Search

The benefits and risks of the intraosseous (IO) route for vascular access in patients with out-of-hospital cardiac arrest (OHCA) remain controversial. This study compares the success rates of establishing the access route, epinephrine administration rates, and time-to-epinephrine between adult patients with OHCA with IO access and those with intravenous (IV) access established by paramedics in the prehospital setting. This was a retrospective study conducted by the San-Min station of Taoyuan Fire Department. Data for IV access were collected between January 1, 2020, and December 31, 2020. Data for IO access were collected between January 1, 2021, and March 10, 2021. Inclusion criteria were adult patients with OHCA who received on-scene resuscitation attempts and in whom either IV or IO route access was established by paramedics. Exclusion criteria were missing data, return of spontaneous circulation before establishing vascular access, cardiac arrest en route to hospital, patients not resuscitated, and OHCA unidentified by the dispatcher. Exposure was defined as IV route vs. IO route (EZ-IO®). The outcome measurements were per-patient based success rates of route establishment (successes/attempts), administration rates of epinephrine (epinephrine administered per case/enrolled OHCAs), and odds ratios of IV versus IO on epinephrine administration. We used nonparametric Mann-Whitney rank sum tests for the analysis in continuous variables and Fisher's exact tests for the analysis of categorical variables and the outcomes. Firth logistic regression method was used for sparse data. Factors associated with epinephrine administration other than vascular access were also analyzed. Time-to-epinephrine (defined as time from paramedic arrival to epinephrine injection) was reviewed and calculated by two independent observers and the Kaplan-Meier method was used to compare the two access routes. A total of 112 adult patients were enrolled in the analysis, including 71 men and 41 women, with an average age of 67 years. There were 90 IV access cases and 22 IO access cases. The groups were compared for median success rates of route establishment (33% vs. 100%, P < 0.001) and administration rates of epinephrine (52% vs. 100%, P < 0.001). The adjusted odds ratio of IO versus IV was 32.445, 95% confidence interval (CI) of 1.844–570.861. Time-to-epinephrine was significantly shorter in the cumulative time-event analysis by the Kaplan-Meier method (P < 0.001). The IO route was significantly associated with higher success rates of route establishment, epinephrine administration, and shorter time-to-epinephrine in the prehospital resuscitation of adult patients with OHCA. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the efficacy and safety of valsartan in Taiwanese patients with essential hypertension. Methods. This 12-week multi-center, open-label, observational, post-marketing surveillance study enrolled 2046 hypertensive patients who were prescribed valsartan 80 or 160 mg as monotherapy or in combination with other antihypertensives based on clinical judgment. The primary endpoint was the incidence rate of dizziness with valsartan 160 mg monotherapy or combination therapy at Week 4. Secondary endpoints included the blood-pressure-lowering efficacy and the overall safety and tolerability of valsartan at Weeks 4 and 12. Results. The monotherapy and combination groups had comparable baseline characteristics. At Week 4, monotherapy was found non-inferior to combination for incidence rate of dizziness (monotherapy, 9.25%; combination, 10%; difference in incidence of dizziness, 0.75%; 95%CI − 0.61% to 2.12%; non-inferiority margin, −1.33%; Wald Test approach). Greater blood pressure (BP) reduction was noted at Week 12 than at Week 4. The antihypertensive effect was greater with combination therapy and the 160-mg dose. BP control (systolic <140 mmHg or diastolic <90 mmHg) was achieved in 80-90% patients. Valsartan was well tolerated; most commonly reported adverse events included dizziness, headache, constipation and cough. Conclusion. Valsartan is an effective treatment option for essential hypertension in Taiwanese patients. [ABSTRACT FROM AUTHOR]

Background: The biatrial substrate properties in patients with paroxysmal atrial fibrillation (AF) originating from the pulmonary veins (PVs) and superior vena cava (SVC) are not available. Objective: The purpose of this study is to characterize the differences of biatrial substrate properties in patients with different types of AF. Methods: A total of 36 patients with paroxysmal AF originating from the PV (PV-AF) and 9 patients with paroxysmal AF initiating from the SVC (SVC-AF) were included. Regional electrogram voltage, conduction velocity (CV), and spectral analysis to identify the AF nest were performed to characterize the biatrial, PVs, and SVC substrate. Results: In the left atrial (LA) body, the bipolar voltage, total activation time, CV, and dominant frequency (DF) were similar between the PV-AF and SVC-AF. However, in the PV regions, the electrogram voltage, CV, and DF were decreased in the PV-AF. The proportions of AF nest in the LA body (72.2% vs. 22.2%, P = .008) and PV regions (100% vs. 22.2%, P <.001) were higher in PV-AF compared with SVC-AF, respectively. On the other hand, lower bipolar voltage, longer total activation time, and slower CV of RA body were recognized in the SVC-AF as compared with the PV-AF. In the SVC, lower bipolar voltage, slower CV, higher DF, and higher proportions of AF nest in SVC (16.7% vs. 66.7%, P = .002) were identified in SVC-AF. Conclusion: These most-remodeled substrates in different types of paroxysmal AF indicated the importance of the atrial substrate in the vicinity of the arrhythmogenic thoracic veins. [ABSTRACT FROM AUTHOR]

Aortic intramural hematoma (IMH) is defined as aortic dissection without identifiable intimal tear and lack of flow in the false lumen of the aorta. Hematoma forms within the aortic wall as a result of either vasa vasorum hemorrhage, a microscopic tear of the intima that is not detectable by imaging modalities or an atherosclerotic plaque with penetrating ulceration rupture. Type A aortic IMH is defined as involvement of the ascending aorta. Type B aortic IMH is defined as involvement of only the descending aorta. The diagnosis is confirmed by computed tomography (CT) scan, magnetic resonance imaging and/or transesophageal echocardiography (TEE). The regional thickening of the aortic wall greater than 7 mm with evidence of intramural blood accumulation is considered IMH. The management of acute type A IMH is still controversial. Asian cohort used serial scans to monitor complications, which was then used to determine the timing of surgery. The treatment policy of institutions was initial medical treatment with timed surgical intervention in cases with complications, according to clinical assessment and on followup imaging studies. The initial therapeutic goal during the acute phase of IMH included the elimination of pain and the reduction of systolic blood pressure to 100–120 mmHg. Close clinical monitoring with transthoracic echocardiography, TEE, and CT scan is carried out to minimize the risk of fatal complications. Aortic diameter > 5.0 cm and hematoma thickness > 12 mm are independent predictors of development of complications and may benefit from urgent surgery. In addition, regression may occur but is less common and not predictable in proximal IMH involving the ascending aorta. Therefore, IMH involving to the aortic valve is usually related to acute mortality and needs early surgical approach. Type B IMH are generally associated with favorable outcome as compared with type A lesion. There was no difference in survival between medical vs. surgical management in patients with type B IMH. [Copyright &y& Elsevier]

Objectives: This study aims to investigate the characteristics of patients after free falls at the Level-I trauma centers. The factors associated with survival were differentiated.Methods: This retrospective study was conducted at the National Taiwan University Hospital, the Hsin-Chu branch, and the Yun-Lin branch, all accredited as Level-I trauma centers between January 2010 and September 2020. Adult patients with falls from height of more than one story (i.e. 3.6 m) were included. Clinical data were obtained from electronic medical records. Odds ratios (OR) were computed with 95% confidence intervals (CIs) for significant parameters for survival.Results: A total of 371 patients were included. Only 2 survived to discharge with poor neurologic outcomes in 101 patients with OHCA. The overall mortality rate was 98% and 11% in patients with and without OHCA. A higher falling height with a one-meter increase (OR, 1.14, 95% CI, 1.10-1.19) was significantly related to OHCA, especially the height over 6 m (OR, 3.07, 95% CI, 1.19-7.94). A higher trauma injury severity score (TRISS) was significantly related to survival among patients without OHCA (OR, 1.07, 95% CI, 1.04-1.11), especially TRISS≧0.945 (OR, 5.21, 95% CI, 1.28-21.24). Patients without severe head/neck injury of Abbreviated Injury Scale (AIS)≧3 (OR, 0.17, 95% CI, 0.07-0.42) were positively associated with survivors among patients without OHCA.Conclusion: Patients with traumatic OHCA following falls had a high mortality rate of 98% and dismal outcomes, compared with non-traumatic OHCA. Falling heights, especially over 6 m was associated with OHCA. Patients without OHCA had a mortality rate of 11%. Patients with a higher TRISS, especially more than 0.945, or without severe head injury had more chances to survive in the non-OHCA group. The study provided the evidence to guide termination of high futility resuscitation for traumatic OHCA secondary to falls to conserve the clinical resources. [ABSTRACT FROM AUTHOR]

Summary Spermatogenesis is a complex and dynamic cellular differentiation process critical to male reproduction and sustained by spermatogonial stem cells (SSCs). Although patterns of gene expression have been described for aggregates of certain spermatogenic cell types, the full continuum of gene expression patterns underlying ongoing spermatogenesis in steady state was previously unclear. Here, we catalog single-cell transcriptomes for >62,000 individual spermatogenic cells from immature (postnatal day 6) and adult male mice and adult men. This allowed us to resolve SSC and progenitor spermatogonia, elucidate the full range of gene expression changes during male meiosis and spermiogenesis, and derive unique gene expression signatures for multiple mouse and human spermatogenic cell types and/or subtypes. These transcriptome datasets provide an information-rich resource for studies of SSCs, male meiosis, testicular cancer, male infertility, or contraceptive development, as well as a gene expression roadmap to be emulated in efforts to achieve spermatogenesis in vitro. Graphical Abstract Highlights • Single-cell transcriptomes of >62,000 spermatogenic cells from mice and humans • Human SSC fate regulation pathways match those of functionally defined mouse SSCs • The hepatic stellate cell activation pathway is associated with SSC fate • Unique 3-gene identifiers distinguish 11 spermatogenic cell types in mice and humans Hermann et al. present single-cell transcriptomes from >62,000 individual spermatogenic cells from immature and adult male mice and adult men. Their analysis facilitates resolution of SSCs and progenitor spermatogonia, elucidates the full range of gene expression changes during male meiosis and spermiogenesis, and derives unique gene expression signatures for eleven mouse and human spermatogenic cell types. [ABSTRACT FROM AUTHOR]

The article presents a reprint of the article "The Question Lung Ying-tai Could Not Answer," by I-Chung Chen which appeared in the August 27, 2006 issue of "China Times." It discusses the civil disobedience movement known as the "Battle of Trafalgar" that happened on March 31, 1990 in London, England. It further discusses the theory of Lung Ying-tai on democracy in reference to the movement. Lung Ying-tai states that a people's revolution may destroy democracy itself.

Abstract: Infectious intracranial aneurysms (IIAs) are uncommon but severe complications of bacterial endocarditis. We report a case of IIA due to a rare nutritionally variant streptococcus, Granulicatella adiacens. The 31-year-old young patient, without any known risk for infective endocarditis had a silent clinical course until rupture of IIAs occurred. Despite antibiotic treatment and surgical clipping of IIAs, a second episode of more severe intracerebral hemorrhage occurred four months later. Mitral valvuloplasty was undertaken and there were no more brain insults in the following four years. Awareness of the possibility of hemorrhagic stroke as the initial presentation of Granulicatella adiacens endocarditis, and the possibility of high recurrence and bacteriological failure rate of Granulicatella adiacens infection may be helpful in early diagnosis and surgical decision, thus limiting future fatal complications. [Copyright &y& Elsevier]

Pragmatic insertion of pargyline, a LSD1 inhibitor, as a surface recognition part in the HDAC inhibitory pharmacophore was planned in pursuit of furnishing potent antiprostate cancer agents. Resultantly, compound 14 elicited magnificent cell growth inhibitory effects against the PC-3 and DU-145 cell lines and led to remarkable suppression of tumor growth in human prostate PC-3 and DU-145 xenograft nude mouse models. The outcome of the enzymatic assays ascertained that the substantial antiproliferative effects of compound 14 were mediated through HDAC6 isoform inhibition as well as selective MAO-A and LSD1 inhibition. Moreover, the signatory feature of LSD1 inhibition by 14 in the context of H3K4ME2 accumulation was clearly evident from the results of western blot analysis. Gratifyingly, hydroxamic acid 14 demonstrates good human hepatocytic stability and good oral bioavailability in rats and exhibits enough promise to emerge as a therapeutic for the treatment of prostate cancer in the near future.

Modulating epigenetic modification has been recognized for over a decade as an effective therapeutic approach to cancer and many studies of histone deacetylase (HDAC), one of the best known epigenetic modulators, have been published. HDAC modulates cell proliferation and angiogenesis and plays an essential role in cell growth. Research shows that up-regulated HDACs are present in many cancer types and synthetic or natural HDAC inhibitors have been used to silence overregulated HDACs. Inhibiting HDACs may cause arrest of cell proliferation, angiogenesis reduction and cell apoptosis. Recent studies indicate that HDAC inhibitors can provide a therapeutic effect in various cancers, such as B-cell lymphoma, leukemia, multiple myeloma and some virus-associated cancers. Some evidence has demonstrated that HDAC inhibitors can increase the expression of immune-related molecules leading to accumulation of CD8 + T cells and causing unresponsive tumor cells to be recognized by the immune system, reducing tumor immunity. This may be a solution for the blockade of PD-1. Here, we review the emerging development of HDAC inhibitors in various cancer treatments and reduction of tumor immunity., (Copyright © 2020 Chen, Sethy and Liou.)

Pluripotent stem cells hold the potential to form the basis of novel approaches to treatment of disease in vivo as well as to facilitate the generation of models for human disease, providing powerful avenues to discovery of novel diagnostic biomarkers and/or innovative drug regimens in vitro. However, this will require extensive maintenance, expansion, and manipulation of these cells in culture, which raises a concern regarding the extent to which genetic integrity will be preserved throughout these manipulations. We used a mutation reporter (lacI) transgene approach to conduct direct comparisons of mutation frequencies in cell populations that shared a common origin and genetic identity, but were induced to undergo transitions in cell fate between pluripotent and differentiated states, or vice versa. We confirm that pluripotent cells normally maintain enhanced genetic integrity relative to that in differentiated cells, and we extend this finding to show that dynamic transformations in the relative stringency at which genetic integrity is maintained are associated with transitions between pluripotent and differentiated cellular states. These results provide insight into basic biological distinctions between pluripotent and differentiated cell types that impact genetic integrity in a manner that is directly relevant to the potential clinical use of these cell types.

Hirudin, isolated from the leech Hirudo medicinalis, inhibits thrombin directly and several expression systems have been used to produce recombinant Hirudin (rHirudin) for pharmaceutical purposes. A DNA fragment containing the Hirudin coding sequence and goat beta-casein secretion signal was chemically synthesized in this study. The synthetic DNA then was further constructed into a goat beta-casein expression vector for mouse transgenesis. Four lines of transgenic mice were successfully developed and one line showed a meaningful anti-thrombin activity of 40,000 anti-thrombin units (ATU)/mL in their milk. In this animal line, Hirudin mRNA was found in samples of uterus and kidney with insignificant anti-thrombin activity (

Matching donor and recipient human leucocyte antigen (HLA-II) could conquer cell-mediated rejection following transplantation. Transgenic pigs carrying HLA genes that "humanize" porcine organs, tissues, and cells were successfully generated. This study further clarifies the effect of HLA-DR transgenes on lymphocyte protein expression, via a proteomic approach. Lymphocytes were isolated from two HLA-DR transgenic pigs and three nontransgenic littermates on 157 d after birth. Soluble protein of 1x10(7) cells was separated using 2-DE. In total, 301 colloidal CBB-stained protein spots detected on all five 2-D gels were quantified. Thirty-three proteins were differentially expressed by a factor of 1.5. These proteins were subsequently identified by MALDI-TOF MS and MALDI-TOF/TOF MS/MS. These proteins were sorted into the following categories: chaperones, T-lymphocyte function, DNA/RNA processing, cytoskeleton-associated proteins, signal transduction, enzymes, and unknown. Previous studies have suggested that some of the identified proteins are associated with lymphocyte activation/proliferation. The identities of the unidentified spots and the systematic effect of these up- and down-regulated proteins on T-cell function in HLA-DR transgenic pigs require further exploration.

The cellular mechanisms of vasorelaxant effects of newly synthesized KMUP-3 and KMUP-4 were investigated in rat aortic smooth muscle (RASM). KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) and KMUP-4 (7-[2-[4-(2-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) elicited concentration-dependent relaxation of endothelium-intact and denuded RASM precontracted with phenylephrine. Relaxant responses were also produced by the PDE inhibitors theophylline, milrinone, rolipram, and zaprinast (1 nM-100 microM). The relaxant responses of KMUP-3 and KMUP-4 were reduced by endothelium removal and by the presence of the NOS inhibitor L-NAME (100 microM), the sGC inhibitor ODQ (1 microM), the adenylyl cyclase (AC) inhibitor SQ 22536 (100 microM), and the prostaglandin inhibitor indomethacin (10 microM). Additionally, the vasorelaxations of both agents were also attenuated by pretreatment with the nonselective K+ channel blocker TEA (10 mM), the KATP channel blocker glibenclamide (1 microM), the voltage-dependent K+ (KV) channel blocker 4-AP (100 microM), and Ca(2+)-dependent K+ (KCa) channel blockers apamin (1 microM) and charybdotoxin (ChTX, 0.1 microM). In addition, elevated extracellular K+ (80 mM) interferes with KMUP-3- and KMUP-4-induced vasorelaxations. Preincubation with both agents (1 microM) significantly enhanced the dilator responses of isoproterenol and SNP. KMUP-3 and KMUP-4 inhibited PDE activities and increased cAMP and cGMP levels in primary culture of RASM that were inhibited by SQ 22536 and ODQ, respectively. In cultured HUVECs, KMUP-3 and KMUP-4 (0.1 microM), more potent than YC-1, significantly increased the expression of eNOS protein. In summary, KMUP-3 and KMUP-4 induce aortic relaxations through both endothelium-dependent and -independent mechanisms. Mechanisms of vasorelaxation induced by both compounds involve multiple processes, such as accumulation of cyclic nucleotides partly as a result of PDE inhibition, K-channel activation, and indomethacin-sensitive endothelium function.

Percutaneous transluminal coronary angioplasty and stenting are established therapeutic modalities for coronary artery disease (CAD). Percutaneous transluminal septal myocardial ablation has become increasingly important for the treatment of symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). We report a case of HOCM combined with CAD involving the left anterior descending coronary artery. Coronary stent graft implantation was performed with uneventful recovery. Coronary stent graft implantation may be beneficial in selected cases of symptomatic HOCM combined with CAD.