Nocturnal blood pressure dipping, blood pressure variability, and cognitive function in early and middle-aged adults.

Higher nighttime blood pressure (BP), less BP dipping, and higher BP variability have been linked with worse cognitive function in the elderly. The goal of this study is to explore whether this relationship already exists in early and middle adulthood. We further examined whether ethnic differences between African Americans and European Americans in BP parameters can explain ethnic differences in cognitive function. 24-h ambulatory BP monitoring and cognitive function were obtained from 390 participants (average age: 37.2 years with a range of 25-50; 54.9% African Americans; 63.6% females). We observed that higher nighttime BP, decreased dipping, and higher variability were significantly associated with lower scores on the Picture Sequence Memory Test. Significant negative associations between variability and overall composite scores were also observed. No significant associations between average 24-h or daytime BP and cognitive function were observed. Ethnic differences in nighttime diastolic pressures and dipping can explain 6.81% to 10.8% of the ethnicity difference in the score of the Picture Sequence Memory Test (ps < .05). This study suggests that the associations of nighttime BP, dipping, and variability with cognitive function already exist in young and middle-aged adults. Ethnic differences in nighttime BP and dipping can at least partially explain ethnic differences in cognitive function. The stronger association of these parameters with cognitive function than daytime or average BP in this age range raises the importance of using ambulatory BP monitoring for more precise detection of abnormal BP patterns in young adulthood.

Adverse events among persons with TB using in-person vs. electronic directly observed therapy.

BACKGROUND: We evaluated patient safety within a randomized crossover trial comparing electronic directly observed therapy (eDOT) to in-person DOT (ipDOT) in persons undergoing TB treatment in New York City, NY, USA.METHODS: Participant symptoms, symptom severity, and clinical management were documented. We assessed adverse event reports (AERs) by DOT method during the two-period crossover. Using Cox proportional-hazards mixed-effects models, we estimated the adjusted hazard ratio (aHR) of participants reporting an adverse event (AE) vs. not reporting an AE.RESULTS: Of 211 participants, 57 (27.0%) reported AEs during the two-period crossover; of these, 54.4% (31/57) were reported while using eDOT vs. 45.6% (26/57) while using ipDOT. Controlling for study group and period, the aHR for eDOT vs. ipDOT was 0.98 (95% CI 0.49-1.93). Although statistically not significant, the wide confidence intervals suggest that a significant association cannot be entirely ruled out. Gastrointestinal symptoms were most frequently reported (42.1%, 24/57). AER types and severity did not differ significantly by DOT method. Days from symptom onset to medical attention was similar across DOT methods (median: 1.0 day, IQR 0.0-2.0). No participants switched DOT methods due to AERs or monitoring concerns.CONCLUSION: Further evaluation to ascertain whether AERs differ when patients use eDOT vs. ipDOT is warranted.

Sleep Variability, Sleep Irregularity, and Nighttime Blood Pressure Dipping.

BACKGROUND: Circadian rhythm regulates many important biological functions in humans. The goal of this study is to explore the impact of day-to-day deviations in the sleep-wake cycle on nighttime blood pressure (BP) dipping and further examine whether the ethnic difference in day-to-day deviations in sleep patterns can explain the ethnic difference in nighttime BP dipping. METHODS: Twenty-four-hour ambulatory BP monitoring and 7-day accelerometer data were obtained from 365 adult participants (age range, 18.7-50.1 years; 52.6% Black participants and 47.3% European Americans; 64.1% females). Systolic BP dipping level was used to represent nighttime BP dipping. The SD of sleep duration was calculated as the index of sleep variability, and the SD of sleep midpoint was calculated as the index of sleep irregularity. RESULTS: A 1-hour increase in the SD of sleep midpoint was associated with a 1.16% decrease in nighttime BP dipping (P<0.001). A 1-hour increase in the SD of sleep duration was associated with a 1.39% decrease in nighttime BP dipping (P=0.017). The ethnic difference in the SD of sleep midpoint can explain 29.2% of the ethnicity difference in BP dipping (P=0.008). CONCLUSIONS: Sleep variability and sleep irregularity are associated with blunted BP dipping in the general population. In addition, data from the present investigation also demonstrate that the ethnic difference in sleep irregularity could partly explain the ethnic difference in BP dipping, an important finding that may help reduce the health disparity between Black participants and European Americans.

Challenges associated with electronic and in-person directly observed therapy during a randomized trial.

BACKGROUND: Electronic directly observed therapy (eDOT) has been proposed as an alternative to traditional in-person DOT (ipDOT) for monitoring TB treatment adherence. Information about the comparative performance and implementation of eDOT is limited.METHODS: The frequency of challenges during DOT, challenge type, and effect on medication observation were documented by DOT method during a crossover, noninferiority randomized controlled trial. A logistic mixed-effects model that adjusted for the study design was used to estimate the percentage of successfully observed doses when challenges occurred.RESULTS: A total of 20,097 medication doses were scheduled for observation with either eDOT (15,405/20,097; 76.7%) or ipDOT (4,692/20,097; 23.3%) for 213 study participants. In total, one or more challenges occurred during 17.3% (2,672/15,405) of eDOT sessions and 15.6% (730/4,692) of ipDOT sessions. Among 4,374 documented challenges, 27.3% (n = 1,192) were characterized as technical, 65.9% (n = 2,881) were patient-related, and 6.9% (n = 301) were program-related. Estimated from the logistic model (n = 6,782 doses, 173 participants), the adjusted percentage of doses successfully observed during problematic sessions was 21.7% (95% CI 11.2-37.8) for eDOT and 4.2% (95% CI 1.1-14.7) for ipDOT.CONCLUSION: Compared to ipDOT, challenges were encountered in a slightly higher percentage of eDOT sessions but were more often resolved to enable successful dose observation during problematic sessions.

A Pilot Randomized Controlled Trial Evaluating Essential Oils for Chemotherapy-Induced Peripheral Neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, debilitating consequence of cancer treatment affecting up to 60% of patients. Pharmacological approaches to CIPN are often ineffective and cause adverse effects. Essential oils are an underutilized non-pharmacological approach to pain reduction. AIMS: To ascertain the efficacy of an essential oil intervention to reduce CIPN. DESIGN: A single-blind, pilot randomized controlled trial. METHODS: Participants (n = 27) were stratified by baseline pain scores and randomized to intervention (n = 13) and placebo groups (n = 14). Participants topically-applied the essential oil intervention or placebo every eight hours for six weeks. Pain was assessed using the Short-Form-McGill Pain Questionnaire-2 weekly and the Visual Analogue Scale daily. Quality-of-life was assessed using the Quality-of-Life: CIPN-20 and Quality-of-Life Adult Cancer Survivor questionnaires. Data were analyzed in SPSS using generalized estimating equations. RESULTS: No significant difference was observed between groups in pain or quality-of-life scores over seven weeks, but improvement was observed in both groups. Participants using the intervention with pain medications showed a significant reduction in pain compared to placebo (p = .001). Educational level (p = .041) and annual income (p = .005) were significant covariates mirroring these social determinates of pain. Older participants felt less negatively about their CIPN (p = .002). Positive placebo effect and spatiotemporal interactions were observed. CONCLUSIONS: This pilot study demonstrated that participants adhered to the intervention for six weeks. Essential oils have potential direct and adjuvant pain-reducing effects and should be studied further.

A prognosticative synopsis of contemporary marginal ice zone research.

Commentary narrated in this theme issue is recast to contextualize the diverse themes presented into a forward-looking conversation that synthesizes, debates opportunities for multidisciplinary advances and highlights topics that deserve enduring sharpened attention. Research oriented towards foundational elements of the marginal ice zone that relates to three unifying topic subclasses-namely (i) wave propagation through sea ice, (ii) floe size distributions and (iii) ice dynamics and break-up-and is encapsulated in mini-reviews provided by Thomson, Horvat and Dumont is revisited to distill it into a blueprint for the future guided by the cutting-edge, present-day knowledge documented herein by leading practitioners in the field. Six threads are signalled as imperative for prospective research, each with a bearing on Arctic and Antarctic sea-ice canopies in which the propensity for marginal ice zones to coexist with pack ice is greater as a result of global climate change reducing sea-ice resilience while increasing the prevalence and forcefulness of injurious storm winds and waves. This article is part of the theme issue 'Theory, modelling and observations of marginal ice zone dynamics: multidisciplinary perspectives and outlooks'.

Marginal ice zone dynamics.

For the best part of my entire career, I have focused on the marginal ice zone, abbreviated to MIZ by most sea ice scientists. Defined perfunctorily by the National Snow & Ice Data Center as the part of the seasonal ice zone where waves, swells and other open ocean processes affect the sea ice, the MIZ habitually extends from the ice edge some 100-200 km into the ice pack with morphology that varies dramatically spatially and with time. In general, the Antarctic MIZ is wider than MIZs in the Arctic, recognizing that increases in the ferocity and incidence of storms and the durability of ice due to global climate change are already affecting the physical attributes of each MIZ. I provide here a somewhat historically tailored preamble to a unique compilation of up-to-the-minute MIZ research in this theme issue that includes the nexus between contemporary theoretical, modelling and experimental projects. A prognosticative synopsis of these projects is also included later in the volume, framed in the context of the ongoing ontogenesis of the research field. This article is part of the theme issue 'Theory, modelling and observations of marginal ice zone dynamics: multidisciplinary perspectives and outlooks'.

Nuclear moments of indium isotopes reveal abrupt change at magic number 82.

In spite of the high-density and strongly correlated nature of the atomic nucleus, experimental and theoretical evidence suggests that around particular 'magic' numbers of nucleons, nuclear properties are governed by a single unpaired nucleon1,2. A microscopic understanding of the extent of this behaviour and its evolution in neutron-rich nuclei remains an open question in nuclear physics3-5. The indium isotopes are considered a textbook example of this phenomenon6, in which the constancy of their electromagnetic properties indicated that a single unpaired proton hole can provide the identity of a complex many-nucleon system6,7. Here we present precision laser spectroscopy measurements performed to investigate the validity of this simple single-particle picture. Observation of an abrupt change in the dipole moment at N = 82 indicates that, whereas the single-particle picture indeed dominates at neutron magic number N = 82 (refs. 2,8), it does not for previously studied isotopes. To investigate the microscopic origin of these observations, our work provides a combined effort with developments in two complementary nuclear many-body methods: ab initio valence-space in-medium similarity renormalization group and density functional theory (DFT). We find that the inclusion of time-symmetry-breaking mean fields is essential for a correct description of nuclear magnetic properties, which were previously poorly constrained. These experimental and theoretical findings are key to understanding how seemingly simple single-particle phenomena naturally emerge from complex interactions among protons and neutrons.

Schizophrenia: A developmental disorder with a risk of non-specific but avoidable decline.

The onset of schizophrenia is determined by biological and social risk factors operating predominantly during development. These result in subtle deviations in brain structure and cognitive function. Striatal dopamine dysregulation follows, causing abnormal salience and resultant psychotic symptoms. Most people diagnosed as having schizophrenia do not progressively deteriorate; many improve or recover. However, poor care can allow a cycle of deterioration to be established, stress increasing dopamine dysregulation, leading to more stress consequent on continuing psychotic experiences, and so further dopamine release. Additionally, long-term antipsychotics can induce dopamine supersensitivity with resultant relapse and eventually treatment resistance. Some patients suffer loss of social and cognitive function, but this is a consequence of the hazards that afflict the person with schizophrenia, not a direct consequence of genetic predisposition. Thus, brain health and cognition can be further impaired by chronic medication effects, cardiovascular and cerebrovascular events, obesity, poor diet, and lack of exercise; drug use, especially of tobacco and cannabis, are likely to contribute. Poverty, homelessness and poor nutrition which become the lot of some people with schizophrenia, can also affect cognition. Regrettably, the model of progressive deterioration provides psychiatry and its funders with an alibi for the effects of poor care.

Isotope Shifts of Radium Monofluoride Molecules.

Isotope shifts of ^{223-226,228}Ra^{19}F were measured for different vibrational levels in the electronic transition A^{2}Π_{1/2}←X^{2}Σ^{+}. The observed isotope shifts demonstrate the particularly high sensitivity of radium monofluoride to nuclear size effects, offering a stringent test of models describing the electronic density within the radium nucleus. Ab initio quantum chemical calculations are in excellent agreement with experimental observations. These results highlight some of the unique opportunities that short-lived molecules could offer in nuclear structure and in fundamental symmetry studies.

Laser spectroscopy of indium Rydberg atom bunches by electric field ionization.

This work reports on the application of a novel electric field-ionization setup for high-resolution laser spectroscopy measurements on bunched fast atomic beams in a collinear geometry. In combination with multi-step resonant excitation to Rydberg states using pulsed lasers, the field ionization technique demonstrates increased sensitivity for isotope separation and measurement of atomic parameters over previous non-resonant laser ionization methods. The setup was tested at the Collinear Resonance Ionization Spectroscopy experiment at ISOLDE-CERN to perform high-resolution measurements of transitions in the indium atom from the [Formula: see text] and [Formula: see text] states to [Formula: see text]p [Formula: see text]P and [Formula: see text]F Rydberg states, up to a principal quantum number of [Formula: see text]. The extracted Rydberg level energies were used to re-evaluate the ionization potential of the indium atom to be [Formula: see text]. The nuclear magnetic dipole and nuclear electric quadrupole hyperfine structure constants and level isotope shifts of the [Formula: see text] and [Formula: see text] states were determined for [Formula: see text]In. The results are compared to calculations using relativistic coupled-cluster theory. A good agreement is found with the ionization potential and isotope shifts, while disagreement of hyperfine structure constants indicates an increased importance of electron correlations in these excited atomic states. With the aim of further increasing the detection sensitivity for measurements on exotic isotopes, a systematic study of the field-ionization arrangement implemented in the work was performed at the same time and an improved design was simulated and is presented. The improved design offers increased background suppression independent of the distance from field ionization to ion detection.

Spectroscopy of short-lived radioactive molecules.

Molecular spectroscopy offers opportunities for the exploration of the fundamental laws of nature and the search for new particle physics beyond the standard model1-4. Radioactive molecules-in which one or more of the atoms possesses a radioactive nucleus-can contain heavy and deformed nuclei, offering high sensitivity for investigating parity- and time-reversal-violation effects5,6. Radium monofluoride, RaF, is of particular interest because it is predicted to have an electronic structure appropriate for laser cooling6, thus paving the way for its use in high-precision spectroscopic studies. Furthermore, the effects of symmetry-violating nuclear moments are strongly enhanced5,7-9 in molecules containing octupole-deformed radium isotopes10,11. However, the study of RaF has been impeded by the lack of stable isotopes of radium. Here we present an experimental approach to studying short-lived radioactive molecules, which allows us to measure molecules with lifetimes of just tens of milliseconds. Energetically low-lying electronic states were measured for different isotopically pure RaF molecules using collinear resonance ionisation at the ISOLDE ion-beam facility at CERN. Our results provide evidence of the existence of a suitable laser-cooling scheme for these molecules and represent a key step towards high-precision studies in these systems. Our findings will enable further studies of short-lived radioactive molecules for fundamental physics research.

From early adversities to immune activation in psychiatric disorders: the role of the sympathetic nervous system.

Increased peripheral levels of cytokines and central microglial activation have been reported in patients with psychiatric disorders. The degree of both innate and adaptive immune activation is also associated with worse clinical outcomes and poor treatment response in these patients. Understanding the possible causes and mechanisms leading to this immune activation is therefore an important and necessary step for the development of novel and more effective treatment strategies for these patients. In this work, we review the evidence of literature pointing to childhood trauma as one of the main causes behind the increased immune activation in patients with psychiatric disorders. We then discuss the potential mechanisms linking the experience of early life adversity (ELA) to innate immune activation. Specifically, we focus on the innervation of the bone marrow from sympathetic nervous system (SNS) as a new and emerging mechanism that has the potential to bridge the observed increases in both central and peripheral inflammatory markers in patients exposed to ELA. Experimental studies in laboratory rodents suggest that SNS activation following early life stress exposure causes a shift in the profile of innate immune cells, with an increase in proinflammatory monocytes. In turn, these cells traffic to the brain and influence neural circuitry, which manifests as increased anxiety and other relevant behavioural phenotypes. To date, however, very few studies have been conducted to explore this candidate mechanism in humans. Future research is also needed to clarify whether these pathways could be partially reversible to improve prevention and treatment strategies in the future.

A fresh look at how ocean waves and sea ice interact.

Because of their capacity to alter floe size distribution and concentration and consequently to influence atmosphere-ocean fluxes, there is a compelling justification and demand to include waves in ice/ocean models and earth system models. Similarly, global wave forecasting models like WAVEWATCH III® need better parametrizations to capture the effects of a sea ice cover such as the marginal ice zone on incoming wave energy. Most parametrizations of wave propagation in sea ice assume without question that the frequency-dependent attenuation which is observed to occur with distance x travelled is exponential, i.e. A = A0 e-αx This is the solution of the simple first-order linear ordinary differential equation dA/dx = - αA, which follows from an Airy wave mode ansatz [Formula: see text] Yet, in point of fact, it now appears that exponential decay may not be observed consistently and a more general equation of the type dA/dx = - αAn is proposed to allow for a broader range of attenuation behaviours should this be necessary to fit data.This article is part of the theme issue 'Modelling of sea-ice phenomena'.

Antarctic ice shelf disintegration triggered by sea ice loss and ocean swell.

Understanding the causes of recent catastrophic ice shelf disintegrations is a crucial step towards improving coupled models of the Antarctic Ice Sheet and predicting its future state and contribution to sea-level rise. An overlooked climate-related causal factor is regional sea ice loss. Here we show that for the disintegration events observed (the collapse of the Larsen A and B and Wilkins ice shelves), the increased seasonal absence of a protective sea ice buffer enabled increased flexure of vulnerable outer ice shelf margins by ocean swells that probably weakened them to the point of calving. This outer-margin calving triggered wider-scale disintegration of ice shelves compromised by multiple factors in preceding years, with key prerequisites being extensive flooding and outer-margin fracturing. Wave-induced flexure is particularly effective in outermost ice shelf regions thinned by bottom crevassing. Our analysis of satellite and ocean-wave data and modelling of combined ice shelf, sea ice and wave properties highlights the need for ice sheet models to account for sea ice and ocean waves.

Micro-calibration of space and motion by photoreceptors synchronized in parallel with cortical oscillations: A unified theory of visual perception.

A fundamental function of the visual system is detecting motion, yet visual perception is poorly understood. Current research has determined that the retina and ganglion cells elicit responses for motion detection; however, the underlying mechanism for this is incompletely understood. Previously we proposed that retinogeniculo-cortical oscillations and photoreceptors work in parallel to process vision. Here we propose that motion could also be processed within the retina, and not in the brain as current theory suggests. In this paper, we discuss: 1) internal neural space formation; 2) primary, secondary, and tertiary roles of vision; 3) gamma as the secondary role; and 4) synchronization and coherence. Movement within the external field is instantly detected by primary processing within the space formed by the retina, providing a unified view of the world from an internal point of view. Our new theory begins to answer questions about: 1) perception of space, erect images, and motion, 2) purpose of lateral inhibition, 3) speed of visual perception, and 4) how peripheral color vision occurs without a large population of cones located peripherally in the retina. We explain that strong oscillatory activity influences on brain activity and is necessary for: 1) visual processing, and 2) formation of the internal visuospatial area necessary for visual consciousness, which could allow rods to receive precise visual and visuospatial information, while retinal waves could link the lateral geniculate body with the cortex to form a neural space formed by membrane potential-based oscillations and photoreceptors. We propose that vision is tripartite, with three components that allow a person to make sense of the world, terming them "primary, secondary, and tertiary roles" of vision. Finally, we propose that Gamma waves that are higher in strength and volume allow communication among the retina, thalamus, and various areas of the cortex, and synchronization brings cortical faculties to the retina, while the thalamus is the link that couples the retina to the rest of the brain through activity by gamma oscillations. This novel theory lays groundwork for further research by providing a theoretical understanding that expands upon the functions of the retina, photoreceptors, and retinal plexus to include parallel processing needed to form the internal visual space that we perceive as the external world.

Translational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia.

Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls. Using an infection-mediated neurodevelopmental mouse model, we show that schizophrenia-relevant behavioral abnormalities and increased inflammatory cytokine expression are associated with reduced prefrontal TSPO levels. On the other hand, TSPO was markedly upregulated in a mouse model of acute neurodegeneration and reactive gliosis, which was induced by intrahippocampal injection of kainic acid. In both models, the changes in TSPO levels were not restricted to microglia but emerged in various cell types, including microglia, astrocytes and vascular endothelial cells. Human PET imaging using the second-generation TSPO radiotracer [11C]DPA-713 revealed a strong trend towards reduced TSPO binding in the middle frontal gyrus of patients with recent-onset schizophrenia, who were previously shown to display increased levels of inflammatory cytokines in peripheral and central tissues. Together, our findings challenge the common assumption that central low-grade inflammation in schizophrenia is mirrored by increased TSPO expression or ligand binding. Our study further underscores the need to interpret altered TSPO binding in schizophrenia with caution, especially when measures of TSPO are not complemented with other markers of inflammation. Unless more selective microglial markers are available for PET imaging, quantification of cytokines and other inflammatory biomarkers, along with their molecular signaling pathways, may be more accurate in attempts to characterize inflammatory profiles in schizophrenia and other mental disorders that lack robust reactive gliosis.

Self-Regulation of Breathing as an Adjunctive Treatment of Insomnia.

Sleep is a quiescent behavioral state during which complex homeostatic functions essential to health and well-being occur. Insomnia is a very common psychiatric disorder leading to a myriad of detrimental effects including loss of concentration, memory, and performance as well as disease. Current pharmaceutical treatments can be expensive, impairing, unhealthy, and habit-forming. Relaxation techniques, such as meditation target the brain and body in contrast to pharmaceutical interventions which solely target neurotransmitter systems in the brain. In this article we present a viewpoint on the treatment of insomnia that techniques of slow, deep breathing (0.1 Hz) in adjunct to sleep hygiene and relaxation therapies may be highly effective in initiating sleep as well as facilitating falling back asleep. The autonomic nervous system is integral to sleep initiation, maintenance, and disruption. Understanding the relationship between the autonomic nervous system and sleep physiology along with the nature of sleep itself remains a challenge to modern science. We present this perspective in light of a prevailing "dysevolution" theory on the pathology of insomnia that proposes hyper-arousal characterized in part by chronic sympathetic hyperactivation and/or parasympathetic hypoactivation disrupts normal sleep onset latency, sleep quality, and sleep duration. We additionally discuss physiological mechanisms responsible for the effectiveness of the breathing treatment we describe. A better understanding of these mechanisms and autonomic pathologies of insomnia may provide support for the effectiveness of such techniques and provide relief to sufferers of this health epidemic.

Factors associated with non-completion of follow-up: 33-month latent tuberculous infection treatment trial.

SETTING: A post-hoc exploratory analysis of a randomized, open-label clinical trial that enrolled 8053 participants from the United States, Canada, Brazil, and Spain. OBJECTIVE: To assess factors associated with non-completion of study follow-up (NCF) in a 33-month latent tuberculous infection treatment trial, PREVENT TB. DESIGN: Participants were randomized to receive 3 months of weekly directly observed therapy vs. 9 months of daily self-administered therapy. NCF was defined as failing to be followed for at least 993 days (33 months) from enrollment. Possible factors associated with NCF were analyzed using univariate and multivariate regression via Cox proportional hazard model. RESULTS: Of 7061 adults selected for analysis, 841 (11.9%) did not complete study follow-up. Homelessness, young age, low education, history of incarceration, smoking, missing an early clinic visit, receiving isoniazid only, and male sex were significantly associated with NCF. Similar results were found in the North American region (United States and Canada) only. In Brazil and Spain, the only significant factor was missing an early clinic visit. CONCLUSIONS: Study subjects at higher risk for NCF were identified by characteristics known at enrollment or in early follow-up. Evaluation of follow-up in other trials might help determine whether the identified factors consistently correlate with retention.