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In low-resource settings where disease burdens remain high and many health facilities lack essentials such as drugs or commodities, functional equipment, and trained personnel, poor quality of care often results and the impact can be profound. In this paper, we systematically quantify the potential gain of addressing quality of care globally using country-level data about antenatal, childbirth, and postnatal care interventions. In this study, we created deterministic models to project health outcomes if quality of care was addressed in a representative sample of 81 low- and middle-income countries (LMICs). First, available data from health facility surveys (e.g., Service Provision Assessment [SPA] and Service Availability and Readiness Assessment [SARA]) conducted 2007-2016 were linked to household surveys (e.g., Demographic and Health Surveys [DHS] and Multiple Indicator Cluster Surveys [MICS]) to estimate baseline coverage for a core subset of 19 maternal and newborn health interventions. Next, models were constructed with the Lives Saved Tool (LiST) using country-specific baseline levels in countries with a linked dataset (n = 17) and sample medians applied as a proxy in countries without linked data. Lastly, these 2016 starting baseline levels were raised to reach targets in 2020 as endline based upon country-specific utilization (e.g., proportion of women who attended 4+ antenatal visits, percentage of births delivered in a health facility) from the latest DHS or MICS population-based reports. Our findings indicate that if high-quality health systems could effectively deliver this subset of evidence-based interventions to mothers and their newborns who are already seeking care, there would be an estimated 28% decrease in maternal deaths, 28% decrease in neonatal deaths, and 22% fewer stillbirths compared to a scenario without any change or improvement in quality of care. Totals of 86,000 (range, 77,800-92,400) maternal and 0.67 million (range, 0.59 million-0.75 million) neonatal lives could be saved, and 0.52 million (range, 0.48 million-0.55 million) stillbirths could be prevented across the 81 countries in the calendar year 2020 when adequate quality care is provided at current levels of utilization. Limitations include the paucity of data to individually assess quality of care for each intervention in all LMICs and the necessary assumption that quality of care being provided among the subset of countries with linked datasets is comparable or representative of LMICs overall. Our findings suggest that efforts to close the quality gap would still produce substantial benefits at current levels of access or utilization. With estimated mortality rate declines of 21%-32% on average, gains from this first step would be significant if quality was improved for selected antenatal, intrapartum, and postnatal interventions to benefit pregnant women and newborns seeking care. Interventions provided at or around the time of childbirth are most critical and accounted for 64% of the impact overall estimated in this quality improvement analysis.

Catalytic fast pyrolysis is a promising way to convert lignin into fine chemicals and fuels, but current approaches lack selectivity and yield unsatisfactory conversion. Understanding the pyrolysis reaction mechanism at the molecular level may help to make this sustainable process more economic. Reactive intermediates are responsible for product branching and hold the key to unveiling these mechanisms, but are notoriously difficult to detect isomer-selectively. Here, we investigate the catalytic pyrolysis of guaiacol, a lignin model compound, using photoelectron photoion coincidence spectroscopy with synchrotron radiation, which allows for isomer-selective detection of reactive intermediates. In combination with ambient pressure pyrolysis, we identify fulvenone as the central reactive intermediate, generated by catalytic demethylation to catechol and subsequent dehydration. The fulvenone ketene is responsible for the phenol formation. This technique may open unique opportunities for isomer-resolved probing in catalysis, and holds the potential for achieving a mechanistic understanding of complex, real-life catalytic processes. The conversion of lignin by catalytic fast pyrolysis into useful fine chemicals is a promising route to fuel production, however selectivity and conversion are still not optimal. Here, the authors investigate the reaction mechanism by detection of reactive intermediates responsible for the formation of key products.

Directional tongue movements are crucial for feeding and speech, ensuring proper food positioning for chewing and swallowing, as well as accurate sound production. While directional tuning in the arm region of the sensorimotor cortex during reaching tasks is well studied, little is known about how three-dimensional (3D) tongue direction is encoded in the orofacial sensorimotor cortex (OSMCx) during natural behaviors. Understanding this neural representation has important implications for rehabilitating individuals with orolingual dysfunctions. This study examines the directional tuning and population dynamics in OSMCx during naturalistic feeding and drinking, and how these are affected by sensory loss. Using biplanar video-radiography, we tracked implanted tongue markers in behaving rhesus macaques ( Macaca mulatta ) and simultaneously recorded 3D positional data with spiking activity from chronically implanted microelectrode arrays in primary motor (MIo) and somatosensory (SIo) areas of the orofacial cortex. In some sessions, tasks were preceded by bilateral nerve block injections to the sensory branches of the trigeminal nerve. Modulation to 3D tongue direction during feeding and drinking was found in most MIo and SIo neurons. Directional information at both individual and population levels was higher in feeding and was more robust in MIo. Following sensory loss, alterations in tongue kinematics were accompanied by changes in directional information in MIo and SIo, manifesting as modifications in both individual neuron tuning characteristics and the broader dynamics of population-level neural activity. This study advances our understanding of single-neuron and population activity in OSMCx and their potential contributions to the sensorimotor control of complex naturalistic tongue movements. By extending current knowledge of orofacial control to 3D tongue movements, our findings demonstrate the specificity and adaptability of population activity in MIo and SIo in response to different behavioral contexts, providing important insights for understanding neural mechanisms underlying skilled tongue control.

Purpose The choice of graft for anterior cruciate ligament (ACL) reconstruction remains controversial. The quadriceps tendon (QT) autograft is a good alternative for ACL reconstruction. However, concerns regarding its use in short-statured patients, related to donor site morbidity, anterior knee pain, or loss of muscle strength remain. This study aimed to compare muscle strength and morbidity between patients with short and normal statures following ACL reconstruction with a QT autograft. Methods A total of 73 female patients (mean age, 33.8 ± 11.5 years) who underwent primary ACL reconstruction between 2016 and 2019 were included. Patients were categorized into two groups: group S, with a height ≤ 163 cm, and group L, with a height > 163 cm. Muscle strength, harvesting site morbidity, and ACL-return to sport after injury scale (ACL-RSI) were evaluated, with a mean timing of the follow-up of 9.0 ± 2.3 months. Results The mean quadriceps strength for the isokinetic measurements at 60° and 240° was 65.0% and 74.0% in group S, respectively, and 70.0% and 75.7% in group L, respectively. There was no significant difference in the postoperative muscle strength or mean ACL-RSI (group S, 70.0; group L, 65.9) between the groups. No donor site morbidity was observed in either group. Conclusion Muscle strength recovery, morbidity, and readiness to return to sports were similar in both groups, which supports the possibility of QT autografts for patients with a small stature. The results of this study may provide useful information for surgeons who are hesitant to perform QT autografts because of patient physique. Level of Evidence IV.

Acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), prolongs the regulatory effects of endocannabinoids and reverses the stress-induced anxiety state in a cannabinoid receptor-dependent manner. However, the neural systems underlying this modulation are poorly understood. A single site, randomized, double-blind, placebo-controlled, parallel study was conducted with 43 subjects assigned to receive once daily dosing of either placebo (n = 21) or JNJ-42165279 (100 mg) (n = 22) for 4 consecutive days. Pharmacodynamic effects were assessed on the last day of dosing and included evaluation of brain activation patterns using BOLD fMRI during an (1) emotion face-processing task, (2) inspiratory breathing load task, and (3) fear conditioning and extinction task. JNJ-42165279 attenuated activation in the amygdala, bilateral anterior cingulate, and bilateral insula during the emotion face-processing task consistent with effects previously observed with anxiolytic agents. Higher levels of anandamide were associated with greater attenuation in bilateral anterior cingulate and left insula. JNJ-42165279 increased the activation during anticipation of an aversive interoceptive event in the anterior cingulate and bilateral anterior insula and right inferior frontal cortex. JNJ-42165279 did not affect fear conditioning or within-session extinction learning as evidenced by a lack of differences on a subjective and neural circuit level. Taken together, these results support the hypothesis that JNJ-42165279 at this dose shares some effects with existing anxiolytic agents in dampening response to emotional stimuli but not responses to conditioned fear.

Treatment for tuberculosis, a leading cause of death worldwide, typically involves 6 months of continuous therapy. In this trial, a strategy involving shorter initial treatment was noninferior to standard treatment.

Transcriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas. Co-expression network analyses integrated all data and identified distinct gene expression perturbations across sex and modes of trauma in PTSD, including one wound-healing module downregulated in men exposed to combat traumas, one IL-12-mediated signaling module upregulated in men exposed to IP-related traumas, and two modules associated with lipid metabolism and mitogen-activated protein kinase activity upregulated in women exposed to IP-related traumas. Remarkably, a high degree of sharing of transcriptional dysregulation across sex and modes of trauma in PTSD was also observed converging on common signaling cascades, including cytokine, innate immune, and type I interferon pathways. Collectively, these findings provide a broad view of immune dysregulation in PTSD and demonstrate inflammatory pathways of molecular convergence and specificity, which may inform mechanisms and diagnostic biomarkers for the disorder.

Even before the COVID-19 pandemic, early childhood educators were increasingly tapping apps, such as Seesaw, Brightwheel, and ClassDojo, to connect with families, document individual children's learning and growth as a form of assessment, and as a way for children to recall and reflect on their experiences (Hooker 2019; Fantozzi 2021). Since 2015,1 have worked with preschool programs to consider how technologies, such as digital portfolios, apps that combine image and audio, and virtual bulletin boards, can support developmentally appropriate practice (DAP) by offering new tools to assist children in creating and expressing their learning and new avenues to connect with families. Just as childrens recall of an event at their early learning program is helped by a visual, presenting information in this way can seem more salient to families. In the case of peeling the clementine, the teachers had spent time during their back-to-school event describing ways to foster independence and fine motor skills through daily tasks, like opening snack containers and buttoning coats.

The mechanisms that govern organelle adaptation and remodelling remain poorly defined. The endo-lysosomal system degrades cargo from various routes, including endocytosis, phagocytosis, and autophagy. For phagocytes, endosomes and lysosomes (endo-lysosomes) are kingpin organelles because they are essential to kill pathogens and process and present antigens. During phagocyte activation, endo-lysosomes undergo a morphological transformation, going from a collection of dozens of globular structures to a tubular network in a process that requires the phosphatidylinositol-3-kinase-AKT-mechanistic target of rapamycin (mTOR) signalling pathway. Here, we show that the endo-lysosomal system undergoes an expansion in volume and holding capacity during phagocyte activation within 2 h of lipopolysaccharides (LPS) stimulation. Endo-lysosomal expansion was paralleled by an increase in lysosomal protein levels, but this was unexpectedly largely independent of the transcription factor EB (TFEB) and transcription factor E3 (TFE3), which are known to scale up lysosome biogenesis. Instead, we demonstrate a hitherto unappreciated mechanism of acute organelle expansion via mTOR Complex 1 (mTORC1)-dependent increase in translation, which appears to be mediated by both S6Ks and 4E-BPs. Moreover, we show that stimulation of RAW 264.7 macrophage cell line with LPS alters translation of a subset but not all of mRNAs encoding endo-lysosomal proteins, thereby suggesting that endo-lysosome expansion is accompanied by functional remodelling. Importantly, mTORC1-dependent increase in translation activity was necessary for efficient and rapid antigen presentation by dendritic cells. Collectively, we identified a previously unknown and functionally relevant mechanism for endo-lysosome expansion that relies on mTORC1-dependent translation to stimulate endo-lysosome biogenesis in response to an infection signal.

Mild traumatic brain injury (mTBI) disproportionately affects military service members and is very difficult to diagnose. To-date, there is currently no blood-based, diagnostic biomarker for mTBI cases with persistent post concussive symptoms. To examine the potential of neuronally-derived (NDE) and astrocytic-derived (ADE) exosome cargo proteins as biomarkers of chronic mTBI in younger adults, we examined plasma exosomes from a prospective longitudinal study of combat-related risk and resilience, marine resiliency study II (MRSII). After return from a combat-deployment participants were interviewed to assess TBI exposure while on deployment. Plasma exosomes from military service members with mTBI (mean age, 21.7 years, = 19, avg. days since injury 151), and age-matched, controls (deployed service members who did not endorse a deployment-related TBI or a pre-deployment history of TBI; mean age, 21.95 years, = 20) were precipitated and enriched against a neuronal adhesion protein, L1-CAM, and an astrocyte marker, glutamine aspartate transporter (GLAST) using magnetic beads to immunocapture the proteins and subsequently selected by fluorescent activated cell sorting (FACS). Extracted protein cargo from NDE and ADE preparations were quantified for protein levels implicated in TBI neuropathology by standard ELISAs and on the ultra-sensitive single molecule assay (Simoa) platform. Plasma NDE and ADE levels of Aβ42 were significantly higher while plasma NDE and ADE levels of the postsynaptic protein, neurogranin (NRGN) were significantly lower in participants endorsing mTBI exposure compared to controls with no TBI history. Plasma NDE and ADE levels of Aβ40, total tau, and neurofilament light (NFL), P-T181-tau, P-S396-tau were either undetectable or not significantly different between the two groups. In an effort to understand the pathogenetic potential of NDE and ADE cargo proteins, neuron-like cultures were treated with NDE and ADE preparations from TBI and non-TBI groups. Lastly, we determined that plasma NDE but not ADE cargo proteins from mTBI samples were found to be toxic to neuron-like recipient cells . These data support the presence of markers of neurodegeneration in NDEs of mTBI and suggest that these NDEs can be used as tools to identify pathogenic mechanisms of TBI.