the treatment of this infection. However, the rate at which the evidence regarding the use of anticoagulants is generated is quite fast, and sometimes it is difficult to interpret and conflicting. After having performed an extensive review of the published literature, this proposal for the use of anticoagulant treatment is made, taking into account available resources in Mexico.

La infección por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) es la causante de la pandemia de enfermedad por coronavirus 2019 (COVID-19), con un índice de letalidad alto. La mayoría de los pacientes graves desarrollan un tipo especial de coagulopatía no descrito hasta ahora y la cual se considera ahora la principal causa de muerte. Por esta razón, el tratamiento anticoagulante se ha convertido en una de las piedras angulares del tratamiento de esta infección. Sin embargo, la velocidad con la que se genera la evidencia respecto al uso de anticoagulantes es muy rápida y, en ocasiones difícil de interpretar y contradictoria. Luego de hacer una revisión extensa de la literatura publicada, se hace esta propuesta para el uso del tratamiento anticoagulante tomando en cuenta los recursos disponibles en México.

Propuesta para manejo de la coagulopatía asociada a la COVID-19 en adultos / A proposal for the management of COVID-19-induced coagulopathy in adults

Resumen La infección por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) es la causante de la pandemia de enfermedad por coronavirus 2019 (COVID-19), con un índice de letalidad alto. La mayoría de los pacientes graves desarrollan un tipo especial de coagulopatía no descrito hasta ahora y la cual se considera ahora la principal causa de muerte. Por esta razón, el tratamiento anticoagulante se ha convertido en una de las piedras angulares del tratamiento de esta infección. Sin embargo, la velocidad con la que se genera la evidencia respecto al uso de anticoagulantes es muy rápida y, en ocasiones difícil de interpretar y contradictoria. Luego de hacer una revisión extensa de la literatura publicada, se hace esta propuesta para el uso del tratamiento anticoagulante tomando en cuenta los recursos disponibles en México.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the cause of the coronavirus disease 2019 (COVID-19) pandemic, which has a high case fatality rate. Most severely ill patients develop a special type of coagulopathy that had not been described before and that is now considered the main cause of death. For this reason, anticoagulant treatment has become one of the cornerstones of the treatment of this infection. However, the rate at which the evidence regarding the use of anticoagulants is generated is quite fast, and sometimes it is difficult to interpret and conflicting. After having performed an extensive review of the published literature, this proposal for the use of anticoagulant treatment is made, taking into account available resources in Mexico.

Safety of a second-generation tyrosine kinase inhibitor and novel targeted therapy for the treatment of a patient with chronic myeloid leukemia and multiple myeloma.

The prevalence of chronic myeloid leukemia and multiple myeloma has increased in recent years partly because of an improved therapeutic armamentarium for both conditions. Likewise, understanding the complexity inherent in designing combination treatment strategies will become increasingly prescient in the coming years. We describe, to the best of our knowledge, the first reported patient to be treated with second-generation tyrosine kinase inhibitor therapy while on novel therapy for myeloma. The combination was well tolerated and effective for the treatment of chronic myeloid leukemia and concurrent myeloma.

First Report of Clover yellow vein virus on White Clover (Trifolium repens) in South Korea.

White clover (Trifolium repens L.) is a herbaceous, perennial plant that has become one of the most widely distributed legumes in the world. It is extensively used in grass-legume pastures, but also has the potential to invade agricultural lands and natural ecosystems. White clover is a well-known natural host for Alfalfa mosaic virus (AMV), Clover yellow vein virus (ClYVV), Soybean dwarf virus (SbDV), Beet western virus (BWYV), Tomato spotted wilt virus (TSWV), Zucchini yellow mosaic virus (ZYMV), etc (1). In July 2013, during a survey to determine the presence of different viruses infecting weed plants in South Korea, three white clover leaf samples showing yellow mosaic symptoms were collected from Taean County, South Chungcheong Do Province, South Korea. In order to identify the infecting virus, total RNA from three leaf samples was extracted using the Tri-reagent (MRC Reagent, Inc., OH) as described by the manufacturer, and was applied to the large-scale oligonucleotide (LSON) chip (3), wherein probes specific to a ClYVV isolate produced a positive reaction. All three samples tested were positive for ClYVV. To confirm this result, ClYVV-specific primers were designed using the sequences of four ClYVV isolates from NCBI (GenBank Accession Nos. AF185959, AF203536, DQ333346, and NC003536). Total RNA was extracted from symptomatic white clover samples using Easy-Spin Total RNA Extraction Kit (iNtRon, Daejeon, Korea) and used as template for RT-PCR. The positive control RNA was used from ClYVV GM isolate (KF975894) and negative control RNA used symptomless white clover plants. The ClYVV coat protein (CP) gene was amplified by RT-PCR using the specific primer pairs ClYVV-CP-F / ClYVV-CP-R (5'-CAAGAGCAGCACGATGAG-3' and 5'-CTCGCTCTATAAAGATCAGAT-3'). DNA fragments of the expected size (1,042 bp) were obtained from the white clover Korea isolate (AB930132), and the PCR product was cloned into a T&A cloning vector (RBC Bioscience, Taipei, Taiwan) and sequenced directly in both directions. BLAST analyses of the nucleotide sequence CP gene fragments revealed the highest identity with 98% with other ClYVV isolates (AF203536). To determine the experimental host range of the ClYVV Korea isolate, we inoculated five species (Chenopodium amaranticolor, C. quinoa, Nicotiana clevelandii, N. benthamiana, and Trifolium repens) in three families using this isolate. All test plants were mechanically inoculated with 0.1 M phosphate buffered saline (Takara, Tokyo, Japan). Each test plant was inoculated nine times and grown in a greenhouse maintained at 27 to 33°C. Necrotic local lesions were produced on inoculated leaves of C. amaranticolor, C. quinoa, and N. clevelandii 4 to 6 days post-inoculation. After 10 to 14 days, C. amaranticolor and C. quinoa showed systemic chlorotic spot symptoms, and N. clevelandii, N. benthamiana, and T. repens showed chlorotic spot, mild mosaic, and mosaic in the upper leaves, respectively. Up to now, in South Korea, ClYVV has been detected in gladiolus (Gladiolus gandavensis) (3) and soybean (Glycine max) (4). ClYVV can be easily transmitted by insect, aphid, or mechanical inoculation and has a host range including tobacco, soybean, etc. The presence of ClYVV could become an important threat to crop production in South Korea. To our knowledge, this is the first report of a ClYVV infection of the white clover plant in South Korea. References: (1) B. L. Denny and P. L. Guy. Australas. Plant Pathol. 38:270, 2009. (2) M. Nam et al. Plant Pathol. J. 30:51, 2014. (3) I. S. Park et al. Korean J. Plant Pathol. 14:74, 1998. (4) J. C. Shin et al. Plant Dis. 98:1283, 2014.

MicroRNA expression profiles in placenta with severe preeclampsia using a PNA-based microarray.

INTRODUCTION: Preeclampsia (PE) is a leading cause of maternal and neonatal mortality and morbidity worldwide. However, the pathophysiology of this disease is not yet fully understood. MiRNA plays an important role in post-transcriptional gene regulation. Recent studies have suggested that dysregulation of miRNAs in placental tissue is involved in the pathogenesis of PE. Therefore, we investigated miRNA profiles in PE placenta to understand the miRNA function in PE pathogenesis. METHODS: MiRNA profiling was performed in 20 formalin-fixed and paraffin-embedded samples (10 placentas from severe PE and 10 from a control group). We used a hybridization-based microarray with a PNA-probe comprised of 158 miRNAs. RESULTS: Thirteen miRNAs (miR-92b, miR-197, miR-342-3p, miR-296-5p, miR-26b, miR-25, miR-296-3p, miR-26a, miR-198, miR-202, miR-191, miR-95, and miR-204) were significantly overexpressed and two miRNAs (miR-21 and miR-223) were underexpressed in PE compared with the control group. Among 15 differentially expressed miRNAs, miR-26b, miR-296-5p, and miR-223 were found to be consistent with results from previous studies. We identified 893 genes that were predicted by at least three of four computational algorithms. Target genes participated in several signaling pathways, adherens junction, focal adhesion, and regulation of the actin cytoskeleton. CONCLUSIONS: Several miRNAs are found to be dysregulated in placentas of PE patients and they seem to be closely associated with the early pathogenesis of PE. Further study is necessary to develop tools for early detection and management.

Different transcriptional responses of heat shock protein 70/90 in the marine diatom Ditylum brightwellii exposed to metal compounds and endocrine-disrupting chemicals.

Environmental hazard assessments using diatoms have been well documented; however, their molecular toxicology has not been sufficiently studied. In this study, we characterized heat shock protein (HSP) 70/90 of the diatom Ditylum brightwellii (Db) and evaluated their transcriptional profiles in response to various environmental stresses (e.g., thermal shocks and metal and non-metal pollutants). Putative DbHSP70 (658aa, 71.7 kDa) and DbHSP90 (707aa, 80.2 kDa) proteins had conserved HSP family motifs but different C-terminus motifs, that is, "EEVD" in DbHSP70 and "MEEVD" in DbHSP90. Phylogenetic analyses of both proteins showed that D. brightwellii was well clustered with other diatoms. Real-time PCR analysis showed that thermal stress considerably upregulated DbHSP70 and DbHSP90. As for chemical pollutants, DbHSP70 greatly responded to CuSO4 and NiSO4 exposure, but not CuCl2 or NiCl2. However, DbHSP90 was significantly upregulated by all the metal compounds tested (CuSO4, NiSO4, CuCl2, and NiCl2). Strikingly, the expression of both genes was not induced by the organic pollutants tested, such as endocrine-disrupting chemicals. These data suggest that DbHSP70 and DbHSP90 are differentially involved in the defense response against various environmental stressors. Moreover, metal toxicity may be specifically affected by the conjugated anion in the metal compounds (e.g., SO4(2-) and Cl(-)).

Effects of pravastatin on serum adiponectin levels in female patients with type 2 diabetes mellitus.

OBJECTIVE: Pravastatin has been reported to elevate circulating adiponectin levels in patients with various insulin resistant state, hypertension, coronary artery disease, and hypercholesterolemia. This study aimed to evaluate whether pravastatin increase serum total and high molecular weight adiponectin levels and improve insulin sensitivity in female patients with type 2 diabetes mellitus and hypercholesterolemia. PATIENTS AND DESIGN: This study was designed as a multicenter, double-blind, placebo-controlled, factorial randomized trial (placebo and pravastatin at 20 or 40 mg per day). A total of 73 female patients with type 2 diabetes and hypercholesterolemia were enrolled. Changes in total and high molecular weight (HMW) serum adiponectin levels, the ratio of HMW adiponectin to total adiponectin, insulin sensitivity measured by homeostasis model assessment of insulin resistance (HOMA-IR) and lipid profiles were evaluated after 16 weeks in each group. RESULTS: Total cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly reduced after 16 weeks in the pravastatin 20 mg and 40 mg treatment groups compared with the placebo group (P = 0.008 and P = 0.004, respectively). However, there were no significant differences between the 20 mg and 40 mg pravastatin treatment groups in terms of total adiponectin and HMW adiponectin serum levels, as well as insulin sensitivity (P = 0.348 and P = 0.991). CONCLUSIONS: In female patients with type 2 diabetes and hypercholesterolemia, 16 weeks pravastatin therapy did not affect on serum total adiponectin or HMW adiponectin levels.

Low-dose filgrastim in patients with breast cancer treated with docetaxel, doxorubicin, and cyclophosphamide.

PURPOSE: The objective of this study was to compare low-dose filgrastim (150 microg/day subcutaneously) with standard-dose subcutaneous filgrastim (300 microg/day) or lenograstim (263 microg/day) in preventing febrile neutropenia and hospitalizations in breast cancer patients receiving the docetaxel-doxorubicin-cyclophosphamide regimen. METHODS: A single-center retrospective data analysis was performed involving 22 adult women with breast cancer who concurrently received the docetaxel-doxorubicin-cyclophosphamide chemotherapy regimen and low-dose filgrastim from March 2004 to February 2007. Data from this study were compared to previously published data in which patients received standard-dose filgrastim or lenograstim. RESULTS: More patients developed febrile neutropenia in the low-dose filgrastim group compared with the standard-dose group (32% versus 7.5%, respectively; p = 0.0014; relative risk [RR] = 4.24; 95% confidence interval [CI], 2.04-7.83). More patients were hospitalized due to febrile neutropenia in the low-dose filgrastim group compared with the standard-dose group (32% versus 6.5%, respectively; p < 0.001; RR = 4.89; 95% CI, 2.32-9.13). More chemotherapy cycles resulted in febrile neutropenia in the low-dose filgrastim group compared with the standard-dose group (6.7% versus 1.2%, respectively; p < 0.001; RR = 5.58; 95% CI, 2.49-12.27). CONCLUSION: In patients with breast cancer treated with the docetaxel-doxorubicin-cyclophosphamide regimen, low-dose filgrastim was associated with a higher frequency of febrile neutropenia, hospitalization due to febrile neutropenia, and cycles with febrile neutropenia compared with a historical control group treated with standard-dose filgrastim or lenograstim.

A prospective randomized study on the mobilization of CD34+ cells comparing continuous intravenous vs subcutaneous administration of rhG-CSF in normal donors.

The efficacy of mobilizing peripheral blood progenitor cells (PBPC) with continuous intravenous (c.i.v.) administration of rhG-CSF was randomly compared to subcutaneous (s.c.) administration, in 15 normal donors in each arm of the study for 6 days. The percentage and absolute numbers of CD34+ cells in the c.i.v. and s.c. groups increased maximally at day 3 and 5, respectively, when compared with the steady-state (day 0) level. Peak CD34+ cell levels were achieved on day 3 in the c.i.v. group, with more rapid results than in the s.c. group (49.3/microl vs 35.9/microl, P=0.043). Plasma rhG-CSF levels declined progressively during mobilization in each group as the WBC increased. The serum level of rhG-CSF did not correlate with CD34+ cell counts in the peripheral blood. Toxicity profiles in the c.i.v. and s.c. groups were similar. Each regimen was effective in successfully mobilizing the target CD34 cell number.

Ventriculoperitoneal shunt related meningioma following excision and radiotherapy for glioma.

A 25-year-old man with a history of childhood cerebellar glioma treated by surgical removal, radiotherapy and a ventriculoperitoneal (VP) shunt presented with a 5 month history of frontal headaches. Imaging revealed a mass surrounding his shunt, which was surgically removed, with the shunt left in situ. Histopathological examination revealed an atypical and invasive meningioma. A similar case of a meningioma related to a shunt appears in the literature, again in the context of radiotherapy following removal of a previous neoplasm. Copyright 1999 Harcourt Publishers Ltd.

Spontaneous CSF rhinorrhoea secondary to a middle cranial fossa defect.

Spontaneous cerebrospinal fluid rhinorrhoea is a clinical entity that is difficult to both diagnose and treat. A case in a 56-year-old woman with a defect in the lateral wall of the sphenoid sinus and middle cranial fossa floor is presented. Pathogenesis and management of this rare condition are discussed. Copyright 1999 Harcourt Publishers Ltd.

Adolescent homicide: towards assessment of risk

Recent murders committed by children and adolescents have raised concern over the detection and management of dangerous youngsters in our society. Yet in the training of child and adolescent mental health professionals the assessment and management of dangerousness to others is frequently given little attention. This paper attempts to begin to redress the balance by reviewing the mental health literature relevant to homicidal children and adolescents. Background and situational factors relevant to risk are described. Background factors include the witnessing of serious violence, both live and on the screen, as well as abuse through neglect and deprivation. Such trauma can assist in the creation of a morbid identity and a cognitive set that make murder possible in certain situations. Other background factors include learning difficulties and problems with impulse control. However even if a youngster is assessed as highly dangerous it is frequently difficult in the current climate to offer adequate intervention. Issues in the prevention of violence are considered.Through abuse my emotions and self-respect were murdered and so I no longer cared. Do people stand trial for killing someone's insides? No, because you can't produce a corpse... (a teenage killer).

Hepatitis in Adolescents.

Hepatitis virus infection poses an important health problem to adolescents because of the morbidity of acute disease, the risk of chronic hepatitis, and the risk of vertical transmission during pregnancy. This paper reviews the epidemiology, clinical course, and prevention of hepatitis viral infections in adolescents.