Universal relation between the conditional auto-correlation function and the cross-correlation function of biphotons.

We systematically studied the relation between the conditional auto-correlation function (CACF) and cross-correlation function (CCF) of biphotons or pairs of single photons. The biphotons were generated from a heated atomic vapor via the spontaneous four-wave mixing (SFWM) process. In practical usage, one single photon of a pair is utilized as the heralding photon, and another is employed as the heralded photon. Motivated by the data of CACF of the heralded photons versus CCF, we proposed a universal formula to predict the CACF. The derived formula was based on general theory and is also valid for the biphoton generation process of spontaneous parametric down-conversion (SPDC). With the formula, we utilized the experimentally determined parameters to predict CACFs, which can well agree with the measured CACFs. The proposed formula enables one to quantitatively know the CACF of heralded single photons without the measurement of Hanbury-Brown-Twiss-type three-fold coincidence count. This study provides a better understanding of biphoton generation using the SFWM or SPDC process. Our work demonstrates a valuable tool for analyzing a vital property of how the heralded photons are close to Fock-state single photons.

Experimental Demonstration of Stationary Dark-State Polaritons Dressed by Dipole-Dipole Interaction.

Dark-state polaritons (DSPs) based on the effect of electromagnetically induced transparency are bosonic quasiparticles, representing the superpositions of photons and atomic ground-state coherences. It has been proposed that stationary DSPs are governed by the equation of motion closely similar to the Schrödinger equation and can be employed to achieve Bose-Einstein condensation (BEC) with transition temperature orders of magnitude higher than that of the atomic BEC. The stationary-DSP BEC is a three-dimensional system and has a far longer lifetime than the exciton-polariton BEC. In this Letter, we experimentally demonstrated the stationary DSP dressed by the Rydberg-state dipole-dipole interaction (DDI). The DDI-induced phase shift of the stationary DSP was systematically studied. Notably, the experimental data are consistent with the theoretical predictions. The phase shift can be viewed as a consequence of elastic collisions. In terms of thermalization to achieve BEC, the µm^{2}-size interaction cross section of the DDI can produce a sufficient elastic collision rate for the stationary DSPs. This Letter makes a substantial advancement toward the realization of the stationary-DSP BEC.

The Beneficial Effects of Combining Anti-Aß Antibody NP106 and Curcumin Analog TML-6 on the Treatment of Alzheimer's Disease in APP/PS1 Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with a multifactorial etiology. A multitarget treatment that modulates multifaceted biological functions might be more effective than a single-target approach. Here, the therapeutic efficacy of combination treatment using anti-Aß antibody NP106 and curcumin analog TML-6 versus monotherapy was investigated in an APP/PS1 mouse model of AD. Our data demonstrate that both combination treatment and monotherapy attenuated brain Aß and improved the nesting behavioral deficit to varying degrees. Importantly, the combination treatment group had the lowest Aß levels, and insoluble forms of Aß were reduced most effectively. The nesting performance of APP/PS1 mice receiving combination treatment was better than that of other APP/PS1 groups. Further findings indicate that enhanced microglial Aß phagocytosis and lower levels of proinflammatory cytokines were concurrent with the aforementioned effects of NP106 in combination with TML-6. Intriguingly, combination treatment also normalized the gut microbiota of APP/PS1 mice to levels resembling the wild-type control. Taken together, combination treatment outperformed NP106 or TML-6 monotherapy in ameliorating Aß pathology and the nesting behavioral deficit in APP/PS1 mice. The superior effect might result from a more potent modulation of microglial function, cerebral inflammation, and the gut microbiota. This innovative treatment paradigm confers a new avenue to develop more efficacious AD treatments.

[Factors Influencing Patient Decisions Regarding Cancer Clinical Trial Participation: A Systematic Review].

BACKGROUND: Cancer is the top cause of death in Taiwan. Cancer clinical trials are crucial for developing new treatments. Understanding the motivations and barriers related to the factors of influence on patient decisions regarding participation in cancer clinical trials may help clinical researchers improve patients' understanding of clinical trials and improve their ability to make autonomous decisions regarding informed consent. PURPOSE: This study was designed to explore the factors affecting patient decisions regarding cancer clinical trial participation using a systematic review of the literature. METHODS: A systematic review was used. Articles were retrieved from electronic databases including Cochrane Library, Embase, PubMed, CINAHLE, and Scopus. The following keywords and MeSH terms were used to search for articles on cancer, clinical trials, participation, factors or motivations, and decision making. A total of 9353 articles published from 2011 to January 2021 that matched the search criteria were extracted. After screening the topics, deleting repetitions, and doing critical appraisals, 40 articles were selected for analysis. Research quality was assessed using Joanna Briggs Institute Levels of Evidence criteria. RESULTS: Eight motivations and nine barriers were found to significantly influence patient participation in cancer clinical trials. These motivations were: (1) trust in health professionals, (2) hope for therapeutic benefits, (3) the last treatment option, (4) altruism, (5) family support, (6) extra care, (7) patients' or others' past therapy experience, and (8) other demographic factors. The barriers to participation identified were: (1) fear of side effects or treatment efficacy, (2) concerns about trial requirements and randomization, (3) heavy financial burden, (4) inability to maintain quality of life, (5) inability to participate due to disease progression, (6) having treatment preferences, (7) health professionals' negative attitudes toward clinical trials, (8) family opposition, and (9) providing trial information at an inappropriate time. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Eight motivational factors and nine barriers influencing patient decisions regarding cancer clinical trial participation were extracted from the selected articles. In addition to personal and situational factors, family and health professionals were found to influence patient decisions regarding cancer clinical trial participation. The authors hope that the findings of this study help clinical researchers further improve patient understanding of clinical trials and help patients make autonomous decisions with regard to informed consent.

Generation of sub-MHz and spectrally-bright biphotons from hot atomic vapors with a phase mismatch-free scheme.

We utilized the all-copropagating scheme, which maintains the phase-match condition, in the spontaneous four-wave mixing (SFWM) process to generate biphotons from a hot atomic vapor. The linewidth and spectral brightness of our biphotons surpass those of the biphotons produced with the hot-atom SFWM in the previous works. Moreover, the generation rate of the sub-MHz biphoton source in this work can also compete with those of the sub-MHz biphoton sources of the cold-atom SFWM or cavity-assisted spontaneous parametric down conversion. Here, the biphoton linewidth is tunable for an order of magnitude. As we tuned the linewidth to 610 kHz, the generation rate per linewidth is 1,500 pairs/(s·MHz) and the maximum two-photon correlation function, gs,as(2), of the biphotons is 42. This gs,as(2) violates the Cauchy-Schwarz inequality for classical light by 440 folds, and demonstrates that the biphotons have a high purity. By increasing the pump power by 16 folds, we further enhanced the generation rate per linewidth to 2.3×104 pairs/(s·MHz), while the maximum gs,as(2) became 6.7. In addition, we are able to tune the linewidth down to 290±20 kHz. This is the narrowest linewidth to date among all single-mode biphoton sources of room-temperature and hot media.

Effects of long-term anti-seizure medication monotherapy on all-cause death in patients with post-stroke epilepsy: a nationwide population-based study in Taiwan.

OBJECTIVE: We aim to compare the effect of long-term anti-seizure medication (ASM) monotherapy on the risk of death and new ischemic stroke in patients with post-stroke epilepsy (PSE). PATIENTS AND METHODS: We identified all hospitalized patients (≥ 20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohort were defined as the stroke patients (1) who had no epilepsy and no ASMs use before the index stroke, and (2) who had epilepsy and ASMs use after 14 days from the stroke onset. The patients with PSE receiving ASM monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new ASM groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) of death and new ischemic stroke within 5 years across all groups, using the new ASM group as the reference. RESULTS: Of 6962 patients with PSE using ASM monotherapy, 3917 (56 %) were on phenytoin, 1623 (23 %) on valproic acid, 457 (7 %) on carbamazepine, and 965 (14 %) on new ASMs. After adjusting for confounders, compared with new ASM users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95 % CI: 1.06-2.55). On the other hand, all ASM groups showed a similar risk of new ischemic stroke in 5 years. CONCLUSIONS: Among patients with PSE on first-line monotherapy, compared to new ASMs, use of phenytoin was associated with a higher risk of death in 5 years.

The risk of cardiac mortality in patients with status epilepticus: A 10-year study using data from the Centers for Disease Control and Prevention (CDC).

OBJECTIVE: To explore whether status epilepticus affected cardiac mortality. METHODS: We used the 2008-2017 multicause mortality data of the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiological Research. The status epilepticus group included patients whose death certificates mentioned status epilepticus as contributing to death. The non-status epilepticus group included patients whose death certificates mentioned epilepsy, other and unspecified convulsions, febrile convulsions, or post-traumatic seizures, as contributing to death. The outcomes for evaluation were death certificates that indicated that myocardial infarction, arrhythmia, heart failure, or cardiac arrest (CA) was the immediate cause of death. The numbers of deaths and population sizes by categorical demographics were recorded and subjected to multiple logistic regression analysis. RESULTS: Among the 14,487 death certificates in status epilepticus group; 3080 patients (21.3%) died of CA. When clinical records were compared to autopsy data, females were at a lower risk of myocardial infarction (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.51-0.61). Patients aged 45-65 years and older than 65 years were at a higher risk of developing all four cardiac complications. Status epilepticus was associated with higher risks of arrhythmia (OR: 1.55, 95% CI: 1.11-2.15) and CA (OR: 4.34, 95% CI: 3.49-5.39) but a reduced risk of myocardial infarction (OR: 0.42, 95% CI: 0.30-0.57) as the cause of immediate death. CONCLUSION: The frequency of CA in patients with status epilepticus increased between 2008 and 2017. Male and elderly patients were at a higher risk of cardiogenic mortality.

Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review.

Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone disease or low bone turnover is the most common type of renal osteodystrophy. The consequences of CKD-MBD include increased fracture risk, greater morbidity, and mortality. Thus, the goal is to prevent the occurrences of fractures by means of alleviating CKD-induced MBD and treating subsequent osteoporosis. Changes in mineral and humoral metabolism as well as bone structure develop early in the course of CKD. CKD-MBD includes abnormalities of calcium, phosphorus, PTH, and/or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification. In patients with CKD-MBD, using either DXA or FRAX to screen fracture risk should be considered. Biomarkers such as bALP and iPTH may assist to assess bone turnover. Before initiating an antiresorptive or anabolic agent to treat osteoporosis in CKD patients, lifestyle modifications, such as exercise, calcium, and vitamin D supplementation, smoking cessation, and avoidance of excessive alcohol intake are important. Managing hyperphosphatemia and SHPT are also crucial. Understanding the complex pathogenesis of CKD-MBD is crucial in improving one's short- and long-term outcomes. Treatment strategies for CKD-associated osteoporosis should be patient-centered to determine the type of renal osteodystrophy. This review focuses on the mechanism, evaluation and management of patients with CKD-MBD. However, further studies are needed to explore more details regarding the underlying pathophysiology and to assess the safety and efficacy of agents for treating CKD-MBD.

Differences in gait and trunk movement between patients after ankle fracture and healthy subjects.

BACKGROUND: Studies have shown that gait asymmetry and activity limitation can persist several months or years after ankle fracture. However, evidence of gait and trunk movement patterns following ankle fracture during the early rehabilitation period is scarce. Thus, we compared gait patterns and trunk movement during the early phase of rehabilitation between patients with ankle fracture and matched controls. METHODS: Ten patients with ankle fractures, and ten age- and sex-matched healthy controls were prospectively enrolled. An automated infrared-assisted, trunk accelerometer-based gait analysis system was used to measure walking speed, step length, and cadence. The median time of the evaluation following ankle fracture was 4.0 months. Trunk movement intensity was evaluated as acceleration root mean square. Trunk movement symmetry and regularity were analysed using the autocorrelation method. Differences in gait characteristics between the patient and control groups were analysed using the Mann-Whitney U test. Follow-up assessment of falls was performed 24 months after the fracture. The correlations between Lower Extremity Functional Scale (LEFS) scores/falls and gait parameters were evaluated using Spearman's rank correlation coefficient. RESULTS: Walking speed (p = 0.019), step length (p = 0.023), cadence (p = 0.003), and trunk movement intensity in anterior-posterior and vertical axis (p = 0.001, p = 0.003, respectively) were all significantly lower in the ankle fracture group than in the control group. Trunk movement symmetry in vertical direction (p = 0.019) decreased significantly in patients with ankle fractures, whereas between-strides regularity did not differ between groups. LEFS scores were moderately correlated with walking speed (r = 0.60, p = 0.044) and step length (r = 0.68, p = 0.021). During the 24 months after the fracture, 3 falls were reported by 3 patients. Trunk acceleration root mean square ratio in mediolateral axis (r = 0.72, p = 0.018) was highly correlated with future falls. CONCLUSION: During early rehabilitation, patients with ankle fracture may develop trunk movement asymmetry in the vertical direction accompanied with slower walking speed and cadence, and smaller step lengths, which can contribute to muscular imbalances and potential injury. Thus, proper rehabilitation strategies should be employed for these patients.

A common polymorphism decreases LRP1 mRNA stability and is associated with increased plasma factor VIII levels.

The low-density lipoprotein receptor-related protein 1 (LRP1) gene is associated with increased levels of plasma factor VIII (FVIII). We aimed to explore eight functional genetic LRP1 variants for their potential roles in regulating FVIII levels and acute ischemic stroke (AIS). This genetic association study enrolled 192 patients with AIS and 134 controls. There were no significant differences in the genetic frequency of the eight functional single-nucleotide polymorphisms (SNPs) between the control and AIS groups. However, while analyzing the association between the eight SNPs and plasma FVIII levels, subjects with T/T genotype of rs1800137 (vs. CC+CT) were found to be associated with higher FVIII levels (23.5IU/dL; 95% confidence interval, 7.4-39.5IU/dL; P=0.0044) after adjusting for age, gender, estimated glomerular filtration rate, O blood type, inflammatory state, and body mass index. An analysis of the mRNA stability and abundance was designed and performed using minigene system transfected into HepG2 cells to assess the possible differences in mRNA stabilities between rs1800137 CC (rs1800137C) and TT (rs1800137T) genotypes. Site-directed mutagenesis revealed that rs1800137T accounts for the observed decrease in mRNA stability. The SNP rs1800137, located in exon 8, has been identified as an exon-splicing enhancer in silico. However, alternative splicing of LRP1 without inclusion of exon 8 was not identified. In transfected HepG2 cells, cycloheximide slowed down the degradation of the rs1800137T-containing minigene. These results demonstrate that synonymous SNP rs1800137 can lead to increased plasma FVIII levels due to decreased mRNA stability via translation-dependent mRNA degradation associated with codon optimality.

Test-Retest Reliability of an Automated Infrared-Assisted Trunk Accelerometer-Based Gait Analysis System.

The aim of this study was to determine the test-retest reliability of an automated infrared-assisted, trunk accelerometer-based gait analysis system for measuring gait parameters of healthy subjects in a hospital. Thirty-five participants (28 of them females; age range, 23-79 years) performed a 5-m walk twice using an accelerometer-based gait analysis system with infrared assist. Measurements of spatiotemporal gait parameters (walking speed, step length, and cadence) and trunk control (gait symmetry, gait regularity, acceleration root mean square (RMS), and acceleration root mean square ratio (RMSR)) were recorded in two separate walking tests conducted 1 week apart. Relative and absolute test-retest reliability was determined by calculating the intra-class correlation coefficient (ICC3,1) and smallest detectable difference (SDD), respectively. The test-retest reliability was excellent for walking speed (ICC = 0.87, 95% confidence interval = 0.74-0.93, SDD = 13.4%), step length (ICC = 0.81, 95% confidence interval = 0.63-0.91, SDD = 12.2%), cadence (ICC = 0.81, 95% confidence interval = 0.63-0.91, SDD = 10.8%), and trunk control (step and stride regularity in anterior-posterior direction, acceleration RMS and acceleration RMSR in medial-lateral direction, and acceleration RMS and stride regularity in vertical direction). An automated infrared-assisted, trunk accelerometer-based gait analysis system is a reliable tool for measuring gait parameters in the hospital environment.

Synthesis of (+)-Antroquinonol: An Antihyperglycemic Agent.

The total synthesis of antroquinonol has been accomplished through Suzuki-Miyaura cross-coupling and Barton-McCombie reaction, and the α,ß-unsaturation was achieved through selenylation and oxidation protocols. In vitro and in vivo studies on the glucose-lowering properties of antroquinonol indicate that it is a potential antidiabetic agent.

Shortened Activated Partial Thromboplastin Time Is Associated With Acute Ischemic Stroke, Stroke Severity, and Neurological Worsening.

BACKGROUND: The role played by hemostasis in the pathogenesis of ischemic strokes is still controversial. The activated partial thromboplastin time (APTT) measures the time necessary to generate fibrin from initiation of the intrinsic pathway. In the present study, we looked for a possible association of ischemic strokes with the shortened APTT. METHODS: The study population consisted of 154 patients with acute ischemic strokes who had been admitted from December 2013 to December 2014 to the Department of Neurology, Chiayi Chang Gung Memorial Hospital, and 71 control subjects with no history of stroke. RESULTS: In a univariate risk analysis, shortened APTT was associated with an odds ratio (OR) for acute ischemic strokes of up to 1.86 (95% confidence interval [CI], 1.06-3.29, P = .031). In a multivariate analysis using a logistic regression model including age, sex, hypertension, diabetes mellitus, and shortened APTT, shortened APTT was still found to significantly add to the risk of ischemic stroke (OR = 2.12 with 95% CI, 1.13-3.98, P = .020). Shortened APTT was also associated significantly with neurological worsening (OR = 3.72 with 95% CI 1.03-13.5, P = .046). As for stroke severity, shortened APTT was associated with an OR for moderate/severe stroke of up to 3.42 (95% CI, 1.53-7.61, P = .003). CONCLUSION: Shortened APTT is a prevalent and independent risk factor for ischemic stroke, stroke severity, and neurological worsening after acute stroke.

Association between the volume of inpatient rehabilitation therapy and the risk of all-cause and cardiovascular mortality in patients with ischemic stroke.

OBJECTIVE: To investigate the relationship between the volume of inpatient rehabilitation therapy and mortality among patients with acute ischemic stroke, as well as to assess whether the association varies with respect to stroke severity. DESIGN: A retrospective study with a cohort of consecutive patients who had acute ischemic stroke between January 1, 2008, and June 30, 2009. SETTING: Referral medical center. PARTICIPANTS: Adults with acute ischemic stroke (N=1277) who were admitted to a tertiary hospital. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Stroke-related mortality. RESULTS: During the median follow-up period of 12.3 months (ranging from January 1, 2008, to December 31, 2009), 163 deaths occurred. Greater volume of rehabilitation therapy was associated with a reduced risk of all-cause and cardiovascular mortality (P for trend <.001 for both). Compared with the first tertile, the third tertile of rehabilitation volume was associated with a 55% lower risk of all-cause mortality (hazard ratio [HR]=.45; 95% confidence interval [CI], .30-.65) and a 50% lower risk of cardiovascular mortality (HR=.50; 95% CI, .31-.82). The association did not vary with respect to stroke severity (P for interaction = .45 and .73 for all-cause and cardiovascular mortality, respectively). CONCLUSIONS: The volume of inpatient rehabilitation therapy and mortality were significantly inversely related in the patients with ischemic stroke. Thus, further programs aimed at promoting greater use of rehabilitation services are warranted.

Ultrasonographic appearance of subungual glomus tumors.

BACKGROUND: To describe the sonographic (US) features of pathologically confirmed subungual glomus tumors. METHODS: We retrospectively analyzed cases of pathologically confirmed subungual glomus tumors in patients presenting between December 1, 2008 and October 31, 2012, selected from cases in the musculoskeletal US database of a single institution. RESULTS: Data on 14 patients with pathologically proven glomus tumors were retrieved from the US database. The tumor size ranged from 1.9 to 10.0 mm (mean ± SD, 5.3 ± 2.3 mm). Well-circumscribed tumors with clear margins were identified on US in 12 cases (86%): 11 (92%) tumors were hypoechoic and 1 (8%) was isoechoic. On power or color Doppler US, 11 of these 12 tumors (92%) appeared hypervascular. Two of the 14 tumors did not show a clearly circumscribed mass on gray-scale US, and bony erosion was the only US finding in one of the two cases. Seven of the 14 patients (50%) showed focal bony erosion in the underlying phalangeal bone. CONCLUSIONS: A hypervascular mass in the nail bed was the most common US finding associated with subungual glomus tumors. We found that focal hypervascularity supports the diagnosis, and bony erosion is commonly associated with digital glomus tumors.

Effect of Cu Film Thickness on Cu Bonding Quality and Bonding Mechanism.

In the hybrid bonding process, the final stage of chemical mechanical polishing plays a critical role. It is essential to ensure that the copper surface is recessed slightly from the oxide surface. However, this recess can lead to the occurrence of interfacial voids between the bonded copper interfaces. To examine the effects of copper film thickness on bonding quality and bonding mechanisms in this study, artificial voids were intentionally introduced at the bonded interfaces at temperatures of 250 °C and 300 °C. The results revealed that as the thickness of the copper film increases, there is an increase in the bonding fraction and a decrease in the void fraction. The variations in void height with different copper film thicknesses were influenced by the bonding mechanism and bonding fraction.

Interactions between internal forces, body stiffness, and fluid environment in a neuromechanical model of lamprey swimming.

Animal movements result from a complex balance of many different forces. Muscles produce force to move the body; the body has inertial, elastic, and damping properties that may aid or oppose the muscle force; and the environment produces reaction forces back on the body. The actual motion is an emergent property of these interactions. To examine the roles of body stiffness, muscle activation, and fluid environment for swimming animals, a computational model of a lamprey was developed. The model uses an immersed boundary framework that fully couples the Navier-Stokes equations of fluid dynamics with an actuated, elastic body model. This is the first model at a Reynolds number appropriate for a swimming fish that captures the complete fluid-structure interaction, in which the body deforms according to both internal muscular forces and external fluid forces. Results indicate that identical muscle activation patterns can produce different kinematics depending on body stiffness, and the optimal value of stiffness for maximum acceleration is different from that for maximum steady swimming speed. Additionally, negative muscle work, observed in many fishes, emerges at higher tail beat frequencies without sensory input and may contribute to energy efficiency. Swimming fishes that can tune their body stiffness by appropriately timed muscle contractions may therefore be able to optimize the passive dynamics of their bodies to maximize peak acceleration or swimming speed.

Sonographic diagnosis of a medial talar avulsion fracture.

Occult talus fractures can be easily misdiagnosed as simple ankle sprains, resulting in painful nonunion, arthrosis, avascular necrosis, and long-term disability. We present a case of ankle injury with medial talar fracture that was negative on plain radiography but was diagnosed with sonography. Sonography is a valuable tool in screening ankle sprains and may assist clinicians in diagnosing the nature of ankle injury, thus guiding the most appropriate therapeutic strategy.

Association Between Magnitude of Differential Blood Pressure Reduction and Secondary Stroke Prevention: A Meta-analysis and Meta-Regression.

Importance: The degree to which more intensive blood pressure reduction is better than less intensive for secondary stroke prevention has not been delineated. Objective: To perform a standard meta-analysis and a meta-regression of randomized clinical trials to evaluate the association of magnitude of differential blood pressure reduction and recurrent stroke in patients with stroke or transient ischemic attack (TIA). Data Sources: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 1980, to June 30, 2022. Study Selection: Randomized clinical trials that compared more intensive vs less intensive blood pressure lowering and recorded the outcome of recurrent stroke in patients with stroke or TIA. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. Risk ratio (RR) with 95% CI was used as a measure of the association of more intensive vs less intensive blood pressure lowering with primary and secondary outcomes. The univariate meta-regression analyses were conducted to evaluate a possible moderating effect of magnitude of differential systolic blood pressure (SBP) and diastolic blood pressure (DBP) reduction on the recurrent stroke and major cardiovascular events. Main Outcomes and Measures: The primary outcome was recurrent stroke and the lead secondary outcome was major cardiovascular events. Results: Ten randomized clinical trials comprising 40 710 patients (13 752 women [34%]; mean age, 65 years) with stroke or TIA were included for analysis. The mean duration of follow-up was 2.8 years (range, 1-4 years). Pooled results showed that more intensive treatment compared with less intensive was associated with a reduced risk of recurrent stroke in patients with stroke or TIA (absolute risk, 8.4% vs 10.1%; RR, 0.83; 95% CI, 0.78-0.88). Meta-regression showed that the magnitude of differential SBP and DBP reduction was associated with a lower risk of recurrent stroke in patients with stroke or TIA in a log-linear fashion (SBP: regression slope, -0.06; 95% CI, -0.08 to -0.03; DBP: regression slope, -0.17; 95% CI, -0.26 to -0.08). Similar results were found in the association between differential blood pressure lowering and major cardiovascular events. Conclusions and Relevance: More intensive blood pressure-lowering therapy might be associated with a reduced risk of recurrent stroke and major cardiovascular events. These results might support the use of more intensive blood pressure reduction for secondary prevention in patients with stroke or TIA.

Serotypes, virulence factors and multilocus sequence typing of Glaesserella parasuis from diseased pigs in Taiwan.

Background: Glaesserella parasuis (G. parasuis) belongs to the normal microbiota of the upper respiratory tract in the swine, but virulent strains can cause systemic infections commonly known as Glässer's disease that leads to significant economic loss in the swine industry. Fifteen serotypes of G. parasuis have been classified by gel immunodiffusion test while the molecular serotyping based on variation within the capsule loci have further improved the serotype determination of unidentified field strains. Serovar has been commonly used as an indicator of virulence; however, virulence can be significantly differ in the field isolates with the same serotype. To date, investigations of G. parasuis isolated in Taiwan regarding antimicrobial resistance, serotypes, genotypes and virulence factors remain unclear. Methods: A total of 276 G.parasuis field isolates were collected from 263 diseased pigs at the Animal Disease Diagnostic Center of National Chiayi University in Taiwan from January 2013 to July 2021. Putative virulence factors and serotypes of the isolates were identified by polymerase chain reaction (PCR) and antimicrobial susceptibility testing was performed by microbroth dilution assay. Additionally, the epidemiology of G. parasuis was characterized by multilocus sequence typing (MLST). Results: Serotype 4 (33.3%) and 5 (21.4%) were the most prevalent, followed by nontypable isolates (15.9%), serotype 13 (9.4%), 12 (6.5%), 14 (6.2%), 7 (3.3%), 1 (1.8%), 9 (1.1%), 11 (0.7%) and 6 (0.4%). Nine out of 10 putative virulence factors showed high positive rates, including group 1 vtaA (100%), fhuA (80.4%), hhdA (98.6%), hhdB (96.0%), sclB7 (99.6%), sclB11 (94.9%), nhaC (98.2%), HAPS_0254 (85.9%), and cirA (99.3%). According to the results of antimicrobial susceptibility testing, ceftiofur and florfenicol were highly susceptible (>90%). Notably, 68.8% isolates showed multidrug resistance. MLST revealed 16 new alleles and 67 new sequence types (STs). STs of these isolated G. parasuis strains were classified into three clonal complexes and 45 singletons by Based Upon Related Sequence Types (BURST) analysis. All the G. parasuis strains in PubMLST database, including strains from the diseased pigs in the study, were defined into two main clusters by Unweighted Pair Group Method with Arithmetic Mean (UPGMA). Most isolates in this study and virulent isolates from the database were mainly located in cluster 2, while cluster 1 included a high percentage of nasal isolates from asymptomatic carriers. In conclusion, this study provides current prevalence and antimicrobial susceptibility of G. parasuis in Taiwan, which can be used in clinical diagnosis and treatment of Glässer's disease.