Antihypertensive Agents and Incident Alzheimer's Disease: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Hypertension is a recognized risk factor for dementia. However, evidence for using antihypertensive agents to reduce the risk of Alzheimer's disease in people with hypertension is inconclusive. OBJECTIVE: To examine the association between antihypertensive agents and the incidence of Alzheimer's disease in adults with hypertension and normal cognition. DESIGN: We conducted a systemic review and performed meta-analyses using Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Web of science and Scopus, from inception to 18th February 2022. SETTING: Cohort and case-control studies. PARTICIPANTS: Adults ≥ 40 years with hypertension and normal cognition. INTERVENTION: Antihypertensive agents. MEASUREMENTS: We performed two separate meta-analyses, pooling the adjusted relative risk (RR) of non-antihypertensive comparator and antihypertensive comparator study design. RESULTS: We included nine studies, totalling 1,527,410 individuals. Meta-analysis of non-antihypertensive user comparator studies found that the use of antihypertensive agents is associated with a reduced risk of incident Alzheimer's disease (RR= 0.94, 95% CI 0.90-0.99; p=0.01). Meta-analysis of antihypertensive comparator studies found evidence that angiotensin II receptor blocker users are associated with a reduction in the risk of Alzheimer's disease compared to other antihypertensive agents (RR= 0.78, 95% CI 0.68-0.88; p< 0.001). CONCLUSION: Our review provides evidence that the use of antihypertensive agents is associated with a lower incidence of Alzheimer's disease. The use of angiotensin II receptor blockers may provide the most benefit among antihypertensive agents. Lowering raised blood pressure may not be the only mechanism for cognitive protection and further investigation of the effects of angiotensin II on cognition is indicated.

Patient acceptance of transvaginal sonographic endometrial thickness assessment compared with hysteroscopy and biopsy for exclusion of endometrial cancer in cases of postmenopausal bleeding.

INTRODUCTION: Available examinations for women with postmenopausal bleeding include transvaginal sonography to measure endometrial thickness (TVS-ET), and invasive endometrial assessment using hysteroscopy/endometrial biopsy. However, selection of the examination method seldom involves consideration of patient preferences. The aim of this study was to examine patient preferences for the method used to investigate postmenopausal bleeding. METHODS: Women were asked to complete an interviewer-administered structured survey before they underwent clinical investigations at a university gynaecology unit from June 2016 to June 2017. Using the standard gamble approach, women were asked to choose between invasive assessment by hysteroscopy/endometrial biopsy (gold standard) or TVS-ET with a risk of missing endometrial cancer. The risk of missing endometrial cancer during TVS-ET was varied until each woman was indifferent to either option. RESULTS: The median detection rate for endometrial cancer required using TVS-ET was 95% (interquartile range=80%-99.9%). In total, 200 women completed the survey, and 77 (38.5%) women required TVS-ET to have a 99.9% detection rate for endometrial cancer. Prior hysteroscopy experience was the only factor that influenced the women's decisions: a significantly higher detection rate was required by this patient group than by patients without previous hysteroscopy experience (P=0.047). CONCLUSION: A substantial proportion of women would accept TVS-ET alone for the investigation of postmenopausal bleeding. In the era of patientcentred care, clinicians should incorporate patient preferences and enable women to make informed choices concerning the management of postmenopausal bleeding.

p53- and p73-independent activation of TIGAR expression in vivo.

TIGAR (TP53-induced glycolysis and apoptosis regulator) functions as a fructose-2,6-bisphosphatase and its expression results in a dampening of the glycolytic pathway, while increasing antioxidant capacity by increasing NADPH and GSH levels. In addition to being a p53 target, p53-independent expression of TIGAR is also seen in many human cancer cell lines that lack wild-type p53. Although human TIGAR expression can be induced by p53, TAp63 and TAp73, mouse TIGAR is less responsive to the p53 family members and basal levels of TIGAR expression does not depend on p53 or TAp73 expression in most mouse tissues in vivo. Although mouse TIGAR expression is clearly induced in the intestines of mice following DNA-damaging stress such as ionising radiation, this is also not dependent on p53 or TAp73.

SBS-managed high-peak-power nanosecond-pulse fiber-based master oscillator power amplifier.

We report on a compactly packaged Yb-doped fiber-based laser architecture featuring an actively pulse controlled, single-longitudinal-mode seeder and multistage amplifier chain terminated by a "folded" rod-type photonic crystal fiber. In this laser source, stimulated Brillouin scattering (SBS) is the power-limiting factor, but is managed by phase modulating the seeder with a pseudo-random noise signal. Pulse energy/peak power of ~2 mJ/1.5 MW at 10 kHz repetition rate are thus obtained within ~1.55 ns pulses of peak spectral brightness >20 kW cm(-2) sr(-1) Hz(-1).

Control of glycolysis through regulation of PFK1: old friends and recent additions.

Regulation of glucose metabolism is a crucial aspect of cell physiology in normal and disease conditions. Many regulatory events are involved in determining the metabolic fate of glucose and the pathways into which it is directed. The first reaction that commits glucose to the glycolytic pathway is catalyzed by the enzyme phosphofructokinase-1 (PFK-1) and is tightly regulated. One of the most potent activators of PFK-1 is fructose 2,6 bisphosphate (F2,6BP) and its cellular levels are correlated with glycolytic flux. F2,6BP is synthesized and degraded by a family of bifunctional enzymes-the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB). The interplay among F2,6BP levels, the enzymes that generate and degrade it, and PFK-1 activity has important consequences for several different aspects of cell metabolism as well as for systemic metabolic conditions. TIGAR, a recently identified F2,6 bisphosphatase (F2,6BPase), could also contribute to this complexity and participate in shaping the metabolic profile of the cell.

Coherent combination of high-power, zigzag slab lasers.

We demonstrate a scalable architecture for a high-power, high-brightness, solid-state laser based on coherent combinations of master oscillator power amplifier chains. A common master oscillator injects a sequence of multikilowatt Nd:YAG zigzag slab amplifiers. Adaptive optics correct the wavefront of each amplified beamlet. The beamlets are tiled side by side and actively phase locked to form a single output beam. The laser produces 19 kW with beam quality <2x diffraction limited. To the best of our knowledge, this is the brightest cw solid-state laser demonstrated to date.

Silver thiogallate, singly resonant optical parametric oscillator pumped by a continuous-wave mode-locked Nd:YAG laser.

We describe a silver thiogallate (AgGaS(2)) singly resonant optical parametric oscillator (OPO), synchronously pumped by a continuous-wave actively mode-locked Nd:YAG laser. The OPO is operated with a signal wavelength near 1.319 microm and an idler wavelength near 5.505 microm. At optimum output coupling, 100 mW of useful signal power and 6 mW of idler power are generated from 625 mW of pump power. The pump is mechanically chopped at a 32:1 duty cycle to prevent thermal lensing of the AgGaS(2) crystals. Pump depletion is as high as 63%. The signal has pulse widths ranging from 45 to 80 ps and spectral widths ranging from below 0.1 to 0.3 nm. The OPO signal can oscillate over a 2-mm range of round-trip cavity-length mismatch.

Frequency upconversion by phase-matched sum-frequency generation in an optical parametric oscillator.

We report the generation of 0.589-,microm radiation from mixing the pump at 1.064 ,microm and the signal at 1.319 microm of a singly resonant, synchronously pumped AgGaS(2) optical parametric oscillator. A KTP crystal is used for the sum-frequency generation (SFG). Both extracavity and intracavity SFG is demonstrated, with overall conversion efficiencies of 3.5% and 10.5%, respectively. Near-transform-limited pulses of less than 50 ps are generated from 100-ps pulses. With a limited available peak pump power, both spatial orderings of the KTP and the AgGaS(2) crystals for intracavity SFG produce similar conversion efficiency and outputs of similar pulse duration, spectral width, and stability.

Noncritical matching of cavity lengths for uninterrupted additive-pulse mode locking of a cw Nd:YLF laser.

Stable interferometrically insensitive operation of an additive-pulse mode-locked Nd:YLF laser is observed over 4.8 microm of continuous detuning of the cavity lengths. This phenomenon continuously persists over 250 microm of coarse cavity-length detuning. Outside this range interferometric mode locking typically associated with additive-pulse mode locking is observed for detuning lengths of over 1 mm. The external cavity of the system consists of a multimode fiber whose four possible second-order proper modes are all excited. The underlying mechanism is a slow process with response times in the subhertz and hertz regions.

Fiberoptic colonoscopic study of experimental chemical colitis.

Acute diffuse chemical colitis was produced in rats with a high degree of reproducibility by the intracolonic administration of 10% acetic acid. The evolution and progression of this colitis was followed by performing serial fiberoptic colonoscopy using a needlescope and biopsy. Hyperemia appeared at 10 hours and ulcerations appeared at 24 hours in acetic acid-treated animals. After 3 days, the ulcers were covered with a yellowish exudate. At 8 weeks there was endoscopic and histologic healing of the lesions. No changes occurred in the saline-treated animals. Concomitant topical applications of epsilon-aminocaproic acid protected against acetic acid-induced injury.