Explore the vast range of titles available.

Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism.

Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more) of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more) of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.

This review article addresses the various aspects of nano-biomaterials used in or being pursued for the purpose of promoting bone regeneration. In the last decade, significant growth in the fields of polymer sciences, nanotechnology, and biotechnology has resulted in the development of new nano-biomaterials. These are extensively explored as drug delivery carriers and as implantable devices. At the interface of nanomaterials and biological systems, the organic and synthetic worlds have merged over the past two decades, forming a new scientific field incorporating nano-material design for biological applications. For this field to evolve, there is a need to understand the dynamic forces and molecular components that shape these interactions and influence function, while also considering safety. While there is still much to learn about the bio-physicochemical interactions at the interface, we are at a point where pockets of accumulated knowledge can provide a conceptual framework to guide further exploration and inform future product development. This review is intended as a resource for academics, scientists, and physicians working in the field of orthopedics and bone repair.

The role of diversity in the maintenance of ecosystems has been studied widely in the past decade. By correlating richness and diversity with basic ecosystem processes, these investigations lend support to the hypothesis that species diversity significantly influences ecosystem functioning and, in turn, provide support for the conservation of biodiversity. Nonetheless, the majority of these investigations demonstrate that conservation of a relatively small number of generally dominant species is sufficient to maintain most processes. Indeed, there is remarkably little evidence to support the contention that less common species, those likely of highest conservation concern, are important in the maintenance of ecosystem functioning. Here we summarize studies, most employing alternative methodological strategies, wherein less common and rare species are demonstrated to make significant contributions to ecosystem functioning. Evidence exists among studies of keystone species, aggregate effects of less common species, and species turnover. Our findings suggest that (1) less common species can make significant ecosystem contributions; (2) further investigation into the effects of rare and less common species on ecosystem maintenance is sorely needed; (3) further investigation should embrace a variety of approaches; and (4) until further research is conducted a prudent conservation approach is warranted wherein the contribution of less common species to ecosystem functioning is assumed.

Background Acute respiratory failure is a common cause for hospitalization and intensive care unit (ICU) admission. Prior literature has found that factors unrelated to patients’ illness severity or clinical needs contribute to substantial variability in ICU admission rates across hospitals. Overuse of the ICU for patients unlikely to benefit from critical care is inefficient, contributes to rising costs, and reduces access to critical care for those who most need it. As part of efforts to improve the efficiency and value of critical care, we utilized human-centered design to create a prototype, system-level intervention designed to optimize ICU utilization for patients hospitalized with acute respiratory failure. Methods We created a multidisciplinary taskforce and conducted four meetings over a 5-month period in 2022 at a VA medical center. We used journey mapping to depict the care continuum of acute respiratory failure patients and identify facilitators/barriers to high-value care; next, we integrated qualitative methods using rapid team-based analysis with human-centered design to develop a system-level intervention to guide triage decisions and tailor care-delivery processes. Results Our taskforce was composed of ten participants (including nurses/physicians/respiratory therapists) with clinical and leadership roles in the emergency department, medical/surgical wards, and ICU. We created a service blueprint map and leveraged it to identify themes influencing ICU utilization among patients with acute respiratory failure, including: (1) hospital organization and care processes (e.g., lack of established ICU admission criteria); (2) available resources outside the ICU (e.g., staffing/bed shortages); and (3) staff interactions (e.g., lack of communication/coordination between clinicians/departments). Informed by these results, the taskforce designed a prototype intervention with four components: (a) create explicit ICU admission criteria; (b) assign levels of care based on patients’ needs; (c) geographically cohort patients with shared needs outside the ICU; and (d) re-engineer rapid-response teams to proactively assess/follow patients outside the ICU. Conclusions We combined qualitative and human-centered design methodologies to develop a prototype intervention designed to improve the value of care for patients with acute respiratory failure. Future studies will pilot test the feasibility and outcomes of the intervention we have developed in this study.

The introduction of three-dimensional printing (3DP) has created exciting possibilities for the fabrication of dosage forms, paving the way for personalized medicine. In this study, oral dosage forms of two drug concentrations, namely 2.50% and 5.00%, were fabricated via stereolithography (SLA) using a novel photopolymerizable resin formulation based on a monomer mixture that, to date, has not been reported in the literature, with paracetamol and aspirin selected as model drugs. In order to produce the dosage forms, the ratio of poly(ethylene glycol) diacrylate (PEGDA) to poly(caprolactone) triol was varied with diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure TPO) utilized as the photoinitiator. The fabrication of 28 dosages in one print process was possible and the printed dosage forms were characterized for their drug release properties. It was established that both drugs displayed a sustained release over a 24-h period. The physical properties were also investigated, illustrating that SLA affords accurate printing of dosages with some statistically significant differences observed from the targeted dimensional range, indicating an area for future process improvement. The work presented in this paper demonstrates that SLA has the ability to produce small, individualized batches which may be tailored to meet patients’ specific needs or provide for the localized production of pharmaceutical dosage forms.

Background Post-hospitalization remote patient monitoring (RPM) has potential to improve health outcomes for high-risk patients with chronic medical conditions. The purpose of this study is to determine the extent to which RPM for patients with congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) is associated with reductions in post-hospitalization mortality, hospital readmission, and ED visits within an Accountable Care Organization (ACO). Methods Nonrandomized prospective study of patients in an ACO offered enrollment in RPM upon hospital discharge between February 2021 and December 2021. RPM comprised of vital sign monitoring equipment (blood pressure monitor, scale, pulse oximeter), tablet device with symptom tracking software and educational material, and nurse-provided oversight and triage. Expected enrollment was for at least 30-days of monitoring, and outcomes were followed for 6 months following enrollment. The co-primary outcomes were (a) the composite of death, hospital admission, or emergency care visit within 180 days of eligibility, and (b) time to occurrence of this composite. Secondary outcomes were each component individually, the composite of death or hospital admission, and outpatient office visits. Adjusted analyses involved doubly robust estimation to address confounding by indication. Results Of 361 patients offered remote monitoring (251 with CHF and 110 with COPD), 140 elected to enroll (106 with CHF and 34 with COPD). The median duration of RPM-enrollment was 54 days (IQR 34–85). Neither the 6-month frequency of the co-primary composite outcome (59% vs 66%, FDR p -value = 0.47) nor the time to this composite (median 29 vs 38 days, FDR p -value = 0.60) differed between the groups, but 6-month mortality was lower in the RPM group (6.4% vs 17%, FDR p-value = 0.02). After adjustment for confounders, RPM enrollment was associated with nonsignificantly decreased odds for the composite outcome (adjusted OR [aOR] 0.68, 99% CI 0.25–1.34, FDR p -value 0.30) and lower 6-month mortality (aOR 0.41, 99% CI 0.00–0.86, FDR p-value 0.20). Conclusions RPM enrollment may be associated with improved health outcomes, including 6-month mortality, for selected patient populations.

Children with ADHD often exhibit fluctuations in attention and heightened reward sensitivity. Psychostimulants, such as methylphenidate (MPH), improve these behaviors in many, but not all, children with ADHD. Given the extent to which psychostimulants are prescribed for children, coupled with variable efficacy on an individual level, a better understanding of the mechanisms through which MPH changes brain function and behavior is necessary. MPH’s primary action is on catecholamines, including dopamine and norepinephrine. Catecholaminergic signaling can influence the tradeoff between flexibility and stability of brain function, which is one candidate mechanism through which MPH may alter brain function and behavior. Time-varying functional connectivity, which models how functional brain networks reconfigure on short timescales, can be used to examine brain flexibility versus stability, and is thus well-suited to test how MPH impacts brain function. Here, we scanned stimulant-naïve children with ADHD (8–12 years) on and off a single dose of MPH. In the MRI machine, participants completed two attention-demanding tasks: 1) a standard go/no-go task and 2) a rewarded go/no-go task. For both tasks, using a within-subjects design, we compared the degree to which brain organization changed throughout the course of the MRI scan, termed whole brain flexibility, on and off MPH. We found that whole brain flexibility decreased on MPH. Further, individuals with greater decreases in whole brain flexibility on MPH exhibited greater improvements in task performance. Together, these results provide novel insights into the neurobiological mechanisms underlying the effectiveness of MPH administration for children with ADHD.

Objective: We sought to determine how the COVID-19 pandemic impacted academic health sciences library workshops. We hypothesized that health sciences libraries moved workshops online during the height of the pandemic and that they continued to offer workshops virtually after restrictions were eased. Additionally, we believed that attendance increased. Methods: In March 2022, we invited 161 Association of American Health Sciences Libraries members in the US and Canada to participate in a Qualtrics survey about live workshops. Live workshops were defined as synchronous; voluntary; offered to anyone regardless of school affiliation; and not credit-bearing. Three time periods were compared, and a chi square test of association was conducted to evaluate the relationship between time period and workshop format. Results: Seventy-two of 81 respondents offered live workshops. A chi square test of association indicated a significant association between time period and primary delivery method, chi-square (4, N=206) = 136.55, p< .005. Before March 2020, 77% of respondents taught in person. During the height of the pandemic, 91% taught online and 60% noted higher attendance compared to pre-pandemic numbers. During the second half of 2021, 65% of workshops were taught online and 43% of respondents felt that attendance was higher than it was pre-pandemic. Overall workshop satisfaction was unchanged (54%) or improved (44%). Conclusion: Most health sciences librarians began offering online workshops following the onset of the COVID-19 pandemic. More than half of respondents were still teaching online in the second half of 2021. Some respondents reported increased attendance with similar levels of satisfaction.

Recent discordance between measured levels of serotypes of dengue virus neutralizing antibody and clinical outcomes suggests a need to reevaluate the process of prescreening dengue vaccine candidates to better predict their clinical benefit before initiation of large-scale human vaccine trials. In the absence of a reliable animal model for dengue, a human dengue virus challenge model (ie, a controlled live dengue virus infectious challenge study) may prove useful and timely to elucidate mechanisms that underlie protection (as well as virulence), thus facilitating down-selection of vaccine candidates before beginning advanced field trials. Dengue challenge studies were safely used in prior decades to study the vector biology, clinical spectrum of illness, and reactogenicity of candidate live dengue virus vaccines of uncertain attenuation. Redeveloping the human dengue challenge model following current regulatory guidance, good manufacturing practice, and good clinical practice could streamline and accelerate vaccine development by offering a time- and resource-efficient method to evaluate the safety and potential efficacy of dengue vaccine and therapeutic candidates. In this article, the development of such a challenge model and its subsequent application is summarized from 2 recent reports.