Comparing prolonged infusion to intermittent infusion strategies for beta-lactam antibiotics in patients with gram-negative bacterial infections: a systematic review and meta-analysis.

INTRODUCTION: Our objective is to determine whether prolonged infusion (PI) of beta-lactam antibiotics yields superior outcomes compared to intermittent infusion (II) in patients with Gram-Negative Bacterial (GNB) infections. METHODS: We systematically searched papers from PubMed, the Cochrane Library, Embase, and Clinicaltrials.gov, targeting mortality as the primary outcome and looking at the clinical cure rate, hospital and intensive care unit (ICU) stay lengths, antibiotic treatment duration, and mechanical ventilation (MV) duration as secondary outcomes. RESULTS: Our meta-analysis of 18 studies, including 5 randomized control trials and 13 observational studies, with a total of 3,035 patients-1,510 in the PI group and 1,525 in the II group, revealed significant findings. PI was associated with reduced mortality (RR, 0.67; 95% CI, 0.55-0.81; p = 0.001; I2 = 4.52%) and a shorter MV duration (SMD, -0.76; 95% CI, -1.37 to -0.16; p = 0.01; I2 = 87.81%) compared to II. However, no differences were found in clinical cure rates, antibiotic treatment duration, length of hospital stay, or length of ICU stay. CONCLUSIONS: The PI approach for administering beta-lactam antibiotics in patients with suspected or confirmed GNB infections may be advantageous in reducing mortality rates and the duration of MV when compared to the II strategy.

Comparison between sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase 4 inhibitors on the risk of incident cancer in patients with diabetes mellitus: A real-world evidence study.

AIMS: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have been demonstrated to be associated with cancer cell mechanisms. However, whether they increase the risk of cancer remains unclear. Thus, this study aimed to determine the association between SGLT-2i use and the incidence of cancer in patients with diabetes mellitus (DM) in Taiwan. MATERIALS AND METHODS: This retrospective cohort study was based on the Taiwan National Health Insurance database. The study population comprised patients with DM, and those who first used SGLT-2is during 2016-2018 were assigned to the study group. Greedy propensity score matching was performed to select patients who first used dipeptidyl peptidase 4 inhibitors (DPP-4is), and these patients were assigned to the control group. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer risk in the study and control groups; this model was adjusted for demographic characteristics, DM severity, comorbidities and concomitant medication use. RESULTS: After controlling for relevant variables, the SGLT-2i cohort (aHR = 0.90, 95% CI = 0.87-0.93) had a significantly lower risk of developing cancer than the DPP-4i cohort, particularly when the SGLT-2i was dapagliflozin (aHR = 0.91, 95% CI = 0.87-0.95) or empagliflozin (aHR = 0.90, 95% CI = 0.86-0.94). Regarding cancer type, the SGLT-2i cohort's risk of cancer was significantly lower than that of the DPP-4i cohort for leukaemia, oesophageal, colorectal, liver, pancreatic, lung, skin and bladder cancer. CONCLUSIONS: SGLT-2i use was associated with a significantly lower risk of cancer than DPP-4i use.

Structure-Based Discovery of A Small Molecule Inhibitor of Histone Deacetylase 6 (HDAC6) that Significantly Reduces Alzheimer's Disease Neuropathology.

Histone deacetylase 6 (HDAC6) is one of the key histone deacetylases (HDACs) that regulates various cellular functions including clearance of misfolded protein and immunological responses. Considerable evidence suggests that HDAC6 is closely related to amyloid and tau pathology, the two primary hallmarks of Alzheimer's disease (AD). It is still unclear whether HDAC6 expression changes with amyloid deposition in AD during disease progression or HDAC6 may be regulating amyloid phagocytosis or neuroinflammation or other neuropathological changes in AD. In this work, the pathological accumulation of HDAC6 in AD brains over age as well as the relationship of its regulatory activity - with amyloid pathogenesis and pathophysiological alterations is aimed to be enlightened using the newly developed HDAC6 inhibitor (HDAC6i) PB118 in microglia BV2 cell and 3D-AD human neural culture model. Results suggest that the structure-based rational design led to biologically compelling HDAC6i PB118 with multiple mechanisms that clear Aß deposits by upregulating phagocytosis, improve tubulin/microtubule network by enhancing acetyl α-tubulin levels, regulate different cytokines and chemokines responsible for inflammation, and significantly reduce phospho-tau (p-tau) levels associated with AD. These findings indicate that HDAC6 plays key roles in the pathophysiology of AD and potentially serves as a suitable pharmacological target through chemical biology-based drug discovery in AD.

BHLHE40 Mediates Cross-Talk between Pathogenic TH17 Cells and Myeloid Cells during Experimental Autoimmune Encephalomyelitis.

TH17 cells are implicated in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). We previously reported that the transcription factor basic helix-loop-helix family member e40 (BHLHE40) marks cytokine-producing pathogenic TH cells during EAE, and that its expression in T cells is required for clinical disease. In this study, using dual reporter mice, we show BHLHE40 expression within TH1/17 and ex-TH17 cells following EAE induction. Il17a-Cre-mediated deletion of BHLHE40 in TH cells led to less severe EAE with reduced TH cell cytokine production. Characterization of the leukocytes in the CNS during EAE by single-cell RNA sequencing identified differences in the infiltrating myeloid cells when BHLHE40 was present or absent in TH17 cells. Our studies highlight the importance of BHLHE40 in promoting TH17 cell encephalitogenicity and instructing myeloid cell responses during active EAE.

Reactive Oxygen Species-Dependent Activation of EGFR/Akt/p38 Mitogen-Activated Protein Kinase and JNK1/2/FoxO1 and AP-1 Pathways in Human Pulmonary Alveolar Epithelial Cells Leads to Up-Regulation of COX-2/PGE2 Induced by Silica Nanoparticles.

The risk of lung exposure to silica nanoparticles (SiNPs) and related lung inflammatory injury is increasing with the wide application of SiNPs in a variety of industries. A growing body of research has revealed that cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) up-regulated by SiNP toxicity has a role during pulmonary inflammation. The detailed mechanisms underlying SiNP-induced COX-2 expression and PGE2 synthesis remain unknown. The present study aims to dissect the molecular components involved in COX-2/PGE2 up-regulated by SiNPs in human pulmonary alveolar epithelial cells (HPAEpiCs) which are one of the major targets while SiNPs are inhaled. In the present study, we demonstrated that SiNPs induced COX-2 expression and PGE2 release, which were inhibited by pretreatment with a reactive oxygen species (ROS) scavenger (edaravone) or the inhibitors of proline-rich tyrosine kinase 2 (Pyk2, PF-431396), epidermal growth factor receptor (EGFR, AG1478), phosphatidylinositol 3-kinase (PI3K, LY294002), protein kinase B (Akt, Akt inhibitor VIII), p38 mitogen-activated protein kinase (MAPK) (p38 MAPK inhibitor VIII), c-Jun N-terminal kinases (JNK)1/2 (SP600125), Forkhead Box O1 (FoxO1, AS1842856), and activator protein 1 (AP-1, Tanshinone IIA). In addition, we also found that SiNPs induced ROS-dependent Pyk2, EGFR, Akt, p38 MAPK, and JNK1/2 activation in these cells. These signaling pathways induced by SiNPs could further cause c-Jun and FoxO1 activation and translocation from the cytosol to the nucleus. AP-1 and FoxO1 activation could increase COX-2 and PGE2 levels induced by SiNPs. Finally, the COX-2/PGE2 axis might promote the inflammatory responses in HPAEpiCs. In conclusion, we suggested that SiNPs induced COX-2 expression accompanied by PGE2 synthesis mediated via ROS/Pyk2/EGFR/PI3K/Akt/p38 MAPK- and JNK1/2-dependent FoxO1 and AP-1 activation in HPAEpiCs.

Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice.

Emerging evidence suggests that peripheral immune cells contribute to Alzheimer's disease (AD) neuropathogenesis. Among these, mast cells are known for their functions in allergic reactions and neuroinflammation; however, little is known about their role in AD. Here, we crossed 5XFAD mice with mast cell-deficient strains and observed the effects on AD-related neuropathology and cognitive impairment. We found that mast cell depletion improved contextual fear conditioning in 5XFAD mice without affecting cued fear conditioning, anxiety-like behavior, or amyloid burden. Furthermore, mast cell depletion led to an upregulation of transcriptomic signatures for putatively protective disease-associated microglia and resulted in reduced markers indicative of reactive astrocytes. We hypothesize a system of bidirectional communication between dural mast cells and the brain, where mast cells respond to signals from the brain environment by expressing immune-regulatory mediators, impacting cognition and glial cell function. These findings highlight mast cells as potential therapeutic targets for AD.

Infiltrating CD8+ T cells exacerbate Alzheimer's disease pathology in a 3D human neuroimmune axis model.

Brain infiltration of peripheral immune cells and their interactions with brain-resident cells may contribute to Alzheimer's disease (AD) pathology. To examine these interactions, in the present study we developed a three-dimensional human neuroimmune axis model comprising stem cell-derived neurons, astrocytes and microglia, together with peripheral immune cells. We observed an increase in the number of T cells (but not B cells) and monocytes selectively infiltrating into AD relative to control cultures. Infiltration of CD8+ T cells into AD cultures led to increased microglial activation, neuroinflammation and neurodegeneration. Using single-cell RNA-sequencing, we identified that infiltration of T cells into AD cultures led to induction of interferon-γ and neuroinflammatory pathways in glial cells. We found key roles for the C-X-C motif chemokine ligand 10 (CXCL10) and its receptor, CXCR3, in regulating T cell infiltration and neuronal damage in AD cultures. This human neuroimmune axis model is a useful tool to study the effects of peripheral immune cells in brain disease.

Compact Sub 6 GHz Dual Band Twelve-Element MIMO Antenna for 5G Metal-Rimmed Smartphone Applications.

In this paper, a twelve-antenna system is designed for 5G smartphones with metal frames. The system is compact and operates on dual bands within the sub-6 GHz frequency range using multiple-input multiple-output (MIMO) technology. Two sets of six-antenna units are included in the system, arranged in a diagonal mirror-image configuration, and positioned at the center of the circuit board's longer edges. The profile height of each of the six-antenna units is only 3 mm, and the overall array dimensions are 105 × 3 × 3.1 mm3. A single antenna unit is 15 × 3 × 3.1 mm3 (0.173 λ × 0.035 λ × 0.036 λ, where λ equals the free-space wavelength of 3450 MHz). The arrangement of the antennas in the six-antenna units is parallel, with a 3 mm separation between adjacent antennas. The antenna structure comprises of an inverted L-shaped feed branch and two inverted L-shaped short-circuit branches integrated into part of the metal frame. The proposed array can form multiple resonance paths, achieving dual-band operation at 3300-3600 MHz and 4800-5000 MHz. The measured isolation of this twelve-antenna system within the operating frequency band is over 10 dB, and the measured antenna efficiency is greater than 36%. Therefore, the system is suitable for use in smartphones with high screen-to-body ratios and metal frames.

Optimizing animal models of autoimmune encephalitis using active immunization.

Background and objectives: Encephalitis is a devastating neurologic disorder with high morbidity and mortality. Autoimmune causes are roughly as common as infectious ones. N-methyl-D-aspartic acid receptor (NMDAR) encephalitis (NMDARE), characterized by serum and/or spinal fluid NMDAR antibodies, is the most common form of autoimmune encephalitis (AE). A translational rodent NMDARE model would allow for pathophysiologic studies of AE, leading to advances in the diagnosis and treatment of this debilitating neuropsychiatric disorder. The main objective of this work was to identify optimal active immunization conditions for NMDARE in mice. Methods: Female C57BL/6J mice aged 8 weeks old were injected subcutaneously with an emulsion of complete Freund's adjuvant, killed and dessicated Mycobacterium tuberculosis, and a 30 amino acid peptide flanking the NMDAR GluN1 subunit N368/G369 residue targeted by NMDARE patients' antibodies. Three different induction methods were examined using subcutaneous injection of the peptide emulsion mixture into mice in 1) the ventral surface, 2) the dorsal surface, or 3) the dorsal surface with reimmunization at 4 and 8 weeks (boosted). Mice were bled biweekly and sacrificed at 2, 4, 6, 8, and 14 weeks. Serum and CSF NMDAR antibody titer, mouse behavior, hippocampal cell surface and postsynaptic NMDAR cluster density, and brain immune cell entry and cytokine content were examined. Results: All immunized mice produced serum and CSF NMDAR antibodies, which peaked at 6 weeks in the serum and at 6 (ventral and dorsal boosted) or 8 weeks (dorsal unboosted) post-immunization in the CSF, and demonstrated decreased hippocampal NMDAR cluster density by 6 weeks post-immunization. In contrast to dorsally-immunized mice, ventrally-induced mice displayed a translationally-relevant phenotype including memory deficits and depressive behavior, changes in cerebral cytokines, and entry of T-cells into the brain at the 4-week timepoint. A similar phenotype of memory dysfunction and anxiety was seen in dorsally-immunized mice only when they were serially boosted, which also resulted in higher antibody titers. Discussion: Our study revealed induction method-dependent differences in active immunization mouse models of NMDARE disease. A novel ventrally-induced NMDARE model demonstrated characteristics of AE earlier compared to dorsally-induced animals and is likely suitable for most short-term studies. However, boosting and improving the durability of the immune response might be preferred in prolonged longitudinal studies.

The Role of Interleukin-17A and NLRP3 Inflammasome in the Pathogenesis of Graves' Ophthalmopathy.

The development of Graves' ophthalmopathy (GO) is associated with autoimmune dysfunction. Recent studies have indicated that IL-17A, inflammasomes, and related cytokines may be involved in the etiology of GO. We sought to investigate the pathogenic role of IL-17A and NLRP3 inflammasomes in GO. Orbital fat specimens were collected from 30 patients with GO and 30 non-GO controls. Immunohistochemical staining and orbital fibroblast cultures were conducted for both groups. IL-17A was added to the cell cultures, and cytokine expression, signaling pathways, and inflammasome mechanisms were investigated using reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and small interfering RNA (siRNA) methods. Immunohistochemical staining showed higher NLRP3 expression in GO orbital tissue than in non-GO controls. IL-17A upregulated pro-IL-1ß mRNA levels and IL-1ß protein levels in the GO group. Furthermore, IL-17A was confirmed to enhance caspase-1 and NLRP3 protein expression in orbital fibroblasts, suggesting NLRP3 inflammasome activation. Inhibiting caspase-1 activity could also decrease IL-1ß secretion. In siRNA-transfected orbital fibroblasts, significantly decreased NLRP3 expression was observed, and IL-17A-mediated pro-IL-1ß mRNA release was also downregulated. Our observations illustrate that IL-17A promotes IL-1ß production from orbital fibroblasts via the NLRP3 inflammasome in GO, and cytokines subsequently released may induce more inflammation and autoimmunity.

Compact Sub 6 GHz Slot Multiantenna System for 5G Laptops.

A sub 6 GHz dual-band closed-slot multiantenna system for 5G laptops is proposed in this paper. It was installed in a clearance space, with dimensions og 217 × 3 mm2 and 1 mm away from the upper edge of the screen ground plane. The dimensions of the clearance space were the same as those of a multisystem consisting of six antennas. The dimensions of the single closed-slot antenna were 32 × 3 mm2 (0.368 λ × 0.034 λ, where λ equals the free-space wavelength of 3450 MHz. The antenna was coupled to an asymmetric T-shaped feed-in section equipped with a chip capacitor for exciting one-half and full wavelength resonance modes of the closed-slot to encompass sub 6 GHz 3300-3600 MHz and 4800-5000 MHz dual-band operations. The design of the antenna features a long and straight slot to generate the high-order mode of the closed slot in the high-frequency (4800-5000 MHz) band (not the low-frequency (3300-3600 MHz) multiplier band). Its structure is simple, and the width of its slot is only 3 mm. The antennas were arranged to be 5 mm apart in the same direction and in parallel to form a six-antenna system in order to utilize the weak electric fields located at the two closed ends of the closed-slot structure when the closed slot was excited. It showed excellent envelope correlation coefficients (ECCs) and isolation performance without the installation of isolation elements. The measured fractional bandwidth of the antenna was 10.15% and 6.73% at the center frequencies of 3450 MHz and 4900 MHz, respectively. Its measured isolation was always over 10 dB, and the efficiency was between 46% and 76%. The ECCs of the system calculated from the measured complex E-field radiation pattern were all below 0.2, which means that it is ideal for use in laptop devices with a high screen-to-body ratio and a metal back cover.

Use of Transcutaneous Electrical Nerve Stimulation to Alleviate Thirst After Surgery: A Randomized Controlled Trial.

PURPOSE: This prospective study investigated the preventive effect of transcutaneous electrical nerve stimulation (TENS) for postoperative thirst. DESIGN: This experimental study was conducted with the CONSORT checklist. METHODS: A total of 105 surgical patients who received general anesthesia were recruited from a medical center. Each patient was randomly assigned to the experimental group (n = 53; 20 min of TENS) or the control group (n = 52; routine care). In each group, oral moisture wetness was measured at 1 min, 20 min, and 50 min post-surgery. Descriptive and inferential statistics (Chi-square test, t test, one-way ANOVA, and generalized estimating equation (GEE) regression analysis) were performed to assess the proposed relationships. FINDINGS: The two groups showed similar characteristics at baseline. The oral moisture wetness was significantly higher in the experimental group than the control group at each post-surgery assessment time (all P < .001). The GEE results showed that patients in the experimental group reported more oral moisture wetness than patients in the control group. CONCLUSIONS: This study demonstrated that TENS can reduce thirst reported by patients after general anesthesia. Thus, this method may have clinical applications for managing postoperative thirst.

ASSESSMENT OF DOSES FROM INGESTION OF RADIONUCLIDES 40 K, 137CS, 226RA AND 232TH IN EDIBLE COMMERCIAL MUSHROOMS FROM TAIWAN.

This study analyzed activity concentration and annual effective dose of radionuclides 40K, 137Cs, 226Ra and 232Th of 44 mushrooms collected from local markets in Taiwan. The 40K activity concentrations were 1570 ± 150 Bq/kg-dw (Agaricus bisporus) > 1084 ± 183 Bq/kg-dw (Flammulina velutipe) > 736 ± 150 Bq/kg-dw (Lentinula edodes). The activity concentrations of 226Ra were 5.04 ± 2.43, 4.00 ± 2.40 and 3.43 ± 2.69 Bq/kg-dw, and 232Th were 3.96 ± 2.18, 3.86 ± 1.43 and 2.90 ± 1.99 Bq/kg-dw for F. velutipe, L. edodes and A. bisporus, respectively. In seven of the 44 samples, 137Cs activity concentrations were detected, and the samples had an average of 1.55 ± 1.75 Bq/kg-dw. The total annual effective dose ranged from 0.90 to 3.50 µSv/y, with an average of 1.94 ± 0.62 µSv/y at an ingestion rate of 0.235 kg-dw/y.

Soil to tobacco component transfer factors for natural radionuclides 40K, 226Ra, and 232Th and the risk assessment of tobacco leaf in smoking.

This study determined the activity concentrations and corresponding transfer factors (TF) of 40K, 226Ra, and 232Th in three tobacco components (root, stem, and leaf). The radiation hazard index parameters were assessed for the tobacco leaf. The activity concentrations in the soil were 589-762, 32-43, and 49-59 Bq kg-dw-1 (dry weight) for 40K, 226Ra, and 232Th, respectively. The average activity concentrations of 40K, 226Ra, and 232Th were 447, 5.41 and 5.69 Bq/kg-dw for the root, 670, 9.64 and 7.61 Bq kg-dw-1 for the stem, and 793, 6.79 and 6.15 Bq kg-dw-1 for the leaf, respectively. The TF values were 0.42-1.42, 0.10-0.49 and 0.06-0.23 for 40K, 226Ra, and 232Th, respectively. The stem and leaf 40K TF values were significantly higher than the root values. The stem 226Ra TF values were significantly higher than the root values. The 226Ra and 232Th activity concentrations and TFs of tobacco components had a significant positive correlation. Based on the activity concentrations of the tobacco leaves, the annual inhalation effective dose to the lungs for an adult smoker was 0.32-0.81 mSv y-1 (average 0.60 mSv y-1). The Excess Lifetime Cancer Risk (ELCR) caused by smoking was an average of 2.39 × 10-3.

Activity concentrations and bioconcentration factors (BCFs) of natural radionuclides (40 K, 226Ra, and 232Th) from cultivated substrates to mushrooms.

This study examined 42 mushroom samples and corresponding cultivated substrates. The radionuclide activity concentrations and bioconcentration factor (BCF) from substrate-to-mushroom were determined. The substrate activity concentrations were 59.1-727.5, 4.5-37.6, and 4.0-53.0 Bq/kg dw (dry weight) for 40 K, 226Ra, and 232Th, respectively. The average 40 K concentrations were 1546.5, 1115.7, and 749.3 Bq/kg dw; the BCFs were 2.49, 3.56, and 5.58 for A. bisporus, F. velutipes, and L. edodes, respectively. The 40 K concentrations were insignificantly correlated with each species' corresponding substrate concentration. The 40 K BCFs had a significantly negative correlation with the substrate concentration for each species. Each mushroom species' 40 K concentration was almost stable, suggesting that 40 K has a regulated homeostasis for a given species. The average 226Ra concentrations were 5.5, 5.4, and 3.4 Bq/kg dw; the BCFs were 0.58, 0.17, and 0.50 for L. edodes, A. bisporus, and F. velutipes, respectively. The average 232Th concentrations were 4.7, 4.7, and 3.0 Bq/kg dw; the BCFs were 0.50, 0.11, and 0.53 for L. edodes, A. bisporus, and F. velutipes, respectively. The 226Ra and 232Th concentrations in mushrooms had a weak to moderate correlation with the cultivated substrate concentrations. The absorption of the 226Ra and 232Th from substrate-to-mushroom was similar to the hypothesis of the linear model that mushroom concentration yields a positive correlation with substrate concentration.

Natural medicine HLXL targets multiple pathways of amyloid-mediated neuroinflammation and immune response in treating alzheimer's disease.

BACKGROUND: Based on the complex pathology of AD, a single chemical approach may not be sufficient to deal simultaneously with multiple pathways of amyloid-tau neuroinflammation. A polydrug approach which contains multiple bioactive components targeting multiple pathways in AD would be more appropriate. Here we focused on a Chinese medicine (HLXL), which contains 56 bioactive natural products identified in 11 medicinal plants and displays potent anti-inflammatory and immuno-modulatory activity. HYPOTHESIS/PURPOSE: We investigated the neuroimmune and neuroinflammation mechanisms by which HLXL may attenuate AD neuropathology. Specifically, we investigated the effects of HLXL on the neuropathology of AD using both transgenic mouse models as well as microglial cell-based models. STUDY DESIGN: The 5XFAD transgenic animals and microglial cell models were respectively treated with HLXL and Aß42, and/or lipopolysaccharide (LPS), and then analyzed focusing on microglia mediated Aß uptake and clearance, as well as pathway changes. METHODS: We showed that HLXL significantly reduced amyloid neuropathology by upregulation of microglia-mediated phagocytosis of Aß both in vivo and in vitro. HLXL displayed multi-modal mechanisms regulating pathways of phagocytosis and energy metabolism. RESULTS: Our results may not only open a new avenue to support pharmacologic modulation of neuroinflammation and the neuroimmune system for AD intervention, but also identify HLXL as a promising natural medicine for AD. CONCLUSION: It is conceivable that the traditional wisdom of natural medicine in combination with modern science and technology would be the best strategy in developing effective therapeutics for AD.

A Bit-Tracking Knowledge-Based Query Tree for RFID Tag Identification in IoT Systems.

In an IoT (Internet of Things) system where each IoT device has one/many RFID tags, there might be many RFID tags. However, when multiple tags respond to the reader's interrogation at the same time, their signals collide. Due to the collision, the reader must request the colliding tags to retransmit their IDs, resulting in higher communication overhead and longer identification time. Therefore, this paper presents a Bit-tracking Knowledge-based Query Tree (BKQT), which uses two techniques: knowledge, which stores all the tag IDs that can possibly occur, and bit tracking, which allows the reader to detect the locations of the collided bits in a collision slot. BKQT constructs a query tree for all possible tags, called a k-tree, by using knowledge while it constructs bit-collision cases and the corresponding actions for each node in this k-tree by using bit tracking. In the identification process, BKQT traverses this constructed k-tree and thus identifies the colliding tags faster by taking the actions according to the happening bit-collision cases. From the simulation results, BKQT can improve the identification time by 44.3%, 46.4%, and 25.1%, compared with the previous knowledge-based protocols, Knowledge Query Tree (KQT), Heuristic Query Tree (H-QT), Query Tree with Shortcutting and Couple Resolution (QTSC), respectively.

Case Series: Unusual Presentation of Acanthamoeba Coinfection in the Cornea.

SIGNIFICANCE: The cases illustrate Acanthamoeba coinfection with Pseudomonas aeruginosa or microsporidia in the cornea. PURPOSE: This case series aimed to alert clinicians toward considering Acanthamoeba coinfection in the cornea when unusual presentation such as perineuritis or epitheliitis was observed in clinical images. Increased suspicion of Acanthamoeba coinfection may facilitate early diagnosis and prompt management, eventually leading to good vision outcomes. CASE SERIES: An 11-year-old boy wearing orthokeratology lens for myopia control complained of pain in the right eye for 1 week. A paracentral corneal ulcer with perineuritis was observed. Culture from corneal tissue revealed P. aeruginosa , and an in vivo confocal microscopic examination showed highly reflective and oval-shaped structures indicating Acanthamoeba coinfection. Corneal lesions gradually improved under 0.02% polyhexamethylene biguanidine, 0.1% propamidine isethionate, and 0.3% ciprofloxacin. At 1 year, the final best-corrected visual acuity was 20/25 with residual paracentral corneal opacity. Another 20-year-old man complained of pain in the right eye for 2 weeks. Multiple raised corneal lesions associated with epitheliitis were found. Moreover, 1% acid-fast staining showed oval-shaped spores, and microsporidia infection was inferred. In addition, polymerase chain reaction results obtained after subjecting the patient to corneal debridement revealed positivity for Acanthamoeba . Polyhexamethylene biguanidine (0.02%) and 0.5% moxifloxacin were prescribed, and the lesions subsided. At a 2-year follow-up, the final best-corrected visual acuity was 20/25. CONCLUSIONS: Perineuritis in orthokeratology lens wearers and epitheliitis without any predisposing factor are unusual presentations of Acanthamoeba coinfection in the cornea. These corneal findings should arouse the suspicion of coinfection and enable the clinicians to conduct the appropriate workup and initiate adequate treatment. This case series demonstrated that early diagnosis and prompt treatment can improve visual prognosis.

4-Acetylantroquinonol B Suppresses Prostate Cancer Growth and Angiogenesis via a VEGF/PI3K/ERK/mTOR-Dependent Signaling Pathway in Subcutaneous Xenograft and In Vivo Angiogenesis Models.

Prostate cancer is a major cause of cancer-related mortality in men in developed countries. The compound, 4-acetylantroquinonol B (4AAQB), is isolated from Antrodia cinnamomea (commonly known as Niu-Chang-Chih), which has been shown to inhibit cancer growth. However, the anticancer activity of 4AAQB has not previously been examined in prostate cancer. This study aimed to investigate the effect of 4AAQB on cancer and angiogenesis, as well as to explore its mechanism of action. Human prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC) were used in cell viability, cell migration, and cell cycle functional assays to evaluate the anticancer and antiangiogenic efficacy of 4AAQB in vitro. The effects of 4AAQB in vivo were determined using xenograft and angiogenesis models. The signaling events downstream of 4AAQB were also examined. The 4AAQB compound inhibited PC3 cell growth and migration, and reduced in vivo cancer growth, as shown in a subcutaneous xenograft model. Furthermore, 4AAQB inhibited HUVEC migration, tube formation, and aortic ring sprouting; it also reduced neovascularization in a Matrigel implant angiogenesis assay in vivo. The 4AAQB compound also decreased metastasis in the PC3 prostate cancer model in vivo. Serum or vascular endothelial growth factor (VEGF)-induced VEGF receptor 2 (VEGFR2), phosphoinositide 3-kinase (PI3K)/Ak strain transforming (Akt), and extracellular signal-regulated kinase ½ (ERK ½) phosphorylation were attenuated by 4AAQB in both PC3 and HUVEC. In conclusion, 4AAQB is a potential candidate for prostate cancer therapy.

Glycemic control was associated with nonprostate cancer and overall mortalities in diabetic patients with prostate cancer.

BACKGROUND: Diabetes mellitus (DM) can worsen the prognosis or survival in prostate cancer (PC) patients. We investigated whether glycemic control impacts mortality in PC patients with existing diabetes. METHODS: All PC patients with or without preexisting DM were enrolled from 2006 to 2017. Mean hemoglobin A1c (HbA1c) values (<7%, 7%-9%, ≥9%) were used to represent glycemic control. Major outcomes included all-cause, PC-specific, and non-PC mortalities. Statistical analyses were performed using Cox regression models with adjusted mean HbA1c and other related confounders. RESULTS: A total of 831 PC patients were enrolled (non-DM group, n = 690; DM group with a record of mean HbA1c values, n = 141). Results showed that the DM group with mean HbA1c level ≥ 9% (n = 14) had significantly increased risk for all-cause and non-PC mortality (hazard ratio [HR], 3.09; 95% CIs, 1.15-8.32; p=0.025 and HR, 5.49; 95% CIs, 1.66-18.16; p = 0.005, respectively), but not for PC-specific mortality (HR, 1.03; 95% CIs, 0.13-8.44; p = 0.975), compared with the non-DM group. CONCLUSION: Our findings indicate that PC patients with DM who had a mean HbA1c level ≥ 9% had higher risks of all-cause and non-PC mortality compared with non-DM subjects. Further large and long-term studies are needed to verify the effect of glycemic control in PC patients with DM.