Pulsar emission amplified and resolved by plasma lensing in an eclipsing binary.

Radio pulsars scintillate because their emission travels through the ionized interstellar medium along multiple paths, which interfere with each other. It has long been realized that, independent of their nature, the regions responsible for the scintillation could be used as 'interstellar lenses' to localize pulsar emission regions1,2. Most such lenses, however, resolve emission components only marginally, limiting results to statistical inferences and detections of small positional shifts3-5. As lenses situated close to their source offer better resolution, it should be easier to resolve emission regions of pulsars located in high-density environments such as supernova remnants 6 or binaries in which the pulsar's companion has an ionized outflow. Here we report observations of extreme plasma lensing in the 'black widow' pulsar, B1957+20, near the phase in its 9.2-hour orbit at which its emission is eclipsed by its companion's outflow7-9. During the lensing events, the observed radio flux is enhanced by factors of up to 70-80 at specific frequencies. The strongest events clearly resolve the emission regions: they affect the narrow main pulse and parts of the wider interpulse differently. We show that the events arise naturally from density fluctuations in the outer regions of the outflow, and we infer a resolution of our lenses that is comparable to the pulsar's radius, about 10 kilometres. Furthermore, the distinct frequency structures imparted by the lensing are reminiscent of what is observed for the repeating fast radio burst FRB 121102, providing observational support for the idea that this source is observed through, and thus at times strongly magnified by, plasma lenses 10 .

Orthodontic pain with fixed appliances and clear aligners: A 6-month comparison.

INTRODUCTION: This prospective study compared pain perception, intensity, and analgesic use among patients treated with fixed appliances (FAs) and clear aligners (CAs) over 6 months. METHODS: Digital surveys were collected from 87 adult patients treated with CA or FA from 2 orthodontic offices. The 7-item survey was sent at 3-time points (preappointment, 2-day postappointment, and 7-day postappointment) for each appointment. Wilcoxon, t test, and Fisher exact chi-square tests were performed with significance set at 0.05. RESULTS: The FA group had a higher rate and intensity of pain 2 days after the second, third, and fifth appointments (P <0.030). At 7 days postappointment, the FA group had a higher rate and intensity of pain for the first and fifth appointments. Dull pain was reported the most in both groups, with a proportion of FA patients reporting throbbing (31%) or sharp (20%) pain (P = 0.035) at 2 days postappointment. The CA group reported the most pain at rest, whereas the FA group reported chewing as the most painful (P = 0.002). The FA group had a higher rate of analgesic consumption after the first appointment (P = 0.037). CONCLUSIONS: Both the FA and CA groups experienced similar rates and intensities of pain 2 days after the delivery of appliances at the first appointment. Although CA pain intensity remained minimal, FA pain peaked 2 days postappointment whenever a new orthodontic stimulus was introduced and remained elevated 7 days postappointment when that stimulus was a new archwire material.

Peripartum Cardiomyopathy is Associated With Abnormalities of Myocardial Deformation and Late Gadolinium Enhancement.

Purpose: Peripartum cardiomyopathy (PPCM) affects women in late pregnancy and postpartum. Cardiovascular magnetic resonance (CMR) can contribute to PPCM diagnosis and management. We explored CMR findings in PPCM, including myocardial strain and late gadolinium enhancement (LGE) patterns. Materials and Methods: This retrospective single-centre study included patients with PPCM who underwent CMR from 2010 to 2018. Exclusions were other cardiomyopathy causes. CMR parameters, including ventricular function, LGE, and myocardial strain, were compared between the PPCM group and healthy controls. Transthoracic echocardiographic data were reviewed to assess functional improvement in PPCM patients. Results: Thirty-two women with PPCM (mean age 42 ± 6 years) and 26 controls (mean age 43 ± 14 years) were included. PPCM patients had significantly lower left ventricular (LV) ejection fractions (median 37.5% vs 60.5%, P < .001), higher LV end-diastolic volumes (median 108 ml/m² vs 76 ml/m², P < .001), and reduced global LV strain compared to controls. Eighteen PPCM patients (58%) had non-ischaemic pattern LGE, with no LGE in controls besides hingepoint LGE (23%). LGE was most prevalent in the basal and mid anteroseptum. LGE patterns included linear mid-wall, subepicardial, and right ventricular side of the septum. Twenty-four patients (92%) showed improvement in LVEF at follow-up echocardiogram (mean LVEF 28% ± 1.9% at diagnosis and 45% ± 3% at follow-up, P < .001). Conclusion: We identified a non-ischaemic pattern LGE that is nonspecific in isolation but could suggest PPCM in the correct clinical context along with abnormal CMR strain values. Future studies should evaluate the clinical application of these findings to facilitate earlier diagnosis and enhance management.

Clinical characteristics of unvaccinated or incompletely vaccinated children with neurological manifestations due to SARS-CoV-2 Omicron infection.

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.

Association of Pectus Excavatum With Ventricular Remodelling and Mitral Valve Abnormalities in Marfan Syndrome.

Background: Marfan syndrome (MFS) is an inherited connective tissue disorder. Pectus excavatum (PEX) is common in MFS. The purpose was to evaluate the association of PEX with cardiovascular manifestations of MFS, biventricular size and function. Methods: MFS adults undergoing cardiac MRI were retrospectively evaluated. Exclusion criteria were incomplete cardiac MRI, significant artifacts, co-existent ischaemic or congenital heart disease. Haller Index (HI) ≥3.25 classified patients as PEX positive (PEX+) and PEX negative (PEX-). Cardiac MRI analysis included assessment of mitral valve prolapse (MVP), mitral annular disjunction (MAD), biventricular volumetry and aortic dimensions. Results: 212 MFS patients were included, 76 PEX+ and 136 PEX- (HI 8.3 ± 15.2 vs 2.3 ± 0.5, P < .001). PEX+ were younger (33.4 ± 12.0 vs 38.1 ± 14.3 years, P = .02) and similar in sex distribution (55% vs 63% male, P = .26) compared to PEX-. MVP and MAD were more frequent in PEX+ vs PEX- (43/76 [57%] vs 37/136 [27%], P < .001; 44/76 [58%] vs 50/136[37%], P = .003, respectively). PEX+ had higher right ventricular end-diastolic and end-systolic volumes (RVEDVi 92 ± 17mL/m2 vs 84 ± 22mL/m2, P = .04; RVESVi 44 ± 10 mL/m2 vs 39 ± 14 mL/m2, P = .02), lower RV ejection fraction (RVEF 52 ± 5% vs 55 ± 6%, P = .01) compared to PEX-. Left ventricular (LV) volumes, LVEF and aortic dimensions were similar. Conclusion: MFS adults with PEX have higher frequency of cardiac manifestations including MV abnormalities, increased RV volumes and lower RVEF compared to those without PEX. Awareness of this association is important for all radiologists who interpret aortic CT or MRI, where HI can be easily measured. PEX in MFS may suggest more severe disease expression necessitating careful screening for MV abnormalities and outcomes surveillance.

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination.

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67-29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12-9.51) and 21.22 (95% CI, 13.78-32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38-12.53) and 37.32 (95% CI, 26.98-51.25) per 100 000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.

Myocardial Injury Pattern at MRI in COVID-19 Vaccine-Associated Myocarditis.

Background There are limited data on the pattern and severity of myocardial injury in patients with COVID-19 vaccination-associated myocarditis. Purpose To describe myocardial injury following COVID-19 vaccination and to compare these findings to other causes of myocarditis. Materials and Methods In this retrospective cohort study, consecutive adult patients with myocarditis with at least one T1-based and at least one T2-based abnormality at cardiac MRI performed at a tertiary referral hospital from December 2019 to November 2021 were included. Patients were classified into one of three groups: myocarditis following COVID-19 vaccination, myocarditis following COVID-19 illness, and other myocarditis not associated with COVID-19 vaccination or illness. Results Of the 92 included patients, 21 (23%) had myocarditis following COVID-19 vaccination (mean age, 31 years ± 14 [SD]; 17 men; messenger RNA-1273 in 12 [57%] and BNT162b2 in nine [43%]). Ten of 92 (11%) patients had myocarditis following COVID-19 illness (mean age, 51 years ± 14; three men) and 61 of 92 (66%) patients had other myocarditis (mean age, 44 years ± 18; 36 men). MRI findings in the 21 patients with vaccine-associated myocarditis included late gadolinium enhancement (LGE) in 17 patients (81%) and left ventricular dysfunction in six (29%). Compared with other causes of myocarditis, patients with vaccine-associated myocarditis had a higher left ventricular ejection fraction and less extensive LGE, even after controlling for age, sex, and time from symptom onset to MRI. The most frequent location of LGE in all groups was subepicardial at the basal inferolateral wall, although septal involvement was less common in vaccine-associated myocarditis. At short-term follow-up (median, 22 days [IQR, 7-48 days]), all patients with vaccine-associated myocarditis were asymptomatic with no adverse events. Conclusion Cardiac MRI demonstrated a similar pattern of myocardial injury in vaccine-associated myocarditis compared with other causes, although abnormalities were less severe, with less frequent septal involvement and no adverse events over the short-term follow-up. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Raman and Neubauer in this issue.

TRPV1 Contributes to Modulate the Nitric Oxide Pathway and Oxidative Stress in the Isolated and Perfused Rat Heart during Ischemia and Reperfusion.

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here, we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the control of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats perfused according to the Langendorff technique were used to study the effects of an agonist of TRPV1, capsaicin (CS), an antagonist, capsazepine (CZ), and their combination CZ+CS. The hearts were subjected to three conditions: (1) control, (2) ischemia and (3) ischemia-reperfusion. We determined cardiac mechanical activity and the levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue after administration of CS, CZ and CZ+CS. Western blots were used to study the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac mechanical activity and elevating the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

Delineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population.

BACKGROUND: Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs. METHODS: We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤ 1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines. RESULTS: Sixty-six patients with pre-biopsy MDC scores of 3-8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n = 3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC. CONCLUSIONS: We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant, was a founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.

Prevalence and risk factors for sessile serrated lesions in an average risk colorectal cancer screening population.

BACKGROUND AND AIM: The reported prevalence and risk factors for sessile serrated lesions (SSLs) show significant variation. We aimed to specifically study the prevalence and potential risk factors of SSLs in an average risk colorectal cancer (CRC) screening population of Chinese subjects. METHODS: This is a case-control study of prospectively collected data from a territory-wide colorectal screening program in Hong Kong. Information on risk factors was obtained from questionnaires completed prior to screening colonoscopy. We compared subjects with SSLs against controls without these lesions to identify potential risk factors using multivariable logistic regression. RESULTS: Of 12 039 asymptomatic screening subjects, 6011 subjects received a screening colonoscopy with 2214 subjects (36.8%) having conventional adenomas, 486 subjects (8.1%) having hyperplastic polyps, and 85 subjects (1.4%) having SSLs only. Of these subjects, three had synchronous advanced adenomas and were excluded from the analysis. More than 60% of these lesions were in the proximal colon. We compared these 82 subjects with SSLs only and 3226 controls without any polyps. After multivariable logistic regression, age ≥ 66 years, smoking, and diabetes mellitus (DM) were significant independent risk factors for SSLs. CONCLUSION: In this study, we report the prevalence of SSLs to be 1.4%. Age ≥ 66 years, smoking, and DM were independent risk factors for these lesions. Our findings provide relevant new data that should be taken into consideration when designing region-specific surveillance programs for SSLs with the ultimate goal of reducing the risk of CRC.

Effects of the ecto-ATPase apyrase on microglial ramification and surveillance reflect cell depolarization, not ATP depletion.

Microglia, the brain's innate immune cells, have highly motile processes which constantly survey the brain to detect infection, remove dying cells, and prune synapses during brain development. ATP released by tissue damage is known to attract microglial processes, but it is controversial whether an ambient level of ATP is needed to promote constant microglial surveillance in the normal brain. Applying the ATPase apyrase, an enzyme which hydrolyzes ATP and ADP, reduces microglial process ramification and surveillance, suggesting that ambient ATP/ADP maintains microglial surveillance. However, attempting to raise the level of ATP/ADP by blocking the endogenous ecto-ATPase (termed NTPDase1/CD39), which also hydrolyzes ATP/ADP, does not affect the cells' ramification or surveillance, nor their membrane currents, which respond to even small rises of extracellular [ATP] or [ADP] with the activation of K+ channels. This indicates a lack of detectable ambient ATP/ADP and ecto-ATPase activity, contradicting the results with apyrase. We resolve this contradiction by demonstrating that contamination of commercially available apyrase by a high K+ concentration reduces ramification and surveillance by depolarizing microglia. Exposure to the same K+ concentration (without apyrase added) reduced ramification and surveillance as with apyrase. Dialysis of apyrase to remove K+ retained its ATP-hydrolyzing activity but abolished the microglial depolarization and decrease of ramification produced by the undialyzed enzyme. Thus, applying apyrase affects microglia by an action independent of ATP, and no ambient purinergic signaling is required to maintain microglial ramification and surveillance. These results also have implications for hundreds of prior studies that employed apyrase to hydrolyze ATP/ADP.

P2Y13 receptors regulate microglial morphology, surveillance, and resting levels of interleukin 1ß release.

Microglia sense their environment using an array of membrane receptors. While P2Y12 receptors are known to play a key role in targeting directed motility of microglial processes to sites of damage where ATP/ADP is released, little is known about the role of P2Y13 , which transcriptome data suggest is the second most expressed neurotransmitter receptor in microglia. We show that, in patch-clamp recordings in acute brain slices from mice lacking P2Y13 receptors, the THIK-1 K+ current density evoked by ADP activating P2Y12 receptors was increased by ~50%. This increase suggested that the P2Y12 -dependent chemotaxis response should be potentiated; however, the time needed for P2Y12 -mediated convergence of microglial processes onto an ADP-filled pipette or to a laser ablation was longer in the P2Y13 KO. Anatomical analysis showed that the density of microglia was unchanged, but that they were less ramified with a shorter process length in the P2Y13 KO. Thus, chemotactic processes had to grow further and so arrived later at the target, and brain surveillance was reduced by ~30% in the knock-out. Blocking P2Y12 receptors in brain slices from P2Y13 KO mice did not affect surveillance, demonstrating that tonic activation of these high-affinity receptors is not needed for surveillance. Strikingly, baseline interleukin-1ß release was increased fivefold while release evoked by LPS and ATP was not affected in the P2Y13 KO, and microglia in intact P2Y13 KO brains were not detectably activated. Thus, P2Y13 receptors play a role different from that of their close relative P2Y12 in regulating microglial morphology and function.

Trauma Teams That Train as One Work as One: Invasive Procedure Training in Residency Education.

BACKGROUND: Invasive surgical procedures occur infrequently in an emergency department setting; however, procedural competence is expected from trauma residents. Emergent procedures are challenging to train in a formal manner because of the urgent nature when they present. To supplement education, new and creative teaching tools such as simulation and multidisciplinary training are being used. Our study organized a multidisciplinary simulated learning workshop with surgery and emergency medicine residents for invasive, emergent procedures. MATERIALS AND METHODS: In total, 14 surgical and 36 emergency medicine residents at our institution participated in a simulated learning experience. Ten workshops were organized, with six to seven residents participating in each session. Using a human cadaveric model, all residents were taught by senior-level residents and attendings from both specialties on how to perform uncommonly or anatomically challenging emergent invasive procedures. A pre- and post-laboratory survey was completed by all the residents to assess confidence in performing each of the 13 procedures. RESULTS: All residents (N = 50), who participated in the study, completed pre- and post-laboratory surveys. Comparison of the pre- and post-laboratory confidence levels indicated significant increases in confidence in performing all procedures. Residents stated that this multidisciplinary approach to education in a controlled setting was helpful and fostered a collaborative relationship between both specialties. CONCLUSIONS: Although some surgical procedures remain uncommon in the emergency department, competency is nevertheless expected for appropriate patient care. Using a collaborative simulation-based cadaver laboratory to teach emergent procedures significantly improved residents' confidence while concurrently fostering professional relationships.

A Subject-Specific Approach to Detect Fatigue-Related Changes in Spine Motion Using Wearable Sensors.

An objective method to detect muscle fatigue-related kinematic changes may reduce workplace injuries. However, heterogeneous responses to muscle fatigue suggest that subject-specific analyses are necessary. The objectives of this study were to: (1) determine if wearable inertial measurement units (IMUs) could be used in conjunction with a spine motion composite index (SMCI) to quantify subject-specific changes in spine kinematics during a repetitive spine flexion-extension (FE) task; and (2) determine if the SMCI was correlated with measures of global trunk muscle fatigue. Spine kinematics were measured using wearable IMUs in 10 healthy adults during a baseline set followed by 10 sets of 50 spine FE repetitions. After each set, two fatigue measures were collected: perceived level of fatigue using a visual analogue scale (VAS), and maximal lift strength. SMCIs incorporating 10 kinematic variables from 2 IMUs (pelvis and T8 vertebrae) were calculated and used to quantify subject-specific changes in movement. A main effect of set was observed (F (1.7, 15.32) = 10.42, p = 0.002), where the SMCI became significantly greater than set 1 starting at set 4. Significant correlations were observed between the SMCI and both fatigue VAS and maximal lift strength at the individual and study level. These findings support the use of wearable IMUs to detect subject-specific changes in spine motion associated with muscle fatigue.

Potential retinal biomarkers for dementia: what is new?

PURPOSE OF REVIEW: To summarize the current findings on clinical retinal diseases and retinal imaging changes with dementia, focusing on Alzheimer's disease. RECENT FINDINGS: Studies observed that clinical retinal diseases such as age-related macular degeneration, open-angle glaucoma and diabetic retinopathy are related to dementia, but the associations are not entirely consistent. In terms of the retinal neuronal structure, multiple retinal neuronal layers are significantly thinner in Alzheimer's disease dementia, such as the parapapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GC-IPL). Recent studies further demonstrated that macular GC-IPL and macular RNFL are also significantly thinner in the preclinical stage of Alzheimer's disease. A thinner RNFL is also associated with a significantly increased risk of developing both cognitive decline and Alzheimer's disease dementia. In addition, studies consistently showed that retinal vascular changes are associated with poorer cognitive performance, as well as prevalent and incident Alzheimer's disease dementia. SUMMARY: The current findings support the concept that changes in the retina, particular in retinal neuronal structure and vasculature, can reflect the status of cerebral neuronal structure and vasculature, highlighting the potential role of retinal changes as biomarkers of dementia.

Spectral-Domain OCT Measurements in Alzheimer's Disease: A Systematic Review and Meta-analysis.

TOPIC: OCT is a noninvasive tool to measure specific retinal layers in the eye. The relationship of retinal spectral-domain (SD) OCT measurements with Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains unclear. Hence, we conducted a systematic review and meta-analysis to examine the SD OCT measurements in AD and MCI. CLINICAL RELEVANCE: Current methods of diagnosing early AD are expensive and invasive. Retinal measurements of SD OCT, which are noninvasive, technically simple, and inexpensive, are potential biomarkers of AD. METHODS: We conducted a literature search in PubMed and Excerpta Medica Database to identify studies published before December 31, 2017, that assessed the associations between AD, MCI, and measurements of SD OCT: ganglion cell-inner plexiform layer (GC-IPL), ganglion cell complex (GCC), macular volume, and choroidal thickness, in addition to retinal nerve fiber layer (RNFL) and macular thickness. We used a random-effects model to examine these relationships. We also conducted meta-regression and assessed heterogeneity, publication bias, and study quality. RESULTS: We identified 30 eligible studies, involving 1257 AD patients, 305 MCI patients, and 1460 controls, all of which were cross-sectional studies. In terms of the macular structure, AD patients showed significant differences in GC-IPL thickness (standardized mean difference [SMD], -0.46; 95% confidence interval [CI], -0.80 to -0.11; I2 = 71%), GCC thickness (SMD, -0.84; 95% CI, -1.10 to -0.57; I2 = 0%), macular volume (SMD, -0.58; 95% CI, -1.03 to -0.14; I2 = 80%), and macular thickness of all inner and outer sectors (SMD range, -0.52 to -0.74; all P < 0.001) when compared with controls. Peripapillary RNFL thickness (SMD, -0.67; 95% CI, -0.95 to -0.38; I2 = 89%) and choroidal thickness (SMD range, -0.88 to -1.03; all P < 0.001) also were thinner in AD patients. CONCLUSIONS: Our results confirmed the associations between retinal measurements of SD OCT and AD, highlighting the potential usefulness of SD OCT measurements as biomarkers of AD.

Metagenomic discovery of feruloyl esterases from rumen microflora.

Feruloyl esterases (FAEs) are a key group of enzymes that hydrolyze ferulic acids ester-linked to plant polysaccharides. The cow's rumen is a highly evolved ecosystem of complex microbial microflora capable of converting fibrous substances to energy. From direct cloning of the rumen microbial metagenome, we identified seven active phagemids conferring feruloyl esterase activity. The genomic inserts ranged from 1633 to 4143 bp, and the ORFs from 681 to 1359 bp. BLAST search reveals sequence homology to feruloyl esterases and esterases/lipases identified in anaerobes. The seven genes were expressed in Escherichia coli, and the proteins were purified to homogeneity. The FAEs were found to cover types B, C, and D in the feruloyl esterase classification system using model hydroxycinnamic acid esters. The release of ferulic acid (FA) catalyzed by these enzymes was established using natural substrates corn fiber (CF) and wheat insoluble arabinoxylan (WIA). Three of the enzymes were demonstrated to cleave diferulates and hence the capability to break down Araf-FA-FA-Araf cross-links. The wide variation in the sequence, activity, and substrate specificity observed in the FAEs discovered in this study is a confirming evidence that combined actions of a full range of FAE enzymes contribute to the high-efficiency fiber digestion in the rumen microbial ecosystem.

The effect of salinity and photoperiod on thermal tolerance of Atlantic and coho salmon reared from smolt to adult in recirculating aquaculture systems.

Land-based, closed containment salmon aquaculture involves rearing salmon from smolt to adult in recirculating aquaculture systems (RAS). Unlike in open-net pen aquaculture, rearing conditions can be specified in RAS in order to optimize growth and physiological stress tolerance. The environmental conditions that yield optimal stress tolerance in salmon are, however, unknown. To address this knowledge gap, we reared Atlantic (Salmo salar) and coho (Oncorhynchus kisutch) salmon in 7 separate RASs for 400 days post-smoltification under 2 photoperiods (24:0 or 12:12, light:dark) and 4 salinities (2.5, 5, 10 or 30 ppt.) and assessed the effects of these conditions on thermal tolerance. We found that over the first 120 days post-smoltification, rearing coho under a 24:0 photoperiod resulted in a ~2 °C lower critical thermal maxima (CTmax) than in coho reared under a 12:12 photoperiod. This photoperiod effect did not persist at 200 and 400 days, which was coincident with an overall decrease in CTmax in coho. Finally, Atlantic salmon had a higher CTmax (~28 °C) compared to coho (~26 °C) at 400 days post-smoltification. Overall, these findings are important for the future implications of RAS and for the aquaculture industry to help identify physiologically sensitive time stages.

The effects of salinity and photoperiod on aerobic scope, hypoxia tolerance and swimming performance of coho salmon (Oncorhynchus kisutch) reared in recirculating aquaculture systems.

Land-based recirculating aquaculture systems (RAS) have been used to rear salmon from smolt to market-sized adults, but high operating costs have limited their wide spread adoption. One clear advantage of using RAS for salmon aquaculture over open net pens is that fish can be reared under optimal conditions in an attempt to maximize growth and physiological performance and reduce overall production costs. However, few studies have attempted to define the optimal conditions for the long-term rearing of salmon. Thus, the goal of this study is to determine the effects of salinity and photoperiod, two factors that can be easily manipulated in RAS, on the physiological performance of coho salmon (Oncorhynchus kisutch) during long-term rearing. To address this goal, post-smolt coho salmon were reared for 150 days in replicate RAS at 2.5, 5, 10 and 30 ppt under either 12:12 and 24:0 (light:dark) photoperiods. Routine metabolic rate, maximum metabolic rate, aerobic scope and hypoxia tolerance were measured at 60 and 120 days of rearing, while swimming performance was assessed at 60 and 150 days of rearing. There were no effects of salinity or photoperiod on metabolic rate measurements, hypoxia tolerance or swimming performance at any sampling time. There were, however, significant effects of salinity and photoperiod on post-swimming hematology. The results suggest that physiological disturbances continue to manifest due to different environmental conditions, despite acclimation, but do not hinder the animal's ability to cope with physiological stressors. Overall, rearing salinity and photoperiod had very few measurable effects on the physiology and performance of coho salmon except the ionoregulatory disturbances following swimming at salinities of 2.5 and 30 ppt.