Quantum correlations between light and the kilogram-mass mirrors of LIGO.

The measurement of minuscule forces and displacements with ever greater precision is inhibited by the Heisenberg uncertainty principle, which imposes a limit to the precision with which the position of an object can be measured continuously, known as the standard quantum limit1-4. When light is used as the probe, the standard quantum limit arises from the balance between the uncertainties of the photon radiation pressure applied to the object and of the photon number in the photoelectric detection. The only way to surpass the standard quantum limit is by introducing correlations between the position/momentum uncertainty of the object and the photon number/phase uncertainty of the light that it reflects5. Here we confirm experimentally the theoretical prediction5 that this type of quantum correlation is naturally produced in the Laser Interferometer Gravitational-wave Observatory (LIGO). We characterize and compare noise spectra taken without squeezing and with squeezed vacuum states injected at varying quadrature angles. After subtracting classical noise, our measurements show that the quantum mechanical uncertainties in the phases of the 200-kilowatt laser beams and in the positions of the 40-kilogram mirrors of the Advanced LIGO detectors yield a joint quantum uncertainty that is a factor of 1.4 (3 decibels) below the standard quantum limit. We anticipate that the use of quantum correlations will improve not only the observation of gravitational waves, but also more broadly future quantum noise-limited measurements.

Descriptive analysis of poisoning cases involving attention deficit hyperactivity disorder medications in Hong Kong.

INTRODUCTION: The number of poisoning cases involving attention deficit hyperactivity disorder (ADHD) medications has reportedly risen with their increased use. However, there is limited relevant evidence from Asia. We analysed the characteristics of poisoning events involving these medications in Hong Kong. METHODS: We retrieved data regarding ADHD medication-related poisoning cases from the Hong Kong Poison Information Centre and conducted a descriptive analysis of the demographic information and poisoning information including sources of cases, exposure reason, exposure location, and outcome. The HKPIC data were linked with the Hospital Authority Clinical Data Analysis and Reporting System (CDARS) via de-identified Accident and Emergency numbers of public hospitals to investigate clinical characteristics. We also retrieved ADHD medication prescription records from the CDARS, then compared trends between poisoning cases and ADHD medication use. RESULTS: We identified 72 poisoning cases involving ADHD medications between 2009 and 2019, of which approximately 70% occurred in the affected individual's residence; most were intentional poisoning events (65.3%). No statistically significant association was observed between ADHD medication prescription trends and poisoning events involving ADHD medications. Of the 66 cases (91.7%) successfully linked to CDARS, 40 (60.6%) occurred in individuals with ADHD (median age: 14 years); 26 (39.4%) occurred in individuals who lacked ADHD (median age: 33 years) but displayed higher rates of other mental disorders including depression and anxiety. CONCLUSION: No significant correlation was evident between ADHD medication prescriptions and poisoning events involving ADHD medications. However, medication management and caregiver education must be emphasised to prevent potential poisoning events.

Mechanically-induced osteophyte in the rat knee.

OBJECTIVES: Osteophytes are common anatomical signs of advanced osteoarthritis. It remains unclear whether they develop from physio-molecular, and/or mechanical stimuli. This study examined the effects of mechanical impact on the knee joint periosteum leading to osteophyte formation. DESIGN: Eighteen mature rats received one single impact load of 53 N (30 MPa) to the periosteum of the experimental medial femoral condyles. Contralateral knees were used as controls. Animals were sacrificed at 24 h, 3, 6 and 9 weeks post-impact. Distal femurs were harvested and prepared for histology. Hematoxylin and Eosin, and Masson's trichrome stained slides were examined by light microscopy. Nuclear density was quantified to assess the tissue reaction. RESULTS: 24 h: The synovium membrane, fibrous and cambium periosteum were damaged. Blood infiltration pooled in the impacted medial collateral ligament (MCL) region. Week 3: A cartilaginous tissue spur, chondrophyte, was found in every rat at the impacted site of the MCL. Chondrophytes were composed of fibrocartilage and cartilage matrix, with signs of cartilage mineralization and remodelling activity. Week 6: Chondrophytes presented signs of more advanced mineralisation, recognized as osteophytes. Week 9: Osteophytes appeared to be more mineralized with almost no cartilage tissue. CONCLUSIONS: Osteophytes can be induced with a single mechanical impact applied to the periosteum in rat knees. These data indicate that a moderate trauma to the periosteal layer of the joint may play a role in osteophyte development.

Frequency-Dependent Squeezing for Advanced LIGO.

The first detection of gravitational waves by the Laser Interferometer Gravitational-Wave Observatory (LIGO) in 2015 launched the era of gravitational-wave astronomy. The quest for gravitational-wave signals from objects that are fainter or farther away impels technological advances to realize ever more sensitive detectors. Since 2019, one advanced technique, the injection of squeezed states of light, is being used to improve the shot-noise limit to the sensitivity of the Advanced LIGO detectors, at frequencies above ∼50 Hz. Below this frequency, quantum backaction, in the form of radiation pressure induced motion of the mirrors, degrades the sensitivity. To simultaneously reduce shot noise at high frequencies and quantum radiation pressure noise at low frequencies requires a quantum noise filter cavity with low optical losses to rotate the squeezed quadrature as a function of frequency. We report on the observation of frequency-dependent squeezed quadrature rotation with rotation frequency of 30 Hz, using a 16-m-long filter cavity. A novel control scheme is developed for this frequency-dependent squeezed vacuum source, and the results presented here demonstrate that a low-loss filter cavity can achieve the squeezed quadrature rotation necessary for the next planned upgrade to Advanced LIGO, known as "A+."

Pre-hospital stroke screening and notification of patients with reperfusion-eligible acute ischaemic stroke using modified Face Arm Speech Time test.

OBJECTIVES: To investigate the effects of pre-hospital stroke screening and notification on reperfusion therapy for patients with acute ischaemic stroke. METHODS: Pre-hospital stroke screening criteria were established based on a modified version of the Face Arm Speech Time (FAST) test. Screening was performed during ambulance transport by emergency medical service (EMS) personnel who completed a 2-hour training session on stroke screening. Temporal trends affecting acute ischaemic stroke investigation and intervention were compared before and after implementation of the pre-hospital screening. RESULTS: From July 2018 to October 2019, 298 patients with suspected stroke were screened by EMS personnel during ambulance transport prior to hospital arrival. Of these 298 patients, 213 fulfilled the screening criteria, 166 were diagnosed with acute stroke, and 32 received reperfusion therapy. The onset-to-door time was shortened by more than 1.5 hours (100.6 min vs 197.6 min, P<0.001). The door-to-computed tomography time (25.6 min vs 32.0 min, P=0.021), door-to-needle time (49.2 min vs 70.1 min, P=0.003), and door-to-groin puncture time for intra-arterial mechanical thrombectomy (126.7 min vs 168.6 min, P=0.04) were significantly shortened after implementation of the pre-hospital screening and notification, compared with historical control data of patients admitted from January 2018 to June 2018, before implementation of the screening system. CONCLUSION: Implementation of pre-hospital stroke screening using criteria based on a modified version of the FAST test, together with pre-arrival notification, significantly shortened the door-to-reperfusion therapy time for patients with ischaemic stroke. Pre-hospital stroke screening during ambulance transport by EMS personnel who complete a 2-hour focused training session is effective for identifying reperfusion-eligible patients with stroke.

Quantum-Enhanced Advanced LIGO Detectors in the Era of Gravitational-Wave Astronomy.

The Laser Interferometer Gravitational Wave Observatory (LIGO) has been directly detecting gravitational waves from compact binary mergers since 2015. We report on the first use of squeezed vacuum states in the direct measurement of gravitational waves with the Advanced LIGO H1 and L1 detectors. This achievement is the culmination of decades of research to implement squeezed states in gravitational-wave detectors. During the ongoing O3 observation run, squeezed states are improving the sensitivity of the LIGO interferometers to signals above 50 Hz by up to 3 dB, thereby increasing the expected detection rate by 40% (H1) and 50% (L1).

Bone mineral density from early to middle adulthood in persons with Down syndrome.

BACKGROUND: While accelerated ageing is recognised among individuals with Down syndrome (DS), the trajectory of their bone health across adulthood remains poorly understood. METHODS: This study aimed to determine the age-related loss of bone mineral density (BMD) of the lumbar spine in 128 adults with DS aged 18 to 54 years compared with 723 counterparts without DS. RESULTS: Men and women with DS had lower level of BMD than counterparts without DS across age groups. Magnitude of decrement in BMD as reflected in the z-scores was similar between younger and older men with DS. Older women with DS, on the contrary, showed greater decrement in older ages especially in their fourth decade of life. Osteopenia and osteoporosis as defined using age-specific and gender-specific T-scores affected greater number of men with DS (38% and 25%) than women (17% and 17%) aged 40-49 years. CONCLUSIONS: Findings supported adults with DS, especially men, to have early bone mineral testing.

Developmental origins of pregnancy-induced cardiac changes: establishment of a novel model using the atrial natriuretic peptide gene-disrupted mice.

Pregnancy evokes many challenges on the maternal cardiovascular system that may unmask predispositions for future disease. This is particularly evident for women who develop pregnancy-related disorders, for example, pre-eclampsia and gestational diabetes or hypertension. Such pregnancy-related syndromes increase the risk for cardiovascular disease (CVD) postpartum. As a result, pregnancy has been termed as a cardiovascular stress test and an indicator or marker to predict the development of CVD later in life. In addition, pregnancy-related disorders impact the development of offspring also placing them at a higher risk for disease. Utilizing pregnancy as a physiological stressor, the current investigation sought to determine whether the cardiovascular system of offspring exposed to gestational hypertension in utero would respond adversely to the stress of pregnancy. Heterozygous atrial natriuretic peptide gene-disrupted (ANP+/-) offspring were generated by either crossing male wildtype ANP+/+ with female knockout ANP-/- to produce ANP+/-KO mice or crossing female wildtype ANP+/+ with male knockout ANP-/- to produce ANP+/-WT mice. To study the cardiovascular stress induced by pregnancy, female ANP+/-WT and ANP+/-KO mice were mated with male wildtype ANP+/+ mice to initiate pregnancy. Cardiac size and molecular expression of the renin-angiotensin (RAS) and natriuretic peptide systems (NPS) were compared between offspring groups. Our data demonstrate that gestational hypertension and lack of maternal ANP did not significantly impact the progression and regression of pregnancy-induced cardiac hypertrophy over gestation and postpartum in ANP+/- offspring. Additionally, the molecular cardiac expression of the RAS and NPS did not differ between offspring groups. Future investigation should assess potential differences in cardiac function and the impact of fetal-programming on offspring cardiovascular adaptations during pregnancy in more severe models of pregnancy-related hypertensive syndrome such as angiotensin II or isoproterenol infusion.

Fundamental movement skills and balance of children with Down syndrome.

BACKGROUND: Conclusive evidence supports the importance of fundamental movement skills (FMS) proficiency in promoting physical activity and countering obesity. In children with Down Syndrome (DS), FMS development is delayed, which has been suggested to be associated with balance deficits. This study therefore examined the relationship between FMS proficiency and balance ability in children with DS, with the aim of contributing evidence to programmes that address FMS delay. METHODS: Participants consisted of 20 children with DS (7.1 ± 2.9 years old) and an age-matched control group of children with typical development (7.25 ± 2.5 years). In the first part of the study, FMS (i.e. locomotor and object control) proficiency of the children was tested using the Test of Gross Motor Development-2. Balance ability was assessed using a force platform to measure centre of pressure average velocity (AV; mm/sec), path length (mm), medio-lateral standard deviation (mm) and antero-posterior standard deviation (mm). In the second part of the study, children with DS participated in 5 weeks of FMS training. FMS proficiency and balance ability were tested post-training and compared to pre-training scores. Verbal and visuo-spatial short-term memory capacities were measured at pre-training to verify the role of working memory in skill learning. RESULTS: FMS proficiency was associated with centre of pressure parameters in children with DS but not in children with typical development. After controlling for age, AV was found to predict significant variance in locomotor (R2  = 0.61, P < 0.001) and object control (R2  = 0.69, P < 0.001) scores. FMS proficiency and mastery improved after FMS training, as did AV, path length and antero-posterior standard deviation (all P < 0.05). Verbal and visuo-spatial short-term memory did not interact with the effects of training. CONCLUSIONS: Children with DS who have better balance ability tend to have more proficient FMS. Skill-specific training improved not only FMS sub-skills but static balance stability as well. Working memory did not play a role in the changes caused by skills training. Future research should examine the causal relationship between balance and FMS.

Ageing in individuals with intellectual disability: issues and concerns in Hong Kong.

INTRODUCTION: The increasing longevity of people with intellectual disability is testimony to the positive developments occurring in medical intervention. Nonetheless, early-onset age-related issues and concerns cause deterioration of their overall wellbeing. This paper aimed to explore the issues and concerns about individuals with intellectual disability as they age. METHODS: Articles that discussed people older than 30 years with an intellectual disability and those that identified ageing health issues and concerns were included. Only studies reported in English from 1996 to 2016 were included. We searched PubMed, Google Scholar, and Science Direct using the terms 'intellectual disability', 'ageing', 'cognitive impairment', 'health', and 'screening'. RESULTS: Apart from the early onset of age-related health problems, dementia is more likely to develop by the age of 40 years in individuals with intellectual disability. Geriatric services to people with intellectual disability, however, are only available for those aged 60 years and older. Cognitive instruments used for the general population are not suitable for people with intellectual disability because of floor effects. In Hong Kong, the Chinese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities is the only validated instrument for people with intellectual disability. The use of appropriate measurement tools to monitor the progression of age-related conditions in individuals with intellectual disability is of great value. CONCLUSIONS: Longitudinal assessment of cognition and function in people with intellectual disability is vital to enable early detection of significant deterioration. This allows for therapeutic intervention before substantial damage to the brain occurs such as dementia that hastens cognitive and functional decline.

Emergency thrombectomy for acute ischaemic stroke: current evidence, international guidelines, and local clinical practice.

Acute ischaemic stroke due to large vessel occlusion leads to grave neurological morbidity and mortality. Conventional intravenous thrombolysis is ineffective in achieving timely reperfusion in this group of patients. The publication of five positive randomised controlled trials of emergency thrombectomy for acute ischaemic stroke in 2015 provided strong evidence to support endovascular reperfusion therapy and represented a paradigm shift in acute stroke management. In this article, we review the current evidence and international guidelines, and report on the findings of a survey study of the clinical practice and opinions of local neurologists, neurosurgeons, and interventional radiologists in emergency thrombectomy. We also discuss the controversies around thrombectomy treatment, local experience, and suggestions to incorporate thrombectomy in acute stroke treatment.

Injuries and envenomation by exotic pets in Hong Kong.

INTRODUCTION: Exotic pets are increasingly popular in Hong Kong and include fish, amphibians, reptiles, and arthropods. Some of these exotic animals are venomous and may cause injuries to and envenomation of their owners. The clinical experience of emergency physicians in the management of injuries and envenomation by these exotic animals is limited. We reviewed the clinical features and outcomes of injuries and envenomation by exotic pets recorded by the Hong Kong Poison Information Centre. METHODS: We retrospectively retrieved and reviewed cases of injuries and envenomation by exotic pets recorded by the Hong Kong Poison Information Centre from 1 July 2008 to 31 March 2017. RESULTS: There were 15 reported cases of injuries and envenomation by exotic pets during the study period, including snakebite (n=6), fish sting (n=4), scorpion sting (n=2), lizard bite (n=2), and turtle bite (n=1). There were two cases of major effects from the envenomation, seven cases with moderate effects, and six cases with mild effects. All major effects were related to venomous snakebites. There were no mortalities. CONCLUSION: All human injuries from exotic pets arose from reptiles, scorpions, and fish. All cases of major envenomation were inflicted by snakes.

Persistence of risk factors associated with maternal cardiovascular disease following aberrant inflammation in rat pregnancy.

INTRODUCTION: Pre-eclampsia is associated with increased risk of subsequent cardiovascular and metabolic disease in the affected mothers. While aberrant inflammation contributes to the pathophysiology of pre-eclampsia, it is unclear whether maternal inflammation contributes to the increased risk of disease. Here, we determined the effect of aberrant inflammation in pregnancy on cardiovascular and metabolic disease risk factors. METHODS: Wistar rats were administered low doses of lipopolysaccharide (LPS) on gestational days (GD) 13.5-16.5 to induce inflammation. Controls included pregnant rats treated with saline and nonpregnant rats treated with LPS or saline. We previously showed that LPS-treated pregnant rats exhibit key features of pre-eclampsia. Echocardiographic parameters, heart weight, blood pressure, blood lipids, pulse-wave velocity, and glucose tolerance, were assessed at 16 weeks postpartum. Messenger RNA levels of transcription factors associated with cardiac growth were measured in left ventricular tissue; histone modifications and global DNA methylation were determined in hearts and livers at GD 17.5 and at 16 weeks postpartum. RESULTS: Compared with saline-treated pregnant rats and nonpregnant rats treated with LPS or saline, LPS-treated pregnant rats exhibited left ventricular hypertrophy and increased blood cholesterol and low-density lipoprotein levels at 16 weeks postdelivery. LPS-treated rats had increased left ventricular mRNA levels of hypertrophy-associated transcription factors at GD 17.5 and increased levels of modified histones in hearts and livers at GD 17.5 and 16 weeks postpartum. Other parameters remained unchanged. CONCLUSION: Aberrant inflammation during pregnancy results in persistent alterations in maternal physiological parameters and epigenetic modifications that could contribute to the pathophysiology of cardiovascular disease.

Mushroom poisoning in Hong Kong: a ten-year review.

INTRODUCTION: Mushroom poisoning is a cause of major mortality and morbidity all over the world. Although Hong Kong people consume a lot of mushrooms, there are only a few clinical studies and reviews of local mushroom poisoning. This study aimed to review the clinical characteristics, source, and outcome of mushroom poisoning incidences in Hong Kong. METHODS: This descriptive case series review was conducted by the Hong Kong Poison Information Centre and involved all cases of mushroom poisoning reported to the Centre from 1 July 2005 to 30 June 2015. RESULTS: Overall, 67 cases of mushroom poisoning were reported. Of these, 60 (90%) cases presented with gastrointestinal symptoms of vomiting, diarrhoea, and abdominal pain. Gastrointestinal symptoms were early onset (<6 hours post-ingestion) and not severe in 53 patients and all recovered after symptomatic treatment and a short duration of hospital care. Gastrointestinal symptoms, however, were of late onset (≥6 hours post-ingestion) in seven patients; these were life-threatening cases of amatoxin poisoning. In all cases, the poisonous mushroom had been picked from the wild. Three cases were imported from other countries, and four collected and consumed the amatoxin-containing mushrooms in Hong Kong. Of the seven cases of amatoxin poisoning, six were critically ill, of whom one died and two required liver transplantation. There was one confirmed case of hallucinogenic mushroom poisoning caused by Tylopilus nigerrimus after consumption of a commercial mushroom product. A number of poisoning incidences involved the consumption of wild-harvested dried porcini purchased in the market. CONCLUSION: Most cases of mushroom poisoning in Hong Kong presented with gastrointestinal symptoms and followed a benign course. Life-threatening cases of amatoxin poisoning are occasionally seen. Doctors should consider this diagnosis in patients who present with gastrointestinal symptoms that begin 6 hours or more after mushroom consumption.

Onset and Regression of Pregnancy-Induced Cardiac Alterations in Gestationally Hypertensive Mice: The Role of the Natriuretic Peptide System.

Pregnancy induces cardiovascular adaptations in response to increased volume overload. Aside from the hemodynamic changes that occur during pregnancy, the maternal heart also undergoes structural changes. However, cardiac modulation in pregnancies complicated by gestational hypertension is incompletely understood. The objectives of the current investigation were to determine the role of the natriuretic peptide (NP) system in pregnancy and to assess alterations in pregnancy-induced cardiac hypertrophy between gestationally hypertensive and normotensive dams. Previously we have shown that mice lacking the expression of atrial NP (ANP; ANP(-/-)) exhibit a gestational hypertensive phenotype. In the current study, female ANP(+/+) and ANP(-/-) mice were mated with ANP(+/+) males. Changes in cardiac size and weight were evaluated across pregnancy at Gestational Days 15.5 and 17.5 and Postnatal Days 7, 14, and 28. Nonpregnant mice were used as controls. Physical measurement recordings and histological analyses demonstrated peak cardiac hypertrophy occurring at 14 days postpartum in both ANP(+/+) and ANP(-/-) dams with little to no change during pregnancy. Additionally, left ventricular expression of the renin-angiotensin system (RAS) and NP system was quantified by real-time quantitative polymerase chain reaction. Up-regulation of Agt and AT(1a) genes was observed late in pregnancy, while Nppa and Nppb genes were significantly up-regulated postpartum. Our data suggest that pregnancy-induced cardiac hypertrophy may be influenced by the RAS throughout gestation and by the NP system postpartum. Further investigations are required to gain a complete understanding of the mechanistic aspects of pregnancy-induced cardiac hypertrophy.

Placental growth factor influences maternal cardiovascular adaptation to pregnancy in mice.

In healthy human pregnancies, placental growth factor (PGF) concentrations rise in maternal plasma during early gestation, peak over Weeks 26-30, then decline. Because PGF in nongravid subjects participates in protection against and recovery from cardiac pathologies, we asked if PGF contributes to pregnancy-induced maternal cardiovascular adaptations. Cardiovascular function and structure were evaluated in virgin, pregnant, and postpartum C56BL/6-Pgf(-) (/) (-) (Pgf(-) (/) (-)) and C57BL/6-Pgf(+/+) (B6) mice using plethysmography, ultrasound, quantitative PCR, and cardiac and renal histology. Pgf(-/-) females had higher systolic blood pressure in early and late pregnancy but an extended, abnormal midpregnancy interval of depressed systolic pressure. Pgf(-/-) cardiac output was lower than gestation day (gd)-matched B6 after midpregnancy. While Pgf(-) (/) (-) left ventricular mass was greater than B6, only B6 showed the expected gestational gain in left ventricular mass. Expression of vasoactive genes in the left ventricle differed at gd8 with elevated Nos expression in Pgf(-) (/) (-) but not at gd14. By gd16, Pgf(-) (/) (-) kidneys were hypertrophic and had glomerular pathology. This study documents for the first time that PGF is associated with the systemic maternal cardiovascular adaptations to pregnancy.

Adolescent testosterone, muscle mass and glucose metabolism: evidence from the 'Children of 1997' birth cohort in Hong Kong.

AIMS: Diabetes rates are high in Asia despite relatively low rates of obesity, which might be related to lower muscle mass. Muscle mass plays an important role in glucose metabolism. Peak muscle mass is obtained in late adolescence. We tested the hypothesis that pubertal testosterone is negatively associated with glucose metabolism mediated by muscle mass. METHODS: Participants aged 15 years (278 boys and 223 girls) were recruited from the Hong Kong's 'Children of 1997' birth cohort in 2012. Multivariable linear regression with multiple imputation and inverse probability weighting was used to examine the adjusted associations of pubertal testosterone with skeletal muscle index, body fat percentage, fasting glucose, insulin and homeostasis model of assessment - insulin resistance. RESULTS: Total testosterone was negatively associated with fasting glucose (-0.008, 95% confidence interval -0.015 to -0.002), insulin (-0.43, 95% confidence interval -0.56 to -0.30) and insulin and homeostasis model of assessment - insulin resistance (-0.09, 95% confidence interval -0.12 to -0.06) adjusted for sex, birth weight, highest parental education, mother's place of birth and physical activity. These associations were attenuated by additional adjustment for skeletal mass index or body fat percentage. CONCLUSIONS: Adolescent glucose metabolism may be influenced by testosterone, perhaps partially via skeletal muscle mass.

Molecular adaptations in vasoactive systems during acute stroke in salt-induced hypertension.

Investigations regarding hypertension and dietary sodium, both factors that influence stroke risk, have previously been limited to using genetically disparate treatment and control groups, namely the stroke-prone, spontaneously hypertensive rat and Wistar-Kyoto rat. In this investigation, we have characterized and compared cerebral vasoactive system adaptations following stroke in genetically identical, salt-induced hypertensive, and normotensive control mice. Briefly, ANP(+/-) (C57BJ/6 × SV129 background) mice were fed chow containing either 0.8% NaCl (NS) or 8.0% NaCl (HS) for 7 weeks. Transient cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Infarct volumes were measured 24-h post-reperfusion and the mRNA expression of five major vasoactive systems was characterized using qPCR. Along with previous publications, our data validate a salt-induced hypertensive state in ANP(+/-) mice fed HS chow as they displayed left ventricular hypertrophy, increased systolic blood pressure, and increased urinary sodium excretion. Following MCAO, mice fed HS exhibited larger infarct volumes than their dietary counterparts. In addition, significant up-regulation in Et-1 and Nos3 mRNA expression in response to salt and stroke suggests implications with increased cerebral damage in this group. In conclusion, our data demonstrate increased cerebral susceptibility to stroke in salt-induced hypertensive mice. More importantly, however, we have characterized a novel method of investigating hypertension and stroke with the use of genetically identical treatment and control groups. This is the first investigation in which genetic confounding variables have been eliminated.

Maternal hypertension programs increased cerebral tissue damage following stroke in adult offspring.

The maternal system is challenged with many physiological changes throughout pregnancy to prepare the body to meet the metabolic needs of the fetus and for delivery. Many pregnancies, however, are faced with pathological stressors or complications that significantly impact maternal health. A shift in this paradigm is now beginning to investigate the implication of pregnancy complications on the fetus and their continued influence on offspring disease risk into adulthood. In this investigation, we sought to determine whether maternal hypertension during pregnancy alters the cerebral response of adult offspring to acute ischemic stroke. Atrial natriuretic peptide gene-disrupted (ANP(-/-)) mothers exhibit chronic hypertension that escalates during pregnancy. Through comparison of heterozygote offspring born from either normotensive (ANP(+/-WT)) or hypertensive (ANP(+/-KO)) mothers, we have demonstrated that offspring exposed to maternal hypertension exhibit larger cerebral infarct volumes following middle cerebral artery occlusion. Observation of equal baseline cardiovascular measures, cerebrovascular structure, and cerebral blood volumes between heterozygote offspring suggests no added influences on offspring that would contribute to adverse cerebral response post-stroke. Cerebral mRNA expression of endothelin and nitric oxide synthase vasoactive systems demonstrated up-regulation of Et-1 and Nos3 in ANP(+/-KO) mice and thus an enhanced acute vascular response compared to ANP(+/-WT) counterparts. Gene expression of Na(+)/K(+) ATPase channel isoforms, Atp1a1, Atp1a3, and Atp1b1, displayed no significant differences. These investigations are the first to demonstrate a fetal programming effect between maternal hypertension and adult offspring stroke outcome. Further mechanistic studies are required to complement epidemiological evidence of this phenomenon in the literature.